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TW200404539A - Acetamides and benzamides that are useful in treating sexual dysfunction - Google Patents

Acetamides and benzamides that are useful in treating sexual dysfunction Download PDF

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Publication number
TW200404539A
TW200404539A TW092114035A TW92114035A TW200404539A TW 200404539 A TW200404539 A TW 200404539A TW 092114035 A TW092114035 A TW 092114035A TW 92114035 A TW92114035 A TW 92114035A TW 200404539 A TW200404539 A TW 200404539A
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TW
Taiwan
Prior art keywords
group
methyl
phenyl
cyano
alkyl
Prior art date
Application number
TW092114035A
Other languages
Chinese (zh)
Inventor
Pramila A Bhatia
Jerome F Daanen
Ahmed A Hakeem
Teodozyj Kolasa
Mark A Matulenko
H Mortell Kathleen
V Patel Meena
O Stewart Andrew
Wang Xueqing
Xia Zhiren
Q Zhang Henry
Original Assignee
Abbott Lab
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Priority claimed from US10/154,373 external-priority patent/US20030232836A1/en
Priority claimed from US10/425,152 external-priority patent/US20040029887A1/en
Application filed by Abbott Lab filed Critical Abbott Lab
Publication of TW200404539A publication Critical patent/TW200404539A/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings

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  • Health & Medical Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyridine Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention relates to the use of compounds of formula (I), for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

Description

200404539 玖、發明說明： 本申請案為2002年5月23曰提出申請之美國專利申請案序 號1〇/154,373之一件部份連續案，其係據此併於本文供參考。 【發明所屬之技術領域】 本發明係關於乙醯胺與苯甲醯胺，及含有此等化合物之組 合物’於治療性功能障礙上之用途。 【先前技術】 臨fjE前1正據顯示多巴胺（DA)在哺乳動物中，於陰莖勃起上 ，係扮演一項角色。性刺激可藉由感官（性慾）訊息抵達哺 礼動物中之大腦皮質而被引發。大腦皮質具有與邊緣結構 ，例如扁桃體，以及中腦結構，例如周圍導管灰白質（pAG) 及下視丘之外延神經元接點。於下視丘中之兩個重要核， 係為中間視葉前區域(MP〇A)與室旁核（ργΝ)。Mp〇A與核 ’在此等區域之兩侧損害完全排除男性性行為時，於性行 為上係扮演一個關鍵角色。神經支配PVN與MPOA核之未定 視丘下部多巴胺能途徑，係與DA劑之勃起前作用有關聯。 DA文體催動劑，例如阿樸嗎啡（ap〇m〇rphine)(⑺设)加，了—田氫_ 6-甲基-4H-二苯并[de，g]喹啉-说⑴二醇）、昆皮洛（quinpir〇le)及（一 )3-(3-羥苯基）-N-丙基六氫吡啶（3-Ppp)之系統投藥，有助於大 白乳中之陰呈勃起，此為一種被画喊淀醇阻斷之作用，該 i哌啶醇為一種中樞DA拮抗劑。因勃起原作用不能被冬培 利酮（domperidone)阻斷，該酮為一種末梢DA拮抗劑，故咸信da 催動劑之勃起前作用，係以中樞方式媒介。 臨床數據亦顯示，在CNS中之DA系統，對於男性性行為 85228 200404539 之調節’係扮演一項角色，如葬山 ^如精由L_多巴在巴金生氏病患200404539 发明 Description of the Invention: This application is a part of a consecutive US Patent Application No. 10 / 154,373 filed on May 23, 2002, which is hereby incorporated herein by reference. [Technical field to which the invention belongs] The present invention relates to the use of acetomine and benzamidine, and a composition containing these compounds' for the treatment of sexual dysfunction. [Previous Technology] Pro-FJE Pro-1 shows that dopamine (DA) plays a role in penile erection in mammals. Sexual stimulation can be triggered by sensory (sexual) messages reaching the cerebral cortex in mammals. The cerebral cortex has junctions with peripheral structures, such as tonsils, and midbrain structures, such as peripheral duct gray matter (pAG) and epithelium of hypothalamus. The two important nuclei in the hypothalamus are the anterior mesothelial region (MPOA) and the paraventricular nucleus (ργN). MpoA and nuclear damage on both sides of these areas play a key role in sexual behavior when the male sex is completely ruled out. The innervation of PVN and the nucleus of MPOA is indeterminate. The dopaminergic pathway in the lower optic mound is related to the pre-erectile effect of DA agents. DA stylistic stimulants, such as apomorphine (apomrphine) (supplied) plus, -Hydro-6-methyl-4H-dibenzo [de, g] quinoline-saidanediol ), Quinpirole and (a) 3- (3-hydroxyphenyl) -N-propylhexahydropyridine (3-Ppp) systemic administration, which helps to erect yin in white milk This is a blockade effect by picodol, which is a central DA antagonist. Because the erectogenic effect cannot be blocked by domperidone, a peripheral DA antagonist, the pre-erection effect of Xianxin da activator is a central mediator. Clinical data also show that the DA system in the CNS plays a role in the regulation of male sexual behavior 85228 200404539, such as the funeral mountain ^ Rujing by L_Dopa in patients with Parkinson's disease

中之性刺激作用，及藉由阿樸嗎A 柯叫u悮馬啡在人類中之勃起前作用 所顯示者。 DA文體係歸屬於藉由偶合至胞内GTp•結合蛋白質以發出 訊息越過細胞膜之蛋白質受體之超族群。數種g蛋白質已被 確認（包括Gs，Gq及Gi)會導致專一胞内事件。 有五種已知DA X f豆’其係被分類成兩個組君竿，〇厂狀與^ _ 狀。狀受體包括D^d5。&狀受體包括a、。及仏。 狀族群受體亞型係經Gs •偶合，且可活化料酸環化酶。A· 狀族群受體亞型係經Gi_偶合，且其會增加胞内鈣含量及抑 制腺苷酸環化酶。 狀族群成員為Gs-偶合之受體，其可活化腺甞酸環化酶 。就mRNA表現及就免疫組織化學研究而言，〇1受體為在cns 中取豐冨且廣泛之DA受體。其係被發現於紋狀體、臥核及 嗅結節，以及邊緣系統、下視丘及交腦中。q受體表現已 被報告於心臟與腎臟中，而不管此等末梢q受體之功能仍_ 待釐清，其對於控制血液流動變數之角色已被確認。此h 雙體，雖然比以受體具有對DA之較高親和力，但很少分佈 在CNS中，且沒有在CNS外部表現之証據。 A -狀族群成員為a偶合之受體，其會抑制腺嘗酸環化酶 ’及增加胞内鈣含量。A受體為最豐富之D2-狀受體，且位 於腦邵區域中，譬如紋狀體與黑質，及在末梢區域中，譬 如心臟、腦垂體及腎臟。A受體已被大量地發現於Calleja小 島中’具有不同群集個體群在腹紋狀體/核臥區域、嗅結節 85228 200404539 、齒回及紋狀體皮質中。 D4受體之表現已藉由原位RNA雜化與免疫組織化學研究作 考証。近來，研究已發現D4表現，在下視丘之鼻内皮質、 側向中隔核、海馬及中間視葉前區域中，係為最高。D4之 定位係與D2在腦中之分佈不同，因D2受體在紋狀體區域中 最豐富。D4受體在下視丘之MPOA中之表現，鑒於下視丘作 為皮質與脊髓途徑間之整合區域之角色，故對於促進陰莖 勃起具有重要性。D4受體參與其他CNS區域，丘腦、下丘腦 及脊髓，不能被排除在外。 本發明確認式（I)乙醯胺與苯甲醯胺在哺乳動物中治療性功 能障礙上之治療用途。更明確言之，此等化合物可用於治 療性功能障礙，包括但不限於男性勃起功能障礙（MED)。 【發明内容】 本發明係關於一種在哺乳動物特別是人類中治療性功能障 礙之方法，其包括對該哺乳動物投予治療上有效量之式（I) 化合物Sexual stimulating effects in humans, as well as the pre-erectile effects of apomorphine A Ko called u 悮 maphine in humans. The DA system belongs to the superfamily of protein receptors that cross the cell membrane by coupling to intracellular GTp • binding proteins. Several g proteins (including Gs, Gq, and Gi) have been confirmed to cause specific intracellular events. There are five known DA X f beans' lines which are classified into two groups, 〇 plant-like and ^ _- like. Receptors include D ^ d5. & like receptors include a. And alas. Receptor subtypes are Gs-coupled and can activate acid cyclase. The A · like group of receptor subtypes is Gi_coupled, and it will increase intracellular calcium content and inhibit adenylate cyclase. Members of the serogroup are Gs-coupled receptors that activate adenylate cyclase. In terms of mRNA performance and in immunohistochemical studies, the 〇1 receptor is a rich and extensive DA receptor in cns. It is found in the striatum, the lying nucleus, and the olfactory nodules, as well as in the limbic system, hypothalamus, and crossbrain. Q-receptor performance has been reported in the heart and kidneys, although the function of these peripheral q-receptors remains to be clarified, and their role in controlling blood flow variables has been identified. Although this h-diploid has a higher affinity for DA than the receptor, it is rarely distributed in the CNS and there is no evidence of external manifestations of the CNS. Members of the A-like group are a coupled receptors that inhibit glandular acid cyclase 'and increase intracellular calcium content. The A receptor is the most abundant D2-like receptor and is located in the brain region, such as the striatum and the substantia nigra, and in the peripheral regions, such as the heart, pituitary, and kidney. A receptors have been found in large numbers in Calleja islands, with groups of individuals in the ventral striatum / nucleus lying region, olfactory nodules 85228 200404539, dentate gyrus, and striatum cortex. The performance of the D4 receptor has been verified by in situ RNA hybridization and immunohistochemical studies. Recently, studies have found that D4 manifestations are highest in the intranasal cortex, lateral septal nucleus, hippocampus, and anterior mediastinal lobe of the hypothalamus. The localization of D4 is different from that of D2 in the brain, because D2 receptors are most abundant in the striatum. The expression of D4 receptors in the MPOA of the hypothalamus is important for the promotion of penile erection in view of the role of the hypothalamus as an integrated region between the cortex and spinal cord pathways. D4 receptors are involved in other CNS regions, the thalamus, hypothalamus, and spinal cord, and cannot be excluded. The present invention confirms the therapeutic use of acetamide and benzamidine of formula (I) for the treatment of sexual dysfunction in mammals. More specifically, these compounds are useful in the treatment of sexual dysfunction, including but not limited to male erectile dysfunction (MED). SUMMARY OF THE INVENTION The present invention relates to a method for treating sexual dysfunction in a mammal, particularly a human, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I)

(I) 或其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 A為芳基、芳烷基、環烷基、環烷基烷基、雜環或雜環烷 基； L 為-N(R7)C(0)-、-C(0)N(R7)-、-N(R7)C(S)-或-C(S)N(R7)·，其 中該-N(R7)C(0)_、-C(0)N(R7)-、-N(R7)C(S)-或-C(S)N(R7> 之左端 85228 200404539 係連接至A，而右端係連接至D ; D為次烷基、氟次烷基或經基次燒基； Z 為 N、C 或 CRg，(I) or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, wherein A is aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclic or heterocycloalkyl; L -N (R7) C (0)-, -C (0) N (R7)-, -N (R7) C (S)-, or -C (S) N (R7) ·, where -N ( The left end of R7) C (0) _, -C (0) N (R7)-, -N (R7) C (S)-, or -C (S) N (R7 >) is connected to A and the right end is 85228 200404539 Is connected to D; D is an alkylene group, a fluoroalkylene group or a sulfonyl group; Z is N, C or CRg,

Ra為氫或烷基；Ra is hydrogen or alkyl;

Rb為氫、燒基或鹵素； 當Z為C時，…為一個键結，而當Z為N或CRB時， 存在； B為Rb is hydrogen, alkyl or halogen; when Z is C, ... is a bond, and when Z is N or CRB, it is present; B is

Ri、R2、R3、R4及R5各獨立為氫、烷氧基、晞基、％義 燒基亞橫酿基、燒基續酸基、院硫基、炔:基、坡氧幾^爲 烷羰基、烷羰基氧基、羧基、氯基、甲醯基、南素、_燒 氧基' ΐ烷基、羥基、羥烷基、巯基、硝基、-NZi Z2、（NZ3 Z4) 烷基、（NZ3Z4)羰基或（NZ3Z4)續醯基；Ri, R2, R3, R4, and R5 are each independently hydrogen, alkoxy, fluorenyl, sulfanyl, sulfenyl, alkynyl, sulfanyl, alkynyl, alkynyl, and peroxo. Carbonyl, alkylcarbonyloxy, carboxyl, chloro, methylamino, sulfanil, _alkoxy ', alkyl, hydroxy, hydroxyalkyl, mercapto, nitro, -NZi Z2, (NZ3 Z4) alkyl, (NZ3Z4) carbonyl or (NZ3Z4) continyl;

Zi與z2各獨立為氫、烷基、烷羰基、烷基磺醯基、芳基、 芳烷基、芳烷基磺醯基、芳基磺醯基或甲醯基； z3與z4各獨立為氫、燒基、芳基或芳垸基； X 為 N(R6)、Ο 或 S ; Y 為 C(R4)或 N ; r6為氫或烷基；及 85228 -10- 200404539 R7為氫或烷基。 發明詳述 所有在本專利說明書中引述之專利、專利申請案及文獻參 考資料，均以其全文併於本文供參考。 在本發明之主要具體實施例中，其係關於一種在哺乳動物 特別是人類中治療性功能障礙之方法，其包括對該哺乳動 物投予治療上有效量之式C0化合物Zi and z2 are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, aralkyl, aralkylsulfonyl, arylsulfonyl or formamyl; z3 and z4 are each independently Hydrogen, alkyl, aryl, or arylfluorenyl; X is N (R6), 0, or S; Y is C (R4) or N; r6 is hydrogen or alkyl; and 85228 -10- 200404539 R7 is hydrogen or alkane base. Detailed Description of the Invention All patents, patent applications, and literature references cited in this patent specification are hereby incorporated by reference in their entirety. In a main embodiment of the present invention, it relates to a method for treating sexual dysfunction in mammals, especially humans, which comprises administering to the mammal a therapeutically effective amount of a compound of formula C0

Ra a/L、d〆 (I) 或其藥學上可接受之鹽、酯、酸胺或前體藥物，其中 A為芳基、芳烷基、環烷基、環烷基烷基、雜環或雜環烷 基； L 為-N(R7)C(0>、-C(0)N(R7)-、-N(R7)C(S)-或-C(S)N(R7)_，其 中該-N(R7)C(0>、-C(0)N(R7)-、-N(R7)C(S)-或-C(S)N(R7)-之左端 係連接至A，而右端係連接至D ; D為次烷基、氟次烷基或羥基次烷基； Z 為 N、C 或 CRB ; ra為氫或烷基； rb為氫、烷基或鹵素； 當Z為C時，…為一個鍵結，而當Z為N或CRB時，…為不 存在， B為 85228 -11 - 200404539Ra a / L, d〆 (I) or a pharmaceutically acceptable salt, ester, acid amine or prodrug thereof, wherein A is aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclic Or heterocycloalkyl; L is -N (R7) C (0 >, -C (0) N (R7)-, -N (R7) C (S)-, or -C (S) N (R7) _ Where the left end of the -N (R7) C (0 >, -C (0) N (R7)-, -N (R7) C (S)-, or -C (S) N (R7)-is connected to A, and the right end is connected to D; D is an alkylene, fluoroalkylene, or hydroxyalkylene; Z is N, C, or CRB; ra is hydrogen or alkyl; rb is hydrogen, alkyl, or halogen; when When Z is C, ... is a bond, and when Z is N or CRB, ... is absent, B is 85228 -11-200404539

燒基亞磧si基、燒基續酸基、燒硫基、決基、燒氧羰基、 燒黢基、燒羧基氧基、叛基、氰基、甲酸基、函素、_燒 氧基、lS烷基、經基、羥烷基、鐃基、硝基、-NZi Z2、（Nz3 z4) fe基、（NZ3 Z4 )談基或（NZ3 Z4 )績酸基； 21與22各獨立為氫、烷基、烷羰基、烷基磺醯基、芳基、 芳烷基、芳烷基磺醯基、芳基磺醯基或甲醯基； Z3與Z4各獨立為氫、烷基、芳基或芳烷基； X 為 N(R6)、0 或 S ; Y 為 C(R4)或 N; R6為氫或燒基；及 R7為氫或燒基。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為Alkylsulfenyl, alkynyl, sulfanyl, sulfanyl, decyl, oxocarbonyl, oxenyl, carboxyloxy, alkyl, cyano, formate, halo, oxyalkyl, lS alkyl, mesityl, hydroxyalkyl, fluorenyl, nitro, -NZi Z2, (Nz3 z4) fe, (NZ3 Z4), or (NZ3 Z4) acid groups; 21 and 22 are each independently hydrogen , Alkyl, alkylcarbonyl, alkylsulfonyl, aryl, aralkyl, aralkylsulfonyl, arylsulfonyl or formamyl; Z3 and Z4 are each independently hydrogen, alkyl, aryl Or aralkyl; X is N (R6), 0, or S; Y is C (R4) or N; R6 is hydrogen or alkyl; and R7 is hydrogen or alkyl. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl ; B is

% ; Z為N ;…為不存在；L為_n(R7)C(0)_ ;且D R2、R3、R4、反5、R7及Ra均如式Φ中之定義。 85228 -12· 200404539 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中’口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式①化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、燒氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、商烷基、亞甲二氧基、硝基、苯基或_ΝΖι & ; B為%; Z is N; ... is absent; L is _n (R7) C (0) _; and D R2, R3, R4, Inverse 5, R7, and Ra are as defined in formula Φ. 85228-12 · 200404539 In another specific embodiment of the present invention, it relates to a method of "orally treating sexual dysfunction" in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, Where A is aryl, where aryl is phenyl, substituted by 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkane Thio, benzyl, cyano, halogen, haloalkoxy, commercial alkyl, methylenedioxy, nitro, phenyl or ΝΝιι &; B is

;Ri為氫、烷氧基、烷基、烷硫基、氰基、鹵素 、輕基、硝基、-NZA或（NZ3Z4)燒基；r2為氫、烷氧基、氰 基、自素或羥基；R3為氫或羥基；心與仏為氫；Z為N;… 為不存在；D為-CIV; L為-N(R7)C(0)-;及尺7與1^均如式（I)中 之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（1)化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、燒氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 、鹵烷氧基' 1¾烷基、亞甲二氧基、硝基、苯基或-ΝΖιΖ2 ; Β為; Ri is hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, light, nitro, -NZA or (NZ3Z4) alkyl; r2 is hydrogen, alkoxy, cyano, autogen or Hydroxy; R3 is hydrogen or hydroxy; heart and tritium are hydrogen; Z is N;… is absent; D is -CIV; L is -N (R7) C (0)-; and rule 7 and 1 ^ are both (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (1), wherein A is an aryl group. Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, and fluorenyl , Cyano, halogen, haloalkoxy '1¾alkyl, methylenedioxy, nitro, phenyl, or -NZιZ2; Β is

’ 為氮、燒乳基、燒基、燒硫基、來基、_素 85228 -13- 200404539 、罗至基、硝基、-ΝΖ! Z2或（NZ3 Z4 )垸基；R2為氫、燒氧基、氰 基、_素或羥基；R3為氫或羥基；r4與r5為氫；Z為N ; — 為不存在；D為-CH(CH3)-; L為_N(R7)C(0)-;及心與1^均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 峻基、苯并噻唑基、呋喃基、咪唑基、L3-噚唑基、吡畊基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、丨，^ p塞唑基 或遠吩基’其中雜環係獨立被〇、1、2或3個取代基取代， 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、_素、 鹵烷氧基、卣烷基或硝基；B為'' Is nitrogen, lactyl, thiol, thiol, phenyl, sulfonyl 85228 -13-200404539, Luo Zhiji, nitro, -NZ! Z2 or (NZ3 Z4) fluorenyl; R2 is hydrogen, benzene Oxy, cyano, hydrogen, or hydroxy; R3 is hydrogen or hydroxy; r4 and r5 are hydrogen; Z is N; — is absent; D is -CH (CH3)-; L is _N (R7) C ( 0)-; and mind and 1 ^ are as defined in formula (I). In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring. , Where the heterocyclic ring is benzimidyl, benzothiazolyl, furanyl, imidazolyl, L3-oxazolyl, pyrargyl, pyrazolyl, daphyl, pyridyl, pyrimidinyl, pyrrolyl, 丨^ P azozolyl or farphenyl 'wherein the heterocyclic ring is independently substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, and , Haloalkoxy, fluorenyl, or nitro; B is

，Z為N ;…為不存在；l為-N(R7 )C(0)-;且D、& 、R2、R3、R4、R5、R7&RA均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、呋喃基、咪唑基、号唑基、吡畊基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、丨，3_噻唑基 或塞力基’其中球％係獨立被〇、1、2或3個取代基取代， 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、_素、 鹵燒氧基、自燒基或硝基；B為 85228 -14- 200404539 ；^C：, Z is N;... Does not exist; l is -N (R7) C (0)-; and D, &, R2, R3, R4, R5, R7 & RA are as defined in formula (1). In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring. Where the heterocyclic ring is benzimidazolyl, benzimidazolyl, furanyl, imidazolyl, oxazolyl, pyrimidinyl, pyrazolyl, damatyl, pyridyl, pyrimidinyl, pyrrolyl, _Thiazolyl or selenium 'wherein the ball% is independently substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, halogen, halogen Oxy, self-burning or nitro; B is 85228 -14- 200404539; ^ C:

Rs ; R1為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 烷基或(nz：3Z4)羰基；R2與R4為氫；r3為氫或羥基；Z為 …為不存在；D為_CH2·; L為_N(R7)C(0)-;及R?與RA均如關於 式（I)之定義。 ' 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并噻唑基、吡唑基、吡啶基或嘧吩基，其中雜環 係獨立被0、1、2或3個取代基取代，取代基獨立選自烷氧 基、烷氧羰基、烷基、氰基、齒素、画烷氧基、齒烷基或 硝基；B為Rs; R1 is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (nz: 3Z4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; Z is ... Does not exist; D is _CH2 ·; L is _N (R7) C (0)-; and R? And RA are as defined for formula (I). '' In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterozygous compound. Ring, wherein the heterocyclic ring is benzimidazolyl, benzothiazolyl, pyrazolyl, pyridyl, or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 1, 2, or 3 substituents, and the substituents are independently selected from Alkoxy, alkoxycarbonyl, alkyl, cyano, halide, alkoxy, haloalkyl or nitro; B is

;Ri為氫、院基、氰基、鹵烷基、鹵素、硝基、) 燒基或(NZSZ4)羰基；&與I為氫；r3為氫或幾基；z為n; …為不存在；D為-αν; L為-N(R7)C(0)-;及心與、均如關於 式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為; Ri is hydrogen, cyano, cyano, haloalkyl, halogen, nitro, alkynyl or (NZSZ4) carbonyl; & and I are hydrogen; r3 is hydrogen or several groups; z is n;… is not Exist; D is -αν; L is -N (R7) C (0)-; and mind and are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl ; B is

*，Z為N;…為不存在；L為-N(R7 )C(〇)-;且D、心 85228 -15- 200404539 、R2、R3、r4、r7&ra均如式(i)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有放里之式（I)化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自晞基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或_NZi & ; B為*, Z is N;... Is absent; L is -N (R7) C (〇)-; and D, Xin 85228 -15- 200404539, R2, R3, r4, r7 & ra are all in formula (i) Definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically acceptable, wherein A is aromatic Group, where aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl Group, cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl or _NZi &; B is

RlYl Rs 、N R4 ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（nz3z4) 燒基或(NZgZ4)羰基；R2與R4為氫；r3為氫或羥基；z為N; …為不存在；D為-CH2-; L為-N(R7)C(〇)-;及R7與RA均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 L氧基、燒氧談基、燒基、燒硫基、爷基、氯基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-ΝΖβζ ; B為RlYl Rs, N R4; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (nz3z4) alkyl or (NZgZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is N;… is absent; D is -CH2-; L is -N (R7) C (〇)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl , Where aryl is phenyl, substituted by 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl Loxy, alkoxy, alkynyl, thiol, hexyl , Chloro, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZβζ; B is

;Ri為氫、燒基、氰基、鹵燒基、鹵素、硝基、（NZ3 ) 烷基或（NZ3Z4)羰基；心與114為氫；r3為氫或羥基；Z為N; …為不存在；D為-CH2 - ; L為-N(R7)CXS)-;及化7與Ra均如式（1) 85228 -16- 200404539 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式(I)化合物，其中A為芳基，其中芳基為苯基， 被0、1 、4或5個取代基取代，取代基獨立選自晞基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或_ΝΖιζ2 ; B為 R叙. 4，心為氫、烷基、氰基、卣烷基、_素、硝基、⑼& k基或(ΝΖ3 Ζ4)羰基；&與r4為氫；r3為氫或幾基；ζ為ν ; …為不存在；D為-CH(CH3)-; I^_N(R7)C(0)-;及心與、均如 式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為四氫萘 基或2,3_二氫-1H-茚基；B為Ri is hydrogen, alkyl, cyano, halogeno, halogen, nitro, (NZ3) alkyl or (NZ3Z4) carbonyl; heart and 114 are hydrogen; r3 is hydrogen or hydroxyl; Z is N;… is not Exists; D is -CH2-; L is -N (R7) CXS)-; and Hua 7 and Ra are as defined in formula (1) 85228 -16- 200404539. In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is an aryl group. Where aryl is phenyl and substituted with 0, 1, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, Halogen, haloalkoxy, _alkyl, methylenedioxy, nitro, phenyl, or _NZιζ2; B is R. 4, and the heart is hydrogen, alkyl, cyano, fluorenyl, Nitro, ⑼ & k group or (NZ3 Z4) carbonyl group; & and r4 are hydrogen; r3 is hydrogen or a few groups; ζ is ν; ... is absent; D is -CH (CH3)-; I ^ _N ( R7) C (0)-; and mind and, are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is tetrahydronaphthyl or 2,3-dihydro-1H-indenyl; B is

^ n .'4 ;心為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 垸基或(NZ3Z4)羰基；112與114為氫；R3為氫或羥基；Z為N; …為不存在；D為-CH2_; L為-N(R7)C(0)-;及R7與RA均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 85228 -17- 200404539 上有效量之式（1)化合物，其中A為芳基，其中芳基為四氫茶 基或2,3-二氫-1H·茚基；B為^ n.'4; the heart is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) fluorenyl or (NZ3Z4) carbonyl; 112 and 114 are hydrogen; R3 is hydrogen or hydroxyl; Z is N;… is absent; D is -CH2_; L is -N (R7) C (0)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal an effective amount of a compound of formula (1) in the treatment 85228 -17- 200404539, Where A is aryl, where aryl is tetrahydrothecyl or 2,3-dihydro-1H · indenyl; B is

，Ri為氫、烷基、氰基、卣烷基、_素、硝基NZ3 a) 烷基或(ΝΖβ4)羰基；化與心為氫；&為氫或羥基；ZgN; …為不存在；D為-CH(CH3)-; L為-N(R7)c(〇)-;及心與、均如 式Φ中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、呋喃基、咪唑基、丨，3_嘮唑基、吡畊基 、吡唑基、嗒啩基、吡啶基、嘧啶基、吡咯基、u_嘧唑^ 或噻吩基，其中雜環係獨立被〇、丨、2或3個取代基取代， 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、_素、 鹵烷氧基、鹵烷基或硝基；B為, Ri is hydrogen, alkyl, cyano, fluorenyl, sulfonium, nitro NZ3 a) alkyl or (NZβ4) carbonyl group; and hydrogen is hydrogen; & is hydrogen or hydroxyl; ZgN;… is absent ; D is -CH (CH3)-; L is -N (R7) c (〇)-; and the meanings of and are as defined in formula Φ. In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring. , Where the heterocyclic ring is benzimidazolyl, benzopyrazolyl, furanyl, imidazolyl, 3-oxazolyl, pyrazolyl, pyrazolyl, pyridyl, pyridyl, pyrimidinyl, pyrrolyl , U_pyrimazole ^ or thienyl, wherein the heterocyclic ring is independently substituted by 0, 丨, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, Haloalkoxy, haloalkyl or nitro; B is

RlTi Rs 足/ R4 ; Z為N ;…為不存在；L為_N(R7)c(〇)_ ;且D、心 、R2、R3、r4、R5、R7&RA均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中性功能障礙治療之方法，纟包括對該哺乳動物投予治療 上有效量之式(1)化合物’其中A為雜環，纟中雜環為苯并味 唑基、苯并噻唑基、呋喃基、咪唑基、 、㈣基、㈣、㈣基”比一= 或嘧吩基，其中雜環係獨立被0、i、2或3個取代基取代， 85228 -18 - 200404539 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、商素、 鹵烷氧基、画烷基或硝基；B為RlTi Rs foot / R4; Z is N; ... is absent; L is _N (R7) c (〇) _; and D, Xin, R2, R3, r4, R5, R7 & RA are all as in formula ① definition. In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (1), wherein A is a heterocyclic ring. "Heterocyclic ring in fluorene is benzotriazole, benzothiazolyl, furanyl, imidazolyl, fluorenyl, fluorenyl, fluorenyl", and the heterocyclic system is independently 0, i, 2 or 3 substituents, 85228 -18-200404539 The substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, quotient, haloalkoxy, picoalkyl or nitro; B is

v，Ri為氫、燒基、氰基、_燒基、函素、硝基&) 坑基或(NZgZ4)羰基；&與R4為氫；r3為氫或羥基；z為n; …為不存在；D為-CIV; L為_N(R7)C(0)-;及心與、均如關於 式（I)之定義。 於本發明之另一項具體貫施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、吡唑基、吡啶基或嘧吩基，其中雜環 係獨被〇、1、2或3個取代基取代，取代基獨立選自烷氧 基、烷氧羰基、烷基、氰基、_素、鹵烷氧基、齒烷基或 硝基；B為v, Ri is hydrogen, alkyl, cyano, alkyl, nitro, nitro &) pit or (NZgZ4) carbonyl; & and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is n; ... Is absent; D is -CIV; L is _N (R7) C (0)-; and mind and are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a miscellaneous compound. Ring, wherein the heterocyclic ring is benzimidazolyl, benzopyrazolyl, pyrazolyl, pyridyl, or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 1, 2, or 3 substituents, and the substituents are independently selected From alkoxy, alkoxycarbonyl, alkyl, cyano, halogen, haloalkoxy, haloalkyl, or nitro; B is

t ’ Ri為氫、烷基、氰基、鹵燒基、鹵素、硝基、⑼ 烷基或(ΝΖβ4)羰基；R2與R4為氫；r3為氫或羥基；Z*N; …為不存在·’ D為-CIV; L為-N(R7)C(0)-•，及以7與、均如關於 式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中&療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；b為t 'Ri is hydrogen, alkyl, cyano, halogeno, halogen, nitro, fluorenyl or (NZβ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; Z * N;… is absent · D is -CIV; L is -N (R7) C (0)-•, and 7 and are as defined for formula (I). In another embodiment of the present invention, it relates to a method for & therapeutic dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is Aryl; b is

R4 ; Z 為 N ; 為不存在；L為-N(R7)C(〇)-;且D、&、 85228 -19- 〜、。、〜，及^均如式射之定義。 万;本發明之另一項具體實施例中 — 中治療性錢障礙之核 、動物 、 八包括對孩哺乳動物投予治療 K式(I)化合物，其中A為芳基’其中芳基為苯基， ? 2、3、4或5個取代基取代，取代基獨立選自烯基 =乳基、燒氧羰基、燒基、燒硫基、宇基'氰基1辛 ㈣基、自燒基、亞甲二氧基、硝基、苯基 B為 12R4; Z is N; is absent; L is -N (R7) C (〇)-; and D, &, 85228 -19- ~ ,. , ~, And ^ are as defined by the formula shot. 10,000; in another specific embodiment of the present invention-the nucleus, animal, and medicament for the treatment of money disorders include administering a compound of formula (I) to a child mammal, wherein A is aryl 'and aryl is benzene Group, substituted with 2, 3, 4, or 5 substituents, the substituents are independently selected from alkenyl = lactyl, oxycarbonyl, thio, thio, yl, cyano, 1-octyl, and self-alkyl , Methylenedioxy, nitro, phenyl B is 12

NT ' /、&心及&為氫，Z為N ; 一為不存在；〇為_CH2 ，l*-n(R7)c(〇)-;及心與、均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、_素 、鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或-ΝΖι心； B為 Ν' ^ N R4; R2、R3&R4為氫；Z為N; —為不存在；D為-CH(CH3)_ ;L為-N(R7)C(0)-;及尺7與^均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；b為 85228 -20- 200404539NT '/, & heart and & are hydrogen, Z is N; one is absent; 0 is _CH2, l * -n (R7) c (〇)-; and heart and, are as in formula ① definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, alkyl, methylenedioxy, nitro, phenyl, or -NRZ; B is N '^ N R4; R2, R3 & R4 is hydrogen; Z is N;-is absent; D is -CH (CH3) _; L is -N (R7) C (0)-; and rule 7 and ^ are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl ; B is 85228 -20- 200404539

，乙為1^，…為不存在；L為-N(R7 )C(0)-; Y、R2、R3、r7&ra均如式①中之定義。 且D、χ、 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式①化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自缔基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、自素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或_ΝΖιζ2 ; B為 孤3 · Y 3 ; R2與R3為氫；X為风心）、〇或S; Υ為Ν; Ζ為Ν; …為不存在；D為-CH2-;[為-N(R7)C(〇)-;且R6、r7&ra均如 式（1)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5彳固取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 、鹵烷氧基、i烷基、亞甲二氧基、硝基、苯基或-NZiZa ; B為, B is 1 ^, ... is absent; L is -N (R7) C (0)-; Y, R2, R3, r7 & ra are as defined in formula ①. And D, χ, in another specific embodiment of the present invention, is a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, wherein A Is aryl, where aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio , Benzyl, cyano, autogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl or ΝΝιζ2; B is solitary3Y3; R2 and R3 are hydrogen; X is Fengxin), 0 or S; Υ is N; Z is N; ... is absent; D is -CH2-; [is -N (R7) C (〇)-; and R6, r7 & ra are as follows ( 1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and is substituted by 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, and fluorene Group, cyano, halogen, haloalkoxy, i-alkyl, methylenedioxy, nitro, phenyl or -NZiZa; B is

;R2 與 R3 為氫；X 為 N(R6)、Ο 或 s ; Y 為 N ; Z為 N ; 為不存在；D 為-CH(CH3)- ; L 為-N(R7)C(0)_ ;且 R6、R7 及 raR2 and R3 are hydrogen; X is N (R6), 0, or s; Y is N; Z is N; is absent; D is -CH (CH3)-; L is -N (R7) C (0) _; And R6, R7 and ra

85228 -21 - 200404539 均如式（i)中之定義。 .r3 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效τ之式①化合物，其中A為雜環；b為85228 -21-200404539 are as defined in formula (i). .r3 In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula ① which is therapeutically effective, wherein A is a heterocyclic ring. ; B is

N % ; ZaN ;…為不存在；L為-N(R7)C(0)_ ; ID、&amp; 、R2、h、&amp;、A及RA均如式（I)中之定義。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中&amp;療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式(1)化合物’其中A為雜環，其中雜環為苯并味 唑基、苯并噻唑基、呋喃基、咪唑基、u_噚唑基、吡畊基 ”比嗅基、塔呼基”比淀基、喃咬基”比洛基、以-遷吐基 或嘍吩基，其中雜環係獨立被〇、丨、2或3個取代基取代， 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、鹵素、 lS燒氧基、函烷基或硝基；B為 \ / 4，ZgN，…為不存在；D*_CH2_; [為-N 供7)c(〇)_ ，及Ri、R2、R3、R4、R7ARa均如式①中之定義。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（1)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘍唑基、呋喃基、咪唑基、13_嘮唑基、吡畊基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、丨，3_嘍唑基 或噻吩基，其中雜環係獨立被〇、丨、2或3個取代基取代， 85228 -22- 200404539 烷基、氰基、齒素、 取代基獨立選自烷氧基、烷氧羰基、 鹵烷氧基、li烷基或硝基；B為 、人广； Z為N; •，及 Ri、R2、R3、 …為不存在；D為-; R4、R7及RA均如式（I)中之定 L 為-N(R7)C(0&gt; 義0 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法’丨包括對該哺乳動物投予治療 上有效=之式ω化合物’其中A為雜環’其中雜環為苯并味 吐基、苯㈣吐基κ基κ基或喧吩基，獨立被〇、 1、2或3個取代基取代，取代基獨立選自垸氧基、燒氧幾基 、烷I、氰基、_素、商烷氧基、自烷基或硝基；㈣ \ f R4 ，心為包括氫、烷基、氰基、鹵烷基、鹵素、硝 基:(nz3z4)燒基或⑽⑹羧基之基團；化與心錢；化為氯 或嫂基’ Z為N ;…為不存在；D為偶· ; L為·N(R7)c(〇&gt; ; 及R?與RA均如式（I)中之定義。 於本發明〈另一項具體實施例中，係關於一種在哺乳動物 中治療，功能障礙之方法，纟包括對該哺乳動物投予治療 上有效=之式(I)化合物，其中A為雜環，其中雜環為苯并味 坐基、苯并4嗤基”比峻基K基或嘆吩基，獨立被〇、 1、=或3個取代基取代，取代基獨立選自燒氧基、燒氧幾基 \基、讯基、自素、自燒氧基、自燒基或硝基；B為 R;AR3 β Ν % ，R1為包括氳、烷基、氰基、自烷基、齒素、硝 85228 -23- 200404539 (ΝΑΖ4)燒基或_324)羰基之基 或羥基； Z為N ;…為不存在； 及心與心均如式（I)中之定義。 &lt;基團；112與114為氫；R3為氫 ;D 為-CH(CH3)_ ; L 為-N(R7)C(0)- 於本發明之另一項具體實施例中 中治療性功能障礙之方法，其 上有效量之式（I)化合物，其中/ 係關於一種在哺乳動物 法’其包括對該哺乳動物投予治療 ’其中A為環烷基；B為N%; ZaN;... Are absent; L is -N (R7) C (0) _; ID, &amp;, R2, h, &amp;, A and RA are as defined in formula (I). In another specific embodiment of the present invention, a method of &amp; treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (1), wherein A It is a heterocyclic ring, wherein the heterocyclic ring is benzotriazole, benzothiazolyl, furanyl, imidazolyl, u-oxazolyl, pyrimidinyl, thiol, talyl, pyridyl "Biloxy, i-methyl, or methynyl, wherein the heterocyclic ring is independently substituted with 0, 1, 2, or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, and cyano Group, halogen, 1S alkoxy group, alkyl group or nitro group; B is \ / 4, ZgN, ... is absent; D * _CH2_; [for -N for 7) c (〇) _, and Ri, R2 , R3, R4, R7ARa are as defined in formula ①. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering treatment to the mammal An effective amount of a compound of formula (1), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, furanyl, imidazolyl, 13-oxazolyl, pyrenyl , Pyrazolyl, daphyl, pyridyl, pyrimidinyl, pyrrolyl, 3-, 3-oxazolyl, or thienyl, wherein the heterocyclic ring is independently substituted with 0, 1, 2, or 3 substituents, 85228 -22 -200404539 alkyl, cyano, halide, and substituent are independently selected from alkoxy, alkoxycarbonyl, haloalkoxy, li alkyl, or nitro; B is, Ren Guang; Z is N; •, and Ri , R2, R3,... Do not exist; D is-; R4, R7, and RA are as defined in formula (I). L is -N (R7) C (0 &gt; meaning 0. In another specific implementation of the present invention In the example, it relates to a method for treating sexual dysfunction in mammals. It includes administering a therapeutically effective compound to the mammal = of the formula [omega] where A is a heterocyclic ring and wherein the heterocyclic ring is benzotyl. , Benzhydryl κ, κ, or phenyl, independently substituted by 0, 1, 2, or 3 substituents, the substituents are independently selected from fluorenyloxy, alkoxyl, alkane I, cyano, and , Commercial alkoxy, self-alkyl or nitro; ㈣ \ f R4, which is a group including hydrogen, alkyl, cyano, haloalkyl, halogen, nitro: (nz3z4) alkyl or carboxyl; Change with money; change into chlorine or The group 'Z is N; ... is absent; D is even ·; L is · N (R7) c (0 &gt;; and R? And RA are as defined in formula (I). In the present invention <another In a specific embodiment, the invention relates to a method for treating and dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically effective, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzene. The acyl group, benzo-4-fluorenyl group is independently substituted with 0, 1, = or 3 substituents, and the substituents are independently selected from alkoxy and alkoxy groups. , Alkyl, autogen, self-oxygen, self-oxyl, or nitro; B is R; AR3 β Ν%, R1 includes fluorene, alkyl, cyano, autoalkyl, dentin, nitrate 85228 -23 -200404539 (ΝΑZ4) alkyl or _324) carbonyl group or hydroxyl group; Z is N; ... is absent; and the heart and the heart are as defined in formula (I). &lt;Groups; 112 and 114 are hydrogen; R3 is hydrogen; D is -CH (CH3) _; L is -N (R7) C (0)-in another embodiment of the present invention is therapeutic A method of dysfunction, in which an effective amount of a compound of formula (I), wherein / relates to a method in mammals which includes administering treatment to the mammal, wherein A is a cycloalkyl group; B is

A N 4，Ζ*Ν ;…為不存在；L為-N(R7)C(0)-;且D、心 、&amp;、R3、R4、R7&amp;RA均如式（1)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為環烷基，其中環烷基為環 己基或金鋼燒基；B為A N 4, Z * N; ... is absent; L is -N (R7) C (0)-; and D, Xin, &amp;, R3, R4, R7 &amp; RA are as defined in formula (1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a cycloalkane Group, wherein the cycloalkyl group is cyclohexyl group or gold steel group; B is

^ N _、4 ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 燒基或(NZ3Z4)羰基；112與114為氫；R3為氫或羥基；Z為N; …為不存在；D為-CH2-; L為-N(R7)C(0)-;及117與1^均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為環烷基，其中環烷基為環 己基或金鋼烷基；B為^ N _, 4; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (NZ3Z4) carbonyl; 112 and 114 are hydrogen; R3 is hydrogen or hydroxyl; Z is N;… is absent; D is -CH2-; L is -N (R7) C (0)-; and 117 and 1 ^ are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a cycloalkane Group, wherein the cycloalkyl group is cyclohexyl or auryl; B is

^ N |'4 ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 85228 -24- 200404539 烷基或(NZSZ1 2 3 4)羰基；&amp;與&amp;為氫；&amp;為氫或羥基；Z*N; …為不存在；D為_CH(CH3)··，L為-N(r7)C(0&gt; ;及心與、均如 式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳烷基；B為^ N | '4; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) 85228 -24- 200404539 alkyl or (NZSZ1 2 3 4) carbonyl; &amp; and &amp; are Hydrogen; &amp; is hydrogen or hydroxyl; Z * N;… is absent; D is _CH (CH3) ··, L is -N (r7) C (0 &gt;; In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aralkyl; B is

3 IN .'4 , Z為N ;…為不存在；L為-N(R7)C(0)-;且D、心 、心、R3、R4、R7及Ra均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳烷基，其中芳烷基之芳 基為苯基，被〇、1、2、3、4或5個取代基取代，取代基獨 亙選自缔基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、 氰基、_素、1¾烷氧基、烷基、亞甲二氧基、硝基、苯 基或-NZ! Z2 ; B為3 IN .'4, Z is N; ... is absent; L is -N (R7) C (0)-; and D, heart, heart, R3, R4, R7, and Ra are all as in formula (I) definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is an arane Group, wherein the aryl group of the aralkyl group is a phenyl group, which is substituted by 0, 1, 2, 3, 4 or 5 substituents, and the substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, Alkylthio, benzyl, cyano, oxo, 1⁄2alkoxy, alkyl, methylenedioxy, nitro, phenyl or -NZ! Z2; B is

-25- 1 ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 燒基或(NZsZ4)羰基；R2與R4為氫；r3為氫或羥基；z為N; …為不存在；D為-CH2-; L為-N(R7)C(〇)-;及1與1^均如式（I) 2 中之定義。 3 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳燒基，其中芳燒基之芳 4 85228 200404539 基為苯基，被0、1、2、 、4或5個取代基取代，取代基獨 立選自烯基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、 氰基、画素、i烷氧基、齒烷基、亞甲二氧基、硝基、苯 基或-ΝΖι Z2 ; B為 \ ’ 4，R1為氫、烷基、氰基、函烷基、卣素、硝基、 烷基或(ΝΖΘ4)羰基；^與]^為氫；心為氫或羥基；-25-1; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (NZsZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is N ... is absent; D is -CH2-; L is -N (R7) C (〇)-; and 1 and 1 ^ are as defined in formula (I) 2. 3 In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aromatic An alkyl group, of which the aryl group of aromatic group is 85 852004200404539 is phenyl group, which is substituted by 0, 1, 2, 4, 4 or 5 substituents, and the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, and alkane Group, alkylthio, benzyl, cyano, pixel, i-alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZιZ2; B is \ '4, R1 is hydrogen, alkyl Cyano, cyano, alkyl, halogen, nitro, alkyl, or (NZΘ4) carbonyl; ^ and] ^ are hydrogen; the heart is hydrogen or hydroxyl;

…為不存在，D為-CH(CH3)-; L為-N(R7)C(〇)-;及心與、均如 式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中/口療丨生功此障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為 於： R5 β ;Ζ為CRB ;…為不存在；L為_N(R7)c(〇)_ ;且D、 R1 R2、R3、R4、R5、R7、R8及RA均如式①中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療T功能障礙之方法，其包括對該哺乳動物投予治療 上有政里之式①化合物，其中A為芳基，其中芳基為苯基， 被0 1、2、3、4或5個取代基取代，取代基獨立選自烯基 认氧基、烷氧羰基、烷基、烷硫基、芊基 '氰基、鹵素 、_烷氧基、卣烷基、亞甲二氧基、硝基、苯基&amp;_ΝΖι B為 85228 26- 200404539... is absent, D is -CH (CH3)-; L is -N (R7) C (〇)-; and the meanings of and are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating this disorder in a mammal / oral treatment, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl; B is at: R5 β; Z is CRB; ... is absent; L is _N (R7) c (〇) _; and D, R1 R2, R3, R4, R5, R7, R8 and RA is as defined in Equation ①. In another specific embodiment of the present invention, it relates to a method for treating T dysfunction in a mammal, which comprises administering to the mammal a compound of formula ①, wherein A is an aryl group, Wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyloxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl'cyano , Halogen, alkoxy, fluorenyl, methylenedioxy, nitro, phenyl &amp; NZO B is 85228 26- 200404539

’ Ri為鼠、纟元乳基、燒基、坑硫基、氯基、_素 、經基、硝基、-NZA或（NZA)燒基；R2為氫、燒氧基、氰 基、_素或羥基；R3為氫或羥基；心與心為氳；Z為CRB ; …為不存在；D為-CIV; L為-N(R7)C(0)-; Rb為氫；及R^Ra 均如式（I)中之定義。 毛本發明之另一項具體貫施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、it烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 本'Ri is murine, ammonium, sulfanyl, sulfanyl, sulfanyl, chloro, hydrazine, meridian, nitro, -NZA or (NZA) sulfanyl; R2 is hydrogen, carboxy, cyano, R3 is hydrogen or hydroxyl; R is heart or heart; Z is CRB; ... is absent; D is -CIV; L is -N (R7) C (0)-; Rb is hydrogen; and R ^ Ra is as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aromatic Group, where aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl Group, cyano, halogen, haloalkoxy, it alkyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B is based

Rs ; Ri為氫、烷氧基、烷基、烷硫基、氰基、自素 、羥基、硝基、_NZlZ：z或（NZJ4)燒基；&amp;為氳、烷氧基、氰 基、1¾素或輕基；Rs為氫或羥基；R4與r5為氫；Z為CRB ; 為不存在；D為_CH2 - ; L為-N(R7 )C(〇)- ; RB為鹵素，其中較 佳鹵素為_F ;及化與RA均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， -27- 85228 200404539 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或_ΝΖιζ2 ; B為Rs; Ri is hydrogen, alkoxy, alkyl, alkylthio, cyano, autogen, hydroxy, nitro, _NZlZ: z or (NZJ4) alkyl; &amp; is pyrene, alkoxy, cyano, 1¾ or light group; Rs is hydrogen or hydroxyl; R4 and r5 are hydrogen; Z is CRB; is absent; D is _CH2-; L is -N (R7) C (〇)-; RB is halogen, where The preferred halogen is _F; and H and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl , Where aryl is phenyl, -27- 85228 200404539 is substituted with 0, 1, 2, 3, 4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkane Thio, benzyl, cyano, halogen, haloalkoxy, _alkyl, methylenedioxy, nitro, phenyl or ΝΝιζ2; B is

Rs ; Ri為氫、烷氧基、烷基、烷硫基、氰基、鹵素 輕基、硝基、-NZl2：2或⑽义)燒基；心為氫、烷氧基、氰 基、鹵素或羥基；R3為氫或羥基；R*4與R5為氫；z為crb ; …為不存在；D為-CH(CH3)_; L為-N(R7)C(0&gt;; Rb為氫；及心 與RA均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中/口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有放昼之式（I)化合物，其中A為芳基；b為 Ά3 .、 N R4，z為CRB ;…為不存在；L為-N(R7)C(0)- ; RB為氫 ;JLD、τ&gt; 1 2、仏3、、尺7及Ra均如式(I)中之定義。 '、、Λ月之另一項具體貫施例中，係關於一種在哺乳動物 上治療':生功能障礙之方法’其包括對該哺乳動物投予治療 文里之式(I)化合物，其中Α為芳基，其中芳基為苯基， 被 0 ' 1、9 、、卜 、、4或5個取代基取代，取代基獨立選自缔基 、氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、 、南、J;占每# Η ,丁、 ，几虱基、南烷基、亞甲二氧基、硝基、苯基4_ΝΖιΖ2 ; 85228 200404539 R；TXR3 N 4，Ri為鼠、燒基、氣基、1¾燒基、_素、硝基、⑼z3 Z4 ) 火元基或（NZ3 Z4 )後基；R2與R4為氫；R;為氫或幾基；z為crb ’—為不存在，D為-CH2 -，L為_N(R7 )C(0)- ; Rb為氯；及r?與 ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、燒氧基、燒氧羧基、燒基、燒硫基、苄基、氰基、商素 、鹵烷氧基、S烷基、亞甲二氧基、硝基、苯基或-ΝΖ! Z2 ; B為 riyYr3 、’心；&amp;為氫、燒基、氰基、！I燒基、由素、硝基、⑼&amp; &amp; ) 燒基或（NZ3 Z4)羰基；R2與R4為氫；R3為氫或羥基；z為crb ，…為不存在；D為-CH2 _ ; L為-N(R7 )C(S)- ; RB為氫；及r7與 Ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為四氫莕 基或2,3_二氫-1H-茚基；B為Rs; Ri is hydrogen, alkoxy, alkyl, alkylthio, cyano, halogeno, nitro, -NZl2: 2 or ammonium); alkyl is hydrogen, alkoxy, cyano, halogen Or hydroxyl; R3 is hydrogen or hydroxyl; R * 4 and R5 are hydrogen; z is crb; ... is absent; D is -CH (CH3) _; L is -N (R7) C (0 &gt;; Rb is hydrogen And Xin and RA are as defined in formula (I). In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal / oral, which comprises administering the mammal to the mammal. There is a compound of formula (I) in the treatment, where A is aryl; b is Ά3., N R4, z is CRB; ... is absent; L is -N (R7) C (0)-; RB Is hydrogen; JLD, τ &gt; 1, 2, 3, 7, 7 and Ra are as defined in formula (I). In another specific embodiment of the embodiment, it is about a mammal Treatment of 'Method of Birth Dysfunction' includes administering to the mammal a compound of formula (I), wherein A is an aryl group, wherein aryl is a phenyl group, and , 4 or 5 substituents, which are independently selected from alkenyl, oxy, and alkoxycarbonyl Alkyl, alkylthio, benzyl, cyano, sulphur, sulphur, succinyl, succinyl, stilbene, stilbene, succinyl, sulphanyl, methylenedioxy, nitro, phenyl 4-NZιZ2; 85228 200404539 R ; TXR3 N 4, Ri is murine, alkynyl, carbyl, 1¾ alkynyl, oxin, nitro, hydrazium Z3 Z4) fire radical or (NZ3 Z4) rear group; R2 and R4 are hydrogen; R; is hydrogen or Z is crb′—is absent, D is —CH2 —, L is —N (R7) C (0) —; Rb is chlorine; and r? And ra are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarboxy, alkoxy, thiothio, and benzyl , Cyano, quotient, haloalkoxy, Salkyl, methylenedioxy, nitro, phenyl or -NZ! Z2; B is riyYr3, 'Heart; &amp; is hydrogen, alkyl, cyano ,! I alkyl, sulfonium, nitro, amidine &amp; &amp;) alkyl or (NZ3 Z4) carbonyl; R2 and R4 are hydrogen; R3 is hydrogen or hydroxyl; z is crb, ... is absent; D is -CH2 _ L is -N (R7) C (S)-; RB is hydrogen; and r7 and Ra are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is tetrahydrofluorenyl or 2,3-dihydro-1H-indenyl; B is

Rl Yl&quot;R3 、nT FU ; Rl為氫、烷基、氰基、_烷基、商素、硝基、 烷基或（NZ3Z4)羰基；112與反4為氫；r3為氫或羥基；Z為crb 85228 -29- 200404539 ，…為不存在；D為-CH2-; L·為-N(R7)C(S)-; RB為氫；及心與 Ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自晞基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、商素 、_烷氧基、_烷基、亞甲二氧基、硝基、苯基或-ΝΖιζ2 ; B為Rl Yl &quot; R3, nT FU; Rl is hydrogen, alkyl, cyano, alkyl, quotient, nitro, alkyl, or (NZ3Z4) carbonyl; 112 and trans 4 are hydrogen; r3 is hydrogen or hydroxyl; Z Is crb 85228 -29- 200404539,… is absent; D is -CH2-; L · is -N (R7) C (S)-; RB is hydrogen; and heart and Ra are as defined for formula (I) . In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, quotient, alkoxy, alkyi, methylenedioxy, nitro, phenyl, or -NZιζ2; B is

RlV^VR3 ·…、一 ’ Ri為IL克基、亂基、_燒基、_素、硝基、讲ζ3 ζ4) 烷基或（NZgZ4)羰基；R2與&amp;為氫；為氫或羥基；ZgcRB ;…為不存在；D為-CH(CH3)_; L*_N(R7)c(〇&gt;;知為氫；且 &amp;、RB及RA均如對式①之定義。 方、本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有放里之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘍唑基、呋喃基、咪唑基、丨,3_噚唑基、吡畊基 、吡唑基、&quot;合畊基、吡啶基、嘧啶基、吡咯基、1，3-嘧唑基 或嘧吩基，其中雜環係獨立被〇、丨、2或3個取代基取代， 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、自素、 鹵燒氧基、卣烷基或硝基；B為 ?2 λ ^ , Z*CRb ;…為不存在；乙為-n队)c(〇)_;知為氫 85228 -30- 200404539 ¥ ;且13、心、R2、R3、r4、心及、均如式①中之定義。 於本發明之另-項具體實施例中，係關於_種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效里之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、呋喃基、咪唑基、丨，3_噚唑基、吡畊基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、丨，3_嘧唑基 或塞；7基，其中雜J衣係獨立被〇、1、2或3個取代基取代， 取代基獨立選自烷氧基、烷氧羰基、烷基、氰基、函素、 鹵烷氧基、函烷基或硝基；B為 N R4，Rl為氫、燒基、氰基、1¾燒基、1¾素、硝基、QSJZ3 Z4) 燒基或（NZSZ4)窥基；R2與R4為氳；r3為氫或羥基；z為CRb •’…為不存在；D為-CH2-; L·為-N(R7)C(0)-; Rb為氫；及％與 Ra均如關於式（I)之定義。 方；本發明之另一項具體貫施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 峻基、苯并嘧唑基、吡唑基、吡啶基或嘧吩基，其中雜環 係獨立被0、1、2或3個取代基取代，取代基獨立選自烷氧 基、燒氧羰基、燒基、氰基、_素、鹵燒氧基、D完基或 硝基；B為 ?2 Ά3 、N r4 ;心為氫、烷基、氰基、_烷基、鹵素、硝基、（NZ3Z4) 虎基或（NZ3Z4)羰基；心與心為氫；r3為氮或羥基；z為crb 85228 -31 - 200404539 ;…為不存在；D為-CH2_,· L為-N(R7)C(0&gt;; rb為氫；及心與 ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中冶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為R1V ^ VR3 ...., 1 'Ri is IL gram group, random group, alkynyl group, thiol, nitro group, ζ3 ζ4) alkyl group or (NZgZ4) carbonyl group; R2 and & are hydrogen; are hydrogen or hydroxyl; ZgcRB; ... is absent; D is -CH (CH3) _; L * _N (R7) c (0 &gt;; is known as hydrogen; and &, RB and RA are as defined for formula ①. Fang, Ben In another specific embodiment of the invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically acceptable, wherein A is a heterocyclic ring, Wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, furanyl, imidazolyl, 3-oxazolyl, pyridoxyl, pyrazolyl, &quot; hypotoxy, pyridyl, pyrimidinyl, pyrrole , 1,3-pyrazolyl or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 丨, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, and cyano , Self prime, haloalkyloxy, fluorenyl, or nitro; B is? 2 λ ^, Z * CRb; ... does not exist; B is -n team) c (〇) _; known as hydrogen 85228 -30 -200404539 ¥; and 13, heart, R2, R3, r4, heart and, are as follows Definition of. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically effective, wherein A is a miscellaneous compound. Ring, wherein the heterocyclic ring is benzimidazolyl, benzopyrazolyl, furanyl, imidazolyl, 3-oxazolyl, pyrargyl, pyrazolyl, daphyl, pyridyl, pyrimidinyl, pyrrole Group, 丨, 3-pyrazolyl group or plug; 7 group, wherein the hetero-J clothing is independently substituted with 0, 1, 2 or 3 substituents, the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, Cyano, halo, haloalkoxy, haloalkyl, or nitro; B is N R4, R1 is hydrogen, alkyn, cyano, 1¾, 1¾, nitro, QSJZ3 Z4), or ( NZSZ4) peptyl; R2 and R4 are 氲; r3 is hydrogen or hydroxyl; z is CRb • '... is absent; D is -CH2-; L · is -N (R7) C (0)-; Rb is hydrogen ; And% and Ra are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is Heterocyclic ring, wherein the heterocyclic ring is benzimidyl, benzopyrazolyl, pyrazolyl, pyridyl, or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 1, 2, or 3 substituents Independently selected from the group consisting of alkoxy, alkoxycarbonyl, alkynyl, cyano, halogen, halooxy, D-endyl, or nitro; B is? 2, Ά3, Nr4; heart is hydrogen, alkyl, cyano , _Alkyl, halogen, nitro, (NZ3Z4) tigeryl or (NZ3Z4) carbonyl; heart and heart are hydrogen; r3 is nitrogen or hydroxyl; z is crb 85228 -31-200404539; ... is absent; D is- CH2_, · L is -N (R7) C (0 &gt;; rb is hydrogen; and heart and ra are as defined for formula (I). In another specific embodiment of the present invention, it relates to a kind of breastfeeding A method for treating sexual dysfunction in an animal, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl; B is

Z 為 crb …為不存在；L為_N(R7)C(0)_ ; Rb為氫Z is crb… is absent; L is _N (R7) C (0) _; Rb is hydrogen

且D、X、γ、r2、r3、r7及Ra均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、_素 、自烷氧基、_烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ; B為And D, X, γ, r2, r3, r7, and Ra are as defined in formula (1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, hydrogen, alkoxy, alkyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B is

，X 為 Ν(Ι^)、〇 或 S ; Y 為 N ; R2 與 R3 為氫；z 為 CRb ;…為不存在；D*-CH2_; Lg-N(R7)c(〇)_; &amp;為氫；且心、 I及RA均如式（1)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中冶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效里&lt;式①化合物，其中A為芳基，其中芳基為苯基， 0、1 、9 〇 、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、_素 85228 -32- 200404539 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-ΝΖιΖ2 ; B為, X is N (Ι ^), 0 or S; Y is N; R2 and R3 are hydrogen; z is CRb; ... is absent; D * -CH2_; Lg-N (R7) c (〇) _; &amp; Is hydrogen; and heart, I and RA are as defined in formula (1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective compound of formula ①, wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 9, 10, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, _ prime 85228 -32- 200404539, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZιZ2; B is

X 為 N(R6)、〇 或 s ·，γ 為 N ; &amp; 與 R3 為氫；z 為 CRb ’…為不存在’ D為_CH(CH3&gt;; l為-N(R7)C(0)- ; Rb為氫；且 A、R7及RA均如式φ中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基； °Y^Yr3 、、n〆R4 ; z為CRB ;…為不存在；L為·N(R7)c(〇y ;且D、 R2、R3、R4、R7、RB 及 ra。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式①化合物，其中A為芳基，其中芳基為苯基， 被〇 1 2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、自素 β少兀氧基、_燒基、亞甲二氧基、硝基、苯基或叫&amp; ; Β為 〇Y^j/R3 r4 ; Z為 CRB 卜-為不存在；D為 _CIi2_; L為-n(R7)c(〇)_ ;R2、R3及R4為氫；rb為氫；及〜與〜均如式①中之定義。 於本發明之另一項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法，纟包括對該哺乳動物投予治療 85228 -33- 200404539 上有效量之式（I)化合物，其中A為芳基，其中芳基為笨基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自晞基 燒氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 鹵烷氧基、画烷基、亞甲二氧基、硝基、苯基或-NZi Z2 ; B為 -N(R7)C(〇).； ;Z*CRb ;…為不存在；D為-CH(CH3)-; L為 R2、R3及R4為氫；rb為氫；及R7與Ra均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中/口療性功能障礙之方法’其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為 - ;z為CRB ·’…為不存在；L為-N(R7)C(0)_ ;且D、X is N (R6), 0 or s, γ is N; &amp; and R3 are hydrogen; z is CRb '... is absent' D is _CH (CH3 &gt;; l is -N (R7) C (0 )-; Rb is hydrogen; and A, R7 and RA are as defined in the formula φ. In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in mammals, which includes: The mammal administers a therapeutically effective amount of a compound of formula (I), wherein A is an aryl group; ° Y ^ Yr3, n 、 R4; z is CRB; ... is absent; L is · N (R7) c ( 〇y; and D, R2, R3, R4, R7, RB and ra. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises treating the mammal A therapeutically effective amount of a compound of formula ①, wherein A is aryl, wherein aryl is phenyl, is substituted with 0, 2, 3, 4 or 5 substituents, and the substituents are independently selected from alkenyl and alkoxy , Alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, self-beta beta alkoxy, alkynyl, methylenedioxy, nitro, phenyl or &amp;; B is 0Y ^ j / R3 r4; Z is CRB BU-is absent; D _CIi2_; L is -n (R7) c (〇) _; R2, R3, and R4 are hydrogen; rb is hydrogen; and ~ and ~ are as defined in formula ①. In another specific embodiment of the present invention Is a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal an effective amount of a compound of formula (I) at 85228-33-200404539, wherein A is an aryl group, and the aryl group is Benzyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from fluorenyloxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, halogen halide Alkoxy, alkylene, methylenedioxy, nitro, phenyl or -NZi Z2; B is -N (R7) C (〇) .;; Z * CRb; ... is absent; D is- CH (CH3)-; L is R2, R3, and R4 are hydrogen; rb is hydrogen; and R7 and Ra are as defined in formula (I). In another specific embodiment of the present invention, a Method of treating sexual dysfunction in / orally in mammals 'which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), where A is aryl; B is-; z is CRB ·' ... is absent ; L is -N (R7) C (0) _; and D,

Ri、R2、R3、r4、r7、rb及Ra均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量I式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自埽基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、南素 鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或_Nn ; B為 85228 -34- 200404539 RW3 R4 i t 〇- ; R1、R2、R3及R4為氫；z為CRB ; RB為氫；〜為 不存在，D為·〇ν; L為-N(R7)C(〇)-;及心與、均如式（I)中之 定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中’台療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式①化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自埽基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或_ΝΖι&amp; ; B為 於：Ri, R2, R3, r4, r7, rb and Ra are defined as in Formula ①. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, sulfanil haloalkoxy, _alkyl, methylenedioxy, nitro, phenyl, or _Nn; B is 85228 -34- 200404539 RW3 R4 it 〇-; R1, R2, R3, and R4 Is hydrogen; z is CRB; RB is hydrogen; ~ is absent, D is · 〇ν; L is -N (R7) C (〇)-; and the same as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, _alkyl, methylenedioxy, nitro, phenyl, or ΝΝιι &amp;; B is for:

I ;R1、R2、R3及R4為氫；z為crb ; rb為氫；…為 不存在，Dg_CH2_; L 為-N(R7)C(0)_;及 r7 與 ra 為氫。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被1個烷基取代基取代；B為 I 了 0一 ； R1、R2、R3及R4為氫；z為crb ; rb為氫；…為 不存在；D為-CH2-; L為-N(R7)C(0)-;及心與、為氫。 85228 -35- 200404539 於本發明之另一項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效里之式（I)化合物，其中A為芳基，其中芳基為苯基， 被1個烷基取代基取代；B為I; R1, R2, R3 and R4 are hydrogen; z is crb; rb is hydrogen; ... is absent, Dg_CH2_; L is -N (R7) C (0) _; and r7 and ra are hydrogen. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and is substituted by 1 alkyl substituent; B is 0 for I; R1, R2, R3 and R4 are hydrogen; z is crb; rb is hydrogen; ... is absent; D is- CH2-; L is -N (R7) C (0)-; and heart and are hydrogen. 85228 -35- 200404539 In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically effective. Where A is aryl, where aryl is phenyl and substituted with 1 alkyl substituent; B is

，Ri、R2、R3及R4為氫；Z為CRB ; rb為氫；…為 不存在·’ D為-CIV·，L為-N(R7)C(0)-; r7為烷基，其中甲基為 較佳；及ra為氫。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式①化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或_NZiZ2 ; B為 RW3 ;R1、R2、心及心為氫；Z為crb ·, rb為氫；…為 不存在，D 為-CH(CH3)_ ; L 為-N(R7)C(〇)-;及 R7 與 RA 均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為四氫萘 85228 -36- 200404539 基或2,3-二氫-1H-茚基；B為 〇-，Rl、R2、R3及汉4為氲；Z為CRB ; RB為氫；一為 不存在，D為-CH2-; L為-N(R7)C(0)_;及心與、為氫。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、呋喃基、咪唑基、丨，3_噚唑基、吡畊基 、吡唑基、嗒畊基吡啶基、嘧啶基、吡咯基、嘧唑基或 嘧吩基，其中雜環係獨立被〇、丨、2或3個取代基取代，取 代基獨互選自氧基、燒氧窥基、烷基、氰基、鹵素、鹵 烷氧基、li烷基或硝基；B為 〇' ; 2為CRb ; Rb為氫；…為不存在；L為-N(R7)C(0)-，且D、Ri、R2、R3、心、R7&amp;Ra均如式①中之定義。 於本發明之另一頁具體實施^，係關於—種在哺乳動物 中治療性功能障礙之方法’其包括對該哺乳動物投予治療 上有效量之式(I)化合物，其中Α為雜環，其中雜環為苯并味 唑基、苯并嘧唑基、呋喃基、咪唑基、13_号唑基、吡畊基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、丨，3_嘍唑基 或遠吩基’其中雜環係獨立被0、丨、2或3個取代基取代^ 取代基獨立選自烷氧基、烷氧羰基、燒基、氯基、_素、 85228 -37- 200404539 鹵烷氧基、自烷基或硝基；B為, Ri, R2, R3, and R4 are hydrogen; Z is CRB; rb is hydrogen; ... is absent · D is -CIV ·, L is -N (R7) C (0)-; r7 is alkyl, where Methyl is more preferred; and ra is hydrogen. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, wherein A is an aryl group, wherein Aryl is phenyl and is substituted by 0, 1, 2, 3, 4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano Group, halogen, haloalkoxy, alkyl, methylenedioxy, nitro, phenyl, or NZiZ2; B is RW3; R1, R2, and heart are hydrogen; Z is crb, and rb is hydrogen ; Is absent, D is -CH (CH3) _; L is -N (R7) C (〇)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is tetrahydronaphthalene 85228 -36- 200404539 or 2,3-dihydro-1H-indenyl; B is 0-, R1, R2, R3 and Han 4 are fluorene; Z is CRB; RB is hydrogen ; One is absent, D is -CH2-; L is -N (R7) C (0) _; and heart and are hydrogen. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring. , Where the heterocyclic ring is benzimidazolyl, benzimidazolyl, furanyl, imidazolyl, 3-oxazolyl, pyrargyl, pyrazolyl, damidylpyridyl, pyrimidinyl, pyrrolyl, Pyrimazolyl or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 丨, 2 or 3 substituents, and the substituents are mutually selected from oxy, oxo, alkyl, cyano, halogen, haloalkoxy Group, li alkyl or nitro group; B is 0 '; 2 is CRb; Rb is hydrogen; ... is absent; L is -N (R7) C (0)-, and D, Ri, R2, R3, heart , R7 &amp; Ra are as defined in formula ①. The specific implementation on another page of the present invention is about a method for treating sexual dysfunction in mammals, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring. , Where the heterocyclic ring is benzotriazolyl, benzopyrazolyl, furanyl, imidazolyl, 13-oxazolyl, pyrargyl, pyrazolyl, daphyl, pyridyl, pyrimidinyl, pyrrolyl,丨, 3-oxazolyl or farphenyl 'wherein the heterocyclic ring is independently substituted with 0, 丨, 2 or 3 substituents ^ The substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, chloro, Element, 85228 -37- 200404539 haloalkoxy, self-alkyl or nitro; B is

，Ri為氩、烷基、氰基、鹵烷基、鹵素、硝基 烷基或（ΝΖΘ4)羰基；R2與I為氫；心為氫或羥基；2為〇^ ，RB為氫；…為不存在；D為_CH2_; L*_N(R7)c(〇)_;及心與 ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、吡唑基、吡啶基或噻吩基，其中雜環 係獨立被〇、1、2或3個取代基取代，取代基獨立選自烷氧 基、烷氧羰基、烷基、氰基、_素、自燒氧基、_烷基或 硝基；B為 R1WR3 6- ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（nz3z4) 烷基或（ΝΖβ4)羰基；R2與R4為氫；r3為氫或羥基；z為crb ;Rb為氫；…為不存在；0為&lt;112-; L為_N(R7)C(0)-;及117與 Ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為環烷基；B為 -38 - 85228 200404539, Ri is argon, alkyl, cyano, haloalkyl, halogen, nitroalkyl, or (NZΘ4) carbonyl; R2 and I are hydrogen; heart is hydrogen or hydroxyl; 2 is 〇 ^, RB is hydrogen; Does not exist; D is _CH2_; L * _N (R7) c (〇) _; and mind and ra are as defined for formula (I). In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring. , Wherein the heterocyclic ring is benzimidazolyl, benzopyrazolyl, pyrazolyl, pyridyl or thienyl, wherein the heterocyclic ring is independently substituted by 0, 1, 2 or 3 substituents, and the substituents are independently selected from alkane Oxy, alkoxycarbonyl, alkyl, cyano, sulfone, self-oxygenated, alkyi, or nitro; B is R1WR3 6-; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, Nitro, (nz3z4) alkyl or (NZβ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is crb; Rb is hydrogen; ... is absent; 0 is &lt;112-; L is _N (R7) C (0)-; and 117 and Ra are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a cycloalkane Base; B is -38-85228 200404539

ZACRb ;…為不存在；L為-N(r7)c(0)-;且D、ZACRb; ... is absent; L is -N (r7) c (0)-; and D,

Ri、R2、R3、R4、R7、RB及RA均如式（J)中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法’其包捂對該哺乳動物投予治療 上有效量之式(I)化合物’其中A為環燒基，其中環燒基為環 己基或金鋼烷基；B為Ri, R2, R3, R4, R7, RB and RA are as defined in formula (J). In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a ring Alkyl, where cycloalkyl is cyclohexyl or auryl; B is

鹵素、硝基、（NZ3Z4&gt; ’ Ri為氫、燒基、氰基、_燒基 烷基或（NZgZ4)羰基；R2與R4為氫；h為氫或羥基；Z*CRB ;RB為氫；…為不存在；D為-〇v; L*_N(R7)c(〇)_;及心與 RA均如式（I)中之定義。 於本發明 &lt; 另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效I之式（I)化合物，其中A為環烷基，其中環烷基為環 己基或金鋼烷基；B為Halogen, nitro, (NZ3Z4 &gt; 'Ri is hydrogen, alkyl, cyano, alkyl, or (NZgZ4) carbonyl; R2 and R4 are hydrogen; h is hydrogen or hydroxyl; Z * CRB; RB is hydrogen; ... is absent; D is -0v; L * _N (R7) c (〇) _; and both heart and RA are as defined in formula (I). In another specific embodiment of the present invention &lt; It relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically effective, wherein A is a cycloalkyl group, wherein the cycloalkyl group is cyclohexyl or gold steel Alkyl; B is

心為氫、燒基、氰基、_烷基、_素、硝基、讲^心) 烷基或（NZSZ4)羰基；反2與&amp;為氫；心為氫或羥基；z為CRb ，RB為氫，…為不存在；D為-CH(CH3)- ; L為-N(R7)C(0)-;及 ^與、均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；b為 85228 -39- 200404539Heart is hydrogen, alkyl, cyano, alkyl, nitro, nitro, alkoxy) alkyl or (NZSZ4) carbonyl; trans 2 and &amp; are hydrogen; heart is hydrogen or hydroxyl; z is CRb, RB is hydrogen, ... is absent; D is -CH (CH3)-; L is -N (R7) C (0)-; and ^ and are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl ; B is 85228 -39- 200404539

，Z為C ,…為一個鍵結；L為_N(R7)c(〇)-;且D、 1、人R2 R3、R4、R5、R7及Ra均如關於式①之定義。 、本發明〈另_項具體實施例中，係關於—種在哺乳動物 中治療：功能障礙之方法，“括對該哺乳動物投予治療 上有效κ式①化合物，其中A為芳基，其中芳基為苯基， 被〇 1、2、3、4或5個取代基取代，取代基獨立選自晞基 烷氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或_ΝΖιζ2 ; B為, Z is C,... Is a bond; L is _N (R7) c (〇)-; and D, 1, human R2, R3, R4, R5, R7, and Ra are as defined for formula ①. 2. In the present invention, in another specific embodiment, it relates to a method for treating mammals: dysfunction, "including administering a therapeutically effective compound of formula κ to the mammal, wherein A is an aryl group, wherein Aryl is phenyl and is substituted by 0, 2, 3, 4 or 5 substituents independently selected from fluorenylalkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, Halogen haloalkoxy, alkyl, methylenedioxy, nitro, phenyl or ΝΝιζ2; B is

、輕基、硝基、-貌基；r2為氫、烷氧基、氰 基、_素或羥基；R3為氫或羥基；r4與r5為氫；Z為C ;… 為個鍵結，D為-CH〗-;L為_N(R7 )C(0)-;及R7與RA均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自晞基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ; 85228 -40- 200404539 B為R2 is hydrogen, alkoxy, cyano, hydrogen, or hydroxyl; R3 is hydrogen or hydroxyl; r4 and r5 are hydrogen; Z is C; ... is a bond, D Is -CH〗-; L is _N (R7) C (0)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZiZ2; 85228 -40- 200404539 B is

鹵素 、羥基、硝基、-ΝΑ'或（NZJ4)燒基；&amp;為氳、烷氧基、氰 基_素或羥基；R3為氫或羥基；R4與R5為氫；z為c ;〜 為—個鍵結；D4_CH(CH3)_; L為娜7)c⑼及〜與心均如 式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（1)化合物，其中A為芳基；；8為 RW3 ^ N R4 ; z 為 C ;—一 為一個鍵結；L· 為-N(R7)C(0)-;且 D、 R1、R2、R3、R4、R7及RA均如式①中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中/口療性功能障礙 &lt; 方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、齒烷氧基、齒烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 ;Rl為氫、烷基、氰基、ΐ烷基、i素、硝基、（νζ3ζ4) 烷基或(NZsZ4)羰基；心與心為氫；為氫或羥基；ζ為c ; 85228 -41- 200404539 …為一個鍵結；D為-CH2-; L為-N(R7)C(0)_;及R7與RA均如式 (I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式①化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、燒氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 、鹵烷氧基、自烷基、亞甲二氧基、硝基、苯基或-NZi z2 ; B為 N R4 ; R1為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 燒基或（NZsZ4)羰基；R2與R4為氫；r3為氫或羥基；z為c; …為一個鍵結；D為-CH(CH3&gt;; i^_n(R7)c(〇&gt;;及心與心均 如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對讀哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、吱喃基、咪唑基、丨，3^号唑基、吡啩基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、嘍唑基 或噻吩基，其中雜環係獨立被〇、丨、2或3個取代基取代， 取代基獨JL選自烷氧基、烷氧羰基、烷基、氰基、自素、 鹵烷氧基、鹵烷基或硝基；B為 ?2 Κι&quot;ΤιΓΚ3 \ / h ; Ζ 為 C ;…為一個鍵結；L 為-N(R7)c(〇)_ ·，且 d、 85228 -42- 200404539Halogen, hydroxyl, nitro, -NA 'or (NZJ4) alkyl; &amp; is pyrene, alkoxy, cyano or hydroxy; R3 is hydrogen or hydroxyl; R4 and R5 are hydrogen; z is c; ~ Is a bond; D4_CH (CH3) _; L is Na7) c⑼ and ~ and the heart are as defined in formula ①. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (1), wherein A is an aryl group. ; 8 is RW3 ^ N R4; z is C;-one is a bond; L · is -N (R7) C (0)-; and D, R1, R2, R3, R4, R7, and RA are as follows Definition in Equation ①. In another specific embodiment of the present invention, it relates to a method of treating sexual dysfunction in a mammal / oral cavity, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A Is aryl, where aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio , Benzyl, cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B is; Rl is hydrogen, alkyl, cyano, fluorenyl, i prime, nitro, (νζ3ζ4) alkyl or (NZsZ4) carbonyl; heart-to-heart is hydrogen; is hydrogen or hydroxyl; ζ is c; 85228 -41- 200404539… is a bond; D is -CH2-; L Is -N (R7) C (0) _; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, wherein A is an aryl group, wherein Aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano Group, halogen, haloalkoxy, alkyl, methylenedioxy, nitro, phenyl or -NZi z2; B is N R4; R1 is hydrogen, alkyl, cyano, haloalkyl, halogen, Nitro, (NZ3Z4) alkyl or (NZsZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is c; ... is a bond; D is -CH (CH3 &gt;; i ^ _n (R7) c (〇 &gt;; and mind and mind are as defined in formula (I). In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in mammals, which includes reading A mammal is administered a therapeutically effective amount of a compound of formula (I), where A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, succinyl, imidazolyl, 3, 3, 3, 3, 4 , Pyridyl, pyrazolyl, dacrotyl, pyridyl, pyrimidinyl, pyrrolyl, oxazolyl, or thienyl, wherein the heterocyclic ring is independently substituted with 0, 丨, 2 or 3 substituents, substituents Sole JL is selected from alkoxy, alkoxycarbonyl, alkyl, cyano, autogen, haloalkoxy, haloalkyl, or nitro; B is? 2 Kι &quot; TΓΓK3 \ / h; Z is C; ... is One bond; L is -N (R7) c (〇) _ ·, and d, 85228 -42- 200404539

Ri、R2、R3、心、r7&amp;ra均如式（1)中之定義。 於本發明之另一項具體實施例中，係關Γ-種在哺乳動物 中治燎性功能障礙之方法，纟包括對該哺乳動物投予治療 上有效量之式①化合物’其中Α為雜環，其中雜環為苯并味 唑基、苯并嘧唑基、呋喃基、咪唑基、丨，3_嘮唑基、吡畊基 ”比峻基、^井基K基、麵基、t各基、U”塞吐基 或碟吩基，其中雜環係獨立被〇、i、2或3個取代基取代， 取代基獨乂選自；^氧基、；^氧羰基、燒基、氰基、齒素、 鹵烷氧基、卣烷基或硝基；B為 ?2 ΚινΥι Ra \ 〜；Rl為氫、烷基、氰基、_烷基、_素、硝基、讲44) 烷基或(NZsZ4)羰基；&amp;與心為氳；R3為氫或羥基；z&amp;c; …為一個鍵結；D為-CH2-; L為-N(R7)C(0)_;及心與心均如關 於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效T之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、吡唑基、吡啶基或嘧吩基，其中雜環 係獨立被0、1、2或3個取代基取代，取代基獨立選自烷氧 基、烷氧羰基、烷基、氰基、1¾素、_烷氧基、_烷基或 硝基；B為Ri, R2, R3, heart, r7 &amp; ra are as defined in formula (1). In another specific embodiment of the present invention, a method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of the formula Ring, wherein the heterocyclic ring is benzotriazole, benzopyrazolyl, furanyl, imidazolyl, 3-oxazolyl, pyridoyl Each group, U ”sethyl or phenoxy, wherein the heterocyclic ring is independently substituted with 0, i, 2 or 3 substituents, and the substituents are independently selected from the group consisting of ^ oxy, ^ oxycarbonyl, alkyl, Cyano, halide, haloalkoxy, fluorenyl, or nitro; B is? 2 ΚινΥι Ra \ ~; Rl is hydrogen, alkyl, cyano, alkyi, nitro, nitro, 44) Alkyl or (NZsZ4) carbonyl; &amp; is 氲 with the heart; R3 is hydrogen or hydroxyl; z &amp;c; ... is a bond; D is -CH2-; L is -N (R7) C (0) _; Both mind and mind are as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (I) which is therapeutically effective, wherein A is a heterocyclic ring. Where the heterocyclic ring is benzimidazolyl, benzopyrazolyl, pyrazolyl, pyridyl, or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 1, 2, or 3 substituents, and the substituents are independently selected from Alkoxy, alkoxycarbonyl, alkyl, cyano, 1¾, alkoxy, alkyi, or nitro; B is

、R4 ;心為氫、燒基、氰基、_燒基、_素、硝基&amp; 燒基或(NZ3 Z4)羧基；&amp;與R4為氫；r3為氫或幾基；z為c ; 85228 -43- 200404539 ^為―個鍵結；D^CHr; L為娜7)贈；及&amp;队均如關 於式（1)之定義。 :本發明〈另一項具體實施例中，係關於一種在哺乳動物 療丨生功把障％之方法，其包括對該哺乳動物投予治療 上有效τ之式①化合物，其中A為芳基；B為 、Υ、I、R3、R7&amp;RA均如式①中之定義 3 ; Z為 C;…為一個鍵結；Lg_N(R7)c(〇&gt;;且!）、χ 万、本發明之另-項具體實施例中，係關於—種在哺乳動物 中/口療性功能障礙之方法，Λ包括對該哺乳動物投予治療 上有效量之式①化合物，其中Α為芳基，其中芳基為苯基， 孝1 2、3、4或5個取代基取代，取代基獨立選自缔基 烷乳基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 4燒氧基、“基、亞甲二氧基、硝基、苯基或视A; B為 ;X為N(R6)、〇或S; 丫為吼）；心與心為氫；^ 氫、k基或氰基；Z為C ;〜為-個鍵結；D為偶_ ; L為 •N(R7)c(o)-;且心、心及心均如式①中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式⑴化合物，其中A為芳基，其中芳基為苯基， 被ο 1、2、3、4或5個取代基取代，取代基獨立選自烯基 、燒氧基、燒氧羰基、燒基、燒硫基、爷基、氰基、齒素 85228 -44- 200404539 、鹵烷氧基、 B為 鹵燒基、亞甲二氧基、 硝基、苯基或-NZiZ2 ; vTCr 、丫 R3 ; X為 N(R6)、Ο 或 S ; γΛΓγρ、 ^ 為L(R4) ’· R2與R3為氫；R4為 氣、纟元基或散基，Z為C，…為一伽蚀々丄, R4; hydrogen is hydrogen, alkynyl, cyano, alkynyl, oxon, nitro &amp; alkynyl or (NZ3 Z4) carboxyl; &amp; and R4 are hydrogen; r3 is hydrogen or several groups; z is c 85228 -43- 200404539 ^ is a bond; D ^ CHr; L is Na 7) gift; and &amp; team are as defined for formula (1). : In another specific embodiment of the present invention, a method for treating dysfunction in a mammal, which comprises administering to the mammal a compound of formula ①, wherein A is an aryl group. ; B is, Υ, I, R3, R7 &amp; RA are as defined in formula ① 3; Z is C; ... is a bond; Lg_N (R7) c (〇 &gt;; and!), Χ 10,000, this In another specific embodiment of the invention, it relates to a method for treating sexual dysfunction in a mammal / oral, Λ comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, wherein A is an aryl group, Wherein the aryl group is phenyl, substituted by 1, 2, 3, 4 or 5 substituents, and the substituents are independently selected from alkenyl alkynyl, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, and halogen 4 alkoxy, "yl, methylenedioxy, nitro, phenyl, or A; B is; X is N (R6), 0, or S; Y is roar); heart and heart are hydrogen; ^ hydrogen , K or cyano; Z is C; ~ is a bond; D is even; L is • N (R7) c (o)-; and heart, heart, and heart are as defined in formula ①. In another specific embodiment of the present invention, A method for treating sexual dysfunction in a dairy animal, comprising administering to the mammal a therapeutically effective amount of a compound of the formula (I), wherein A is an aryl group, wherein the aryl group is a phenyl group, is 1, 2, 3, 4 or 5 substituents are substituted, and the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyn, thiothio, hexyl, cyano, halo 85228 -44- 200404539, haloalkoxy, and B is Haloalkyl, methylenedioxy, nitro, phenyl or -NZiZ2; vTCr, γR3; X is N (R6), 〇 or S; γΛΓγρ, ^ is L (R4) ', R2 and R3 are hydrogen ; R4 is gas, unitary or scattered basis, Z is C, ... is a gamma eclipse

^ 调鍵結；D為 _CH(CH3)_; L 為-N(R7)C(0)-;且R0、R7及RA均如式①中之定義。 於本發明之另一項具體實施例中，#的、 係關於一種在哺乳動物 中治療性功能障礙之方法，其舍杠姐』一 括'對孩哺乳動物投予治療 上有=量之式（I)化合物，其中A為環烷基；B為^ Tuning bond; D is _CH (CH3) _; L is -N (R7) C (0)-; and R0, R7 and RA are as defined in formula ①. In another specific embodiment of the present invention, # 's is about a method of treating sexual dysfunction in mammals, and its sister "contains" the formula for the treatment of child mammals = I) a compound wherein A is cycloalkyl; B is

r3 、’ R4 ; ZAC;…為-個鍵結；L為-N(R7)C(0)_;且D、 R1、尺2、R3、1^4、R7及Ra均如式（I)中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中心療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中人為環烷基，其中環烷基為環 己基或金鋼燒基；B為 JXR . N 4，R1為氫、烷基、氰基、_烷基、！I素、硝基、（NZ3Z4) 烷基或(NZsZ4)羰基；R2與R4為氫；r3為氫或羥基；z為c; …為一個鍵結；D為-CH2-; L為-N(R7)C(0)-;及R7與RA均如式 (1)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中’口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為環烷基，其中環烷基為環 85228 -45- 200404539 己基或金鋼燒基；B為 R1-^WR3 、/ R4 ; &amp;為氫、燒基、氰基、_烷基、_素、硝基、@2^4) 烷基或(NZ3 Z4)羰基；&amp;與&amp;為氫；R3為氫或羥基；z為c ; …為一個鍵結；D為-CH(CH3)-; I^_N(R7)c(〇&gt;;及心與〜均 如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中/口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為r3, 'R4; ZAC; ... is a bond; L is -N (R7) C (0) _; and D, R1, ruler 2, R3, 1 ^ 4, R7, and Ra are all like formula (I) In the definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal center, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein the human is a cycloalkyl group. , Where cycloalkyl is cyclohexyl or gold-steel; B is JXR. N 4, R1 is hydrogen, alkyl, cyano, alkyl, etc. I prime, nitro, (NZ3Z4) alkyl or (NZsZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is c; ... is a bond; D is -CH2-; L is -N ( R7) C (0)-; and R7 and RA are as defined in formula (1). In another specific embodiment of the present invention, it relates to a method for 'oral treatment of sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is Cycloalkyl, where cycloalkyl is cyclo 85228-45-200404539 hexyl or gold-steel; B is R1- ^ WR3, / R4; &amp; is hydrogen, alkyl, cyano, alkyi, Nitro, @ 2 ^ 4) alkyl or (NZ3 Z4) carbonyl; & and &amp; are hydrogen; R3 is hydrogen or hydroxyl; z is c; ... is a bond; D is -CH (CH3)-; I ^ _N (R7) c (〇 &gt;; and Xin and ~ are as defined in formula (I). In another specific embodiment of the present invention, it relates to a therapeutic function in mammals / oral A method of dysfunction comprising administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl; B is

Ri 汉3、h、R5、R7及Ra均如式（I)中之定義 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效里之式①化合物，其中A為芳基，其中芳基為苯基， 被0 1、2、3、4或5個取代基取代，取代基獨立選自晞基 烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷乳基、_烷基、亞甲二氧基、硝基、苯基或-NZiZa ; B為 ’ ri為氫、烷氧基、烷基、烷硫基、氰基、自素 、趙基、硝基、或（ΝΖΑ)燒基；&amp;為氫、燒氧基、氰 85228 -46- 200404539 基、鹵素或羥基；&amp;為氫或羥基；以4與&amp;為氫；Z為N;… 為不存在；D為-CH2-; L為-C(0)N(R7)-;及R#RA均如式（1)中 之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自缔基 、烷氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 、鹵烷氧基、卣烷基、亞甲二氧基、硝基、苯基或_ΝΖιζ2 ;Ri Han 3, h, R5, R7 and Ra are as defined in formula (I). In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in mammals, which includes A compound of formula ① which is therapeutically effective in mammals, where A is aryl, where aryl is phenyl, and is substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from amidino Oxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, haloalkoxy, _alkyl, methylenedioxy, nitro, phenyl, or -NZiZa; B is' ri Is hydrogen, alkoxy, alkyl, alkylthio, cyano, cyano, oxo, nitro, or (NZOA) alkyl; &amp; is hydrogen, alkyl, cyano 85228 -46- 200404539, Halogen or hydroxyl; &amp; is hydrogen or hydroxyl; 4 and &amp; are hydrogen; Z is N; ... is absent; D is -CH2-; L is -C (0) N (R7)-; and R # RA is as defined in formula (1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl , Cyano, halogen, haloalkoxy, fluorenyl, methylenedioxy, nitro, phenyl, or ΝΝιζ2;

Ri為氫、烷氧基、烷基、烷硫基、氰基' _素 、羥基、硝基、-NZJ2或（ΝΖβ4)垸基；&amp;為氫、烷氧基、氰 基、_素或羥基；R3為氫或羥基；心與心為氫；Ζ*Ν 為不存在；D為 _CH(CH3)-; I^-C(0)N(R7)-;及 R7 與 ra均如式（1) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（1)化合物，其中A為芳基；b為Ri is hydrogen, alkoxy, alkyl, alkylthio, cyano ', hydroxyl, nitro, -NZJ2 or (NZβ4) fluorenyl; &amp; is hydrogen, alkoxy, cyano, or Hydroxyl; R3 is hydrogen or hydroxyl; heart and heart are hydrogen; Z * N is absent; D is _CH (CH3)-; I ^ -C (0) N (R7)-; and R7 and ra are both of the formula (1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (1), wherein A is an aryl group. ; B is

1 ; Z為N ;…為不存在；L為-C(0)N(R7)_ ;且D、心 R2、反3、R4、R7及RA均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 85228 -47- 200404539 中治療性功能障礙之方法 上有效量之式（I)化合物，: 被〇、1、2、3、4或5個耳 法’其包括對該哺乳動物投予治療 ，其中A為芳基，其中芳基為苯基， 、3、4或5個取代基取代，取代基獨立選自晞基 烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷基、亞甲二氧基、硝基、苯基或-ΝΖι &amp; ; 燒氧基、烷氧羰基、烷 苄基、氰基、鹵素 、鹵燒氧基、南燒基、亞 B為1; Z is N; ... is absent; L is -C (0) N (R7) _; and D, R2, R3, R4, R7, and RA are as defined in formula (I). In another embodiment of the present invention, it relates to a compound of formula (I) which is effective in the method of treating sexual dysfunction in mammals 85228-47-200404539, and is: 0, 1, 2, 3, 4 or 5 ear methods, which includes administering treatment to the mammal, where A is aryl, where aryl is phenyl, and 3, 4 or 5 substituents are substituted, and the substituents are independently selected from fluorenylalkoxy Carbonyl, alkyl, alkylthio, benzyl, cyano, halogen, haloalkyl, methylenedioxy, nitro, phenyl or -NZι &amp;; alkoxy, alkoxycarbonyl, alkylbenzyl, Cyano, halogen, halooxy, sulphanyl, B-sub is

N R4 ; Rl為氫、烷基、氰基、齒烷基、_素、硝基、（NZ3Z4) 烷基或(NZ^4)羰基；&amp;與及4為氫；r3為氫或羥基；Z*N; -為不存在；D為-CH2- ; L·為-C(0)N(R7)_ ;及r7與Ra均如式（工） 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2 ' 3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、_素 、鹵烷氧基、_烷基、亞甲二氧基、硝基、苯基或-ΝΖι &amp; ; B為N R4; R1 is hydrogen, alkyl, cyano, acyl, nitro, nitro, (NZ3Z4) alkyl or (NZ ^ 4) carbonyl; &amp; and 4 are hydrogen; r3 is hydrogen or hydroxyl; Z * N;-is absent; D is -CH2-; L · is -C (0) N (R7) _; and r7 and Ra are as defined in formula (work). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2 '3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, alkyl, methylenedioxy, nitro, phenyl, or -NZι &amp;; B is

1 in ·、4 ; Ri為氫、燒基、氰基、鹵燒基、鹵素、硝基、（NZ3Z4) 烷基或(NZ3Z4)羰基；R2與R4為氫；R3為氫或羥基；Z為N; …為不存在；D為-CH(CH3)- ; L為_C(0)N(R7)·;及R7與RA均如 式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 85228 -48- 200404539 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、燒氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、齒烷基、亞甲二氧基、硝基、苯基或_NZi &amp; ; B為1 in ·, 4; Ri is hydrogen, alkyl, cyano, halogeno, halogen, nitro, (NZ3Z4) alkyl or (NZ3Z4) carbonyl; R2 and R4 are hydrogen; R3 is hydrogen or hydroxyl; Z is N;… is absent; D is -CH (CH3)-; L is _C (0) N (R7) ·; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal 85228-48-200404539, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), Where A is aryl, where aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkane Thio, benzyl, cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or _NZi &amp;; B is

ι , Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、 燒基或（ΝΖΘ4)複基；匕與心為氫；心為氫或羥基；z為n; …為不存在；D為-CH2CH2-; Lg_C(0)N(R7)-;及心與、均如 式(ί)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中冶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中Α為芳基；Β為ι, Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, alkynyl or (NZΘ4) complex; dagger and heart are hydrogen; heart is hydrogen or hydroxyl group; z is n;… is absent ; D is -CH2CH2-; Lg_C (0) N (R7)-; and the definition of Xin Yu, are as in formula (ί). In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aromatic Base; B is

，取代基獨立選自烯基 丨化合物，其中A為芳基， 、4或5個取代基取代，部The substituents are independently selected from alkenyl compounds, where A is aryl, 4 or 5 substituents are substituted, and

85228 烷基、烷硫基、苄基、氰基、鹵素 亞甲二氧基、硝基、苯基或-NZiZ2 ; -49- 200404539 / ，R2、R3及R4為氫，Z為N ;為不存在；D為_ch2_ ;L*-C(〇)N(r7&gt;;及心與、均如式（I)中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式(1)化合物，其中A為芳基，其中芳基為苯基， 被0 1、2、3、4或5個取代基取代，取代基獨立選自烯基 B為 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、_燒氧基、“基、亞甲二氧基、硝基、苯基4_NZiZ2 ;85228 alkyl, alkylthio, benzyl, cyano, halomethylenedioxy, nitro, phenyl or -NZiZ2; -49- 200404539 /, R2, R3 and R4 are hydrogen, Z is N; is not Existing; D is _ch2_; L * -C (〇) N (r7 &gt;), and the same as defined in formula (I). In another specific embodiment of the present invention, it relates to a kind of breastfeeding A method for treating sexual dysfunction in animals, comprising administering to the mammal a therapeutically effective amount of a compound of formula (1), wherein A is aryl, wherein aryl is phenyl, and is Or 5 substituents, the substituents are independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, alkoxy, "yl, methylene Dioxy, nitro, phenyl 4_NZiZ2;

r3 ，反2、R3及R4為氫；Z為N;…為不存在；d為_ch(CH3)_ ;La-C(〇)N(R7&gt;;及心與、均如式（1)中之定義。 於本發明（另—項具體實施例中，係㈣一種在哺乳動物 中’口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有=量之式（I)化合物，其中A為環烷基；B為 Γ\ο 'x^cR3 N R4，Z為N ;…為不存在；L為;且D、心 、R2、R3、r4、r7及RA均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中冶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效K式（I)化合物，其中A為環烷基，其中環烷基為環 己基或金鋼烷基；B為 85228 -50- 200404539r3, trans2, R3 and R4 are hydrogen; Z is N; ... is absent; d is _ch (CH3) _; La-C (〇) N (R7 &gt;); In the present invention (another specific embodiment, it is a method of treating oral sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutic formula (I) Compound, where A is cycloalkyl; B is Γ \ ο 'x ^ cR3 N R4, Z is N; ... is absent; L is; and D, Xin, R2, R3, r4, r7, and RA are as follows: The definition in ①. In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective compound of formula (I), Where A is cycloalkyl, where cycloalkyl is cyclohexyl or auryl; B is 85228 -50- 200404539

\ N R4 ;心為氫、烷基、氰基、卣烷基、齒素、硝基、（NZ3Z4) 烷基或（NZSZ4)羰基；R2與&amp;為氳；化為氫或羥基；2：為1^; …為不存在；D為_CH2_; L為-C(0)N(R7)-;及R7與ra均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中冶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效f之式（I)化合物，其中A為環烷基，其中環烷基為環 己基或金鋼燒基；B為\ N R4; Heart is hydrogen, alkyl, cyano, fluorenyl, dentin, nitro, (NZ3Z4) alkyl or (NZSZ4) carbonyl; R2 and &amp; are fluorene; turn into hydrogen or hydroxyl; 2: Is 1 ^;… is absent; D is _CH2_; L is -C (0) N (R7)-; and R7 and ra are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective compound of formula (I), wherein A is a ring Alkyl, where cycloalkyl is cyclohexyl or gold-steel; B is

1，Ri為氫、燒基、氰基、鹵燒基、鹵素、硝基、⑽A) 火元基或(NZgZ4)羰基；&amp;與R4為氫；&amp;為氫或羥基；Z*N; …為不存在；D為-CH(CH3)-·，L為-C(〇)N(R7)_;及心與ra均如 式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為1, Ri is hydrogen, alkyl, cyano, halogeno, halogen, nitro, fluorene A) a radical or (NZgZ4) carbonyl; &amp; and R4 are hydrogen; &amp; is hydrogen or hydroxyl; Z * N; … Is absent; D is -CH (CH3)-·, L is -C (〇) N (R7) _; and both heart and ra are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl ; B is

且D、心、R2、R3、R4、R5、及RA均如式(I)中之定義。 於本發明之另一項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 85228 -51- 200404539 被0、1、2、3、4或5個取代基取代，取代基獨立選自埽基 、烷氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、_素 、鹵烷氧基、i烷基、亞甲二氧基、硝基、苯基或-NZi Z2 ;And D, heart, R2, R3, R4, R5, and RA are all as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aromatic Group, where aryl is phenyl, 85228 -51- 200404539 is substituted with 0, 1, 2, 3, 4 or 5 substituents independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, Alkylthio, fluorenyl, cyano, halogen, haloalkoxy, i-alkyl, methylenedioxy, nitro, phenyl or -NZi Z2;

Rs ; Ri為氫、烷氧基、烷基、烷硫基、氰基、_素 、羥基、硝基、-NZJ2或（NZ3Z4)燒基；R2為氫、烷氧基、氰 基、鹵素或羥基；R3為氫或羥基；114與115為氫；Z為CRb ; rb 為氫；…為不存在；D為_CH2_; L為-C(0)N(R7)_;及117與1^均 如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自晞基 、燒氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、_燒氧基、_烷基、亞甲二氧基、硝基、苯基或-NZi z2 ; B為Rs; Ri is hydrogen, alkoxy, alkyl, alkylthio, cyano, hydrogen, hydroxy, nitro, -NZJ2 or (NZ3Z4) alkyl; R2 is hydrogen, alkoxy, cyano, halogen or Hydroxyl; R3 is hydrogen or hydroxyl; 114 and 115 are hydrogen; Z is CRb; rb is hydrogen; ... is absent; D is _CH2_; L is -C (0) N (R7) _; and 117 and 1 ^ Both are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, alkynyl, alkyl, methylenedioxy, nitro, phenyl, or -NZi z2; B is

Rl Yi&quot;R3 R5 ; Rl為氫、烷氧基、烷基、烷硫基、氰基、鹵素 、藉基、硝基、-NZA或（NZ3Z4)fe基；R2為氫、烷氧基、氰 基、齒素或羥基；r3為氫或羥基；心與心為氫；Z為CRb ; Rb 為氣；〜為不存在；D為-CH(CH3)_ ; L為-C(0)N(R7)-;及R7與 85228 -52- 200404539Rl Yi &quot; R3 R5; Rl is hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, borrowed, nitro, -NZA or (NZ3Z4) fe; R2 is hydrogen, alkoxy, cyano R3 is hydrogen or hydroxyl; heart and heart are hydrogen; Z is CRb; Rb is qi; ~ is absent; D is -CH (CH3) _; L is -C (0) N ( R7)-; and R7 and 85228 -52- 200404539

Ra均如式（I)中之定義。 ' 月之另一項具體貫施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效里之式（1)化合物，其中A為芳基；B為Ra is as defined in formula (I). In another specific embodiment, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (1), wherein A is an aryl group. ; B is

Ν 4 ; Ζ為crb ; Rb為氫；…為不存在；L為-C(0)N(R7)- ;且〇、r η 、R2、R3、R4、R7&amp;RA均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中&amp;療性功能障礙之方法，其包括對該哺乳動物投予治療 有放里之式（J)化合物，其中A為芳基，其中芳基為苯基， 被 0、] 、〇 ’ 2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-NZJ2 ; B為 4，Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) ^基或（ΝΖ34)羰基；R2與R4為氫；R3為氫或羥基；z為crb ’ rb為氫·’…為不存在；D為-CIV; L為-c(o)n(r7)-;及心與 RA均如式（I)中之定義。 木本發明之另一項具體實施例中，係關於一種在哺乳動物 中療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中Α為芳基，其中芳基為苯基， ^Zjh· A 1 υ、ί、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 85228 -53- 200404539 鹵烷氧基、ii烷基、亞甲二氧基、硝基、苯基或_ΝΖι &amp; ; B為 R；WR3 N R4，&amp;為氫、烷基、氰基、齒烷基、_素、硝基、 烷基或（ΝΖβ4)羰基；化與心為氫；R3為氫或羥基；ZgCRB ，Rb為氫，…為不存在；D為_CH(ai^_ ; L為_c(〇)N(R7&gt; ;及 R7與RA均如式（I)中之定義。 万；本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為 °Y^YR3 、、rT R4 ’ z 為 CRb，Rb 為氫；…為不存在；l 為 _c(〇)n(R7)_ ;且〇、R2、r3、R4、心及、均如式①中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中’口療丨生功犯障礙之方法，其包括對該哺乳動物投予治療 上有效置足式①化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、芊基 '氰基、鹵素 、齒垸氧基、燒基、亞甲二氧基、硝基、苯基或-ΝΖιΖ2 ; B為Ν 4; Z is crb; Rb is hydrogen; ... is absent; L is -C (0) N (R7)-; and 〇, r η, R2, R3, R4, R7 &amp; RA are all represented by formula (I) In the definition. In another embodiment of the present invention, it relates to a method of &amp; treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (J) for treatment, wherein A is Aryl, where aryl is phenyl, substituted with 0,], 0 '2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio Group, benzyl, cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl or -NZJ2; B is 4, Ri is hydrogen, alkyl, cyano, haloalkane R2 and R4 are hydrogen; R3 is hydrogen or hydroxyl; z is crb 'rb is hydrogen ·' ... is absent; D is -CIV; L Is -c (o) n (r7)-; and mind and RA are as defined in formula (I). Another embodiment of the present invention relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is an aryl group. Where aryl is phenyl, ^ Zjh · A 1 υ, ί, 2, 3, 4 or 5 substituents are substituted, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio Group, benzyl, cyano, halogen 85228 -53- 200404539 haloalkoxy, iialkyl, methylenedioxy, nitro, phenyl or ΝΝιι &amp;; B is R; WR3 N R4, &amp; Is hydrogen, alkyl, cyano, alkynyl, sulfonium, nitro, alkyl, or (NZβ4) carbonyl; hydration and hydrogen are hydrogen; R3 is hydrogen or hydroxyl; ZgCRB, Rb is hydrogen, ... does not exist; D is _CH (ai ^ _; L is _c (〇) N (R7 &gt;; and R7 and RA are as defined in formula (I). 10,000; In another specific embodiment of the present invention, it is about A method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl; B is ° Y ^ YR3, and rT R4'z is CRb, Rb is hydrogen; ... is absent; l is _c (〇) n (R7) _; and 〇, R2, r3, R4, Xinhe, are as defined in formula ①. Another-specific in the present invention In the embodiment, the invention relates to a method of “oral therapy” for dysfunction in mammals, which comprises administering a therapeutically effective compound of formula ① to the mammal, wherein A is aryl and aryl is benzene. Group, substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, amidino'cyano, halogen, Dentoxy, alkynyl, methylenedioxy, nitro, phenyl, or -NZιZ2; B is

、，R2、R3&amp;R4為氫；Z為CRB ; RB為氳；…為不存在 D為CH2 - , L為-C(0)N(R7,及R7與ra均如式（I)中之定義。 於本發明之另-項具體實施例中，係、關於—種在哺乳動物 85228 -54- 200404539 中治療性功能障礙之方法，纟包括對該哺乳動物投予治療 上有效量之式(I)化合物’其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自晞基 烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 '❸完氧基、自燒基、亞甲二氧基、硝基、苯基或视&amp; ; B為 。上R3 / ，R2尺3及以4為氫·’ Z為CRB ; Rb為氫；…為不存在 ’ D為_CH(CH3)·; LA_C(0)N(R7)J及汉7與心均如式①中之定 義0 糸本發明之另一項具體實施例中，係關於一種在哺乳動物 中/口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效T之式（I)化合物，其中A為芳基；B為 0 、 ' ;Ζ為CRb ; Rb為氫；…為不存在；L·為-C(0)N(R7)_ ，且D、&amp;、r2、r3 ' r4、化及、均如式①中之定義。 杰本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或_ΝΖι &amp; ; B為 85228 -55- 200404539,, R2, R3 &amp; R4 are hydrogen; Z is CRB; RB is 氲; ... is absent D is CH2-, L is -C (0) N (R7, and R7 and ra are both in formula (I) Definition. In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal 85228-54-200404539, which comprises administering to the mammal a therapeutically effective amount of the formula ( I) Compound 'wherein A is aryl, wherein aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents independently selected from fluorenylalkoxy, alkoxycarbonyl, alkane Group, alkylthio group, benzyl group, cyano group, halogen 'fluorenyloxy group, self-burning group, methylenedioxy group, nitro group, phenyl group or R &B; Let 4 be hydrogen · 'Z is CRB; Rb is hydrogen; ... is absent' D is _CH (CH3) ·; LA_C (0) N (R7) J and Han 7 and the heart are as defined in formula ① 0另一 Another embodiment of the present invention relates to a method for treating sexual dysfunction in a mammal / orally, which comprises administering to the mammal a compound of formula (I) which is therapeutically effective, wherein A is Aryl; B is 0, '; Z is CRb; Rb is hydrogen … Is absent; L · is -C (0) N (R7) _, and D, &amp;, r2, r3 'r4, and are defined as in formula ①. Another specific aspect of the invention In an embodiment, the present invention relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl, and aryl is phenyl. Substituted by 0, 1, 2, 3, 4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, haloalkane Oxy, haloalkyl, methylenedioxy, nitro, phenyl or ΝΝιι &amp;; B is 85228 -55- 200404539

〇-;R1、R2、R3及R4為氫；Z為CRB ; RB為氳；〜 不存在；D為-αν ; L為_C(0)N(R7)-;及R7與RA均如式①中之 定義。 糸本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為笨基Y 被0、1、2、3、4或5個取代基取代，取代基獨立選自埽基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、南素 、鹵烷氧基、齒烷基、亞甲二氧基、硝基、苯基或_ΝΖι &amp; ;〇-; R1, R2, R3 and R4 are hydrogen; Z is CRB; RB is 氲; ~ does not exist; D is -αν; L is _C (0) N (R7)-; and R7 and RA are both of the formula The definition in ①.另一 Another embodiment of the present invention relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is benzyl Y is substituted by 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, southernin, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or ΝΝιι &amp;

;Ri、R2、R3&amp;R4為氫；Z為 CRb ; Rb為氫·，…為 不存在·，D為-CH2-; L為_C(0)N(R7)_;及化與^為氫。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被1個烷基取代基取代；B為Ri, R2, R3 &amp; R4 are hydrogen; Z is CRb; Rb is hydrogen ·, ... is absent ·, D is -CH2-; L is _C (0) N (R7) _; and 与 is hydrogen. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 1 alkyl substituent; B is

;Ri、R2、R3及R4為氫；Z為CRB ; RB為氫；…為 不存在；D為-αν; L為-C(0)N(R7)-;及心與、為氳。 85228 -56- 200404539 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被1個烷基取代基取代，其中較佳烷基取代基為甲基；B為 〇-;Ri、R2、R3及R4為氫；z為crb ; rb為氫；…為 不存在；D為-CH2·; L為-C(0)N(R7)_;及 r#ra為氫。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被1個烷基取代基取代，其中較佳烷基取代基為甲基；B為Ri, R2, R3 and R4 are hydrogen; Z is CRB; RB is hydrogen; ... is absent; D is -αν; L is -C (0) N (R7)-; and heart and are 氲. 85228-56- 200404539 In another embodiment of the present invention is a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), Where A is aryl, where aryl is phenyl, substituted by 1 alkyl substituent, and the preferred alkyl substituent is methyl; B is 0-; Ri, R2, R3, and R4 are hydrogen; z is crb; rb is hydrogen; ... is absent; D is -CH2 ·; L is -C (0) N (R7) _; and r # ra is hydrogen. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and is substituted by 1 alkyl substituent, of which the preferred alkyl substituent is methyl; B is

RlVvR3RlVvR3

XXR Λ ^N+ R4 ο- ; R1、R2、R3及R4為氫；ζ為crb ; rb為氫；…為 不存在；D為-CH2-; L為-C(S)N(R7)_;及r7與RA為氬。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自晞基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、ΐ烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 Λ 4 .. '，益 85228 -57-XXR Λ ^ N + R4 ο-; R1, R2, R3 and R4 are hydrogen; ζ is crb; rb is hydrogen; ... is absent; D is -CH2-; L is -C (S) N (R7) _; And r7 and RA are argon. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, fluorenyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B is Λ 4 .. ', Yi 85228 -57-

I 200404539 〇- ;Ri、R2、R3及R4為氫；z為crb ; rb為氫；…為 不存在；D 為-CH(CH3)- ; L 為-C(0)N(R7)_ ;及 R7 與 1^均如式（I) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中心療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被1個烷基取代基取代，其中較佳燒基取代基為甲基；B為I 200404539 〇-; Ri, R2, R3 and R4 are hydrogen; z is crb; rb is hydrogen; ... is absent; D is -CH (CH3)-; L is -C (0) N (R7) _; And R7 and 1 ^ are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal center, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is an aryl group. Where aryl is phenyl and is substituted by 1 alkyl substituent, of which the preferred alkyl substituent is methyl; B is

I ，Ri、R2、R3及R4為氫；Z為CRB ; RB為氫；…為 不存在；D為-CH(CH3)-; L為_C(0)N(R7&gt;·;及心與RA為氫。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 吐基、苯并噻唑基、呋喃基、咪唑、1，3-呤唑基、吡畊基、 外匕峻基、塔畊基、被淀基、喊淀基、吨嘻基、1，3-魂吨基或 4吩基，其中雜環係獨立被〇、1、2或3取代基取代，取代 基獨立選自烷氧基、烷氧羰基、烷基、氰基、齒素、函燒 氧基、自烷基或硝基；B為I, Ri, R2, R3, and R4 are hydrogen; Z is CRB; RB is hydrogen; ... is absent; D is -CH (CH3)-; L is _C (0) N (R7 &gt;...; and heart and RA is hydrogen. In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidyl, benzothiazolyl, furanyl, imidazole, 1,3-pyrazolyl, pyrenyl, exogenyl, targyl, benzyl, Dyridyl, tolyl, 1,3-pyridyl, or 4-phenyl, wherein the heterocyclic ring is independently substituted with 0, 1, 2, or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, Alkyl, cyano, halide, alkoxy, self-alkyl or nitro; B is

;Z為CRB ; RB為氫；…為不存在；L為-C(0)N(R7 )- 85228 -58- 200404539 ’且D、K、R2、r3、r4、117及〜均如式①中之定義。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法，纟包括對該喷乳動物投予治療 上有效量之式(1)化合物，其巾A為雜環，其巾雜環為苯并咪 咬基、苯并基、吱喃基、咪唆基' 仏以基”比呼基 、吡唑基、嗒畊基、吡啶基、嘧啶基、吡咯基、砂嘍唑基 或11塞力基’其中雜環係獨立被〇、丨、2或3個取代基取代， 耳代基獨乂選自境氧基、燒氧羰基、燒基、氰基、商素、 li垸氧基、函烷基或硝基；B為 I 了 °&quot; ; Rl為氫、燒基、氰基、卣烷基、卣素、硝基、（nz3z4) 烷基或（ΝΖβ4)羰基；R2與R4為氫；r3為氫或羥基；z*CRb ，rb為氳；…為不存在；D為·CH2-; l為-C(0)N(R7)-;及化與 ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中心療性功能障域之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為雜環，其中雜環為苯并咪 唑基、苯并嘧唑基、吡唑基、吡啶基或嘧吩基，其中雜環 係獨立被〇、1、2或3個取代基取代，取代基獨立選自烷氧 基、烷氧羰基、烷基、氰基、鹵素、函烷氧基、_烷基或 硝基；B為 85228 -59-Z is CRB; RB is hydrogen; ... is absent; L is -C (0) N (R7)-85228 -58- 200404539 'and D, K, R2, r3, r4, 117 and ~ are all as formula ① In the definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in mammals, which comprises administering a therapeutically effective amount of a compound of formula (1) to the sprayed animal, the towel A It is a heterocyclic ring, and its heterocyclic ring is benzimidyl, benzoyl, succinyl, imidyl ', pyrenyl, pyridyl, pyrazolyl, daphnyl, pyridyl, pyrimidinyl, and pyrrole Group, oxazolidyl group or 11 selenium group wherein the heterocyclic system is independently substituted by 0, 丨, 2 or 3 substituents, and the alkynyl group is selected from the group consisting of alkoxy, alkoxycarbonyl, alkynyl, and cyano , Shangsu, li 垸 oxy, haloalkyl, or nitro; B is I °; &quot; Rl is hydrogen, alkyl, cyano, fluorenyl, halogen, nitro, (nz3z4) alkyl, or (NZβ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z * CRb, rb is 氲; ... is absent; D is · CH2-; l is -C (0) N (R7)-; and Both Hua and Ra are as defined with respect to formula (I). In another embodiment of the present invention, it relates to a method of treating sexual dysfunction in a mammalian center, which comprises administering therapy to the mammal. Formula of effective amount I) A compound wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzopyrazolyl, pyrazolyl, pyridyl, or pyrenyl, wherein the heterocyclic ring is independently 0, 1, 2, or 3 Substituent substitution, the substituent is independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, halogen, alkoxy, alkyl, or nitro; B is 85228 -59-

I I200404539 〇- ; Ri為氫、烷基、氰基、鹵烷基、#素、硝基、（nz3z4) 烷基或（NZgZ4)羰基；R2與R4為氳；r3為氫或羥基；z為CRb ;Rb為氳；…為不存在；d為-CH2-; L為-C(0)N(R7)-;及R7與I I200404539 〇-; Ri is hydrogen, alkyl, cyano, haloalkyl, # prime, nitro, (nz3z4) alkyl or (NZgZ4) carbonyl; R2 and R4 are 氲; r3 is hydrogen or hydroxyl; z is CRb; Rb is 氲; ... is absent; d is -CH2-; L is -C (0) N (R7)-; and R7 and

Ra均如關於式（I)之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為環烷基；B為 \ ’ R4，Z為CRb ; Rb為氫；…為不存在；L為七⑼N(R?)_ ’且D尺1、反2、R3、R4、R7及Ra均如式（I)中之定義。 於本發月之另一項具體貫施例中，係關於一種在哺乳動物 中/口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中人為環烷基，其中環烷基為環 己基或金鋼烷基；B為Ra is as defined for formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a cycloalkane B is \ 'R4, Z is CRb; Rb is hydrogen; ... is absent; L is seven ⑼N (R?) _' And D rule 1, trans 2, R3, R4, R7, and Ra are as follows ( I). In another specific embodiment of the present month, it relates to a method of treating sexual dysfunction in a mammal / orally, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein Artificial cycloalkyl, wherein cycloalkyl is cyclohexyl or auryl; B is

JXR N 4，R1為氫、烷基、氰基、1¾烷基、_素、硝基、（NZ3Z4) 烷基或（NZSZ4)羰基；R2與I為氫；r3為氫或羥基；2為〇心 ,RB為氫，…為不存在；Da_CH2_; 乙為-CN(R分；及反7與 RA均如式(I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，纟包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為環烷基，其中環烷基為環 85228 -60- 200404539 己基或金鋼燒基；B為JXR N 4, R1 is hydrogen, alkyl, cyano, 1¾ alkyl, _ prime, nitro, (NZ3Z4) alkyl or (NZSZ4) carbonyl; R2 and I are hydrogen; r3 is hydrogen or hydroxyl; 2 is Heart, RB is hydrogen, ... is absent; Da_CH2_; B is -CN (R points; and trans 7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it is about A method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is a cycloalkyl group, and wherein the cycloalkyl group is cyclo 85228 -60-200404539 hexyl Or gold steel burning base; B is

t ’Ri為氣、燒基、氰基、鹵 燒基或（ΝΑΖΟ羰基；化與心為氫； ’ rb為氲；…為不存在；d為-CHi〖 、鹵烷基、鹵素、硝基、（NZ3Z4) 氫；R3為氫或羥基；Z為CRb R·7與RA均如式（I)中之定義。 D 為-CH(CH3)- ; L 為 _C(0)N(R7)_ ;及 於本發明之另一項具體實施例中 係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；t 'Ri is a gas, an alkyl group, a cyano group, a halogeno group, or a (NHAZO carbonyl group; and hydrogen is hydrogen;' rb is 氲; ... is absent; d is -CHi〗, haloalkyl, halogen, nitro , (NZ3Z4) hydrogen; R3 is hydrogen or hydroxyl; Z is CRb R7 and RA are as defined in formula (I). D is -CH (CH3)-; L is _C (0) N (R7) _; And in another embodiment of the present invention is a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is Aryl;

R5 5 ; Z為C ;…為一個键結；L·為-C(0)N(R7)-;且D、 Ri、R2、R3、R4、R5、R7及RA均如式①中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被〇、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或_NZi &amp; ; B為R5 5; Z is C; ... is a bond; L · is -C (0) N (R7)-; and D, Ri, R2, R3, R4, R5, R7 and RA are as defined in formula ① . In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl or _NZi &amp;; B is

5 ; Ri為氫、燒氧基、燒基、燒硫基、氯基、鹵素 輕基、硝基、-NZJ2或（NZJ4)燒基；R2為氫、烷氧基、氰 85228 -61 - 200404539 基、li素或喪基；r3為氫或輕基；r4與r5為氫；z為c ;… 為一個鍵結；D為-CH2_; L·為-C(0)N(R7)_;及R7與RA均如式（工) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自埽基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-ΝΖιζ2 ; B為5; Ri is hydrogen, alkoxy, alkyn, thio, chloro, halogen, nitro, -NZJ2 or (NZJ4) carb; R2 is hydrogen, alkoxy, cyan 85228 -61-200404539 R3 is hydrogen or light group; r4 and r5 are hydrogen; z is c; ... is a bond; D is -CH2_; L · is -C (0) N (R7) _; And R7 and RA are as defined in formula (工). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZιζ2; B is

;Ri為氫、燒氧基、垸基、燒硫基、氰基、鹵素 、護基、硝基、-NZ^2或（NZ^4)燒基；r2為氫、烷氧基、氰 基、lS素或羥基；R3為氫或羥基；R4與R5為氫；Z為C ; 一 為一個鍵結；D為-CH(CH3)-; L為C(〇)N(R7)-;及R7與RA均如 式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基；B為Ri is hydrogen, alkoxy, fluorenyl, thiothio, cyano, halogen, protecting group, nitro, -NZ ^ 2 or (NZ ^ 4) thio; r2 is hydrogen, alkoxy, cyano LS element or hydroxyl; R3 is hydrogen or hydroxyl; R4 and R5 are hydrogen; Z is C; one is a bond; D is -CH (CH3)-; L is C (〇) N (R7)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl ; B is

;Z為C ;…為〆個鍵結；L為-C(0)N(R7)-;且D、Z is C; ... is a bond; L is -C (0) N (R7)-; and D,

Ri、R2、R3、R4、R7及RA均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 85228 -62- 200404539 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自晞基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或_ΝΖιζ2 ; B為Ri, R2, R3, R4, R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal 85228-62-200404539, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), Where A is aryl, where aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkane Thio, benzyl, cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl or ΝΝιζ2; B is

R4 ; Ri為氫、烷基、氰基、_燒基、！I素、硝基、（NZ3Z4) 燒基或(NZgZ4)羰基；1^2與1^4為氫；r3為氫或羥基；Z為C; …為一個鍵結；D為-CH2-; L·為-C(0)N(R7)-;及R7與RA均如式 (I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、燒氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-ΝΖιζ2 ; B為 R〇R4; Ri is hydrogen, alkyl, cyano, alkynyl,! I element, nitro, (NZ3Z4) alkyl or (NZgZ4) carbonyl; 1 ^ 2 and 1 ^ 4 are hydrogen; r3 is hydrogen or hydroxyl; Z is C;… is a bond; D is -CH2-; L -Is -C (0) N (R7)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZιζ2; B is R.

R3 、N R4 ; Ri為氫、烷基、氰基、li烷基、齒素、硝基、（NZ3Z4) 燒基或(NZ^)羰基；1與心為氫；R3為氫或羥基；z為C; …為一個鍵結；D為-CH(CH3)-; L為-C(0)N(R7)_;及R7與RA均 如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 85228 -63- 200404539 中/口療性功能障礙之方法’其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為萘基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自埽基 、燒氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、齒烷基、亞甲二氧基、硝基、苯基或—NZiZa ; B為R3, N R4; Ri is hydrogen, alkyl, cyano, lialkyl, halide, nitro, (NZ3Z4) alkyl or (NZ ^) carbonyl; 1 and hydrogen are hydrogen; R3 is hydrogen or hydroxyl; z Is C;… is a bond; D is -CH (CH3)-; L is -C (0) N (R7) _; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method of treating sexual dysfunction in a mammal 85228-63-200404539, which comprises administering to the mammal a therapeutically effective amount of formula (I) Compounds in which A is aryl, wherein aryl is naphthyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl , Alkylthio, benzyl, cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or --NZiZa; B is

xXXR Λ Ν 4 ; Ri為氫、烷基、氰基、函烷基、鹵素、硝基、（νζ3ζ4) 燒基或(ΝΖ3Ζ4)羰基；112與114為氫；r3為氫或羥基；ζ為c; …為一個鍵結；D為-CH2-; L為_C(0)N(R7)_;及％與1^均如式 (1)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為莕基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自缔基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ; B為xXXR Λ Ν 4; Ri is hydrogen, alkyl, cyano, alkynyl, halogen, nitro, (νζ3ζ4) alkyl or (NRZ3Z4) carbonyl; 112 and 114 are hydrogen; r3 is hydrogen or hydroxyl; ζ is c … Is a bond; D is -CH2-; L is _C (0) N (R7) _; and% and 1 ^ are as defined in formula (1). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is fluorenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B is

3 Ν ·Μ ; &amp;為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 烷基或(nz3z4)羰基；r2與r4為氫；r3為氫或羥基；Z為c ; …為一個鍵結；D為-CH(CH3)- ; L為-C(0)N(R7)-;及R7與RA均 如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 85228 -64- 200404539 中心療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（1)化合物，其中A為芳基；b為3 Ν · Μ; &amp; is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (nz3z4) carbonyl; r2 and r4 are hydrogen; r3 is hydrogen or hydroxyl; Z is c; ... is a bond; D is -CH (CH3)-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal at 85228-64-200404539, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (1), Where A is aryl; b is

R3 ; Z為C ;…為〆個鍵結；L為-C(0)N(R7)-;且D、X 、Y、、R3、R7及RA均如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵素 、鹵烷氧基、卣烷基、亞甲二氧基、硝基、苯基或-ΝΖι &amp; ; B為R3; Z is C; ... is a bond; L is -C (0) N (R7)-; and D, X, Y, R3, R7, and RA are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, haloalkoxy, fluorenyl, methylenedioxy, nitro, phenyl, or -NZι &amp;; B is

R2與R3為氫；x為n(r6) Ο或S; Y為N; Z為C; …為一個键結；D為-CH2-; L為-C(0)N(R7)·;且R6、R7及、均 如式（I)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（I)化合物，其中A為芳基，其中芳基為苯基， 被0、1、2、3、4或5個取代基取代，取代基獨立選自烯基 、烷氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵素 、鹵烷氧基、齒烷基、亞甲二氧基、硝基、苯基或-ΝΖι &amp; ; B為 85228 -65- 200404539R2 and R3 are hydrogen; x is n (r6) 0 or S; Y is N; Z is C;… is a bond; D is -CH2-; L is -C (0) N (R7) ·; and R6, R7 and R are as defined in formula (I). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, and fluorenyl , Cyano, halogen, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZι &amp;; B is 85228 -65- 200404539

，尺2與R3為氫；X為N(R6)、〇或s; Y為N; Z為c; 為個鍵結；D為-CH(CH3)-; L 為-C(0)N(R7)·;且 R6、心及、 均如式（I)中之定義。 、本I明之另一項具體實施例中，係關於一種在哺乳動物 中’口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有，量之式①化合物，其中八為環烷基；8為 N R4 , Ζ為C ;…為一個鍵結；L·為-C(0)N(R7)-;且D、 R1、心、R3、、心及、均如式①中之定義。 於本發明艾另一項具體實施例中，係關於一種在哺乳動物 中心療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效里 &lt; 式①化合物，其中A為環烷基，其中環烷基為環 己基或金鋼烷基；B為 R:lV3 . 及N R4 ; Rl為氫、烷基、氰基、自烷基、_素、硝基、 烷基或（NZSZ4)羰基；心與心為氫；心為氫或羥基；Zgc; …為一個鍵結；D為_CIV; L為_C(0)N(R7)·;及心與、均如式 (I)中之定義。 於本發明芩另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效K式（I)化合物，其中A為環烷基，其中環烷基為環 己基或金鋼垸基；B為 85228 -66 - 200404539, Ruler 2 and R3 are hydrogen; X is N (R6), 0 or s; Y is N; Z is c; is a bond; D is -CH (CH3)-; L is -C (0) N ( R7) ;; and R6, Xinhe, are as defined in formula (I). 2. In another specific embodiment of the present invention, it relates to a method of "orally treating sexual dysfunction" in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, in which eight are ring Alkyl; 8 is N R4, Z is C; ... is a bond; L · is -C (0) N (R7)-; and D, R1, heart, R3 ,, and and are all as in formula ① Definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal center, which comprises administering to the mammal a therapeutically effective compound of formula ①, wherein A is a cycloalkyl group. , Where cycloalkyl is cyclohexyl or auryl; B is R: 1V3. And N R4; R1 is hydrogen, alkyl, cyano, alkyl, nitro, nitro, alkyl, or (NZSZ4) Carbonyl; heart and heart are hydrogen; heart is hydrogen or hydroxyl; Zgc;… is a bond; D is _CIV; L is _C (0) N (R7) ·; In the definition. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective compound of formula (I), wherein A is a cycloalkyl group. , Where cycloalkyl is cyclohexyl or gold-steel fluorenyl; B is 85228 -66-200404539

、N R4 ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（nz3z4) 烷基或（NZ3Z4)羰基；112與1^4為氫；r3為氫或羥基；Z為c; …為一個鍵結；D為_CH(CH3)- ; L為-C(0)N(R7)-;及R7與RA均 如式（I)中之定義。 於另一項具體實施例中，本發明係關於式（II)化合物, N R4; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (nz3z4) alkyl or (NZ3Z4) carbonyl; 112 and 1 ^ 4 are hydrogen; r3 is hydrogen or hydroxyl; Z is c; ... is a bond; D is _CH (CH3)-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (I). In another embodiment, the present invention relates to a compound of formula (II)

或係揭示其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 A為芳基、芳说基、環燒基或環燒基燒基； L 為-n(r7)c(o)-、-C(〇)N(R7)-、-N(R7)C(S)-4_C(S)N(R7)-，其 中-n(r7)c(o)-、-C(0)N(R7)-、-N(R7)C(S)-及-C(S)N(R7)-之左端係 連接至A，而右端係連接至D ; D為次烷基、氟次烷基或羥 基次燒基； z係選自N、C或CRB ;Or revealing a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, wherein A is aryl, aryl, cycloalkyl or cycloalkyl; L is -n (r7) c (o )-, -C (〇) N (R7)-, -N (R7) C (S) -4_C (S) N (R7)-, where -n (r7) c (o)-, -C (0 The left end of N (R7)-, -N (R7) C (S)-, and -C (S) N (R7)-is connected to A, and the right end is connected to D; D is an alkylene group, and fluorinated Alkyl or hydroxy secondary group; z is selected from N, C or CRB;

Ra為氫或燒基；Ra is hydrogen or alkyl;

Rb為氫、燒基或鹵素； 當Z為C時， 存在；B為 為一個键結，而當Z為N或CRB時，…為不Rb is hydrogen, alkyl or halogen; when Z is C, it is present; B is a bond, and when Z is N or CRB, ... is not

85228 -67- 20040453985228 -67- 200404539

Ri、R2、&amp;及心各獨立為氫、燒氧基、晞基、烷基、烷基 亞磺醯基、烷基績醯基、烷硫基、炔基、烷氧殽基、垸羧 基、燒談基氧基、叛基、氰基、甲酸基、1¾素、齒燒氧基 、鹵燒基、經基、經燒基、競基、硝基、-NZiZ2、（NZ3Z4)：)^ 基、（nz3z4)羰基或（NZ3Z4)磺醯基；Ri, R2, &amp; each independently are hydrogen, alkoxy, fluorenyl, alkyl, alkylsulfinylfluorenyl, alkylfluorenyl, alkylthio, alkynyl, alkoxymethyl, and carboxyl , Alkoxy, alkoxy, cyano, formate, 1¾, oxy, halo, halo, warp, warp, nitro, -NZiZ2, (NZ3Z4):) ^ Group, (nz3z4) carbonyl or (NZ3Z4) sulfofluorenyl;

Zi與Zz各獨立為氫、烷基、烷藏基、燒基續醯基、芳基、 芳坑基、芳基續醒基、芳基績驢基或甲酸基； z3與z4各獨立為氫、烷基、芳基或芳烷基； X 為 N(R6)、Ο 或 S ; Y 為 C(R4)或 N ; r6為氫或烷基；及 R7為氫或燒基。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中A為芳基；B為 ;Z 為 N;…為不存在；L 為-N(R7)C(0)_ ;且 D、Rj 、R2、R3、r4、R7及RA均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 燒基、燒硫基、+基、氰基、||素、自院氧基、_燒基、 亞甲二氧基、硝基苯基或-NZi Z2 ; B為Zi and Zz are each independently hydrogen, alkyl, alkyl, alkynyl, sulfonyl, aryl, aryl, aryl, aryl, phenyl, aryl, or carboxylic acid; z3 and z4 are each independently hydrogen , Alkyl, aryl or aralkyl; X is N (R6), 0 or S; Y is C (R4) or N; r6 is hydrogen or alkyl; and R7 is hydrogen or alkyl. In another specific embodiment of the present invention, a compound of formula (π) is disclosed, where A is aryl; B is; Z is N; ... is absent; L is -N (R7) C (0) _ And D, Rj, R2, R3, r4, R7, and RA are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, thio, thio, +, cyano, | | element, self-oxy, alkynyl, methylenedioxy, nitro Phenyl or -NZi Z2; B is

、Ν ·、4 ; Ri為氫、烷基、氰基、i烷基、_素、硝基、（NZ3Z4) 85228 -68- 200404539 燒基或（NZsZ4)羰基；r2與r4為氫；r3為氫或羥基；z為N; …為不存在；D為-CH2-; L·為-N(R7)C(0)-;及心與RA均如式（II) 中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 燒基、fe硫基、苄基、氰基、_素、齒烷氧基、自烷基、 亞甲二氧基、硝基、苯基或-NZl Z2 ; B為 、〆R4，Rl為氫、烷基、氰基、函烷基、i素、硝基、（nz3z4) 烷基或(NZgZ4)羰基；R2與R4為氫；R3為氫或羥基；&amp;為氫或 羥基，Z為N;…為不存在；D為-CH(CH3)- ; L為-N(R7)C(0)-; 及Ry與RA均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物，其 中A為芳基’其中芳基為四氫莕基或2,3-二氫_lH_茚基；b為 \ / R4 ;心係選自氫、烷基、氰基、_烷基、自素、硝 基、（ΝΑΖΟ烷基或羰基；^與心為氫；心為氫或羥基 ;2為化…為不存在；D為-αν; L*_N(R7)c(〇)_;及心與、 均如式（II)中之定義。 於本發明又另一項具體實施例中，係揭示式（II)化合物， 中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自晞基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、卣素、南烷氧基、_烷基、 85228 -69- 200404539 亞甲二氧基、硝基、苯基或-NZ! Z2 ; B為 ?2 λ / PU ;心為氫、烷基、氰基、齒烷基、鹵素、硝基、讲 烷基或(NZ]Z4)羰基；&amp;與I為氫；&amp;為氫或羥基；Z*N; …為不存在；d為-αν; l為-N(R7)qs)-;及^與、均如式（II) 中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物，其 中Af芳基’其中芳基為四氫莕基或2,3_二氫_1H_茚基；B為 Ά · 、N R4，Ri係選自氫、烷基、氰基、鹵烷基、自素、硝 基、（ΝΖβ4)烷基或（NZ〆4)羰基；化與心為氫；r3為氫或羥基 ·’ Z為N;…為不存在；〇為_〇^((：玛&gt;;Lg_N(R7)c(〇)_;及心 與Ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， /、中A為_環，其中雜環為苯并咪嗤基、苯并隹峻基、吱喃 基、咪唑基、1，3-噚唑基、吡畊基、吡唑基、嗒畊基、吡啶 基密咬基、响洛基、1，3-嘍唑基或嘧吩基，其中雜環係獨 乂被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 烷氧羰基、烷基、氰基、_素、_烷氧基、_烷基或硝基 ;Β* A:. 4，Ζ為Ν，…為不存在；l為_N(R7)C(0)_ ;且D、R! R2 R3、汉4、R7及RA均如式（Π)中之定義。 万；本發明之另一項具體實施例中，係揭示式（II)化合物， 85228 -70- 200404539 其中A為雜環，其中雜環為苯并咪唑基、苯并噻唑基、呋喃 基、咪唑基、1，3_ $唑基、吡畊基、吡唑基、嗒畊基、吡啶 基、嘧呢基、吡咯基、；[，3_嘧唑基或噻吩基，其中雜環係獨 i被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 烷氧羰基、烷基、氰基、画素、_烷氧基、自烷基或硝基 ;Bg ?2 \ ^〜；心為氫、烷基、氰基、_烷基、鹵素、硝基、 fe基或(NZSZ4)羰基；R2與心為氫；r3為氫或羥基；z*N; …為不存在；D為-d; I^-N(R7)C(0)-;及R7與RA均如關於 式（Π)之定義。 於本發明之另一項具體實施例中，係揭示式（阳化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并遠唆基、吡吱 基、说咬基或嘧吩基，其中雜環係獨立被〇、1、2或3個取 代基取代，取代基獨立選自烷氧基、烷氧羰基、烷基、氰 基、画素、齒烷氧基、_烷基或硝基；B為, N ·, 4; Ri is hydrogen, alkyl, cyano, i-alkyl, hydrogen, nitro, (NZ3Z4) 85228 -68- 200404539 alkyl or (NZsZ4) carbonyl; r2 and r4 are hydrogen; r3 is Hydrogen or hydroxyl; z is N;… is absent; D is -CH2-; L · is -N (R7) C (0)-; and heart and RA are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (I) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, thio, benzyl, cyano, halogen, alkoxy, self-alkyl, methylenedioxy, nitro, phenyl Or -NZl Z2; B is, 〆R4, Rl is hydrogen, alkyl, cyano, alkynyl, itin, nitro, (nz3z4) alkyl or (NZgZ4) carbonyl; R2 and R4 are hydrogen; R3 is Hydrogen or hydroxyl; &amp; is hydrogen or hydroxyl, Z is N; ... is absent; D is -CH (CH3)-; L is -N (R7) C (0)-; and Ry and RA are both as follows: II). In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is aryl ', wherein aryl is tetrahydrofluorenyl or 2,3-dihydro-1H-indenyl; b is \ / R4; the heart is selected from the group consisting of hydrogen, alkyl, cyano, _alkyl, autogen, nitro, (NAZO alkyl or carbonyl; ^ is hydrogen with heart; heart is hydrogen or hydroxyl group; 2 is chemical ... is not Existing; D is -αν; L * _N (R7) c (〇) _; and mind and are as defined in formula (II). In yet another specific embodiment of the present invention, the formula (II) is disclosed ) Compound, where A is aryl, wherein aryl is phenyl, substituted by 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkane Group, alkylthio, benzyl, cyano, halogen, alkanoyl, alkyl, 85228 -69- 200404539 methylenedioxy, nitro, phenyl or -NZ! Z2; B is? 2 λ / PU; Heart is hydrogen, alkyl, cyano, acyl, halogen, nitro, alkyl, or (NZ) Z4) carbonyl; &amp; and I are hydrogen; & is hydrogen or hydroxyl; Z * N;… is absent; d is -αν; l is -N (R7) qs)-; and ^ and are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (11) is disclosed, wherein Af aryl 'wherein aryl is tetrahydrofluorenyl or 2,3_dihydro_1H_indenyl; B is Ά · , N R4, Ri are selected from hydrogen, alkyl, cyano, haloalkyl, autogen, nitro, (NZβ4) alkyl or (NZ〆4) carbonyl group; and hydrogen is hydrogen; r3 is hydrogen or hydroxyl · 'Z is N; ... is absent; 0 is _〇 ^ ((: Ma>; Lg_N (R7) c (〇) _; and heart and Ra are as defined in formula (II). In the present invention In another specific embodiment, it is disclosed that the compound of formula (II), wherein A is a ring, wherein the heterocyclic ring is benzimidyl, benzylidene, sulfanyl, imidazolyl, 1, 3-oxazolyl, pyridoyl, pyrazolyl, dacrotyl, pyridylpyridyl, ringyl, 1,3-oxazolyl, or pyrenyl, wherein the heterocyclic ring is independently 0, 1 , 2 or 3 substituents, the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, _ prime, _ alkoxy, _ alkyl or nitro; B * A :. 4, Z is N, ... is absent; l is _N (R7) C (0) _; and D, R! R2 R3, Han 4, R7, and RA are as defined in formula (Π). In another specific embodiment of the invention, the compound of formula (II) is disclosed, 85228 -70- 200404539 where A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzothiazolyl, furyl, imidazolyl, 1 , 3_ $ azolyl, pyridyl, pyrazolyl, daphyl, pyridyl, pyrimyl, pyrrolyl, [3_pyrimidyl or thienyl, wherein the heterocyclic ring is i, 0, 1 , 2 or 3 substituents, the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, pixel, alkoxy, alkyl or nitro; Bg? 2 \ ^ ~; Is hydrogen, alkyl, cyano, alkyl, halogen, nitro, fe, or (NZSZ4) carbonyl; R2 and hydrogen are hydrogen; r3 is hydrogen or hydroxyl; z * N; ... is absent; D is- d; N (R7) C (0)-; and R7 and RA are as defined for formula (Π). In another specific embodiment of the present invention, the formula (positive compound, where A Is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzo remote fluorenyl, pyridyl, sulfanyl, or pyrenyl, wherein the heterocyclic ring is independently substituted by 0, 1, 2, or 3 substituents Independently selected from alkoxy, alkoxycarbonyl, alkyl , Cyano, pixel, alkoxy, alkyl, or nitro; B is

t &amp;為氫、烷基、氰基、！I烷基、！I素、硝基、 燒基或(NZ3 Z4)叛基，R2與R4為氫；r3為氫或經基；z為]sf ; …為不存在；D為-Ον ; L為_N(R7)C(0)-;及R?與RA均如關於 式（Π)之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中A為芳基；B為 85228 -71 - 200404539t &amp; is hydrogen, alkyl, cyano,! I alkyl ,! I element, nitro group, alkynyl group or (NZ3 Z4) rebel group, R2 and R4 are hydrogen; r3 is hydrogen or mesogen; z is] sf;… is absent; D is -0ν; ) C (0)-; and R? And RA are as defined for formula (Π). In another specific embodiment of the present invention, the compound of formula (π) is disclosed, wherein A is aryl; B is 85228 -71-200404539

R4 ; Z為N ;…為不存在；L為-N(R7 )C(0)-; 且 D、R2、 R3、R4、R7及RA均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中Α為芳基’其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代’取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、！|素、_烷氧基、自烷基、 亞甲二氧基、硝基、苯基或-NZJ2 ; B為R4; Z is N; ... is absent; L is -N (R7) C (0)-; and D, R2, R3, R4, R7, and RA are as defined in formula (II). In another specific embodiment of the present invention, it is disclosed that the compound of formula (II), wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, and! | Prime, _alkoxy, self-alkyl, methylenedioxy, nitro, phenyl or -NZJ2; B is

·μ ; R2、R3及R4為氫；z為N ;…為不存在；〇為-CH2- ，L為-N(R7 )C(0)- ; R7與RA均如式（π)中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代’取代基獨立選自晞基、燒氧基、燒氧羰基、 烷基、烷硫基、苄基、氰基、_素、由烷氧基、齒烷基、 亞甲二氧基、硝基、苯基或-NZi Z2 ; B為Μ; R2, R3, and R4 are hydrogen; z is N; ... is absent; 0 is -CH2-, L is -N (R7) C (0)-; R7 and RA are both as in formula (π) definition. In another specific embodiment of the present invention, a compound of formula (I) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and the 'substituent group is substituted with 0, 1, 2, 3, 4, or 5 substituents. Independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, hydrogen, alkoxy, oxyalkyl, methylenedioxy, nitro, phenyl Or -NZi Z2; B is

’ L為-N(R7 )C(0)- ; R7與RA均如式（η)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為芳基；B為'L is -N (R7) C (0)-; R7 and RA are as defined in formula (η). In another specific embodiment of the present invention, the compound of formula (11) is disclosed, wherein A is aryl; B is

;ZgN;…為不存在；l 為-N(R7)C(0)-;且 D、X、 γ、R2、R3、R7及RA均如式（π)中之定義。 85228 -72- 200404539 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自晞基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、_素、自烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZJ2 ; B為ZgN; ... is absent; l is -N (R7) C (0)-; and D, X, γ, R2, R3, R7, and RA are as defined in formula (π). 85228 -72- 200404539 In another embodiment of the present invention, the compound of formula VII is disclosed, wherein A is aryl, wherein aryl is phenyl, and is substituted by 0, 1, 2, 3, 4 or 5 Substituents, the substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, molybdenum, self-alkoxy, alkyl, methylenedioxy, Nitro, phenyl or -NZJ2; B is

;R2 與 R3 為氫；X 為 N(R6)、〇或 s; Y為 N; Z為 N; …為不存在；D為_CH2-; L為-N(R7)C(0)_ ;且r6、r7&amp;ra均如 式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、_素、齒烷氧基、商烷基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為; R2 and R3 are hydrogen; X is N (R6), 0 or s; Y is N; Z is N;… is absent; D is _CH2-; L is -N (R7) C (0) _; And r6, r7 &amp; ra are as defined in formula (II). In another specific embodiment of the present invention, the compound of the formula (I) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, alkoxy, commercial alkyl, methylenedioxy, nitro, phenyl Or -NZiZ2; B is

R3 ; R2 與 R3 為氫；X 為 N(R6)、0或 S;Y 為N;Z 為 N; ·—為不存在；D 為 _CH(CH3)_ ; L 為-N(R7)C(0)_ ;且 、R7 及、 均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為環烷基；B為 人FU ; z為N ;…為不存在；L為-N(R7)C(0)-;且D、&amp; 、R2、R3、R4、R7及RA均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 85228 -73- 200404539 其中A為環燒基’其中壤燒基為環己基或金鋼燒基；B為R3; R2 and R3 are hydrogen; X is N (R6), 0 or S; Y is N; Z is N; ·-is absent; D is _CH (CH3) _; L is -N (R7) C (0) _; and R7 and R are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is cycloalkyl; B is human FU; z is N; ... is absent; L is -N (R7) C ( 0)-; and D, &amp;, R2, R3, R4, R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (II) is disclosed, 85228 -73- 200404539 where A is a cycloalkyl group, wherein the soil alkyl group is cyclohexyl or gold steel alkyl group; B is

，Ri為鼠、燒基、氣基、基'鹵素、硝基、（NZ3 &amp;) 烷基或(NZ3Z4)羰基；112與114為氫；R3為氫或羥基；Z為N; …為不存在；D為-CH2-; L為-N(R7)C(0)-;及117與1^均如式（Π) 中之定義。, Ri is murine, alkyl, alkyl, halogen, nitro, (NZ3 &amp;) alkyl or (NZ3Z4) carbonyl; 112 and 114 are hydrogen; R3 is hydrogen or hydroxyl; Z is N;… is not Exists; D is -CH2-; L is -N (R7) C (0)-; and 117 and 1 ^ are as defined in formula (Π).

於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為環烷基，其中環烷基為環己基或金鋼烷基；B為In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; B is

R3 、νΓ % &amp;為氫、烷基、氰基、画烷基、卣素、硝基、（NZ3Z4) 院基或(NZ3Z4)羰基；心與114為氫；r3為氫或羥基；z為N; …為不存在；D為-CH(CH3)- ; L為-N(R7)C(0)-;及R7與RA均如 式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為芳烷基；B為R3, νΓ% &amp; are hydrogen, alkyl, cyano, cyanoalkyl, halogen, nitro, (NZ3Z4) or NZ3Z4) carbonyl; heart and 114 are hydrogen; r3 is hydrogen or hydroxyl; z is N;… is absent; D is -CH (CH3)-; L is -N (R7) C (0)-; and R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (Π) is disclosed, wherein A is an aralkyl group; B is

Z為N;…為不存在；[為_N(R7)C(0)_ ;且D、&amp; R2、R3、R4、r7&amp;ra均如式（Π)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為芳烷基，其中芳烷基之芳基為苯基，被0、1、2、 3、4或5個取代基取代，取代基獨立選自晞基、烷氧基、燒 氧羧基、纟元基、燒硫基、苄基、氰基、齒素、函燒氧基、 鹵烷基、亞甲二氧基、硝基、苯基或-ΝΖ! Z2 ; B為 85228 •74- 200404539 r2Z is N; ... is absent; [is _N (R7) C (0) _; and D, &amp; R2, R3, R4, r7 &amp; ra are as defined in formula (Π). In another specific embodiment of the present invention, the compound of formula (11) is disclosed, wherein A is an aralkyl group, wherein the aryl group of the aralkyl group is a phenyl group, and is 0, 1, 2, 3, 4 or 5 Each substituent is substituted, and the substituent is independently selected from the group consisting of fluorenyl, alkoxy, alkoxycarbonyl, fluorenyl, thiothio, benzyl, cyano, halide, alkoxy, haloalkyl, and methylene di Oxy, nitro, phenyl or -NZ! Z2; B is 85228 • 74- 200404539 r2

r4 ，Ri為氫、燒基、孰基、卣fe基、自素、硝基、（NZ3 Z4) 烷基或(NZ3Z4)羰基；112與114為氫； R3為氫或羥基；Z為N;…為不存在；D為-CH2-; L為-N(R7)C(0)-;及心與Ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為芳烷基，其中芳烷基之芳基為苯基，被〇、1、2、 3、4或5個取代基取代，取代基獨立選自烯基、烷氧基、烷 氧羰基、烷基、烷硫基、苄基、氰基、齒素、函烷氧基、 鹵烷基、亞甲二氧基r4, Ri is hydrogen, alkyl, fluorenyl, fluorenyl, sulfonium, nitro, (NZ3 Z4) alkyl or (NZ3Z4) carbonyl; 112 and 114 are hydrogen; R3 is hydrogen or hydroxyl; Z is N; ... is absent; D is -CH2-; L is -N (R7) C (0)-; and both heart and Ra are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (Π) is disclosed, wherein A is an aralkyl group, wherein the aryl group of the aralkyl group is a phenyl group, and is 0, 1, 2, 3, 4 or 5 Substituents, each of which is independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halide, alkoxy, haloalkyl, methylenedioxy base

•R4 ; Κ為氫、烷基、氰基、i烷基、_素、硝基、（νζ3ζ4) 烷基或(ΝΖ3Ζ4)羰基；R2與R4為氫；R3為氫或羥基；ζ為Ν; …為不存在；D為-CH(CH3)- ; L為-N(R7)C(0)-;及心與RA均如 式（Π)中之定義。 於本發明之另一項具體實施例中，係揭示式（η)化合物， 其中Α為芳基；Β為• R4; K is hydrogen, alkyl, cyano, ialkyl, nitro, nitro, (νζ3ζ4) alkyl, or (NZ3Z4) carbonyl; R2 and R4 are hydrogen; R3 is hydrogen or hydroxyl; ζ is N; ... is absent; D is -CH (CH3)-; L is -N (R7) C (0)-; and both heart and RA are as defined in formula (Π). In another specific embodiment of the present invention, the compound of formula (η) is disclosed, wherein A is aryl; B is

R2 .r3R2 .r3

且D ; z 為 CRb ;…為不存在；l 為 _n(R7)c(〇)_ Ri、R2、R3、R4、R7、Rb及Ra均如式(π)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基’其中务基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨互選自缔基、烷氧基、烷氧羰基、 烷基、烷硫基、芊基、氰基、_素、_烷氧基、_烷基、 85228 - 75- 200404539 亞甲二氧基、硝基苯基或-NZi Z2 ; B為 ?2And D; z is CRb; ... is absent; l is _n (R7) c (〇) _ Ri, R2, R3, R4, R7, Rb, and Ra are as defined in formula (π). In another specific embodiment of the present invention, it is disclosed that the compound of formula (π), wherein A is an aryl group, wherein the amyl group is a phenyl group, is substituted with 0, 1, 2, 3, 4 or 5 substituents, The substituents are mutually selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, alkoxy, alkoxy, alkyl, 85228-75- 200404539 methylenedioxy Group, nitrophenyl or -NZi Z2; B is? 2

RitVR3 λ f R4 ;心為氫、烷基、氰基、烷基、齒素、硝基、⑽Z3Z4) 燒基或（ΝΖΘ4)羰基；：^與心為氬；r3為氫或羥基；Z為CRb ;Rb為氫；…為不存在；D為-CH2_ ; L為-N(R7)C(0)_ ;及117與 Ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 燒基、燒硫基、苄基、氰基、卣素、_燒氧基、自燒基、 亞甲二氧基、硝基、苯基或-NZiZa ; B為RitVR3 λ f R4; the heart is hydrogen, alkyl, cyano, alkyl, dentin, nitro, fluorene Z3Z4) alkenyl or (NZΘ4) carbonyl; ^ is argon with the heart; r3 is hydrogen or hydroxyl; Z is CRb Rb is hydrogen; ... is absent; D is -CH2_; L is -N (R7) C (0) _; and 117 and Ra are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (11) is disclosed, wherein A is aryl, wherein aryl is phenyl, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkynyl, thiol, benzyl, cyano, halogen, alkynyl, self-alkyl, methylenedioxy, nitro, Phenyl or -NZiZa; B is

&amp; ; Ri為氫、烷基、氰基、鹵烷基、_素、硝基、（Nz3Z4) 燒基或(NZSZ4)羰基或（NZ3Z4)羰基；^與心為氫；r3為氫或羥 基；Z為CRb ; Rb為氫；…為不存在；D為-CH2-; L為-N(R7)C(S)-;及心與Ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自晞基、烷氧基、烷氧羰基、 ^元基、fe硫基、+基、氰基、画素、自燒氧基、完基、 亞甲二氧基、硝基、苯基或-NZiZ? ; B為&amp;; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (Nz3Z4) alkyl or (NZSZ4) carbonyl or (NZ3Z4) carbonyl; ^ is hydrogen with heart; r3 is hydrogen or hydroxyl Z is CRb; Rb is hydrogen; ... is absent; D is -CH2-; L is -N (R7) C (S)-; and heart and Ra are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (Π) is disclosed, wherein A is aryl, wherein aryl is phenyl, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituents are independently selected from the group consisting of fluorenyl, alkoxy, alkoxycarbonyl, sulfonyl, fethio, +, cyano, pixel, self-oxyl, cumyl, methylenedioxy, nitro, benzene Base or -NZiZ ?; B is

85228 -76- 200404539 ,Rb為氫；…為不存在；D為-ch(ch3)-; l為-n(r7)c(〇)-;及 汉7與Ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并噻唑基、呋喃 基、咪唑基、1，3_噚唑基、吡畊基、吡唑基、嗒畊基、吡啶 基、嘧啶基、吡咯基、U-嘧唑基或嘍吩基，其中雜環係獨 乂被〇、1、2或3個取代基取代，取代基獨立選自烷氧基、 烷氧羰基、烷基、氰基、i素、iS烷氧基、i烷基或硝基 ;6為 R；IXR3 Λ N R4，2為Crb ;…為不存在；L為-N(R7)C(0)-; RB為氫 ’且D、Ri、R2、R3、R4、心及Ra均如式⑻中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并噻嗅基、呋喃 基、咪嗤基、1，3-嘮唑基、吡畊基、吡唑基、嗒啡基、吡啶 基、响咳:基、吡咯基、1,3-噻唑基或噻吩基，其中雜環係獨 立被〇、1、2或3個取代基取代，取代基獨立選自烷氧基、 境氧羰基、烷基、氰基、面素、！|烷氧基、_烷基或硝基 ;B為 ?2 、r4 ; R!為氫、烷基、氰基、由烷基、_素、硝基、 烷基或（NZ3Z4)羰基；R2與R4為氫；R3為氫或羥基；Z為CRb ;…為不存在；D為-CH2-; L為-N(R7)C(0)-; Rb為氫；及117與 RA均如關於式（II)之定義。85228 -76- 200404539, Rb is hydrogen; ... is absent; D is -ch (ch3)-; l is -n (r7) c (〇)-; and Han 7 and Ra are as in formula (II) definition. In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzothiazolyl, furanyl, imidazolyl, 1,3- Oxazolyl, pyridyl, pyrazolyl, daphyl, pyridyl, pyrimidinyl, pyrrolyl, U-pyrazolyl, or pyrenyl, in which the heterocyclic ring is independently 0, 1, 2, or 3 Substituted by a substituent, the substituent is independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, i prime, iS alkoxy, i alkyl, or nitro; 6 is R; IXR3 Λ N R4, 2 is Crb ... is absent; L is -N (R7) C (0)-; RB is hydrogen 'and D, Ri, R2, R3, R4, heart and Ra are as defined in formula (2). In another specific embodiment of the present invention, a compound of formula VII is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzothiol, furanyl, imidino, 1,3- Oxazolyl, pyrimidinyl, pyrazolyl, daphnyl, pyridyl, stilbyl, pyrrolyl, 1,3-thiazolyl, or thienyl, wherein the heterocyclic ring is independently 0, 1, 2, or 3 Each substituent is substituted, and the substituent is independently selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, cyano, noodles, and so on! Alkoxy, alkyl, or nitro; B is? 2, r4; R! Is hydrogen, alkyl, cyano, alkyl, nitro, nitro, alkyl, or (NZ3Z4) carbonyl; R2 and R4 is hydrogen; R3 is hydrogen or hydroxyl; Z is CRb; ... is absent; D is -CH2-; L is -N (R7) C (0)-; Rb is hydrogen; and 117 and RA are both as for formula (II) Definition.

85228 -77- 200404539 於本發明之另一項具體實施例中，係揭示式（n)化合物， 其中A為雜環’其中雜環為苯并咪唑基、苯并嘧唑基、吡唑 基吡啶基或嘧吩基，其中雜環係獨立被〇、丨、2或3個取代 基取代’取代基獨立選自烷氧基、烷氧羰基、烷基、氰基 、_素、_烷氧基、鹵烷基或硝基；B為 ?285228 -77- 200404539 In another embodiment of the present invention, the compound of formula (n) is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, pyrazolylpyridine Or pyrenyl, wherein the heterocyclic ring is independently substituted with 0, 1, 2, or 3 substituents. The substituent is independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, , Haloalkyl or nitro; B is? 2

Rl 、hT〜；心為氫、烷基、氰基、鹵烷基、鹵素、硝基^ ) 烷基或（NZsZ4)羰基；R2與R4為氫；r3為氫或羥基；2為(：：1^ ,…為不存在；D為-CH2-; L·為-N(R7)C(0)_ ; RB為氫；及R7與 Ra均如關於式（II)之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基；β為R1, hT ~; heart is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro ^) alkyl or (NZsZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; 2 is (:: 1 ^, ... are absent; D is -CH2-; L · is -N (R7) C (0) _; RB is hydrogen; and R7 and Ra are as defined for formula (II). In the present invention In another specific embodiment, the compound of formula (π) is disclosed, wherein A is aryl; β is

r3 . ;Z為CRB ;…為不存在；l為-N(R7)C(0)-;且D、X 、Y、R2、R3、R7、RB及RA均如式（Π)中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 燒基、燒硫基、爷基、氰基、由素、_燒氧基、齒燒基、 亞甲一氧基、硝基、苯基或-ΝΖ! Z2 ; B為r3 .; Z is CRB; ... is absent; l is -N (R7) C (0)-; and D, X, Y, R2, R3, R7, RB and RA are as defined in formula (Π) . In another specific embodiment of the present invention, the compound of the formula (I) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, hexyl, cyano, sulfonyl, alkynyl, alkynyl, methylene monooxy, nitro, phenyl Or -NRZ! Z2; B is

;X為N(R6)、Ο或S; Y為N; 112與心為氫；Z為CRb ;Rb為氫；…為不存在；D為-CH2-; L為-N(R7)C(0)_ ;且R6、 R7&amp;RA均如式（II)中之定義。 85228 -78 - 200404539 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、函素、函烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZi Z2 ; B為X is N (R6), 0 or S; Y is N; 112 and heart are hydrogen; Z is CRb; Rb is hydrogen; ... is absent; D is -CH2-; L is -N (R7) C ( 0) _; and R6, R7 &amp; RA are as defined in formula (II). 85228 -78-200404539 In another specific embodiment of the present invention, the compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is 0, 1, 2, 3, 4 or 5 Substituents, each of which is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, functional element, alkoxy, alkyl, and methylenedioxy Group, nitro, phenyl or -NZi Z2; B is

rC 入 &gt; R3 ; X 為 N(R6)、〇 或 s ; Y 為 N; R2 與 R3 為氫；Z 為 CRb ;Rb為氫；〜為不存在；D為-CH(CH3)- ; L為-N(R7)C(0)-;且 心、R7及RA均如式⑼中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基；Β為 0 丫S^R3 〜，z 為 crb ;…為不存在；l 為 _n(R7)c(〇)-;且 d、r2 、R3、、R7、rb及Ra均如式⑼中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、_素、i烷氧基、自烷基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為rC into> R3; X is N (R6), 0 or s; Y is N; R2 and R3 are hydrogen; Z is CRb; Rb is hydrogen; ~ is absent; D is -CH (CH3)-; L Is -N (R7) C (0)-; and Xin, R7 and RA are as defined in formula (2). In another specific embodiment of the present invention, the compound of formula (π) is disclosed, wherein A is an aryl group; B is 0 ^ S3R3 ~, z is crb; ... is absent; l is _n (R7 ) c (〇)-; and d, r2, R3, R7, rb and Ra are as defined in formula (i). In another specific embodiment of the present invention, a compound of formula (II) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, i-alkoxy, self-alkyl, methylenedioxy, nitro, Phenyl or -NZiZ2; B is

^ 4 ’ Ζ為CRb ; rb為氫；…為不存在；D為·CH2- ; L 為N(R7)C(〇&gt; ; R2、R3及化4為氫；及R^RA均如式（Π)中之定 義。 於本發月之另一項具體實施例中，係揭示式（II)化合物， 85228 -79- 200404539 其中A為芳基，其中方基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自埽基、烷氧基、烷氧黢基、 燒基、院硫基、芊基、氰基、_素、_燒氧基、鹵燒基、 亞甲二氧基、硝基、苯基或-NZi Z2 ; B為^ 4 'Z is CRb; rb is hydrogen; ... is absent; D is · CH2-; L is N (R7) C (0 &gt;; R2, R3, and H4 are hydrogen; and R ^ RA are as follows: (Π) Definition. In another specific example of this month, the compound of formula (II) is disclosed, 85228 -79- 200404539 where A is an aryl group, and the square group is phenyl group. , 2, 3, 4 or 5 substituents, which are independently selected from fluorenyl, alkoxy, alkoxyfluorenyl, alkyl, thio, fluorenyl, cyano, , Haloalkyl, methylenedioxy, nitro, phenyl or -NZi Z2; B is

|'4 ; Z為CRB ; RB為氫；…為不存在；D為-CH(CH3)_ ; L為-N(R7)C(0)- ; R2、R3及R4為氫；及r7與Ra均如式⑻中之 定義。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為芳基；B為 ?2 〇-;Z為CRB ;…為不存在；L為-N(R7)C(0)-;且D、 心、R2、R3、R4、R7、RB及RA均如式（π)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、燒氧後基、 烷基、烷硫基、苄基、氰基、_素、！|烷氧基、完基、 亞甲二氧基、硝基、苯基或-NZiZ] ; B為| '4; Z is CRB; RB is hydrogen; ... is absent; D is -CH (CH3) _; L is -N (R7) C (0)-; R2, R3 and R4 are hydrogen; and r7 and Ra is as defined in formula (2). In another specific embodiment of the present invention, the compound of formula (Π) is disclosed, wherein A is aryl; B is? 2 0-; Z is CRB; ... is absent; L is -N (R7) C (0)-; and D, Xin, R2, R3, R4, R7, RB and RA are as defined in formula (π). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, post-oxygenation, alkyl, alkylthio, benzyl, cyano, oxo, and! Alkoxy, cumenyl, methylenedioxy, nitro, phenyl, or -NZiZ]; B is

XXR Λ 'N( R4 ό_ ; R1、R2、&amp;及心為氫；z為crb ; rb為氫；…為 不存在；D為-〇V; L為-N(R7)C(0)-;及心與！^均如式⑼中 之定義。 85228 -80- 200404539 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、芊基、氰基、卣素、函烷氧基、齒烷基、 亞甲二氧基、硝基、苯基或-NZiZ? ; B為 ύ- ; &amp;、R2、R3及R4為氫；Ζ為CRB ; RB為氫；…為 不存在，D為-CH〗-，L為_N(R7 )C(0)•，及R7與Ra為氮。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被1個垸基取代基取代； B為XXR Λ 'N (R4 ό_; R1, R2, &amp; and the heart is hydrogen; z is crb; rb is hydrogen; ... is absent; D is -0V; L is -N (R7) C (0)- ; And heart and ^ are as defined in formula 85 85228 -80- 200404539 In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is aryl and aryl is benzene Group, substituted with 0, 1, 2, 3, 4 or 5 substituents independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, halogen , Alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZiZ ?; B is ω-; &amp;, R2, R3, and R4 are hydrogen; Z is CRB; RB is hydrogen; ... is absent, D is -CH〗-, L is _N (R7) C (0) •, and R7 and Ra are nitrogen. In another embodiment of the present invention, the formula (II) is disclosed A compound in which A is aryl, wherein aryl is phenyl, and is substituted with 1 fluorenyl substituent; B is

RiN^^R3RiN ^^ R3

VXXR Λ Ν+ R4 0- ; Ri、R2、R3及R4為氫；Z為CRB ; RB為氫；…為 不存在；D為-CH2-; L為-N(R7)C(0)_;及R7與RA為氫。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、_素、烷氧基、函烷基、 亞甲二氧基、硝基、苯基或-NZiZ? ; B為 ?2VXXR Λ Ν + R4 0-; Ri, R2, R3 and R4 are hydrogen; Z is CRB; RB is hydrogen; ... is absent; D is -CH2-; L is -N (R7) C (0) _; And R7 and RA are hydrogen. In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is aryl, wherein aryl is phenyl, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, hydrogen, alkoxy, functional alkyl, methylenedioxy, nitro, benzene Base or -NZiZ ?; B is? 2

aXR Λ N+ R4 0- ; Ri、R2、R3及R4為氫；Z為CRB ; RB為氫；…為 85228 -81 - 200404539 不存在；D為-ch(ch3)-; L為-n(r7)c(0)-;及r7與ra均如式⑻ 中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物，其 中A為芳基，其中芳基為四氫莕基或2,3-二氫茚基；B為aXR Λ N + R4 0-; Ri, R2, R3 and R4 are hydrogen; Z is CRB; RB is hydrogen; ... 85228 -81-200404539 does not exist; D is -ch (ch3)-; L is -n (r7 ) c (0)-; and r7 and ra are as defined in formula ⑻. In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is tetrahydrofluorenyl or 2,3-dihydroindenyl; B is

R3 N+ R4 〇- ;R1、R2、R3及R4為氫；z為crb ; RB為氳；…為 不存在，D為_CH2·; L為-N(R7)C(0)_;及117與1^為氫。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并嘧唑基、呋喃 基、咪唑基、U-噚唑基、吡畊基、吡唑基、嗒畊基、吡啶 基、嘧啶基、吡咯基、13-噻唑基或噻吩基，其中雜環係獨 互被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 k氧故基、纟元基、氰基、_素、函燒氧基、_燒基或硝基 ;8為R3 N + R4 〇-; R1, R2, R3 and R4 are hydrogen; z is crb; RB is 氲; ... is absent, D is _CH2 ·; L is -N (R7) C (0) _; and 117 And 1 ^ is hydrogen. In another specific embodiment of the present invention, a compound of formula VII is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzopyrazolyl, furanyl, imidazolyl, and U-oxazolyl , Pyrargyl, pyrazolyl, daphyl, pyridyl, pyrimidinyl, pyrrolyl, 13-thiazolyl, or thienyl, wherein the heterocyclic ring is substituted with 0, 1, 2 or 3 substituents Is independently selected from the group consisting of alkoxy, k-oxyalkyl, fluorenyl, cyano, sulfone, alkoxy, alkynyl, or nitro; 8 is

R3 N+ ! Ο- ，Ζ為CRb ; Rb為氫；…為不存在；L為_n(R7)C(0)_ ’且D、Ri、R2、R3、R4、r7&amp;ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并噻唑基、呋喃 基味嗤基、1，3-嘮唑基、吡啡基、吡唑基、嗒啡基、吡啶 基 由咬基、外1：洛基、1，3〃塞也基或隹吩基，其中雜環係獨 互被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 85228 -82- 200404539 心氧叛基、燒基、氰基、_素、齒燒氧基、函烷基或硝基 ;BgR3 N +! Ο-, Z is CRb; Rb is hydrogen; ... is absent; L is _n (R7) C (0) _ 'and D, Ri, R2, R3, R4, r7 &amp; ra are all as follows: II). In another specific embodiment of the present invention, a compound of formula (II) is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzothiazolyl, furanyl sulfanyl, 1,3- Oxazolyl, pyridinyl, pyrazolyl, daphnyl, and pyridyl are derived from octyl, outer 1: rockyl, 1, 3 acetoyl or fluorenyl, wherein heterocyclic systems are independently , 2 or 3 substituents, the substituents are independently selected from the group consisting of alkoxy, 85228 -82- 200404539 cardioxy, alkynyl, cyano, oxone, oxyalkyl, alkynyl, or nitro; Bg

0- ; R1為氫、烷基、氰基、it烷基、鹵素、硝基、（NZ3Z4) 燒基或（NZsZ4)羰基；^與心為氫；r3為氫或羥基；z為CRb ，Rb為氫；…為不存在；D為-CH2-; L為-N(R7)C(0)·;及R7與 Ra均如關於式（II)之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為雜環，其中雜環為苯并咪唑基、苯并嘧唑基、吡唑 基、说咬基或嘧吩基，其中雜環係獨立被〇、1、2或3個取 代基取代，取代基獨立選自烷氧基、烷氧羰基、烷基、氰 基、自素、鹵烷氧基、_烷基或硝基；B為 ?20-; R1 is hydrogen, alkyl, cyano, it alkyl, halogen, nitro, (NZ3Z4) alkanyl or (NZsZ4) carbonyl; ^ and hydrogen are hydrogen; r3 is hydrogen or hydroxyl; z is CRb, Rb Is hydrogen; ... is absent; D is -CH2-; L is -N (R7) C (0) ·; and R7 and Ra are as defined for formula (II). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, pyrazolyl, pyridyl, or pyrimidine Phenyl, wherein the heterocyclic ring is independently substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, autogen, haloalkoxy, alkane Or nitro; B is? 2

VXXR Λ Ν+ R4VXXR Λ Ν + R4

I °' ，Rl為氫、燒基、氰基、齒虎基、i素、硝基、（nz3z4) 燒基或（NZ^Z4)羰基；&amp;與r4為氫；&amp;為氫或羥基；z為CRb ，Rb為氲；一為不存在；D為-CH2_; L為·Ν(ϊ17)(：(0)-;及R7與 Ra均如關於式（II)之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為環烷基；B為 ?2 R1^W-R3 \ isT R4 ; Z為CRb ;…為不存在；乙為-N(R7)c(〇)_ ;且D、 Ri、R2、R3、R4、r7、rb及心均如式⑼中之定義。 85228 -83- 200404539 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中Α為環烷基，其中環烷基為環己基或金鋼烷基；Β為I ° ', R1 is hydrogen, alkynyl, cyano, odontyl, itin, nitro, (nz3z4) alkyl or (NZ ^ Z4) carbonyl; &amp; and r4 are hydrogen; &amp; is hydrogen or hydroxyl Z is CRb, Rb is 氲; one is not present; D is -CH2_; L is · N (ϊ17) (:( 0)-; and R7 and Ra are as defined for formula (II). In the present invention In another specific embodiment, the compound of formula (11) is disclosed, wherein A is cycloalkyl; B is? 2 R1 ^ W-R3 \ isT R4; Z is CRb; ... is absent; B is -N (R7) c (〇) _; and D, Ri, R2, R3, R4, r7, rb, and xin are as defined in formula 85 85228 -83- 200404539 In another specific embodiment of the present invention, Is a compound of formula (II), wherein A is cycloalkyl, wherein cycloalkyl is cyclohexyl or auryl; B is

;;Ri為氫、烷基、氰基、_烷基、素、硝基、（NZ3Z4) 烷基或（ΝΖβ4)羰基；R2與r4為氫；&amp;為氫或羥基；z為Crb ’ Rb為氫；…為不存在；Da-CH2-; L為-N(R7)C(0)-;及以7與 Ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為環烷基，其中環烷基為環己基或金鋼烷基；; Ri is hydrogen, alkyl, cyano, _alkyl, prime, nitro, (NZ3Z4) alkyl or (NZβ4) carbonyl; R2 and r4 are hydrogen; &amp; is hydrogen or hydroxyl; z is Crb 'Rb Is hydrogen; ... is absent; Da-CH2-; L is -N (R7) C (0)-; and 7 and Ra are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (11) is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group;

&amp;，Ri為氫、烷基、氰基、_烷基、函素、硝基、⑽Z3z4) k基或（ΝΖβ4)羰基；：^與心為氫；&amp;為氫或羥基；/為^^ ,RB為氫，…為不存在；D為_CH(CH3)_ ; L為_N(R7)c(〇)_ ;及 R7與RA均如式（Π)中之定義。 係揭示式（II)化合物， 於本發明之另一項具體實施例中 其中A為芳基；β為&amp;, Ri is hydrogen, alkyl, cyano, _alkyl, functional element, nitro, hydrazone Z3z4) k group or (NZβ4) carbonyl group: ^ is hydrogen with heart; &amp; is hydrogen or hydroxyl group; ^, RB is hydrogen, ... is absent; D is _CH (CH3) _; L is _N (R7) c (〇) _; and R7 and RA are as defined in formula (Π). Is a compound of formula (II), in another embodiment of the present invention, wherein A is aryl; β is

Ri 、 R2 、 R ;乙為-N(R7)C(0)-;且D、 K、I、R3、r4、心及、均如式⑼中之定義。Ri, R2, R; B is -N (R7) C (0)-; and D, K, I, R3, r4, Xinhe, are as defined in formula (2).

一， -Μ %签、尽丞或_JNZ^乙2 ; Β為 85228 -84- 200404539 R1\^L/R3 XX ·、…_ 4 , R!為鼠、纪基、氰基、_燒基、_素、硝基、讲^3 z4) fe基或(NZ3 Z4 )談基，R2與R_4為氫；R3為氫或經基；z為c ; …為一個鍵結；D為-CH2 _ ; L為-N(R7)C(0)-;及R7與ra均如式 (II)中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 fe基、烷硫基、苄基、氰基、_素、_烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZi Z2 ; B為 λ NT心；心為氫、烷基、氰基、函烷基、鹵素、硝基^^心） 燒基或(NZ3Z4)羰基；化與114為氫；R3為氫或羥基；Z為C; …為一個鍵結；D為_CH(CH3)·; L為-N(R7)C(0&gt;;及R7與RA均 如式（II)中之定義 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并,塞唑基、呋喃 基、咪唑基、1，3-嘮唑基、吡畊基、吡唑基、嗒嗜基、吡啶 基、嘧啶基、吡咯基、1，3-嘧唑基或嘧吩基，其中雜環係獨 立被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 燒氧羰基、烷基、氰基、！|素、画烷氧基、i烷基或硝基 ;8為First, -M% sign, complete or _JNZ ^ B2; Β is 85228 -84- 200404539 R1 \ ^ L / R3 XX ·, ..._ 4, R! Is rat, kiji, cyano, _ thio , _ Prime, nitro, ^ 3 z4) fe group or (NZ3 Z4) group, R2 and R_4 are hydrogen; R3 is hydrogen or via group; z is c;… is a bond; D is -CH2 _ L is -N (R7) C (0)-; and R7 and ra are as defined in formula (II). In another specific embodiment of the present invention, the compound of the formula (I) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Independently selected from alkenyl, alkoxy, alkoxycarbonyl, fe-based, alkylthio, benzyl, cyano, _ prime, _alkoxy, _alkyl, methylenedioxy, nitro, phenyl Or -NZi Z2; B is λ NT; heart is hydrogen, alkyl, cyano, functional alkyl, halogen, nitro ^) alkyl or (NZ3Z4) carbonyl; and 114 are hydrogen; R3 is hydrogen Or a hydroxyl group; Z is C;… is a bond; D is _CH (CH3) ·; L is -N (R7) C (0 &gt;; and R7 and RA are as defined in formula (II) in the present invention In another specific embodiment, the compound of formula (II) is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzo, thiazolyl, furyl, imidazolyl, 1,3-fluorene An oxazolyl, pyrimidinyl, pyrazolyl, daphthyl, pyridyl, pyrimidinyl, pyrrolyl, 1,3-pyrazolyl or pyrenyl group, wherein the heterocyclic ring system is independently 0, 1, 2 or 3 Substituted by a substituent, the substituent is independently selected from alkoxy, oxocarbonyl, alkyl, cyano ! | Su, Videos alkoxy, or nitro group I; 8

85228 Z為C ;…為一個键結；L為-N(R7)C(0)- ; RB為氫 -85- 200404539 ;且〇、R!、r2、R3、R4、R7&amp;Ra均如式⑼中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為雜環’其中雜環為苯并咪唾基、苯㈣録、咬喃 基、咪唑基、1，3· $唑基、p比畊基、峨唑基、嗒畊基、说啶 基、嘧啶基、吡咯基、u·,塞唑基或嘧吩基，其中雜環係獨 立被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 烷氧叛基、烷基、氰基、鹵素、鹵烷氧基、鹵烷基或硝基 ;6為 ?2 H…、 Ν ，Rl為氫、烷基、氰基、鹵烷基、鹵素、硝基、（ΝΖ3Ζ4) 烷基或(ΝΖβ4)羰基；化與心為氫；Rs為氫或羥基；2為(：：； …為一個鍵結；D為-CH2-; L為-N(R7)C(0)_; rb為氫；及心與 RA均如關於式（II)之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并嘧唑基 、p比也 基、P比淀基或遠吩基’其中雜環係獨立被〇、1、2或3個取 代基取代，取代基獨立選自烷氧基、烷氧羰基、烷基、氰 基、i素、函烷氧基、（I烷基或硝基；B為 R285228 Z is C; ... is a bond; L is -N (R7) C (0)-; RB is hydrogen-85-200404539; and 〇, R !, r2, R3, R4, R7 &amp; Ra are as follows: Definition in. In another specific embodiment of the present invention, a compound of the formula VII is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidalyl, benzyl, sulfanyl, imidazolyl, 1,3. Oxazolyl, p-pyridyl, erazolyl, dacrotyl, pyridyl, pyrimidinyl, pyrrolyl, u ·, sedazolyl or pyrenyl, wherein the heterocyclic ring is independently 0, 1, 2 or 3 Each substituent is substituted, and the substituent is independently selected from alkoxy, alkoxyalkyl, alkyl, cyano, halogen, haloalkoxy, haloalkyl, or nitro; 6 is? 2 H ..., Ν, and R1 is Hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (NZβ4) carbonyl group; hydrogenation with heart; Rs is hydrogen or hydroxyl; 2 is (::;… is a bond D is -CH2-; L is -N (R7) C (0) _; rb is hydrogen; and Xin and RA are as defined for formula (II). In another embodiment of the present invention Is a compound of formula (11), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, ppyridyl, ppyridyl, or farphenyl, wherein the heterocyclic ring is independently 0, 1, 2 or 3 substituents, the substituents are independently selected Alkoxy, alkoxycarbonyl, alkyl, cyano, i element, alkoxy, (I alkyl or nitro; B is R2

Ν 鹵烷基、鹵素、硝基、（NZ3Z4) ; I為氫、烷基、氰基 燒基或(NZSZ4)羰基；及2與1為氫；r3為氫或羥基；z為C; …為一個鍵結；D為-CH2-; L為-N(R7)C(0)-; RB為氫；及R7與 RA均如關於式（II)之定義。 於本發明之另一項具體實施例中，係揭示式化合物， -86- 85228 200404539 其中A為芳基；B為N haloalkyl, halogen, nitro, (NZ3Z4); I is hydrogen, alkyl, cyano, or (NZSZ4) carbonyl; and 2 and 1 are hydrogen; r3 is hydrogen or hydroxyl; z is C; ... is One bond; D is -CH2-; L is -N (R7) C (0)-; RB is hydrogen; and R7 and RA are as defined for formula (II). In another specific embodiment of the present invention, it is a compound of the formula, -86- 85228 200404539, wherein A is aryl; B is

Z為C ;…為一個鍵結Z is C; ... is a bond

乙為 _N(R7)C(0)_ ;且 D、X 、Y、R2、R3、R7及RA均如式⑼中之定義。 於本發明《另-項具體實施例巾，係㈣示式（π)化合物， 其中Α為芳基，其中芳基為笨基，被〇、i、2、3、4或5個 取代基取代，取代基獨立選自缔基、燒氧基、燒氧幾基、 鹵烷氧基、i烷基、 基、燒硫基、芊基、氰基、卣素 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 ri ’、、 ,X 為 N(R6)、〇 或 S ; Y 為 Cd) ; R2 與 R3 為氫 ;R4為 氯、：k基或氰基’ Z為C ; 一為一個鍵結；D為_CH2 _ ; L為 -N(R7 )c(o)-;且心、r7及ra均如式㈤中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、_素、_烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZi Z2 ; B為B is _N (R7) C (0) _; and D, X, Y, R2, R3, R7, and RA are as defined in formula (2). In the present invention, "Another Specific Embodiment" is a compound of the formula (π), wherein A is an aryl group, wherein the aryl group is a benzyl group, and is substituted by 0, i, 2, 3, 4, or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxy, haloalkoxy, i alkyl, thio, thio, fluorenyl, cyano, halogen, methylenedioxy, nitro, Phenyl or -NZiZ2; B is ri ',, X is N (R6), 0 or S; Y is Cd); R2 and R3 are hydrogen; R4 is chlorine, k group or cyano group; Z is C; One is a bond; D is _CH2 _; L is -N (R7) c (o)-; and Xin, r7, and ra are as defined in formula ㈤. In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, alkoxy, alkyl, methylenedioxy, nitro, Phenyl or -NZi Z2; B is

;X為N(R6)、Ο或S ; Y&amp;c(r4);心與心為氫；心為 氫、烷基或氰基；Z為C ;…為一個鍵結；D為_CH(CH3)_ ; L 為-N(R7)C(0)-;且&amp;、&amp;及RA均如式⑼中之定義。 於本發明之另一項具體實施例中，係揭示式（H)化合物 其中A為環烷基；B為 85228 -87- 200404539X is N (R6), 0 or S; Y &amp; c (r4); heart and heart are hydrogen; heart is hydrogen, alkyl or cyano; Z is C; ... is a bond; D is _CH ( CH3) _; L is -N (R7) C (0)-; and &amp;, &amp; and RA are as defined in formula (2). In another specific embodiment of the present invention, the compound of formula (H) is disclosed, wherein A is cycloalkyl; B is 85228 -87- 200404539.

、N R4 ; Ζ 為 C ;…為一個鍵結；L 為·Ν(Ϊ17)(3(0)-;且 D、 Ri、R2、R3、R4、117及RA均如式⑻中之定義。 於本發明之另一項具體實施例中，係揭示式（n)化合物， 其中Α為環烷基，其中環烷基為環己基或金鋼烷基；β為, N R4; Z is C;... Is a bond; L is · N () 17) (3 (0)-; and D, Ri, R2, R3, R4, 117, and RA are as defined in formula ⑻. In another specific embodiment of the present invention, the compound of formula (n) is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; β is

Πι為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 基或(NZSZ4)羰基；r2與r4為氫；r3為氫或羥基；z為c; …為一個鍵結；D為-CH2-; L為-N(R7)C(0)-;及R7與RA均如式 (II)中之定義。 於本發明之另一項具體實施例中，係揭示式化合物， 其中A為環烷基，其中環烷基為環己基或金鋼烷基；3為Πι is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) or (NZSZ4) carbonyl; r2 and r4 are hydrogen; r3 is hydrogen or hydroxyl; z is c; ... is a bond ; D is -CH2-; L is -N (R7) C (0)-; and R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, the compound of the formula is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; 3 is

* ; Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3 Z4) 燒基或(ΝΖΘ4)羰基；R2與R4為氫；r3為氫或羥基；z為c; …為一個鍵結；D為-CH(CH3)-; L·為-N(R7)C(0)-;及R7與RA均 如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基；Β為 ?2 、〆R4 ; Ζ為Ν ;…為不存在；L為_C(0)N(R7)-;且D、心 、R2、、R4、R7及RA均如式(π)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基’其中芳基為苯基，被〇、1、2、3、4或5個 85228 -88 - 200404539 取代基取代，取代基獨立選自烯基、燒氧基、燒氧羰基、 坑基、燒硫基、苄基、氰基、齒素、||燒氧基、齒燒基、 硝基、苯基或-NZiZ2 ; B為 亞甲二氧基*; Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3 Z4) alkenyl or (NZΘ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is c;… Is a bond; D is -CH (CH3)-; L · is -N (R7) C (0)-; and R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group; B is? 2 and 〆R4; Z is N; ... is absent; L is _C (0) N (R7)-; and D, Xin, R2, R4, R7 and RA are as defined in formula (π). In another specific embodiment of the present invention, a compound of formula (II) is disclosed, wherein A is aryl ', wherein aryl is phenyl, and is 0, 1, 2, 3, 4, or 5 85228 -88- 200404539 Substituted by substituents, the substituents are independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, pit, thiothio, benzyl, cyano, halide, || alkoxy, halide, nitro, Phenyl or -NZiZ2; B is methylenedioxy

、R4 ; R!為氫、燒基、氰基、||燒基、齒素、硝基、⑼z4) 烷基或(NZgZ4)羰基；&amp;與&amp;為氫；R3為氫或羥基；z為N; …為不存在；D為-CH2 ; L為-C(0)N(R7)-;及R7與RA均如式（I!) 中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自缔基、燒氧基、燒氧談基、 烷基、烷硫基、苄基、氰基、自素、函烷氧基、卣烷基、 亞甲二氧基、硝基、苯基或-NZJ2 ; B為 ?2 R1AR3.... \ n R4，Ri為氫、燒基、氰基、_垸基、_素、硝基、⑼z3 z4 ) 燒基或(NZ3 Z4 )羰基；R2與R4為氫；R3為氫或經基；z為]Sf ; …為不存在，D為-CH(CH3)-，L為-C(0)N(R7)-;及R7與ra均如 式⑼中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代’取代基獨立選自丨布基、燒氧基、貌氧談基、 烷基、烷硫基、苄基、氰基、_素、画烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-ΝΖ!Ζ2 ; B為 85228 -89- 200404539, R4; R! Is hydrogen, alkyl, cyano, || alkyl, halo, nitro, ⑼z4) alkyl or (NZgZ4) carbonyl; &amp; and &amp; are hydrogen; R3 is hydrogen or hydroxyl; z Is N;… is absent; D is -CH2; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (I!). In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxy, alkyl, alkylthio, benzyl, cyano, autogen, alkoxy, fluorenyl, methylenedioxy, nitro , Phenyl or -NZJ2; B is? 2 R1AR3 .... \ n R4, Ri is hydrogen, alkyl, cyano, fluorenyl, oxon, nitro, hydrazium z3 z4) alkyl or (NZ3 Z4) Carbonyl; R2 and R4 are hydrogen; R3 is hydrogen or meridian; z is] Sf; ... is absent, D is -CH (CH3)-, L is -C (0) N (R7)-; and R7 and Ra is as defined in formula (2). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Substituents are independently selected from the group consisting of clothyl, alkoxy, amyloxy, alkyl, alkylthio, benzyl, cyano, cyanine, alkoxy, alkyl, methylenedioxy, nitrate Group, phenyl or -NZ! Z2; B is 85228 -89- 200404539

xXXR N 4 ; R1為氫、烷基、氰基、li烷基、鹵素、硝基、（NZ3Z4) 燒基或(NZgZ4)羰基；^與心為氫；r3為氫或羥基；z為N; …為不存在；D為-CH2CH2-; L為-C(0)N(R7)-;及心與1^均如 式(Π)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基；Β為xXXR N 4; R1 is hydrogen, alkyl, cyano, lialkyl, halogen, nitro, (NZ3Z4) alkyl or (NZgZ4) carbonyl; ^ and hydrogen are hydrogen; r3 is hydrogen or hydroxyl; z is N; ... is absent; D is -CH2CH2-; L is -C (0) N (R7)-; and Xin and 1 ^ are as defined in formula (Π). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is aryl; B is

為不存在；L 為-C(0)N(R7)-;且 D、R2、 R3、R4、R7及RA均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、自素、鹵烷氧基、_烷基、 亞甲一氧基、硝基、苯基或-NZi Z2 ; B為Is not present; L is -C (0) N (R7)-; and D, R2, R3, R4, R7, and RA are as defined in formula (II). In another embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, autogen, haloalkoxy, alkyl, methylene monooxy, nitro, Phenyl or -NZi Z2; B is

;R2、¥R4為氫；Z為N;…為不存在； ;L為-C(0)N(R7)-;及A與RA均如式（π)中之定義 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中Α為芳基，其中芳基為苯基，被〇、丨、2、3、4或5個 取代基取代，取代基獨立選 烷基、烷硫基、苄基、氰基 埽基、烷氧基、烷氧羰基、 _素、齒烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZj] ; β為 85228 -90- 200404539R2, R4 is hydrogen; Z is N; ... is absent; L is -C (0) N (R7)-; and A and RA are as defined in formula (π) in another aspect of the present invention In a specific embodiment, the compound of the formula (11) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4, or 5 substituents, and the substituents independently select alkyl , Alkylthio, benzyl, cyanofluorenyl, alkoxy, alkoxycarbonyl, molybdenum, haloalkoxy, _alkyl, methylenedioxy, nitro, phenyl, or -NZj]; β For 85228 -90- 200404539

N λ N 4, R2、R3及R4為氳；Z為N;…為不存在；D為-CH(CH3)_ ;L為-C(0)N(R7)-;及^與、均如式（II)中之定義。 於本發明之另一項具體貫施例中，係揭示式（〗〗）化合物， 其中A為ί展燒基；b為 \ nT R4 ; Z 為 N ;…為不存在；L 為 _c(〇)n(R7)_ ;且 D、Ri 、R2、R3、R4、R7及RA均如式⑼中之定義。 於本發明之另一項具體實施例中，係揭示式（n)化合物 其中A為環烷基，其中環烷基為環己基或金鋼烷基；b為 R1^Y^YR3 \ N/ r4 ; 為氫、垸基、氰基、鹵烷基、鹵素、硝基、z4) 燒基或(NZ3Z4)羰基；112與114為氫；r3為氫或羥基；z為N; …為不存在；D為-CH2-; L為-C(0)N(R7)-;及R7與RA均如式（π) 中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物 其中A為環烷基，其中環烷基為環己基或金鋼烷基；B為N λ N 4, R2, R3 and R4 are 氲; Z is N; ... is absent; D is -CH (CH3) _; L is -C (0) N (R7)-; and Definition in formula (II). In another specific embodiment of the present invention, the compound of formula (〗 〖) is disclosed, where A is a fluorenyl group; b is \ nT R4; Z is N; ... is absent; L is _c ( 〇) n (R7) _; and D, Ri, R2, R3, R4, R7, and RA are as defined in formula (1). In another specific embodiment of the present invention, it is disclosed that the compound of formula (n) wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; b is R1 ^ Y ^ YR3 \ N / r4 ; Is hydrogen, fluorenyl, cyano, haloalkyl, halogen, nitro, z4) alkyl or (NZ3Z4) carbonyl; 112 and 114 are hydrogen; r3 is hydrogen or hydroxyl; z is N;… is absent; D is -CH2-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (π). In another specific embodiment of the present invention, it is disclosed that the compound of formula (II) wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; B is

;Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 烷基或(NZ3Z4)羰基；112與114為氫；R3為氫或羥基；Z為N; …為不存在；D為-CH(CH3)- ; L為-C(0)N(R7)-;及R7與RA均如 式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基；B為Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (NZ3Z4) carbonyl; 112 and 114 are hydrogen; R3 is hydrogen or hydroxyl; Z is N; Exists; D is -CH (CH3)-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is aryl; B is

85228 -91 - 20040453985228 -91-200404539

\ ; z為CRb ;…為不存在；l為七⑼风心)· Rl、R2、R3、R4、R7、Rb及RA均如式（II)中之定義。\; z is CRb; ... is absent; l is Qiqifengxin) · Rl, R2, R3, R4, R7, Rb and RA are as defined in formula (II).

且D 於本發明之另一項具體貫施例中，係揭示式（H)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代’取代基獨IL選自烯基、燒氧基、燒氧羰基、 烷基、烷硫基、芊基、氰基、卣素、_烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZ!Z2 ; B為 ?2 R1^|T|R3 \ nT R4 ;心為氫、烷基、氰基、_烷基、函素、硝基、⑼44) 烷基或（NZSZ4)羰基；R2與R4為氫；r3為氫或羥基；z為CRb ，Rb為氫；…為不存在；D為-CH2 · ; L為-C(0)N(R7)-;及R7與 RA均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為芳基’其中芳基為苯基，被0、1、2、3、4或5個 取代基取代’取代基獨立選自晞基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、齒素、_烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZlZ2 ; B為 R1 Arr；. N 4，R1為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) k基或（NZsZ4)羰基；r2與r4為氫；r3為氫或羥基；z為crb ;rb為氫；一為不存在；d 為-CH(CH3)-; L 為-C(0)N(R7)-;及 心與RA均如式（11)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 85228 -92- 200404539 其中A為芳基；B為And D is another specific embodiment of the present invention, which discloses a compound of formula (H), wherein A is aryl, wherein aryl is phenyl, and is substituted by 0, 1, 2, 3, 4 or 5 Group substituted 'substituent IL selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, halogen, alkoxy, alkyi, methylenedioxy , Nitro, phenyl, or -NZ! Z2; B is? 2 R1 ^ | T | R3 \ nT R4; the heart is hydrogen, alkyl, cyano, alkyi, alkyn, nitro, ⑼44) alkyl Or (NZSZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is CRb and Rb is hydrogen; ... is absent; D is -CH2 ·; L is -C (0) N (R7)-; And R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, the compound of formula (11) is disclosed, wherein A is aryl 'wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents' Substituents are independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halide, alkoxy, _alkyl, methylenedioxy, nitro, Phenyl or -NZlZ2; B is R1 Arr;. N 4, R1 is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) k group or (NZsZ4) carbonyl group; r2 and r4 are hydrogen R3 is hydrogen or hydroxyl; z is crb; rb is hydrogen; one is absent; d is -CH (CH3)-; L is -C (0) N (R7)-; and both heart and RA are as follows ( 11). In another specific embodiment of the present invention, the compound of formula (II) is disclosed, 85228 -92- 200404539 where A is aryl; B is

\ν、νΓ〜；z為CRB ;…為不存在；l為_c(0)N(R7)_ ;且D、 心、R3、R4、R7、Rb及RA均如式（π)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 fe基、fe硫基、苄基、氰基、鹵素、_燒氧基、函虎基、 亞甲二氧基、硝基、苯基或-ΝΖ! Z2 ; B為\ ν, νΓ ~; z is CRB; ... is absent; l is _c (0) N (R7) _; and D, Xin, R3, R4, R7, Rb, and RA are all as in formula (π) definition. In another specific embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, fe, fe, thio, benzyl, cyano, halogen, alkoxy, haloyl, methylenedioxy, nitro, benzene Base or -NZ! Z2; B is

3 N〜；R2、R3及r4為氫；Z為crb ; RB為氳；一·為不存 在，D為-CH2 -，L為-C(0)N(R7)-;及與ra均如式（η)中之定 義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為方基’其中方基為苯基’被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、燒氧基、燒氧談基、 燒基、垸硫基、苄基、氰基、lS素、_燒氧基、自燒基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為3 N ~; R2, R3, and r4 are hydrogen; Z is crb; RB is 氲; one is absent, D is -CH2-, and L is -C (0) N (R7)-; Definition in formula (η). In another specific embodiment of the present invention, it is disclosed that the compound of formula (11), wherein A is a square group 'where the square group is phenyl' is substituted with 0, 1, 2, 3, 4 or 5 substituents, The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxy, alkoxy, sulfanyl, benzyl, cyano, 1S, alkoxy, self-alkyl, methylenedioxy, nitro , Phenyl or -NZiZ2; B is

^ ν ，'4 ;R2、R3及R4為氫；Z為crb;Rb*氫；…為不存 在；D為-CH(CH3)-; L為-C(0)N(R7)-;及反7與、均如式⑼中之 定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為芳基；B為 85228 -93- 200404539 0- ; z*Crb ;…為不存在；Lg_c(〇)N(R7)_;且〇、 R1、R2、R3、R4、R7、RB及RA均如式（Π)中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代’取代基獨iL選自烯基、垸氧基、虎氧羰基、 烷基、烷硫基、芊基、氰基、自素、卣烷氧基、函烷基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為^ ν, '4; R2, R3, and R4 are hydrogen; Z is crb; Rb * hydrogen; ... is absent; D is -CH (CH3)-; L is -C (0) N (R7)-; and The inverse 7 and are as defined in formula (2). In another specific embodiment of the present invention, the compound of formula (11) is disclosed, wherein A is an aryl group; B is 85228 -93- 200404539 0-; z * Crb; ... is absent; Lg_c (〇) N (R7) _; and 0, R1, R2, R3, R4, R7, RB, and RA are as defined in formula (Π). In another specific embodiment of the present invention, a compound of formula (I) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and the 'substituent group is substituted with 0, 1, 2, 3, 4, or 5 substituents. The sole iL is selected from the group consisting of alkenyl, fluorenyloxy, oxocarbonyl, alkyl, alkylthio, fluorenyl, cyano, autogen, fluorenylalkoxy, alkenyl, methylenedioxy, nitro, benzene Base or -NZiZ2; B is

0- ; Rl、R2、反3及R4為氫；z為CRB ; rb為氫；…為 不存在；D為-Civ ; L為_C(0)N(R7)-;及r7與Ra均如式（π)中 之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 火元基、燒硫基、卞基、散基、画素、_燒氧基、_燒基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 R1^V^r^R3 ό- ; Ri、R2、R3及R4為氫；Ζ為CRB ; RB為氫；…為 不存在；D為-CH2-; L為-C(0)N(R7)-;及心與！^為氫。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 85228 -94- 200404539 其中A為芳基，其中芳基為苯基，被1個烷基取代基取代； B為 °&quot; ; R1、R2、R3&amp;R4為氫；z 為 crb ; RB為氫；--·為 不存在；D為-〇V; L為-C(0)N(R7)-;及R7與RA為氫。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被1個烷基取代基取代， 其中較佳烷基取代基為甲基；B為0-; Rl, R2, trans 3 and R4 are hydrogen; z is CRB; rb is hydrogen; ... is absent; D is -Civ; L is _C (0) N (R7)-; and r7 and Ra are both As defined in formula (π). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, sulfonyl, sulfanyl, fluorenyl, sulfanyl, cyano, thiol, thiol, methylenedioxy, nitro, Phenyl or -NZiZ2; B is R1 ^ V ^ r ^ R3;-Ri, R2, R3, and R4 are hydrogen; Z is CRB; RB is hydrogen; ... is absent; D is -CH2-; L is- C (0) N (R7)-; and heart and! ^ Is hydrogen. In another specific embodiment of the present invention, the compound of formula (11) is disclosed, 85228-94-200404539, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by an alkyl substituent; B is ° &quot;; R1, R2, R3 &amp; R4 is hydrogen; z is crb; RB is hydrogen;-is absent; D is -0V; L is -C (0) N (R7)-; and R7 and RA is hydrogen. In another specific embodiment of the present invention, the compound of formula (π) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with an alkyl substituent, and the preferred alkyl substituent is Methyl; B is

;Ri、R2、R3 及 R4 為氫；Z 為 CRB ; RB 為氫 不存在；D為-CH2_; L為-C(0)N(R7)-;及心與^為氫。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為方基’其中方基為苯基’被1個燒基取代基取代， 其中較佳烷基取代基為甲基；B為Ri, R2, R3 and R4 are hydrogen; Z is CRB; RB is hydrogen does not exist; D is -CH2_; L is -C (0) N (R7)-; and heart and ^ are hydrogen. In another specific embodiment of the present invention, it is disclosed that the compound of formula (Π), wherein A is a square group 'where the square group is phenyl' is substituted by 1 alkyl group substituent, and the preferred alkyl substituent is Methyl; B is

;&amp;、R2、R3&amp;R4為氫；Z為CRB ; RB為氫；…為 不存在；D為-CH2-; L為-C(S)N(R7)-;及心與!^為氫。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被〇、；[、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 坑基、燒硫基、芊基、氰基、_素、_燒氧基、齒燒基、 85228 -95- 200404539 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為; &amp;, R2, R3 &amp; R4 is hydrogen; Z is CRB; RB is hydrogen; ... is absent; D is -CH2-; L is -C (S) N (R7)-; and heart and! ^ is hydrogen. In another embodiment of the present invention, the compound of formula (II) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, [, 2, 3, 4, or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, pit, sulfanyl, fluorenyl, cyano, sulfonyl, sulfonyl, dentyl, 85228 -95- 200404539 Oxy, nitro, phenyl or -NZiZ2; B is

a XR r4 〇- ;Ri、R2 ' R3及R4為氫；Z為crb ; RB為氫；…為 不存在；D為-CH(CH3)-; L為-C(0)N(R7)-;及心與！^均如式⑻ 中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為雜環，其中雜環為苯并咪唑基、苯并嘧唑基、吱喃 基、咪唑基、1，3-噚唑基、吡畊基、吡唑基、嗒啡基、吡啶 基密淀基、比洛基、1，3-碟吃基或η塞吩基，其中雜環係獨 立被0、1、2或3個取代基取代，取代基獨立選自烷氧基、 烷氧故基、烷基、氰基、齒素、卣烷氧基、_烷基或硝基 ;B4 0- . ’ Z為CRb ; rb為氫；…為不存在；L為_C(0)n(R7&gt;a XR r4 〇-; Ri, R2 'R3 and R4 are hydrogen; Z is crb; RB is hydrogen; ... is absent; D is -CH (CH3)-; L is -C (0) N (R7)- ; And heart with! ^ All are as defined in formula ⑻. In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, succinyl, imidazolyl, 1, 3-oxazolyl, pyrimidinyl, pyrazolyl, daphnyl, pyridyl, melidyl, biloyl, 1,3-diethyl, or η-sedenyl, wherein the heterocyclic ring is independently 0, 1 , 2 or 3 substituents, the substituents are independently selected from the group consisting of alkoxy, alkoxy, alkyl, cyano, halide, alkoxy, alkyl, or nitro; B4 0-. 'Z Is CRb; rb is hydrogen; ... is absent; L is _C (0) n (R7 &gt;

，且 D、R!、p rw K2、R3、R4、心及Ra均如式⑻中之定義。 於本發明&gt; $ 力一项具體實施例中，係揭示式（II)化合物， 其中A為雜璟，甘 其中雜環為苯并咪唑基、苯并嘧唑基、呋喃 基、咪唑基、 τ 、 了吱基、吡畊基、吡唑基、嗒畊基、吡啶 基、喊淀基、 m谷基、1，3-噻唑基或嘧吩基，其中雜環係獨 立被0、1、2忒飞加 、 或3個取代基取代，取代基獨立選自烷氧基、 燒氧致基、燒其 &amp; &amp;、氣基、i素、鹵烷氧基、齒烷基或硝基 ;Bg 85228 96- 200404539, And D, R !, prw K2, R3, R4, heart, and Ra are as defined in formula ⑻. In a specific embodiment of the present invention, a compound of formula (II) is disclosed, in which A is heteropyrene, and wherein the heterocycle is benzimidazolyl, benzopyrazolyl, furanyl, imidazolyl, τ, succinyl, pyridinyl, pyrazolyl, daphnyl, pyridyl, alkyl, glutenyl, 1,3-thiazolyl, or pyrenyl, wherein the heterocyclic system is independently 0, 1, 2 忒 Feijia, or 3 substituents, the substituents are independently selected from the group consisting of alkoxy, oxo, oxo, &; Bg 85228 96- 200404539

RlRl

JXR Λ N+ R4 〇-,Rl為氫、烷基、氰基、li烷基、自素、硝基、（nz3z4) 烷基或（NZsZ4)羰基；心與r4為氫；r3為氫或羥基 ，Z 為 CRb ;Rb為氫；…為不存在；D為-CH2-; L為-C(0)N(R7&gt;;及心與 RA均如關於式（π)之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并嘍唑基、吡唑 基、说咬基或碟吩基’其中雜環係獨立被〇、1、2或3個取 代基取代，取代基獨立選自烷氧基、烷氧羰基、烷基、氰 基、i素、i烷氧基、（¾烷基或硝基；B為JXR Λ N + R4 〇-, R1 is hydrogen, alkyl, cyano, lialkyl, autogen, nitro, (nz3z4) alkyl or (NZsZ4) carbonyl; r4 is hydrogen; r3 is hydrogen or hydroxyl, Z is CRb; Rb is hydrogen; ... is absent; D is -CH2-; L is -C (0) N (R7 &gt;; and Xin and RA are as defined for formula (π). In a specific embodiment, it is disclosed that the compound of formula (11), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, pyrazolyl, sulfonyl or phenphenyl The ring system is independently substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, i-prime, i-alkoxy, (alkyl or nitro) ; B is

,XXR Λ R4 o- , Ri為氫、烷基、氰基、鹵烷基、鹵素、硝基、（NZ3Z4) 烷基或（NZsZ4)羰基；&amp;與&amp;為氳；心為氳或羥基；z為CRb ，Rb為氫，…為不存在；D為-CH2-; L·為-C(0)N(R7)-;及R7與 RA均如關於式（II)之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為環烷基；Β為 ?2 \ nT h , Ζ為CRb，…為不存在；L為-C(〇)N(R分；且D、, XXR Λ R4 o-, Ri is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, (NZ3Z4) alkyl or (NZsZ4) carbonyl; &amp; and &amp; are 氲; the heart is 氲 or hydroxyl Z is CRb, Rb is hydrogen, ... is absent; D is -CH2-; L · is -C (0) N (R7)-; and R7 and RA are as defined for formula (II). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is a cycloalkyl group; B is? 2 \ nT h, Z is CRb, ... is absent; L is -C (〇 ) N (R points; and D,

Ri、R2、R3、R4、R7、Rb&amp;ra均如式⑼中之定義。 於本發明之另一項具體貫施例中，係揭示式（n)化合物， 其中Α為環烷基，其中環烷基為環己基或金鋼烷基；3為Ri, R2, R3, R4, R7, Rb &amp; ra are as defined in formula (2). In another specific embodiment of the present invention, the compound of formula (n) is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; 3 is

85228 -97- 200404539 R:crtcR3 'N R4 ; Rl為氫、烷基、氰基、自烷基、1¾素、硝基、（NZ3Z4) 烷基或（NZgZ4)羰基；心與心為氫；r3為氫或羥基；z為crb ,rb為氫；…為不存在；d為-CH2-; L·為-C(0)N(R7)-;及R7與 ra均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為環烷基，其中環烷基為環己基或金鋼烷基；B為85228 -97- 200404539 R: crtcR3 'N R4; Rl is hydrogen, alkyl, cyano, self-alkyl, 1¾ prime, nitro, (NZ3Z4) alkyl or (NZgZ4) carbonyl; heart and heart are hydrogen; r3 Is hydrogen or hydroxyl; z is crb, rb is hydrogen; ... is absent; d is -CH2-; L · is -C (0) N (R7)-; and R7 and ra are both as in formula (II) definition. In another specific embodiment of the present invention, the compound of formula (11) is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; B is

RitVR3 λ isT〜&amp;為氫 '烷基、氰基、鹵烷基、鹵素、硝基 烷基或（NZsZ4)羰基；R2與R4為氫；r3為氫或羥基；z為CRb ;為氫；…為不存在；D為_CH(CH3&gt; ; L為_c(〇)n(R7)_ ;及 R7與RA均如式（Π)中之定義。 於本發明之另一項具體實施例中，係揭示式（I〗）化合物， 其中A為芳基；b為 R1WR3 .... 、n R4 ，Z 為 C ,…為一個鍵結；L 為 _c(〇)n(R7)_ ;且 D、 Ri、R2、R3、R4、R7及RA均如式（η)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基，其中芳基為苯基，被〇、丨、23、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、芊基、氰基、南素、_烷氧基、自烷基、 亞甲二氧基、硝基、苯基或-NZ! Z2 ; B為 λ νΓ % , &amp;為氫、烷基、氰基、鹵烷基、鹵素、硝基、（ΝΖ&amp;) 85228 -98- 200404539 k基或(NZ3 Z4 )談基，1與R4為氫；R3為氫或經基；z為c; …為一個鍵結；D為-CH2-; L為-C(0)N(R7)-;及R7與RA均如式 (II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 坑基、燒硫基、芊基、氯基、鹵素、||燒氧基、齒垸基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為RitVR3 λ isT ~ &amp; is hydrogen 'alkyl, cyano, haloalkyl, halogen, nitroalkyl or (NZsZ4) carbonyl; R2 and R4 are hydrogen; r3 is hydrogen or hydroxyl; z is CRb; is hydrogen; ... is absent; D is _CH (CH3 &gt;; L is _c (〇) n (R7) _; and R7 and RA are as defined in formula (Π). In another specific embodiment of the present invention In the formula, a compound of formula (I) is disclosed, where A is aryl; b is R1WR3 ..., n R4, Z is C, ... is a bond; L is _c (〇) n (R7) _ And D, Ri, R2, R3, R4, R7, and RA are as defined in formula (η). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, where A is an aryl group; Where aryl is phenyl and substituted by 0, 丨, 23, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano Group, Nansu, alkoxy, alkyl, methylenedioxy, nitro, phenyl or -NZ! Z2; B is λ νΓ%, &amp; is hydrogen, alkyl, cyano, haloalkane Group, halogen, nitro, (NZ &amp;) 85228 -98- 200404539 k group or (NZ3 Z4) group, 1 and R4 are hydrogen; R3 Hydrogen or a radical; z is c; ... is a bond; D is -CH2-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (II). In another specific embodiment of the invention, the compound of the formula (II) is disclosed, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. Independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, pit, sulfanyl, fluorenyl, chloro, halogen, || alkoxy, haloyl, methylenedioxy, nitro, phenyl Or -NZiZ2; B is

^ Μ ; Ri為氫、烷基、氰基、1¾烷基、_素、硝基、（NZ3 Z4) 烷基或(NZ3Z4)羰基；以2與114為氫；R3為氫或羥基；z為C; …為一個鍵結，D為·CH(CH3)- ; L為-C(0)N(R7 )-;及R7與RA均 如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（II)化合物， 其中A為芳基，其中芳基為莕基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自晞基、烷氧基、烷氧羰基、 燒基、燒硫基、苄基、氰基、_素、_燒氧基、_燒基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為^ Μ; Ri is hydrogen, alkyl, cyano, 1¾ alkyl, 素 prime, nitro, (NZ3 Z4) alkyl or (NZ3Z4) carbonyl; 2 and 114 are hydrogen; R3 is hydrogen or hydroxyl; z is C; ... is a bond, D is · CH (CH3)-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (II) is disclosed, wherein A is an aryl group, wherein the aryl group is a fluorenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of fluorenyl, alkoxy, alkoxycarbonyl, alkynyl, thiol, benzyl, cyano, thiol, thiol, thiol, methylenedioxy, nitro, Phenyl or -NZiZ2; B is

^ n |'4 ; Ri為氫、烷基、氰基、鹵素、硝基、（NZ3Z4)燒 基或（NZ3Z4)羰基；R2、R3及r4為氳；Z為C ;…為一個鍵結 ，D為-CH2 - ; L為-C(0)N(R7)-;及R7與RA均如式（π)中之定義。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為芳基，其中芳基為莕基，被〇、1、2、3、4或5個 85228 -99- 200404539 取代基取代，取代基獨立選自缔基、垸氧基、燒氧談基 烷基、烷硫基、苄基、氰基、自素、齒烷氧基、_烷基 亞甲一乳基、硝基、苯基或-NZ! Z2 ; B為^ n | '4; Ri is hydrogen, alkyl, cyano, halogen, nitro, (NZ3Z4) alkyl or (NZ3Z4) carbonyl; R2, R3 and r4 are 氲; Z is C; ... is a bond, D is -CH2-; L is -C (0) N (R7)-; and R7 and RA are as defined in formula (π). In another specific embodiment of the present invention, the compound of formula (Π) is disclosed, wherein A is aryl, wherein aryl is fluorenyl, and is 0, 1, 2, 3, 4 or 5 85228 -99- 200404539 Substituted by substituents, the substituents are independently selected from the group consisting of alkenyl, fluorenyloxy, alkoxyalkyl, alkylthio, benzyl, cyano, autogen, alkoxy, and alkylmethylene-lactyl , Nitro, phenyl or -NZ! Z2; B is

RityRs \ N/ R4 ; &amp;為氫、烷基、氰基、自烷基、_素、硝基、 烷基或(NZSZ4)羰基；&amp;與&amp;為氫；心為氲或羥基；2為〇 …為一個键結；D為-CH(CH3)-; L為-C(0)N(R7)-;及心與、均 如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為芳基；Β為 ;Z為C ;…為一個鍵結；L為_c(〇)N(R7)_ ;且D、χ 、Y、R2、R3、R7及ra均如式（Π)中之定義。 於本發明之另一項具體實施例中，係揭示式（11)化合物， 其中A為芳基’其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、卣素、_烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZJ2 ; B為RityRs \ N / R4; &amp; is hydrogen, alkyl, cyano, self-alkyl, prime, nitro, alkyl, or (NZSZ4) carbonyl; &amp; and &amp; are hydrogen; heart is hydrazone or hydroxyl; Is 0 ... is a bond; D is -CH (CH3)-; L is -C (0) N (R7)-; and the meanings are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is an aryl group; B is; Z is C; ... is a bond; L is _c (〇) N (R7) _; And D, χ, Y, R2, R3, R7, and ra are as defined in formula (Π). In another specific embodiment of the present invention, a compound of formula (11) is disclosed, wherein A is aryl 'wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, alkoxy, _alkyl, methylenedioxy, nitro, Phenyl or -NZJ2; B is

;R2 與 R3 為氫；X 為 N(R6)、〇 或 S ; Y 為 N ; Z 為 C ; …為一個鍵結；D為-CH2 _ ; L為-C(0)N(R7)_ ;且、R7及RA均 如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（Π)化合物， 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個R2 and R3 are hydrogen; X is N (R6), 0, or S; Y is N; Z is C;… is a bond; D is -CH2_; L is -C (0) N (R7) _ And R7 and RA are as defined in formula (II). In another specific embodiment of the present invention, a compound of formula (Π) is disclosed, wherein A is aryl, wherein aryl is phenyl, and is 0, 1, 2, 3, 4, or 5

85228 100- 200404539 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、苄基、氰基、齒素、_烷氧基、_烷基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為85228 100- 200404539 Substituted by substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halide, alkoxy, alkyl Methyldioxy, nitro, phenyl or -NZiZ2; B is

R3 ; R2 與 R3 為氫；X 為 N(R6)、Ο或 S; Y 為 N; Z 為 C; …為一個鍵結；D 為-CH(CH3)-; L 為-C(0)N(R7)-;且 R6、117及 Ra 均如式（II)中之定義。 於本發明之另一項具體實施例中，係揭示式（π)化合物， 其中Α為環烷基；Β為R3; R2 and R3 are hydrogen; X is N (R6), 0 or S; Y is N; Z is C;… is a bond; D is -CH (CH3)-; L is -C (0) N (R7)-; and R6, 117 and Ra are as defined in formula (II). In another embodiment of the present invention, a compound of formula (π) is disclosed, wherein A is a cycloalkyl group; B is

、Ν ·、4 ; Z 為 C ;…為，個鍵結；L 為 _c(〇)N(R7)_ ;且 D、 &amp;、R2、R3、r4、1^7及RA均如式（π)中之定義。 於本發明之另一項具體實施例中，係揭示式⑼化合物， 其中Α為環烷基，其中環烷基為環己基或金鋼烷基；8為, N ·, 4; Z is C; ... is a bond; L is _c (〇) N (R7) _; and D, &amp;, R2, R3, r4, 1 ^ 7, and RA are as follows: (Π). In another specific embodiment of the present invention, the compound of formula (I) is disclosed, wherein A is a cycloalkyl group, wherein the cycloalkyl group is a cyclohexyl group or a gold steel alkyl group; 8 is

t，Ri為氫、烷基、氰基、_烷基、_素、硝基、⑼2^4) 燒基或(NZSZ4)羰基；R2與R4為氫； 火恭’ 2只氏4為氧；R3為氫或羥基；Z為C; ;Dg-CH2-; L為-C(0)N(R7)_;及心與、均如式 …為一個鍵結；D為-CH2-; L為 (Π)中之定義。 於本發明之另一項具體實施例中，t, Ri is hydrogen, alkyl, cyano, _alkyl, _, nitro, fluorene 2 ^ 4) alkyl or (NZSZ4) carbonyl; R2 and R4 are hydrogen; Huo Gong '2 only 4 is oxygen; R3 is hydrogen or hydroxyl; Z is C;; Dg-CH2-; L is -C (0) N (R7) _; and the heart and the same formula are a bond; D is -CH2-; L is (Π). In another specific embodiment of the present invention,

，R3為氨或複基；Z為C; 85228 -101- 200404539 ； D^-CH(CH3&gt;； L4-C(0)N(R7&gt;; ^R7#Ra„ 如式（II)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 1 台療性功能障礙之方法，纟包括對該哺乳動物投予治療 上有二文量之式①化合物，或其藥學上可接受之鹽、醋 '酿 版或可體藥物’且併用藥學上可接受之載劑。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 2療性功能障礙之方法，纟包括對該哺乳動物投予治療 有效K 2-(H[(3-甲基苯甲醯基）胺基]甲基}_4-六氯錢基） 氧㈣，或其藥學上可接受之鹽、醋、醯胺或前體藥 ’且併用藥學上可接受之載劑。 中t本發明m具體實施财，係關於—種在哺乳動物 :療丨生U早♦(万法，丨包括對該哺乳動物投予治療 二:量之式(1)化合物’或其藥學上可接受之鹽、酿、醯 胺或則體樂物，且併用磷酸二酯酶5抑制劑。 於^發明之另—項具體實施例中，係關於—種在哺乳動物 〇療陡功ι卜4ε〈万法，其包括對該哺乳動物投予治療 Μ效量之2·(Η[(3_甲基苯甲醮基)胺基]甲基Μ.六氫錢基） :祕氧化物，或其藥學上可接受之鹽、酿、醯胺或前體藥 ’且併用鱗fe二醋酶5抑制劑。 於^發明之另—項具體實施例中，係關於—種在喷乳動物 口療陡功犯障％《万法，其包括對該哺乳動物投予治療 上有效量之式（1)化合物’或其藥學上可接受之鹽、酿、醮 胺或前體藥物，且併用昝μ φ &gt; 汗用^上腺素能受體拮抗劑。 85228 -102- =明之另一項具體實施例中，係關於一種在哺乳動物 中=性功能障礙之方法，纟包括對㈣乳動物投予治療 =量之2譜甲基苯甲酸基)胺基]甲基}_4嫌 物疋1化物，或其藥學上可接受之鹽、酉旨、驢胺或前體藥 物，且併用腎上腺素能受體拮抗劑。 於么本發明之另—項具體實施例中，係關於—種在哺乳動物 療f力犯障礙（方法，其包括對該哺乳動物投予治療 上有式①化合物’或其藥學上可接受之鹽、酿、醯 胺或前體藥物，且併用多巴胺催動劑。 於本發明（另-項具體實施例中，係關於一種在哺乳動物 中口療η力Μ障礙（方法，纟包括對該哺乳動物投予治療 上有效量之2_(1_{[(3_甲基苯甲醯基）胺基]甲基卜4-六㈣淀基） 峨錠Ν_氧化物，或其藥學上可接受之鹽、酉旨、醯胺或前體藥 物’且併用多巴胺催動劑。 於本發明之另-項具體實施例中，係關於一種在男性人類 中’口療男性勃起功能障礙之方法，其包括對需要此種治療 之男性人類投予治療上有效量之式①化合物，或其藥學上 可接文之鹽、酯、醯胺或前體藥物，且併用藥學上可接受 之載劑。 於本發明之另一項具體實施例中，係關於一種在男性人類 中治療男性勃起功能障礙之方法，其包括對需要此種治療 之男性人類投予治療上有效量之2_(1_{[(3呷基苯甲醯基）胺基] 甲基氫ϋ比淀基）峨鉸％氧化物，或其藥學上可接受之鹽 、酯、縫胺或前體藥物，且併用藥學上可接受之載劑。 85228 -103- 200404539 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中’口療男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之式①化合物，或其藥學上可接受之鹽、 酉旨、酿胺或前體藥物，且併用磷酸二酯酶5抑制劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療男性勃起功能障礙之方法，其包括對該哺乳動物投 予’口療上有效量之2-(1-{[(3-甲基苯甲醯基）胺基]甲基卜4-六氫 吡哫基）吡錠N-氧化物，或其藥學上可接受之鹽、酯、醯胺 或前體藥物，且併用磷酸二酯酶5抑制劑。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之式①化合物，或其藥學上可接受之鹽、 酯、醯胺或前體藥物’且併用腎上腺素能受體拮抗劑。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治燎男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之2-(H[(3-甲基苯甲醯基）胺基]甲基}_4_六氫 吡：基)吡錠N_氧化物’或其藥學上可接受之鹽、酯、醯胺 或前體藥物，且併用腎上腺素能受體拮抗劑。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之式①化合物，或其藥學上可接受之鹽、 酯、醯胺或前體藥物，且併用多巴胺催動劑。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療男性勃起功能障礙之方法，其包括舞該哺乳動物投 24.1. 85228 -104- 200404539 予治療上有效量之2-(H㈣基苯㈣基）胺基]甲基六氣 吡呢基风錠N-氧化物，或其藥學上可接受之鹽、醋、酿胺 或前體藥物，且併用多巴胺催動劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法’ #包括對需要此種治療之 哺乳動物投予治療上有效量之式①化合物，或其藥學上可 接受之鹽、酯、醯胺或前體藥物，且併用藥學上可接受之 載劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，#包括對需要此種治療之 哺乳動物投予治療上有效量之2_(1_{[(3_甲基苯甲酿基)胺基]甲 基}-4-六氫吡啶基）吡錠N_氧化物，或其藥學上可接受之鹽、 酯、醯胺或前體藥物，且併用藥學上可接受之載劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之式（I)化合物，或其藥學上可接受之鹽、酯 、酸胺或前體藥物，且併用磷酸二酯酶5抑制劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中/口療女性性功能障礙之方法’其包括對該哺乳動物投予 冶療上有效量之2-(1_{[(3-甲基苯甲醯基）胺基]甲基卜孓六氫吡 咬基）峨錠N-氧化物，或其藥學上可接受之鹽、酯、醯胺或 前體藥物，且併用磷酸二酯酶5抑制劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 85228 -105- 200404539 治療上有效量之式（I)化合物，或其藥學上可接受之鹽、酯 、醯胺或前體藥物，且併用腎上腺素能受體拮抗劑。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之2-(1-{[(3-甲基苯甲醯基）胺基]甲基}斗六氫吡 啶基）吡錠N-氧化物，或其藥學上可接受之鹽、酯、醯胺或 前體藥物，且併用腎上腺素能受體拮抗劑。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之式（I)化合物，或其藥學上可接受之鹽、酯 、醒胺或前體藥物，且併用多巴胺催動劑。 於本發明之另一項具體實施例中’係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之2-(1-{[(3-甲基苯甲醯基）胺基]甲基}斗六氫吡 啶基）吡錠N-氧化物，或其藥學上可接受之鹽、酯、醯胺或 前體藥物，且併用多巴胺催動劑。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中^療病症之方法，其中病症為心與血管病症、炎性病症 、注意力不足活動過度病症、阿耳滋海默氏疾病、藥物濫 用、巴金生氏病、精神分裂症、焦慮、心情病症或抑鬱， 其包括對需要此種治療之哺乳動物投予治療上有效量之式① 化合物，或其藥學上可接受之鹽、酯、醯胺或前體藥物。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療病症之方法，其中病症為心與血管病症、炎性病症 85228 -106- 200404539 、注意力不足活動過度病症、阿耳滋海默氏疾病、藥物ί監 用、巴金生氏病、精神分裂症、焦慮、心情病症或抑鬱， 其包括對需要此種治療之哺乳動物投予治療上有效量之2-(1-{[(3-甲基苯甲醯基）胺基]甲基}-4-六氫吡啶基）吡錠N-氧化物， 或其藥學上可接受之鹽、酯、酿胺或前體藥物。 於本發明之另一項具體實施例中，係關於式（III)化合物, R3 is ammonia or complex; Z is C; 85228 -101- 200404539; D ^ -CH (CH3 &gt;; L4-C (0) N (R7 &gt;; ^ R7 # Ra „as defined in formula (II) In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula ① which has a dichotomous amount, or a pharmacy The acceptable salt, vinegar is a "vintage" or a potable drug, and a pharmaceutically acceptable carrier is used. In another specific embodiment of the present invention, it relates to a kind of therapeutic dysfunction in mammals. A method comprising the step of administering to the mammal a therapeutically effective K 2- (H [(3-methylbenzylidene) amino] methyl} _4-hexachlorobenzyl) oxine, or a pharmaceutically acceptable Salt, vinegar, ammonium, or prodrugs, and use a pharmaceutically acceptable carrier. The invention is specifically implemented in terms of-a species in mammals: treatment 丨 health U early ♦ (wanfa, 丨This includes administering to the mammal a therapeutic amount 2: a quantity of a compound of formula (1) 'or a pharmaceutically acceptable salt, ferment, ammonium, or amusement, and a phosphodiesterase 5 inhibitor In another specific embodiment of the invention, it relates to a kind of treatment of mammals in mammals. 4ε <10,000 methods, which includes administering 2 · (Η [(3 _Methyl benzamidine) amine] methyl M. hexahydrobenzyl): a secret oxide, or a pharmaceutically acceptable salt, alcohol, amidine, or prodrug thereof, and used in combination 5. Inhibitor. In another specific embodiment of the invention, it relates to a method of dysfunction in oral therapy of sprayed animals. The method includes administration of a therapeutically effective amount to the mammal ( 1) Compound 'or a pharmaceutically acceptable salt, alcohol, ammonium or prodrug thereof, and a combination of 昝 μφ &gt; adrenergic receptor antagonist for sweat. 85228 -102- = another item of the Ming In a specific embodiment, it relates to a method of = sexual dysfunction in mammals, which includes administering treatment to a milk animal = amount of 2-spectrum methylbenzoate) amino] methyl} _4 suspects1 Compound, or a pharmaceutically acceptable salt, formula, donkey amine, or prodrug thereof, and an adrenergic receptor antagonist is used in combination. In an embodiment, the present invention relates to a method for treating dysfunction disorder in a mammal (method, which comprises administering to the mammal a compound of formula ① or a pharmaceutically acceptable salt, ferment, amidine or precursor thereof). And a dopamine activator. In the present invention (another specific embodiment, it relates to a method for orally treating a dysfunction disorder in a mammal (method, which includes administering to the mammal a therapeutically effective amount of 2_ (1 _ {[(3_methylbenzylidene) amino] methylbull 4-hexafluorenyl) eodonium N_ oxide, or a pharmaceutically acceptable salt, hydrazone, amidine or Prodrugs and dopamine agonists. In another embodiment of the present invention, it relates to a method of "orally treating male erectile dysfunction" in male humans, which includes treating male humans in need of such treatment. A therapeutically effective amount of a compound of formula (1), or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, is administered in combination with a pharmaceutically acceptable carrier. In another specific embodiment of the present invention, it relates to a method for treating male erectile dysfunction in male humans, which comprises administering a therapeutically effective amount of 2_ (1 _ {[( 3 fluorenyl benzamidine) amine group] methyl hydrogen sulfonium group) eganyl oxide, or a pharmaceutically acceptable salt, ester, ammonium or prodrug thereof, and a pharmaceutically acceptable Vehicle. 85228 -103- 200404539 In another embodiment of the present invention, a method of "orally treating male erectile dysfunction" in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula ① Or a pharmaceutically acceptable salt, formula, amine or prodrug thereof, and a phosphodiesterase 5 inhibitor is used in combination. In another specific embodiment of the present invention, it relates to a method for treating male erectile dysfunction in a mammal, which comprises administering to the mammal an effective amount of 2- (1-{[( 3-methylbenzyl) amine] methyl] 4-hexahydropyridyl) pyridine N-oxide, or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and used in combination Phosphodiesterase 5 inhibitor. In another embodiment of the present invention, a method for treating male erectile dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable compound thereof. Accept salts, esters, amidines or prodrugs' and use adrenergic receptor antagonists. In another embodiment of the present invention, a method for treating male erectile dysfunction in a mammal includes administering to the mammal a therapeutically effective amount of 2- (H [(3- Methyl benzamidine) amino] methyl} -4_hexahydropyridine: yl) pyridine N_oxide 'or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and epinephrine Receptor antagonist. In another embodiment of the present invention, a method for treating male erectile dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable compound thereof. Accepted salts, esters, amidines or prodrugs with dopamine agonists. In another specific embodiment of the present invention, it relates to a method for treating male erectile dysfunction in a mammal, which comprises dancing the mammal to a 24.1. 85228 -104- 200404539 to a therapeutically effective amount of 2- (H-Hydroxyphenylfluorenyl) amino] methylhexapirfenyl wind tablet N-oxide, or a pharmaceutically acceptable salt, vinegar, amine or prodrug thereof, and combined with a dopamine activator. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal '# comprising administering a therapeutically effective amount of a compound of formula ① to a mammal in need of such treatment, or A pharmaceutically acceptable salt, ester, amidine or prodrug, and a pharmaceutically acceptable carrier. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal. #Include a therapeutically effective amount of 2_ (1 _ {[( 3-methylbenzyl) amino] methyl} -4-hexahydropyridyl) pyridine N_oxide, or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and used in combination Pharmaceutically acceptable carrier. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable compound thereof. Acceptable salts, esters, acid amines or prodrugs, and combined with phosphodiesterase 5 inhibitors. In another embodiment of the present invention, it relates to a method of treating female sexual dysfunction in a mammal / orally, which comprises administering to the mammal an effective amount of 2- (1 _ {[( 3-methylbenzylidene) amino] methylbuxahydropyridyl) eolide N-oxide, or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and phosphoric acid Diesterase 5 inhibitor. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal, which comprises administering a therapeutically effective amount of a compound of formula (I) to the mammal in 85228-105-200404539. Or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and combined with an adrenergic receptor antagonist. In another embodiment of the present invention, a method for treating female sexual dysfunction in a mammal includes administering to the mammal a therapeutically effective amount of 2- (1-{[((3- Methyl benzamidine) amino] methyl} hexahydropyridyl) pyridine N-oxide, or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and combined with epinephrine Body antagonist. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable compound thereof. Acceptable salts, esters, amines, or prodrugs with dopamine agonists. In another embodiment of the present invention, it is a method for treating female sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of 2- (1-{[((3- Methyl benzamidine) amino] methyl} hexahydropyridyl) pyridine N-oxide, or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, and a dopamine agonist . In another specific embodiment of the present invention, the invention relates to a method for treating a disease in a mammal, wherein the disease is a heart and blood vessel disease, an inflammatory disease, a hyperattention disorder, and Alzheimer's disease. Disease, drug abuse, Parkinson's disease, schizophrenia, anxiety, mood disorder or depression, which includes administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable salt thereof , Esters, amidines or prodrugs. In another specific embodiment of the present invention, it relates to a method for treating a disorder in a mammal, wherein the disorder is a cardiac and vascular disorder, an inflammatory disorder 85228-106-200404539, a hyperattention disorder, Aer Ziheimer's disease, drug supervision, Parkinson's disease, schizophrenia, anxiety, mood disorder, or depression, which include administering a therapeutically effective amount of 2- (1- { [(3-methylbenzylidene) amino] methyl} -4-hexahydropyridyl) pyridine N-oxide, or a pharmaceutically acceptable salt, ester, amine or prodrug thereof. In another specific embodiment of the present invention, it relates to a compound of formula (III)

(III)(III)

或其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 Xi為一個鍵結或CRBRc ; X2為一個键結或CRd Re ; 其條件是，當Xi為一個鍵結時，則x2為crdre ; 進一步條件是，當x2為一個键結時，則Xi為CRBRc ; A為芳基、芳烷基、環烷基或環烷基烷基； 1^為-风117)(：(0)-、-C(0)N(R7)-、-N(R7)C(S)-或-C(S)N(R7)_，其 中-N(R7)C(0)-、-C(0)N(R7)-、-N(R7)C(S)-及-C(S)N(R7)-之左端係 連接至A，而右端係連接至D ; 乙2為一個鍵結或次烷基； D為次烷基、氟次烷基或羥基次烷基； RA、RB、Rc、RD及心係獨立為氫或烷基； B為 85228 107 _ 200404539Or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, wherein Xi is a bond or CRBRc; X2 is a bond or CRd Re; provided that when Xi is a bond, then x2 Is crdre; further condition is that when x2 is a bond, then Xi is CRBRc; A is aryl, aralkyl, cycloalkyl, or cycloalkylalkyl; 1 ^ is -wind 117) (: (0 )-, -C (0) N (R7)-, -N (R7) C (S)-or -C (S) N (R7) _, where -N (R7) C (0)-, -C (0) The left end of N (R7)-, -N (R7) C (S)-and -C (S) N (R7)-is connected to A, and the right end is connected to D; B 2 is a bond Or alkylene; D is alkylene, fluoroalkylene or hydroxyalkylene; RA, RB, Rc, RD and the heart are independently hydrogen or alkyl; B is 85228 107 _ 200404539

&amp;、R2、R3及R4各獨立為氫、烷氧基、烯基、烷基、烷基 亞磺醯基、烷基磺醯基、烷硫基、炔基、烷氧羰基、烷羰 基、烷羰基氧基、羧基、氰基、甲醯基、鹵素、鹵烷氧基 _ 、鹵燒基、經基、輕燒基、銳基、硝基、-NZ! Z2、（NZ3 Z4)燒 基、（NZ3Z4)羰基或（NZ3Z4)續醯基；21與22各獨立為氫、烷基 、烷羰基、烷基磺醯基、芳基、芳烷基、芳烷基磺醯基、 芳基續S盛基或甲醯基； Z3與z4各獨立為氫、烷基、芳基或芳烷基； X 為 N(R6)、0 或 S ; Y 為 C(R4)或 N ; 心為氫或燒基；及 0 R7為氫或燒基。 於本發明之另一項具體實施例中，係關於式（111)化合物， 其中A為芳基；B為 ?2 RW3 'N R4 ; Xi*CRbRc ; X^CRdRe ; L為娜7)⑽；且L2 士D、Rl、R2、r3、ι、R7、Ra、Rb、&amp;、RrRe均如式 中之定義。 於本發明之另-項具體實施例中，係關於式⑽化合物， 85228 -108- 200404539 其中A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代’取代基獨立選自烯基、烷氧基、烷氧羧基、 少元基、燒硫基、卞基、氣基、卣素、_燒氧基、_燒基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 ?2 R1\^WR3 \ n R4，Ri為鼠、纟元基、氣基、1¾ fe基、_素、硝基、Z4) 燒基或(ΝΖ3 Ζ4)衆基，R2與R4為氮；R3為氫或藉基；&amp;為心 ;Xz為CRD RE ; D為-CH2 - ; L2為一個鍵結；且匕為啊心抑办 •’及 ra、Rb、Rc、rd、Re、Ri、R2、R3、R4 及 r7 均如式（即 中之定義。 於本發明之另一項具體實施例中，係關於式（ΠΙ)化合物， 其中Α為方基’其中方基為冬基’被〇、1、2、3、4或5個 取代基取代，取代基獨立選自杯基、燒氧基、燒氧羰基、 燒基、娱:硫基、爷基、氰基、S素、1¾燒氧基、自燒基、 亞甲二氧基、硝基、苯基或-NZiZ? ; B為 ?2 R1^Y^y^R3 \ nT R4 ; Rq為氫、燒基、氰基、鹵燒基、_素、硝基、βζ3 Z4) 燒基或(NZ3Z4)羧基；&amp;與R4為氫；&amp;為氫或幾基；Xig ci^I^ ;X2 為 CRDRE ; D 為-CH2- ; L2 為一個鍵結；且 L g_N(R7)C(0)_ ;&amp;Ra、RB、RC、RD、RE 及 R7 為氫。 於本發明之另一項具體實施例中，係關於式（ΠΙ)化合物， 其中Α為雜環；Β為&amp;, R2, R3 and R4 are each independently hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkoxycarbonyl, alkylcarbonyl, Alkylcarbonyloxy, carboxyl, cyano, methylamidino, halogen, haloalkoxy, haloalkyl, meridian, light alkyl, sharp, nitro, -NZ! Z2, (NZ3 Z4) alkyl , (NZ3Z4) carbonyl or (NZ3Z4) continyl; 21 and 22 are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, aralkyl, aralkylsulfonyl, aryl S Sheng group or formyl group; Z3 and z4 are each independently hydrogen, alkyl, aryl or aralkyl group; X is N (R6), 0 or S; Y is C (R4) or N; heart is hydrogen or Alkyl; and R 7 is hydrogen or alkyl. In another specific embodiment of the present invention, it is a compound of formula (111), wherein A is an aryl group; B is? 2 RW3'N R4; Xi * CRbRc; X ^ CRdRe; L is Na 7) ⑽; And L2, D1, R1, R2, r3, ι, R7, Ra, Rb, &amp;, RrRe are as defined in the formula. In another specific embodiment of the present invention, it is a compound of formula VIII, 85228 -108- 200404539 where A is aryl, wherein aryl is phenyl, and is substituted by 0, 1, 2, 3, 4 or 5 Substituents are independently selected from the group consisting of alkenyl, alkoxy, alkoxycarboxyl, minor groups, thiol, fluorenyl, alkyl, halogen, alkynyl, alkynyl, methylenedioxy , Nitro, phenyl, or -NZiZ2; B is? 2 R1 \ ^ WR3 \ n R4, Ri is murine, fluorenyl, carbyl, 1¾ fe, nitro, nitro, Z4) alkyl or (NRZ3) Zn4) alkene, R2 and R4 are nitrogen; R3 is hydrogen or borrowed group; &amp; is heart; Xz is CRD RE; D is -CH2-; L2 is a bond; ra, Rb, Rc, rd, Re, Ri, R2, R3, R4, and r7 are all as defined in the formula (i.e., in another specific embodiment of the present invention, it relates to a compound of formula (III), where A Is a square group 'where the square group is winteryl' is substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from calixyl, alkoxy, alkoxycarbonyl, alkynyl, sulfur: sulfur Base, ethynyl, cyano, S element, 1⁄2-alkyloxy, self-alkylated, methylene Oxy, nitro, phenyl, or -NZiZ ?; B is? 2 R1 ^ Y ^ y ^ R3 \ nT R4; Rq is hydrogen, alkynyl, cyano, haloalkyl, _ prime, nitro, βζ3 Z4 ) Alkyl or (NZ3Z4) carboxyl; &amp; and R4 are hydrogen; &amp; is hydrogen or several groups; Xig ci ^ I ^; X2 is CRDRE; D is -CH2-; L2 is a bond; and L g_N ( R7) C (0) _; &amp; Ra, RB, RC, RD, RE and R7 are hydrogen. In another specific embodiment of the present invention, it relates to a compound of formula (II), wherein A is a heterocyclic ring; B is

，Χι 為 CRB ，X〗為 CR〇 Re，L 為-N(R7 )C(0)-;且 D、, Xι is CRB, X is CR〇Re, L is -N (R7) C (0)-; and D,

85228 -109- 200404539 l2、x、γ、ra、rb、κ、Rd、Re、r2、&amp; 及 R?均如式⑽ 中之定義。 於本發明之另一項具體實施例中，係關於式（III)化合物， 其中A為雜環，其中雜環為苯并咪唑基、苯并嘧唑基、呋喃 基、咪唑基、1，3-噚唑基、吡畊基、吡唑基、嗒畊基、吡啶 基、喊淀基、咐哈基、1，3_ p塞峻基或魂吩基，其中雜環係被 2或3個取代基取代，取代基獨立選自燒氧基、燒氧 叛基、烷基、氰基、_素、_燒氧基、_燒基或硝基；B為85228 -109- 200404539 l2, x, γ, ra, rb, κ, Rd, Re, r2, &amp; and R? Are as defined in formula ⑽. In another specific embodiment of the present invention, it relates to the compound of formula (III), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, furanyl, imidazolyl, 1, 3 -Oxazolyl, pyridyl, pyrazolyl, daphyl, pyridyl, oxidyl, halkydyl, 1,3-pyridyl, or phenoxy, wherein the heterocyclic system is substituted by 2 or 3 Substituent, the substituent is independently selected from alkoxy, alkoxy, alkyl, cyano, _ prime, _oxy, _ or nitro; B is

&amp;與R3為氫；為CRB Rc ; X2為CRD RE ; X為风化) 〇 或 S，Y 為 N; D 為-CH2- ; L2 為一個鍵結；l 為-N(R7)C(0)- ，且 Ra、Rb、Rc、Rd、Re、r2、R3&amp;R7為氫；及心為氩或 燒基’其中較佳燒基為甲基。 於本發明之另一項具體實施例中，係關於式（in)化合物， 其中A為雜環，其中雜環為苯并咪唑基，被丨個烷基取代基 取代’其中較佳烷基取代基為甲基；B為&amp; is hydrogen with R3; is CRB Rc; X2 is CRD RE; X is weathering) 〇 or S, Y is N; D is -CH2-; L2 is a bond; l is -N (R7) C (0 )-, And Ra, Rb, Rc, Rd, Re, r2, R3 &amp; R7 are hydrogen; and the center is argon or an alkyl group, wherein the preferred alkyl group is methyl. In another specific embodiment of the present invention, it relates to a compound of formula (in), wherein A is a heterocyclic ring, wherein the heterocyclic ring is a benzimidazolyl group, which is substituted by one alkyl substituent, among which the preferred alkyl group is substituted. Is methyl; B is

R2與 R3為氫；XACRbRc ; X2為 CRdre ; X 為 n(R6) 、0或 S,Y 為n,D 為-CH2 - ; L2 為一個鍵結；l 為-N(R7)c(〇) ，及 Ra、Rb、Rc、Rd、Re、r2、R3 及 R7 為氫；及 為氫或 烷基，其中較佳烷基為甲基。 於本發明之另一項具體實施例中，係關於式（111)化合物， 其中A為芳基；B為 85228 -110- 200404539R2 and R3 are hydrogen; XACRbRc; X2 is CRdre; X is n (R6), 0 or S, Y is n, D is -CH2-; L2 is a bond; l is -N (R7) c (〇) And Ra, Rb, Rc, Rd, Re, r2, R3, and R7 are hydrogen; and are hydrogen or an alkyl group, with a preferred alkyl group being a methyl group. In another specific embodiment of the present invention, it is a compound of formula (111), wherein A is aryl; B is 85228 -110- 200404539.

4，Xi 為一個鍵結；χ2 為 CRdRe ; L 為 _N%)c(〇)_; 且 L2、D、Rl、R2、R3、R4、&amp;、Ra、％、&amp;、知及％ 均如 式（III)中之定義。 於本發明之另-項具體實施例中，係關於式⑽化合物， 其中A為芳基’其中芳基為苯基，被〇、1、2、3、4或5個 I代基取代’取Μ獨立選㈣基、燒氧 、 燒基、燒硫基、宇基、氨基、函素、自燒氧基、：燒基、 亞甲二氧基、硝基苯基或-ΝΖ! Ζ2 ; Β為4, Xi is a bond; χ2 is CRdRe; L is _N%) c (〇) _; and L2, D, R1, R2, R3, R4, &amp;, Ra,%, &amp; Both are as defined in formula (III). In another specific embodiment of the present invention, it relates to a compound of formula (I), where A is aryl ', where aryl is phenyl, and substituted with 0, 1, 2, 3, 4 or 5 I groups. Μ Independently selected fluorenyl, oxo, oxo, thio, yl, amino, halo, self-oxyl, alkynyl, methylenedioxy, nitrophenyl, or -NZ! Zn2; Β for

為氫、燒基、氰基、自燒基、_素、確基、购&amp; 烷基或(ΝΖβ4)羰基；心與心為氫；心為氫或羥基；&amp;為一個 鍵結；Χ2為CRDRE ; D為-Ch2_ ; L2為一個鍵結；l為_Ν⑻剛-，及Ry、RA、RD及RE均如式（ΠΙ)中之定義。 於本發明之另-項具體實施例中，係關於式（m)化合物， 其中A為芳基，其中芳基為苯基，被〇、 、2、3、4或 5 個 取代基取代，取代基獨立選自烯基、、卢^ β 砭虱基、烷氧羰基、 烷基、烷硫基、苄基、氰基、！i素、鹵 口化乳基、lS燒基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 為氫、燒基、氰基、齒燒基、自素、硝基、㈣⑻ 烷基或(ΝΖΘ4)羰基；R2與R4為氫；R3為氫或羥基；&amp;為一個 鍵結；X2為 CRDRE ; D 為 _CH2- ·, L2為一個鍵結；L 為 _N(R7)c(〇)_ ，及 R7、Ra、Rd 及 Re 為戴i。 85228 -111- 200404539 於本發明之另一項具體實施例中，係關於式（m)化合物， 其中A為雜環；b為Is hydrogen, alkyl, cyano, self-alkyl, thiol, alkoxy, alkoxy or (NZβ4) carbonyl; heart and heart are hydrogen; heart is hydrogen or hydroxyl; &amp; is a bond; X2 Is CRDRE; D is -Ch2_; L2 is a bond; l is _Ν⑻ 刚-, and Ry, RA, RD, and RE are as defined in formula (II). In another specific embodiment of the present invention, it relates to a compound of formula (m), wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 2, 2, 3, 4, or 5 substituents. The group is independently selected from the group consisting of alkenyl, β, β-alkynyl, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, and! I, halogenated lactyl, 1S alkyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B is hydrogen, alkyl, cyano, oxal, sulfonium, nitro, fluorene Alkyl or (NZΘ4) carbonyl; R2 and R4 are hydrogen; R3 is hydrogen or hydroxyl; &amp; is a bond; X2 is CRDRE; D is _CH2- ·, L2 is a bond; L is _N (R7 ) c (〇) _, and R7, Ra, Rd and Re are Dai i. 85228 -111- 200404539 In another specific embodiment of the present invention, it relates to the compound of formula (m), wherein A is a heterocyclic ring; b is

;Χι 為一個键結；X2 為 CRDRE ; L 為 _n(R7)C(0)-;且 D、L2、X、γ、Ra、R〇、Re、r2、r3 及 r7 均如式（m)中之定 義。 於本發明之另一項具體實施例中，係關於式（ΙΙΙ)化合物， 其中Α為雜環，其中雜環為苯并咪唑基、苯并嘧唑基、呋喃 基、咪唆基、1，3_巧唑基、吡畊基、吡唑基、嗒畊基、吡啶 基、喊淀基、吡咯基、1，3_嘍唑基或嘧吩基，其中雜環係被 〇、1、2或3個取代基取代，取代基獨立選自烷氧基、烷氧 羰基、烷基、氰基、_素、_烷氧基、！|烷基或硝基；B為; Xι is a bond; X2 is CRDRE; L is _n (R7) C (0)-; and D, L2, X, γ, Ra, R0, Re, r2, r3, and r7 are as follows (m ). In another specific embodiment of the present invention, it relates to a compound of formula (III), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidazolyl, benzimidazolyl, furanyl, imidino, 1, 3-Azozolyl, pyrimilyl, pyrazolyl, daxylyl, pyridyl, alkyl, pyrrolyl, 1,3-oxazolyl or pyrenyl, in which the heterocyclic system is 0,1,2 Or 3 substituents, the substituent is independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, _ prime, _ alkoxy,! | Alkyl or nitro; B is

R3 3，R2與R3為氫；Xi為一個鍵結；χ2為CRdRe ; χ為n(r6) 〇或 s，Y為 n, D 為-CH2- ; l2為一個鍵結；l 為-N(R7)c(〇)_ ，及心、Ra、Rd、Re及R?均如式（ΙΠ)中之定義。 於本發明之另一項具體貫施例中，係關於式（III)化合物， 其中A為雜環，其中雜環為苯并咪峻基，被1㈣基取代基 取代，其中較佳烷基取代基為甲基；6為R3 3, R2 and R3 are hydrogen; Xi is a bond; χ2 is CRdRe; χ is n (r6) 〇 or s, Y is n, D is -CH2-; l2 is a bond; l is -N ( R7) c (〇) _, and Xin, Ra, Rd, Re, and R? Are as defined in formula (II). In another specific embodiment of the present invention, it relates to a compound of formula (III), wherein A is a heterocyclic ring, wherein the heterocyclic ring is a benzimidyl group, which is substituted by a 1 fluorenyl substituent, and preferably an alkyl group is substituted. Is methyl; 6 is

R2兵R3為氫，—個鍵結；&amp;為CRdRe; χ為琢6) 或 Y 為 N，D 為-CHr; L2 為一個鍵結；L 為 _n(r7)c(0)_ ;且〜、Rd、〜及〜為氫；及\為氫或燒基，其中較佳燒 基為甲基。R2 and R3 are hydrogen, a bond; &amp; is CRdRe; χ is Zhu 6) or Y is N, D is -CHr; L2 is a bond; L is _n (r7) c (0) _; And ~, Rd, ~, and ~ are hydrogen; and \ is hydrogen or an alkyl group, and a preferred alkyl group is methyl.

85228 -112- 20040453985228 -112- 200404539

於本發明之另-項具體實施例中，係關於式⑽化合物， 其中A為芳基；b為 rC Xl為一個鍵結；x^CRdRe; L為-n(R7)c(〇)_;且 D、L2、X、Y、RA、RD、Rp、R、p 芬 D A E 2心及心均如式（ΙΠ)中之定 義。 於本發明之另-項具體實施例中，係關於式㈣化合物， 其中A為芳基，其中芳基為苯基，被〇、丨、2、3、4或5個 取代基取代，取代基獨立選㈣基]完氧基、減談基、 垸基、燒硫基、爷基、氰基、自素、商燒氧基、商燒基、 亞甲一氧基、硝基、苯基或-ΝΖ! Z2 ; B為 F A R3 ; R2與R3為氫；Xl為一個鍵結；&amp;為CRdRe ; X為啊) 、〇或S; 丫為哪）；D為.CH2·; l2為一個鍵結；L為學)c(〇)_ ;R4為氫、烷基或氰基；及〜、Ra、Rd、Re、〜及心均如 式（ΠΙ)中之定義。 於本孓明之另一項具體貫施例中，係關於式贝1)化合物， 其中A為芳基，其中芳基為苯基，被〇、丨、2、3、4或5個 取代基取代，取代基獨立選自烯基、烷氧基、烷氧羰基、 烷基、烷硫基、芊基、氰基、_素、_烷氧基、鹵烷基、 亞甲二氧基、硝基、苯基或-NZiZ2 ; B為 入、3，匕與&amp;為氫；χι為一個鍵結；x2為CRdRe ; X為N(r6) 、〇或s; Y為C(R4); D為码L2為一個鍵結；[為以㈣哪-85228 -113- 200404539 I及R7為氫；及心 L 為-N(R7)C(0)-; Rb及Rc均如式（ΙΠ) ;為氫、烷基或氰基；Ra、Rd、％ 為氫或fe基’其中較佳燒基為甲基。 係關於式（III)化合物， 於本發明之另一項具體實施例中 其中A為芳基；B為 ，Xi為CRb R〇 ; X2為一個鍵結 且 L2、D、· Rl、r2、&amp;、r4、Rs、R?、~ 中之定義。 於本發明之另-項具體實施例中，係關於式⑽化合物， 其中A為芳基，其中芳基為苯基，被〇、丄、2、3、4或5個 取代基取代，取代基獨立選自缔基、燒氧基、垸氧㈣、 燒基、燒硫基、爷基、氰基、_素、南燒氧基、Μ基、 亞甲一氧基、硝基、苯基或-ΝΖ〗Ζ2 ; Β為 R5 ; R1、R2、R3、R4 及 R5 為氫；X^CRbRc ; &amp; 為 一個鍵結；D 為-CH2_ ; L2為-CH2_ ; L 為 _N(R7)C(0)-;且 rb、&amp; 及R7均如式（III)中之定義。 於本發明之另一項具體實施例中，係關於式（in)化合物， 其中A為芳基，其中芳基為苯基，被0、i、2、3、4或5個 取代基取代，取代基獨立選自細基、燒氧基、燒氧殽基、 燒基、燒硫基、苹基、氰基、_素、_燒氧基、充基、 亞甲二氧基、硝基、苯基或-ΝΖΘ2 ; B為 85228 -114- 200404539In another specific embodiment of the present invention, it is a compound of formula (I), wherein A is an aryl group; b is rC Xl is a bond; x ^ CRdRe; L is -n (R7) c (〇) _; In addition, D, L2, X, Y, RA, RD, Rp, R, p, DAE 2 and the heart are as defined in formula (II). In another specific embodiment of the present invention, it relates to a compound of formula (I), wherein A is aryl, wherein aryl is phenyl, substituted with 0, 丨, 2, 3, 4, or 5 substituents. Independently selected fluorenyl] alkoxy, thiol, fluorenyl, sulfanyl, hexyl, cyano, autogen, sulfonyl, sulfonyl, methylene monooxy, nitro, phenyl, or -NZ! Z2; B is FA R3; R2 and R3 are hydrogen; X1 is a bond; &amp; is CRdRe; X is ah), 0 or S; where is ya); D is .CH2 ·; l2 is a Bonding; L is the science) c (〇) _; R4 is hydrogen, alkyl or cyano; and ~, Ra, Rd, Re, ~ and Xin are as defined in formula (II). In another specific embodiment of the present invention, it is a compound of formula 1), wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 丨, 2, 3, 4, or 5 substituents. The substituent is independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, glucone, alkoxy, haloalkyl, methylenedioxy, nitro , Phenyl, or -NZiZ2; B is 3, 3, and D & is hydrogen; χι is a bond; x2 is CRdRe; X is N (r6), 0 or s; Y is C (R4); D is Code L2 is a bond; [Let's take which-85228-113-200404539 I and R7 are hydrogen; and the heart L is -N (R7) C (0)-; Rb and Rc are as shown in formula (IΠ); Hydrogen, alkyl, or cyano; Ra, Rd,% are hydrogen or fe ', and the preferred alkyl is methyl. Refers to the compound of formula (III), in another specific embodiment of the present invention, wherein A is aryl; B is, Xi is CRb R0; X2 is a bond and L2, D, · Rl, r2, &amp;, R4, Rs, R ?, ~. In another specific embodiment of the present invention, it relates to a compound of formula (I), wherein A is an aryl group, wherein aryl is a phenyl group, and is substituted with 0, 丄, 2, 3, 4, or 5 substituents. Independently selected from the group consisting of alkenyl, alkoxy, alkoxy, sulfonyl, sulfanyl, hexyl, cyano, hydrogen, sulfanyl, M, methyleneoxy, nitro, phenyl, or -ΝZ〗 Z2; B is R5; R1, R2, R3, R4 and R5 are hydrogen; X ^ CRbRc; &amp; is a bond; D is -CH2_; L2 is -CH2_; L is _N (R7) C (0)-; and rb, &amp; and R7 are as defined in formula (III). In another specific embodiment of the present invention, it relates to a compound of formula (in), wherein A is aryl, wherein aryl is phenyl, and is substituted by 0, i, 2, 3, 4, or 5 substituents. The substituent is independently selected from the group consisting of fine group, alkoxy group, alkoxy group, alkoxy group, thio group, pyridyl group, cyano group, thiol, thiol group, filling group, methylenedioxy group, nitro group, Phenyl or -NZΘ2; B is 85228 -114- 200404539

，Ri、R2、R3、R4 及 R5 為氣，Χι 為 CRb R〇，X2 為 一個键結；D 為-CH2_ ; L2S -CH2- ; L 為 _N(R7)C(0)_ ;且 RB、Rc 及R7為氫。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對需要此種治療之哺乳 動物投予治療上有效量之式（IV)化合物, Ri, R2, R3, R4 and R5 are gas, X is CRb R0, X2 is a bond; D is -CH2_; L2S -CH2-; L is _N (R7) C (0) _; and RB , Rc and R7 are hydrogen. In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering a therapeutically effective amount of a compound of formula (IV) to a mammal in need of such treatment.

或其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 Xi為一個键結或CRBRc ; x2為一個键結或crdre ; 其條件是，當Χι為一個鍵結時，則x2為crdre ; 進一步條件是，當x2為一個键結時，則Xi為CRBRc ; A為芳基、芳烷基、環烷基或環烷基烷基； 1^為-!^(117)(：(0)-、-C(0)N(R7)-、-N(R7)C(S)-或-C(S)N(R7)-，其 中-N(R7)C(0)-、-C(0)N(R7)-、-N(R7)C(S)-及-C(S)N(R7)_ 之左端係 連接至A，而右端係連接至D ; 乙2為一個键結或次烷基； D為次燒基、氟次燒基或基次燒基；Or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof, wherein Xi is a bond or CRBRc; x2 is a bond or crdre; provided that when X is a bond, x2 is crdre; further condition is that when x2 is a bond, then Xi is CRBRc; A is aryl, aralkyl, cycloalkyl or cycloalkylalkyl; 1 ^ is-! ^ (117) (:( 0)-, -C (0) N (R7)-, -N (R7) C (S)-or -C (S) N (R7)-, where -N (R7) C (0)-,- The left end of C (0) N (R7)-, -N (R7) C (S)-and -C (S) N (R7) _ is connected to A, and the right end is connected to D; B 2 is a bond A junction or an alkylene group; D is a secondary alkyl group, a fluorine secondary alkyl group or a secondary alkylene group;

Ra、Rb、、Rd及Re係獨立為鼠或燒基’ 85228 -115- 200404539 B為Ra, Rb, Rd, and Re are independently murine or alkyl. 85228 -115- 200404539 B is

&amp;、&amp;、&amp;及R4各獨立為氫、烷氧基、烯基、烷基、境其 亞續酿基、燒基績Si基、纪硫基、決基、燒氧羰基、乾# 基、烷羰基氧基、羧基、氰基、甲醯基、_素、由燒氧夷 、鹵烷基、羥基、羥烷基、巯基、硝基、-NZA、（NZ3Z4_ 基、（NZ3Z4)羰基或（NZ3Z4)磺醯基； Ζι與Z2各獨立為氫、挺基、燒幾基、燒基續驗基、芳爲 芳烷基、芳烷基磺醯基、芳基磺醯基或甲醯基；4與心各獨 立為氫、烷基、芳基或芳烷基； X 為 N(R6)、〇 或 s ; Y 為 C(R4)或 N; 心為氫或燒基；及 R7為氫或燒基。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能'障礙之方法，纟包括對該哺乳動物投予治療 上有ί量之式（IV)化合物，其中A為芳基；B為 R:^XR3 . N R4，X^CRBRc ; x^CRdRe ; L為-N(R7)c(c〇-; iL2 ' D ' H R3、R4、R7、Ra、Rb、^、Rj^Re 均如式(IV) 85228 -116- 200404539 中之定義。 万、本發明《另—項具體實施例中，係關於-種在哺乳動物 中…療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效κ式（IV)化合物，其中A為芳基，其中芳基為苯基 被〇 1、2、3、4或5個取代基取代，取代基獨立選自晞 基烷氧基、烷氧羰基、烷基、烷硫基、芊基、氰基、鹵 素、_燒氧基、鹵燒基、亞甲二氧基、硝基、苯基或视&amp; ;B為 ?2&amp;, &amp;, &amp; and R4 are each independently hydrogen, alkoxy, alkenyl, alkyl, alkynyl, alkynyl, Si, sulfenyl, decyl, oxycarbonyl, dry # Group, alkylcarbonyloxy, carboxyl group, cyano group, formamyl group, sulfonium group, alkoxy group, haloalkyl group, hydroxy group, hydroxyalkyl group, mercapto group, nitro group, -NZA, (NZ3Z4_ group, (NZ3Z4) Carbonyl or (NZ3Z4) sulfofluorenyl; Z and Z2 are each independently hydrogen, acryl, alkynyl, alkynyl, and aryl are aralkyl, aralkylsulfonyl, arylsulfonyl, or methyl Fluorenyl; 4 and X are each independently hydrogen, alkyl, aryl, or aralkyl; X is N (R6), 0, or s; Y is C (R4) or N; X is hydrogen or alkyl; and R7 In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutic formula (IV ) Compound, where A is aryl; B is R: ^ XR3. N R4, X ^ CRBRc; x ^ CRdRe; L is -N (R7) c (c〇-; iL2'D'H R3, R4, R7 , Ra, Rb, ^, Rj ^ Re are as defined in formula (IV) 85228 -116- 200404539. According to the present invention, in another embodiment, a method for treating sexual dysfunction in mammals, which comprises administering to the mammal a therapeutically effective compound of formula (IV), wherein A is an aryl group. Where aryl is phenyl substituted by 0, 2, 3, 4 or 5 substituents, the substituents are independently selected from fluorenylalkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano , Halogen, halooxy, halohalo, methylenedioxy, nitro, phenyl, or A &B;? 2

RlV^W-R3 4，Ri為氳、烷基、氰基、鹵烷基、鹵素、硝基、㈤Ζ3ζ4) 烷基或(NZd4)羰基；R2與R4為氫；R3為氫或羥基；Xi*CRbR^ ,X2為CRdRe，D為-CH2-; L2為一個鍵結；] 且R7、RA、RB、&amp;、Rd及Re均如式口V)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基，其中芳基為苯基 ，被0、1、2、3、4或5個取代基取代，取代基獨立選自烯 基、燒氧基、燒氧羰基、烷基、烷硫基、苄基、氰基、鹵 素、||燒氧基、_烷基、亞甲二氧基、硝基、苯基或_NZiz2RlV ^ W-R3 4, Ri is fluorene, alkyl, cyano, haloalkyl, halogen, nitro, ㈤Z3ζ4) alkyl or (NZd4) carbonyl; R2 and R4 are hydrogen; R3 is hydrogen or hydroxyl; Xi * CRbR ^, X2 is CRdRe, D is -CH2-; L2 is a bond;] and R7, RA, RB, &amp;, Rd and Re are as defined in formula V). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, || alkoxy, _alkyl, methylenedioxy, nitro, phenyl, or _NZiz2

R3 、hT、R4 ;心為氫、烷基、氰基、鹵烷基、鹵素、硝基、⑺z3z4) 烷基或(NZgZ4)羰基；&amp;與R4為氫；r3為氫或羥基； ;X2為 CRDRE ; D 為-CH2- ; L2為一個鍵結；二為-N(R7)C(0)-; 85228 117- 200404539 且 R?、RA、RB、Re、RrRe 為氫。 、晷月之另項具體實施例中，係關於一種在哺乳動物 中’口療性功能障礙之方法，纟包括對該哺乳動物投予治療 上有放里之式（IV)化合物，其中A為雜環，· B為 ,R2 Y 3，Xl 為 CRbRc ; χ2 為 CRDRE ; L為-N(R7)C(0)-;且D、 L2、X、γ、p η Β、R〇、RD、RE、r2、r3&amp;r7 均如式（IV) 中之定義。 於本發明之另—項具體實施例中，係關於-種在哺乳動物 中治療性功能障礙乏女、、土 ^ . / ，/、匕括對該哺乳動物投予治療 上有效量之式㈣化合物’其中Α為雜環，其中雜環為苯并 咪咬基、苯㈣峻基、吱喃基、咪啥基令W井 基峨圭基、，合_基”比嗓基”密咬基”比嘻基、口”塞峻 基或嗓吩基，其中雜環係被0小2或3個取代基取代，取 代f獨立選自㈣基、職羰基1基、氰基、㈣、自 燒氧基、_燒基或硝基；B為 ，R2與 R3為虱，xiACRbRc; x^CRdRe; 、◦或 S ; Y 為 N ; D 為 _CH，_ . T 五 2 , 2 為—個鍵結；L· 為-N(R7)C(〇)_ ;且〜' Ra、Rb、K、Rd、〜及〜均如式㈣中之定義。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法’纟包括對該哺乳動物投予治療 上有效量之式㈣化合物’其中A為雜環’其中雜環為苯并 咪吐基，被丨㈣基取代基取代’其中較佳燒基取代基為甲 85228 -118- 200404539 基；B為R3, hT, R4; heart is hydrogen, alkyl, cyano, haloalkyl, halogen, nitro, hydraz3z4) alkyl or (NZgZ4) carbonyl; &amp; and R4 are hydrogen; r3 is hydrogen or hydroxyl; X2 CRDRE; D is -CH2-; L2 is a bond; two is -N (R7) C (0)-; 85228 117-200404539 and R ?, RA, RB, Re, RrRe are hydrogen. In another specific embodiment of the present invention, a method for treating oral sexual dysfunction in a mammal comprises the step of administering to the mammal a compound of formula (IV), wherein A is Heterocycle, · B is, R2 Y 3, X1 is CRbRc; χ2 is CRDRE; L is -N (R7) C (0)-; and D, L2, X, γ, p η Β, R0, RD, RE, r2, r3 &amp; r7 are as defined in formula (IV). In another specific embodiment of the present invention, it is a formula for administering a therapeutically effective amount to a mammal in the treatment of sexual dysfunction in mammals. Compound 'wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzimidyl, benzamyl, succinyl, imisyl, etc., and it is a "pyridyl" group. "Beeki", "Hou", or phenyl, wherein the heterocyclic system is substituted with 0 or 2 or 3 substituents, and the substitution f is independently selected from fluorenyl, carbonyl1, cyano, fluorene, and self-ignition Oxy, alkynyl or nitro; B is, R2 and R3 are lice, xiACRbRc; x ^ CRdRe;, ◦ or S; Y is N; D is _CH, _. T 5 2, 2 is a bond L · is -N (R7) C (〇) _; and ~ 'Ra, Rb, K, Rd, ~, and ~ are as defined in formula (2). In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal. '纟 comprising administering to the mammal a therapeutically effective amount of a compound of the formula' wherein A is a heterocyclic ring ' The heterocyclic ring is benzimidyl, which is substituted with a fluorenyl substituent. Among them, the preferred substituent is methyl 85228 -118- 200404539; B is

3 ’ R2與 R3 為氫；X^CRbRc ; x2gCRi)RE ; χ 為 n(R6) 〇 或 S, γ 為 n, d 為-CH2 - ; L2 為一個鍵結；L 為 _n(r7 )c(〇)_ ，且ra、RB、&amp;、rd、re及r7為氫；及心為氫或烷基，其 中較佳烷基為甲基。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基；b為3 'R2 and R3 are hydrogen; X ^ CRbRc; x2gCRi) RE; χ is n (R6) 〇 or S, γ is n, d is -CH2-; L2 is a bond; L is _n (r7) c (〇) _, and ra, RB, &amp;, rd, re, and r7 are hydrogen; and R is hydrogen or an alkyl group, with a preferred alkyl group being a methyl group. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is aryl ; B is

^ ; Χι 為一個鍵結；X2 為 CRDRE ; L 為-N(R7)C(0)-; 且L2、D、Ri、r2、r3、心、r7、Ra、知及心均如式（IV)中 之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基，其中芳基為苯基 ，被0、1、2、3、4或5個取代基取代，取代基獨立選自烯 基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵 素、i烷氧基、函烷基、亞甲二氧基、硝基、苯基或-NZiZg ;B為^; Xι is a bond; X2 is CRDRE; L is -N (R7) C (0)-; and L2, D, Ri, r2, r3, heart, r7, Ra, Zhi and heart are all according to formula (IV ). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, i-alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZiZg; B is

1 &amp;為氫、烷基、氰基、lS烷基、鹵素、硝基、（NZ3Z4) 烷基或（NZ3Z4)羰基；心與心為氫；R3為氫或羥基；Xi為一個 鍵結，X?為 CRj) Re，D 為，1^2 為一個键結；L 為-N(R^ )C(0)- 85228 -119· 200404539 ，及R7、RA、rd及RE均如式（IV)中之定義。 於本發明4另-項具體實施例中，係關於一種在哺乳動物 中/口療性功能障礙4方法，其包括對該哺乳動物投予治療 上有效量 &lt; 式（IV)化合物，其中A為芳基，其中芳基為苯基 被〇、1、2、3、4或5個取代基取代，取代基獨立選自烯 基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵 素、i烷氧基、鹵烷基、亞甲二氧基、硝基、苯基或 ;Bg ?2 ΧΧ4·^ ，Ri為氫、烷基、氰基、_烷基、鹵素、硝基、⑼ 烷基或（NZsZ4)羰基；&amp;與R4為氫；&amp;為氫或羥基；&amp;為一個 鍵尨，X2為 CRDRE , D為-CH2-; L2為一個鍵結；Lg_N(R7)c(〇)_ ’及R7、RA、rd及re為氯。1 &amp; is hydrogen, alkyl, cyano, 1S alkyl, halogen, nitro, (NZ3Z4) alkyl or (NZ3Z4) carbonyl; heart and heart are hydrogen; R3 is hydrogen or hydroxyl; Xi is a bond, X? Is CRj) Re, D is, 1 ^ 2 is a bond; L is -N (R ^) C (0)-85228 -119 · 200404539, and R7, RA, rd, and RE are all according to formula (IV ). In another specific embodiment of the present invention 4, the present invention relates to a method for treating sexual dysfunction in or mammals, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A Is aryl, wherein aryl is phenyl substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, Benzyl, cyano, halogen, i-alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or Bg? 2 × 4 × ^, Ri is hydrogen, alkyl, cyano, _alkyl , Halogen, nitro, amidine alkyl or (NZsZ4) carbonyl; & and R4 are hydrogen; &amp; is hydrogen or hydroxyl; &amp; is a bond 一个, X2 is CRDRE, D is -CH2-; L2 is a bond Lg_N (R7) c (〇) _ 'and R7, RA, rd and re are chlorine.

於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為雜環；3為In another embodiment of the present invention, a method for treating sexual dysfunction in a mammal comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is a heterocyclic ring. ; 3 is

3 ’ Xi 為一個鍵結，x2 為 CRDRE ; L 為 _N(R7)C(0)_ ; J D、L2、X、γ、Ra、Rd、Re、&amp;、〜及〜均如式㈣中之 定義。 於本發明之另一項具體實施例中，係關於-種在哺乳動物 中治療性功能障礙之方法，纟包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為雜環，其中雜環為苯并 咪唑基、苯并噻唑基、呋喃基、咪唑基、丨，3_噚唑基、吡畊 85228 -120- 200404539 基吡唑基、哈喑基、吡啶基、嘧啶基、吡咯基、1,3_噻唑 基或遠吩基，纟中雜環係_、卜2或3個取代基取代，取 代基獨立選自烷氧基、、虎氧羰基、烷基、氰基、_素、鹵 烷氧基、_烷基或硝基；B為 3, R2與R3為氫；Xl為一個鍵結；χ為N(R^ '〇^S，Y^N，D^ -CH2- ^ L2 Λ ~ in ^ ^ ； L ^ -N(R7)C(0). ，及K、Ra、Rd、Re及均如式（jy)中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為雜環，其中雜環為苯并 咪唑基，被丨個烷基取代基取代，其中較佳烷基取代基為甲 基；B為3 'Xi is a bond, x2 is CRDRE; L is _N (R7) C (0) _; JD, L2, X, γ, Ra, Rd, Re, &amp;, ~, and ~ are as in formula ㈣ Definition. In another specific embodiment of the present invention, the invention relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is miscellaneous Ring, in which the heterocyclic ring is benzimidazolyl, benzothiazolyl, furanyl, imidazolyl, 3-oxazolyl, pyridine 85228 -120- 200404539 ylpyrazolyl, halideyl, pyridyl, pyrimidine Group, pyrrolyl group, 1,3-thiazolyl group, or farphenyl group, substituted with heterocyclic ring system, 卜, 2 or 3 substituents, the substituents are independently selected from alkoxy, oxocarbonyl, alkyl, and cyano Group, _ prime, haloalkoxy, _alkyl or nitro group; B is 3, R2 and R3 are hydrogen; X1 is a bond; χ is N (R ^ '〇 ^ S, Y ^ N, D ^ -CH2- ^ L2 Λ ~ in ^ ^; L ^ -N (R7) C (0)., And K, Ra, Rd, Re, and all are as defined in formula (jy). In another aspect of the present invention In a specific embodiment, the present invention relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzo Imidazolyl Alkyl substituents, of which the preferred alkyl substituent is methyl; B is

R3; R2與R3為氫；X!為一個鍵結；; X為n(R6) 、0或 S, γ 為N; D 為-CH2- ; L2 為一個键結；l g-N(R7)C(0)_ ;Ra、Rd、Re及&amp;為氫；及心為氫或烷基，其中較佳烷基 為甲基。 \ 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基；；8為R3; R2 and R3 are hydrogen; X! Is a bond; X is n (R6), 0 or S, γ is N; D is -CH2-; L2 is a bond; l gN (R7) C ( 0) _; Ra, Rd, Re, and &amp; are hydrogen; and R is hydrogen or an alkyl group, with a preferred alkyl group being a methyl group. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is aromatic Base; 8 for

，Xi 為一個鍵結；X2 為 CRD RE ; L 為 _N(R7 )C(〇)-;且 D L2 X、Y、Ra、Rd、Re、R2、R3 及 R7 均如式（IV)中之 85228 -121- 200404539 定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基，其中芳基為笨基 ，被〇、1、2、3、4或5個取代基取代，取代基獨立選自烯 基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵 素、_烷氧基、函烷基、亞甲二氧基、硝基、苯基或-ΝΖι乙, Xi is a bond; X2 is CRD RE; L is _N (R7) C (〇)-; and D L2 X, Y, Ra, Rd, Re, R2, R3, and R7 are all as in formula (IV) 85228-121- 200404539. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is aryl , Where aryl is a benzyl group, substituted by 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, or -NZιethyl

R3; R2與R3為氫；Xi為一個鍵結；χ2為CRdre; χ為N(r6) 、〇 或 S ; Y 為 C(R4) ; D 為-CH2-; L2為一個鍵結；l 為-N(R7)C(0)-’心為氫、燒基或氰基；且心、Ra、Rd、Re及r7均如式（jv) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基，其中芳基為苯基 ，被0、1、2、3、4或5個取代基取代，取代基獨立選自烯 基、燒氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵 素、_燒氧基、||烷基、亞甲二氧基、硝基、苯基或-NZi z2 ;BgR3; R2 and R3 are hydrogen; Xi is a bond; χ2 is CRdre; χ is N (r6), 0 or S; Y is C (R4); D is -CH2-; L2 is a bond; l is -N (R7) C (0)-'He is hydrogen, thio or cyano; and He, Ra, Rd, Re and r7 are as defined in formula (jv). In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is aryl Where aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl , Cyano, halogen, alkoxy, || alkyl, methylenedioxy, nitro, phenyl, or -NZi z2; Bg

R3; R2與R3為氫；Xi為一個鍵結；x^CRdRe; 乂為风心） 、O 或 S ; Y 為 C(R4) ; D 為-CH2-; L2為一個鍵結；L 為-N(R7)C(0)-;R4為氫、烷基或氰基；Ra、Rd、Re及r7為氫；及為氫 85228 -122- 200404539 或貌基，其中較佳烷基為甲基。 、；本發明之另一項具體實施例中，係關於一種在哺乳動物 中冶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基；B為 尺5 ’ Χι 為 CRB Rc ; Χ2 為一個鍵結；[為-N(R7 )C(0)-; 且:2、D、Rl、R2、R3、R4、R5、R7、RA、RB 及 Rc 均如式(IV) 中之定義。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中'口療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基，其中芳基為苯基 被〇、1、2、3、4或5個取代基取代，取代基獨立選自晞 基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵 素_烷氧基、ΐ烷基、亞甲二氧基、硝基、苯基或-NZiZ2 ;Β*R3; R2 and R3 are hydrogen; Xi is a bond; x ^ CRdRe; 乂 is the center of wind), O or S; Y is C (R4); D is -CH2-; L2 is a bond; L is- N (R7) C (0)-; R4 is hydrogen, alkyl, or cyano; Ra, Rd, Re, and r7 are hydrogen; and is hydrogen 85228 -122- 200404539 or aryl, of which the preferred alkyl is methyl . In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is Aryl; B is 5 'Xι is CRB Rc; χ2 is a bond; [is -N (R7) C (0)-; and: 2, D, Rl, R2, R3, R4, R5, R7, RA, RB and Rc are as defined in formula (IV). In another specific embodiment of the present invention, it relates to a method of 'oral treatment of sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is Aryl, where aryl is phenyl substituted with 0, 1, 2, 3, 4 or 5 substituents, each of which is independently selected from fluorenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl Group, cyano, halogen-alkoxy, fluorenyl, methylenedioxy, nitro, phenyl, or -NZiZ2; B *

;Ri、R2、R3、R4 及 R5 為氫；&amp; 為 CRbRc ; χ2 為 個鍵結；D 為-CH2- ; L2A -CH2- ; L 為-N(R7)C(〇)-;且 RB、心 及h均如式（iv)中之定義。 万；本發明之另一項具體實施例中，係關於一種在哺乳動物 中❶療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，其中A為芳基，其中芳基為苯基 85228 200404539 ，贩u、1、2、3、4或5個取代基取代，取代基獨立選自缔 基、烷氧基、烷氧羰基、烷基、烷硫基、苄基、氰基、鹵 素' _烷氧基、_烷基、亞甲二氧基、硝基、苯基或_NZiz2 ，B為Ri, R2, R3, R4, and R5 are hydrogen; &amp; is CRbRc; χ2 is a bond; D is -CH2-; L2A -CH2-; L is -N (R7) C (〇)-; and RB , Heart and h are as defined in formula (iv). In another embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), wherein A is Aryl, where aryl is phenyl 85228 200404539, substituted with u, 1, 2, 3, 4 or 5 substituents, the substituents are independently selected from alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio , Benzyl, cyano, halogen'_alkoxy, _alkyl, methylenedioxy, nitro, phenyl, or _NZiz2, B is

;Ri、R2、R3、r4 及 r5 為氫；Xl 為 CRbRc ; χ2 為 個鍵結；D 為-CH2- ; L2為-CH2_ ; L 為-N(R7)C(0)_ ;且 RB、κ 及R7為氫。 於本發明4另一項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法，其包括對該哺乳動物投予治療 上有效量之式（IV)化合物，或其藥學上可接受之鹽、酯、醯 胺或如體藥物，且併用藥學上可接受之載劑。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 中治療性功能障礙之方法’纟包括對該哺乳動物投予治療 t有j量之式（IV)化合物，或其藥學上可接受之鹽、酯、酿 胺或别體藥物’且併用磷酸二酯酶5抑制劑。 於本發明之另-項具體實施例中，係關於—種在哺乳動物 中治療性功能障礙之方法’纟包括對該哺乳動物投予治療 上有效量之式(1¥)化合物’或其藥學上可接受之鹽、醋、酿 胺或前體藥物，且併用腎上腺素能受體拮抗劑。 於本發明之另—項具體實施例中，個於—種在哺乳動物 中治療性功能障礙之方法’纟包括對該哺乳動物投予治療 上有效量之綱化合物，或其藥學上可接受之鹽、酿、柄 85228 -124- 200404539 胺或前體藥物，且併用多巴胺催動劑。 於本發明之另一項具體實施例中，係關於—種在男性人類 中治療男性勃起功能障礙之方法，其包括對需要此種治療 之男性人類投予治療上有效量之式（IV)化合物，或其藥學上 可接雙之鹽、酯、醯胺或前體藥物，且併用藥學上可接受 之載劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之式（IV)化合物，或其藥學上可接受之鹽、 酿、醯胺或前體藥物，且併用磷酸二酯酶5抑制劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之式（IV)化合物，或其藥學上可接受之鹽、 酯、醯胺或前體藥物，且併用腎上腺素能受體拮抗劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中心療男性勃起功能障礙之方法，其包括對該哺乳動物投 予治療上有效量之式（IV)化合物，或其藥學上可接受之鹽、 酯、醯胺或前體藥物，且併用多巴胺催動劑。 a '本毛明之另項具體實施例中，係關於一種在哺乳動物 中/口療女性性功能障礙之方法，纟包括對需要此種治療之 哺乳動物投予Μ療上有效量之式（IV)化合物，或其藥學上可 矣殳之農酉曰、驗胺或前體藥物，且併用藥學上可接受之 載劑。 於本發明之另-項具體實施例中，係關於一種在哺乳動物 85228 200404539 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之式（IV)化合物，或其藥學上可接受之鹽、酿 、酿胺或前體藥物，且併用磷酸二酯酶5抑制劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之式（IV)化合物，或其藥學上可接受之鹽、酉旨 、醯胺或前體藥物，且併用腎上腺素能受體拮抗劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療女性性功能障礙之方法，其包括對該哺乳動物投予 治療上有效量之式（IV)化合物，或其藥學上可接受之鹽、酿 、醯胺或前體藥物，且併用多巴胺催動劑。 於本發明之另一項具體實施例中，係關於一種在哺乳動物 中治療病症之方法，其中病症為心與血管病症、炎性病症 、注意力不足活動過度病症、阿耳滋海默氏疾病、藥物濫 用、巴金生氏病、精神分裂症、焦慮、心情病症或抑鬱， 其包括對需要此種治療之哺乳動物投予治療上有效量之式 (IV)化合物’或其藥學上可接受之鹽、酿、醯胺或前體藥物。 1發明之定義 當於整個本專利說明書與隨文所附之申請專利範圍中使用 時，下述術語具有下述意義： 於本文中使用之”細基，一到，係意謂直鏈或分枝鏈烴，含 有2至10個碳，及含有至少一個藉由移除兩個氫所形成之碳 •碳雙鍵。缔基之代表性實例，包括但不限於乙烯基、2_丙 烯基、2-甲基-2-丙晞基、3- 丁烯基' 4-戊晞基、5-己晞基、2- 85228 -126- 200404539 庚晞基、2-甲基-1-庚晞基及3_癸埽基。 於本又中使用之”烷氧基”一詞，係意謂如本文中定義之烷 基，經過氧原子附加至母分子部份基團。烷氧基之代表2 實例，包括但不限於甲氧基、乙氧基、丙氧基、2_丙氧基、 丁氧基、第三-丁氧基、戊氧基及己氧基。 於本文中使用之”烷氧羰基”一詞，係意謂如本文中定義之 烷氧基，經過如本文中定義之羰基附加至母分子部份基團 。烷氧羰基之代表性實例，包括但不限於甲氧羰基、乙氧 羰基及第三-丁氧羰基。 於本文中使用之”烷氧基磺醯基”一詞，係意謂如本文中定 義之纪氧基，經過如本文中定義之磺醯基附加至母分子部 份基團。燒氧基磺醯基之代表性實例，包括但不限於甲氧 續S盛基、乙氧磺酿基及丙氧續酿基。 於本文中使用之”烷基”一詞，係意謂含有丨至1〇個碳原子 之直鏈或分枝鏈烴。烷基之代表性實例，包括但不限於甲 基、乙基、正-丙基、異丙基、正-丁基、第二-丁基、異丁 基、第三-丁基、正-戊基、異戊基、新戊基、正-己基、3_ 甲基己基、2,2-二甲基戊基、2,3-二甲基戊基、正-庚基、正_ 辛基、正-壬基及正-癸基。 於本文中使用之”烷羰基&quot;一詞，係意謂如本文中定義之烷 基，經過如本文中定義之羰基附加至母分子部份基團。烷 羰基之代表性實例，包括但不限於乙醯基、1-酮基丙基、2,2-二甲基-1_酮基丙基、1-酮基丁基及1-酮基戊基。 於本文中使用之”烷羰基氧基” 一詞，係意謂如本文中定義 85228 -127- 200404539 之烷羰基，經過氧原子附加至母分子部份基團。烷羰基氧 基之代表性實例，包括但不限於乙醯基氧基、乙基羰基氧 基及第三-丁基羰基氧基。 ’’次烷基π —詞係意謂衍生自1至10個碳原子之直鏈或分枝 鏈烴之二價基團。實例為&lt;氐-、-012&lt;^12_、-01(013)-、- ch(ch2ch3)-、-ch2ch2ch2-及-ch2ch2ch2ch2-〇 於本文中使用之π烷基亞磺醯基π —詞，係意謂如本文中定 義之燒基，經過如本文中定義之亞續酸基附加至母分子部 份基團。烷基亞磺醯基之代表性實例，包括但不限於甲基 亞續酿基與乙基亞續si基。 於本文中使用之”烷基磺醯基” 一詞，係意謂如本文中定義 之燒基，經過如本文中定義之續醯基附加至母分子部份基 團。烷基磺醯基之代表性實例，包括但不限於甲磺醯基與 乙基續醯基。 於本文中使用之”烷硫基”一詞，係意謂如本文中定義之烷 基，經過硫原子附加至母分子部份基團。烷硫基之代表性 實例，包括但不限於甲硫基、乙硫基、第三-丁基硫基及己 硫基。 於本文中使用之”炔基” 一詞，係意謂直鏈或分枝鏈烴基， 含有2至10個碳原子，及含有至少一個碳-碳參键。炔基之 代表性實例，包括但不限於乙块基、1-丙決基、2-丙決基、 3- 丁炔基、2-戊炔基及1- 丁炔基。 於本文中使用之π芳基π —詞係意謂苯基或雙環狀稠合環系 統或三環狀稠合環系統，其中一或多個稠合環係為苯基。 85228 -128- 200404539 雙％狀稠合環系統之實例為經稠合至另一個苯基或經稠合 至環烷基之苯基’其中環烷基係選自環戊烷、環己烷環庚 烷或環辛烷。三環狀稠合環系統之實例為經稠合至苯基之 雙環狀稠合環系統。芳基之代表性實例，包括但不限於蒽 基、藍香油烴基、蔡基、5,6,7,8_四氫萘基、5,6,7,8_四氫小莕 基、1，2,3,4-四氫萘基、（1SH，2,3,4_四氫_丨_萘基、（1职，2,3 4四 氳丨-奈基、氫印基、茚基、3-二氫-1H-茚基' 2,3-二氫-1H-茚-5- 基、1-莕基、2-莕基及苯基。 本發明之芳基係被〇、1、2、3、4或5個取代基取代，取 代基獨立選自烷氧基、烯基、烷基、烷基亞磺醯基、烷基 飧醯基、烷硫基、炔基、烷氧羰基、烷羰基、烷羰基氧基 I基、氰基、甲醯基、_素、_燒氧基、齒燒基、經基 、羥烷基、巯基、亞甲二氧基、硝基、-NZiz2、⑼心心)羰基 及（NZgZ4)磺醯基。本發明之芳基可進一步被如本文中定義 义另一個芳基或芳烷基取代，其中該另一個芳基或芳烷基 之芳基部份係被0、1、2、3、4或5個取代基取代，取代基 獨立選自烷氧基、烯基、烷基、烷基亞磺醯基、烷基磺醯 基、燒硫基、炔基、烷氧羰基、烷羰基、烷羰基氧基、羧 基來基、甲®^基、素、自燒氧基、_燒基、經基、藉 烷基、巯基、亞甲二氧基、碕基、-NZlZ2、（NZ3Z4織基及(NZA) 續SS基。代表性實例，包括但不限於13-苯并二氧伍圜烯一5-基、3-苄基苯基、1，1L聯苯各基、2-溴苯基、3-溴苯基、4-溴 苯基、4-溴基-3-甲基苯基、4-溴基-2-甲基苯基、2-氯苯基、3-氯苯基、4-氯苯基、3-氣基-4-氟苯基、4-氯基-3-甲氧苯基、3-85228 -129- 200404539 氯基-2-甲基苯基、2-氯基-5-甲基苯基、2-氯基-6-甲基苯基、4-氯基-2,6-二甲基苯基、3-氯基-4-氟苯基、5-氯基-2-甲基苯基、 4-氯基_3_甲基苯基、3-氯基-4-甲基苯基、2-氯基-5-三氟甲基苯 基、3-氯基-4-三氟甲氧苯基、2-氰基苯基、3-氰基苯基、4-氰 基苯基、2,3-二溴基-5-甲基苯基、2,3-二氯苯基、3,4-二氯苯基 、3,5-二氯苯基、2,6-二氯-3-甲基苯基、2,6-二乙基苯基、3,4-二氟苯基、2,4-二氟苯基、3,5-二氟苯基、3,5-二甲氧基苯基、 2,5-二甲氧基苯基、2,3-二甲基苯基、2,6-二甲基苯基、2,5-二 甲基苯基、3,5-二甲基苯基、3,4-二甲基苯基、3-(二甲胺基）苯 基、3-乙氧苯基、4-(乙氧羰基）苯基、3_乙基苯基、2_乙基·6_ 甲基苯基、2-氟苯基、3-氟苯基、4-氟苯基、2-氟基-5-甲基苯 基、4-氟基-3-甲基苯基、4-氟基-2-甲基苯基、4-氟基-3_三氟甲 基苯基、3-氟基-5-三氟甲基苯基、2-氟基-5-三氟甲基苯基、2_ 氟基-3-三氟甲基苯基、4-碘基各甲基苯基、3-異丙氧基苯基 、3-異丙基苯基、2-異丙基-6-甲基苯基、2-甲氧苯基、3-甲氧 苯基、4-甲氧苯基、2-甲氧基-6-甲基苯基、3-甲氧基-2-甲基苯 基、3-甲基苯基、2_甲基苯基、‘甲基苯基、5_甲基冬硝基苯 基、4-甲基-3-三氟甲基苯基、3_甲基硫苯基、2_硝基苯基、3_ 硝基苯基、4-硝基苯基、2,4,6-三溴基-3-甲基苯基、五氟苯基 、3-(第二-丁基）苯基、2,4,6-三氯苯基、2,4,6-三氟笨基、2_三氟 甲基苯基、3-三氟甲基苯基' 4-三氟甲基苯基、2_三氟甲氧 苯基、3-三氟甲氧苯基、4-三氟甲氧苯基、3,4,5_三甲氧基苯 基及3-乙烯基苯基。 於本文中使用之&quot;芳烷基”一詞，係意謂如本文中定義之芳 85228 -130- 200404539 基’經過如本文中定義之烷基附加至母分子部份基團。芳 烷基之代表性實例，包括但不限於苯基甲基、孓苯基乙基、 3-苯基丙基及3-(2-甲基苯基）丙基。 於本文中使用之”芳基續醯基” 一詞，係意謂如本文中定義 之芳基，經過如本文中定義之磺醯基附加至母分子部份基 團。芳基磺驗基之代表性實例，包括但不限於苯磺醯基、2_ 甲基苯磺驢基、2-硝基苯基磺醯基及3_硝基苯基磺醯基。 於本文中使用之方燒基橫酸基”一詞，係意謂如本文中定 義之芳烷基，經過如本文中定義之磺醯基附加至母分子部 份基團。芳燒基磺醯基之代表性實例，包括但不限於（苯基 甲基）磺醯基、（2-苯基乙基）續醯基及（3_苯基丙基）績醯基。 於本文中使用之”羰基” 一詞，係意謂-C(O)-基團。 於本文中使用之’’羧基” 一詞，係意謂-C02H基團。 於本文中使用之π氰基” 一詞，係意謂-CN基團。 於本文中使用之”環烷基” 一詞，係意謂單環狀、雙環狀或 三環狀環系統。單環狀環系統之實例為含有3至8個碳原子 之飽和環狀烴基。單環狀環系統之實例包括環丙基、環丁 基、環戊基、環己基、環庚基及環辛基。雙環狀環系統之 實例為經橋接之單環狀環系統，其中單環狀環之兩個非相 鄰碳原子，係藉由一與三個其他碳原子間之次烷基橋基連 接（_CH2·、-CH2CH2•及-CH2CH2CH2-)。雙環狀環系統之代表 性實例，包括但不限於雙環并[3·1·1]庚烷、雙環并[2.2.1]庚烷 、雙環并[2.2.2]辛烷、雙環并[3.2.2]壬烷、雙環并ρ.3.1]壬烷及 雙環并[4·2·1]壬烷。三環狀環系統之實例為雙環狀環系統， 85228 -131- 200404539 其中雙環狀環之兩個非相鄰碳原子係藉由一與三個碳原子 間之一個键結或次烷基橋基連接（_CH2-、_CH2CH2-及一 CH2 CH2 CH2 -)。三環狀環系統之代表性實例，包括但不限於 三環并[3.3.1.03，7]壬烷與三環并[3·3·1.13,7]癸烷（金鋼烷基）。 本發明之環烷基係被0、1、2、3或4個取代基取代，取代 基獨立選自烷氧基、烯基、烷基、烷基亞磺醯基、烷基磺 醯基、烷硫基、炔基、烷氧羰基、烷羰基、烷羰基氧基、 叛基、氰基、甲醯基、i素、1¾烷氧基、_烷基、羥基、 羥烷基、銃基、硝基、-NZ〗Z2、（NZ3Z4)羰基或（NZ3Z4)磺醯基 。被0、1、2、3或4個取代基取代之環烷基之代表性實例 ，包括但不限於2-甲基環己基、2-氰基環己基及2-甲氧基環 己基。 於本文中使用之一詞”氟次烷基”，係意謂至少一個氟化物 原子（-F)，經過如本文中定義之次烷基附加至母分子部份基 團。氟次烷基之代表性實例為-CH(F)-、-CH(F)CH2 -、-C〇F)2 CH2 - 、-CH(F)CH(F)-、-CH(CF3)-、-CH(CH2CF3)-及-CH2CH2CH2CH(F)-。 於本文中使用之n甲醯基&quot;一詞，係意謂_C(〇)h基團。 於本文中使用之π鹵基”或”鹵素&quot;術語，係意謂_α、-Br、 -I 或-F。 於本文中使用之n i烷氧基”一詞，係意謂至少一個如本文 中定義之卣素，經過如本文中定義之烷氧基附加至母分子 部份基團。鹵燒氧基之代表性實例，包括但不限於2-氟基小 氯基乙氧基、氯基甲氧基、2-氟基乙氧基、三氟甲氧基及五 氟乙氧基。 85228 -132- 200404539 、\本文中使用之自燒基，，一詞，係意謂至少-個如本文中 —我之自素、纟'^過如本文中定義之烷基附加至母分子部份 基圏。㈣基之代表性實例，包括但不限於氯基甲基、2-氟 基乙基、Z氟甲基、五氣乙基及2·氯基氟基戊基。 万、本文中使用之”雜環&quot;或&quot;雜環族&quot;術語，係意謂單環狀 又衣狀或一 ％狀裱系統。單環狀環系統之實例為任何 &gt; 或 員衰/有^原子，獨立選自氧、氮及硫；或5-、6-或7_ 員％，含有一、二或三個雜原子，其中雜原子係獨立選自 氮、氧及硫。5-員環具有〜2個雙鍵，而6•與7_員環具有〇_3 個雙鍵。單環狀環系統之代表性實例，包括但不限於一氮 四圜基、一氮七圜烷基、氮丙啶基、二氮七圜烯基、丨，3_二 氧伍圜基、一氧陸圜基、二硫陸圜基、吱喃基、咪咬基、 二氫咪唑基、四氫咪唑基、異噻唑基、異嘍唑啉基、異嘧 上4基、兴吟峻基、異二氫崎吨基、異四氫$。坐基、嗎福 淋基、巧二嗤基、二氫$二峻基、氧二唆咬基、巧嗤基、 二氫气吐基、四氫嘮唑基、六氫吡畊基、六氫吡啶基、哌 喃基、吡畊基、吡唑基、二氫吡唑基、四氫吡唑基、吡啶 基、嘧啶基、嗒畊基、吡咯基、二氫吡咯基、四氫吡咯基 、四氫呋喃基、四氫，塞吩基、四畊基、四唑基、遠二唑基 、遠一吐淋基、達二吐淀基、遠峻基、P塞峡淋基、P塞吐症 基、嗓吩基、硫代嗎福琳基、1，1-二氧化硫代嗎福淋基（硫 代嗎福淋减）、硫代成喃基、三呼基、三吐基及三硫陸圜基 。雙環狀環系統之實例為任何上述單環狀環系統，經稠合 至苯基、環己基、環戊基或另一個單環狀雜環。雙環狀環 85228 -133- 200404539 系統之代表性實例，包括但不限於例如苯并咪唑基、苯并 二氧陸圜晞基、苯并0基、笨并違吩基、苯并三唾基、 苯并气峻基、料吱喃基、苯并嗓喃基、苯并硫代略喃基 、峰啉基、啕唑基、啕哚基、2,3_二氫吲哚基、吲畊基、嗉 啶基、異苯并呋喃基、異苯并嘍吩基、異♦朵基、異喳啉 基、呔畊基、哌喃并吡啶基、喹啉基、喹畊基、喹喏啉基 、喹唑啉基、四氫異喳啉基、四氫喹啉基及硫代哌喃并吡 哫基。二％狀裱系統之實例為任何上述雙環狀環系統，經 稠合至苯基、環己基、環戊基或另一個單環狀雜環。三環 狀環系統之代表性實例，包括但不限於吖啶基、咔唑基、 咔啉基、二苯并[b，d]呋喃基、二苯并噏吩基、萘并[2,3七] p夫喃、莕并[2,3七&gt;塞吩基、钟哨基、啡遠p井基、啡吟呼基、 p塞嗯基、p塞吟晞基及u山基。 本發明之雜環係被0、1、2或3個取代基取代，取代基獨 立選自燒氧基、缔基、燒基、燒基亞績g蠢基、燒基續醯基 、烷硫基、炔基、烷氧羰基、烷羰基、烷羰基氧基、羧基 、氰基、甲醯基、_素、画烷氧基、_烷基、羥基、經烷 基、巯基、硝基、-NZiZ〗、（NZ3Z4)羰基及(NZ3Z4)磺醯基。本 發明之雜環基團可進一步被如本文中定義之另一雜環基團 取代，其中該另一個雜環基團係被0、1、2或3個取代基取 代，取代基獨立選自烷氧基、烯基、烷基、烷基亞磺醯基 、燒基續驗基、燒硫基、決基、燒氧黢基、燒羰基、燒羰 基氧基、叛基、氰基、甲酸基、画素、iS燒氧基、_燒基 、羥基、羥烷基、巯基、硝基、-NZiZ2、（NZ3Z4)羰基及(nz3z4) 85228 -134- 200404539 磺醯基。代表性實例，包括但不限於1,3-二甲基比嗅_5_基 、5-氟基-1，3-苯并遠嗅-2-基、1_甲基-1H-苯并咪吐_2_基、6_氯基 外匕淀-2·基及4-p比咬-2_基六氫咐;呼-1-基。 於本文中使用之”雜環烷基”一詞，係意謂如本文中定義之 雜環，經過如本文中定義之烷基附加至母分子部份基圏。 雜環烷基之代表性實例，包括但不限於吡啶各基甲基、2-p密 淀-2-基丙基及4-ρ比淀-2-基六氫外b p井-1-基甲基。 於本文中使用之”雜環羰基”一詞，係意謂如本文中定義之 雜環，經過如本文中定義之羰基附加至母分子部份基團。 吡啶-3-基羧基^林-3-基羰基及4-吡啶-2-基六氫P比畊基甲 基羰基。 於本文中使用之π羥基” 一詞，係意謂-OH基團。 於本文中使用之’’羥烷基”一詞，係意謂至少一個如本文中 定義之羥基，經過如本文中定義之烷基附加至母分子部份 基團。幾烷基之代表性實例，包括但不限於經甲基、2-幾乙 基、3-羥丙基、2-乙基斗羥庚基及2,4-二羥基丁基。 於本文中使用之π羥基次烷基” 一詞，係意謂至少一個如本 文中定義之羥基，經過如本文中定義之次烷基附加至母分 子部份基團。羥基次烷基之代表性實例為_CH2CH(OH)CH2-、 -CH(CH2 OH)…-CH(CH2 CH2 OH)_ 及-CH2 CH2 CH(OH)C^^ 於本文中使用之”巯基” 一詞，係意謂_SH基團。 於本文中使用之”亞甲二氧基，，一詞，係意謂-〇CH20-基團 ’其中亞甲一氧基之氧原子，係經過兩個相鄰碳原子連接 至母分子部份基團。代表性實例，包括但不限於1，3_苯并二 85228 -135- 200404539 氧伍圜烯-5-基。 於本文中使用之”硝基，，一詞，係意謂-no2基團。 於本文中使用之”氮保護基，，一詞，係意謂意欲保護胺基以 在合成程序期間防止不期望反應之基團。氮保護基包括胺 基甲酸酯類、醯胺類、N_芊基衍生物及亞胺衍生物。較佳 氮保護基為乙醯基、苯甲醯基、苄基、芊氧羰基（Cbz)、甲 醯基、苯磺醯基、三甲基乙醯基、第三·丁氧羰基（B〇c)、第 三-丁基乙醯基、三氟乙醯基及三苯基甲基（三苯甲基）。 於本文中使用之，，-NZi Z2，，一詞，係意謂兩個基團Z!與Z2， 其係經過氮原子附加至母分子部份基團。Ζι與Z2各獨立選自 氫、燒基、燒羰基、烷基磺醯基、芳基、芳烷基、芳烷基 續酿基、芳基磺醯基、甲醯基、雜環、雜環烷基及雜環烷 基羰基。Z!與Z2各獨立選自氫、烷基、烷羰基、烷基磺醯基 及甲醯基。-NZi Z2之代表性實例，包括但不限於胺基、甲胺 基、二甲胺基、乙醯胺基、（乙醯基）(甲基）胺基及（甲磺醯基） 胺基。 於本文中使用之Π-ΝΖ3 Ζ4 π —詞，係意謂兩個基團，z3與Z4 ’其係經過氮原子附加至母分子部份基團。Z3與Z4各獨立選 自氫、烷基、芳基或芳烷基。-NZ3Z4之代表性實例，包括但 不限於胺基、甲胺基、二甲胺基、乙基甲胺基、苯基胺基 、（苯基甲基）月安基、（2-苯基乙基）胺基、（苯基）(甲基）胺基及二 乙胺基。 於本文中使用之，’(NZS Z4)燒基’’ 一詞，係意謂如本文中定義 之-NZgZ4，經過如本文中定義之烷基附加至母分子部份基團 85228 -136- 200404539 。（NZ3Z4)燒基之代表性實例，包括但不限於胺基甲基、（二 甲胺基）甲基及（甲胺基）甲基。 於本文中使用之Π(ΝΖ3Ζ4)羰基” 一詞，係意謂如本文中定義 之-NZsZ4，經過如本文中定義之羰基附加至母分子部份基團 。（NZ3Z〇羰基之代表性實例，包括但不限於胺基羰基、（甲 胺基）羰基、（二甲胺基）羰基、（苯基甲胺基）羰基、（(苯基）(甲 基)胺基)黢基、（苯基胺基）羧基、（乙基甲胺基)羰基及（二乙胺 基)羧基。 於本文中使用之&quot;(NZ; Z4)續醯基”一詞，係意謂如本文中定 “之-NZ3 Ζ4，經過如本文中定義之續醯基附加至母分子部份 基團。（NZ; Z4 )½醯基之代表性實例，包括但不限於胺基磺 醯基、（甲胺基）續醯基、（二甲胺基）續醯基、（苯基甲胺基）續Ri, R2, R3, r4 and r5 are hydrogen; Xl is CRbRc; χ2 is a bond; D is -CH2-; L2 is -CH2_; L is -N (R7) C (0) _; and RB, κ and R7 are hydrogen. In another specific embodiment of the present invention 4, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable compound thereof. Accepted salts, esters, amidines, or ex vivo drugs, and combined with a pharmaceutically acceptable carrier. In another specific embodiment of the present invention, it relates to a method for treating sexual dysfunction in a mammal, which comprises administering to the mammal a compound of formula (IV) in an amount of j, or a pharmaceutically acceptable amount thereof. Acceptable salts, esters, amines or allopathic drugs' and use of phosphodiesterase 5 inhibitors in combination. In another specific embodiment of the present invention, a method for treating sexual dysfunction in a mammal '纟 includes administering to the mammal a therapeutically effective amount of a compound of formula (1 ¥)' or a pharmacological agent thereof. Acceptable salts, vinegar, amines or prodrugs, and combined with adrenergic receptor antagonists. In another specific embodiment of the present invention, a method for treating sexual dysfunction in a mammal 'includes administering to the mammal a therapeutically effective amount of a class of compounds, or a pharmaceutically acceptable amount thereof. Salt, stuffed, stalk 85228-124- 200404539 amine or prodrug, and dopamine activator. In another specific embodiment of the present invention, a method for treating male erectile dysfunction in male humans, which comprises administering a therapeutically effective amount of a compound of formula (IV) to male humans in need of such treatment. Or pharmaceutically acceptable salts, esters, amidines, or prodrugs, and use a pharmaceutically acceptable carrier. In another embodiment of the present invention, it relates to a method for treating male erectile dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable compound thereof. Acceptable salts, alcohols, ammonium or prodrugs, and combined with phosphodiesterase 5 inhibitors. In another embodiment of the present invention, it relates to a method for treating male erectile dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable compound thereof. Acceptable salts, esters, amidines or prodrugs, and combined with adrenergic receptor antagonists. In another specific embodiment of the present invention, the invention relates to a method for treating male erectile dysfunction in a mammal center, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable compound thereof. Acceptable salts, esters, amidines, or prodrugs with dopamine agonists. a 'In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal / orally, which comprises administering to a mammal in need of such treatment a therapeutically effective amount of formula (IV ) Compound, or a pharmaceutically acceptable agrochemical, amine test or prodrug thereof, and a pharmaceutically acceptable carrier. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal 85228 200404539, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or A pharmaceutically acceptable salt, alcohol, amine, or prodrug, and a phosphodiesterase 5 inhibitor is used in combination. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable compound thereof. Acceptable salts, hydrazones, amidines or prodrugs, and combined with adrenergic receptor antagonists. In another specific embodiment of the present invention, it relates to a method for treating female sexual dysfunction in a mammal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable compound thereof. Acceptable salts, brewers, amidines, or prodrugs, with dopamine agonists. In another embodiment of the present invention, the present invention relates to a method for treating a disorder in a mammal, wherein the disorder is a heart and blood vessel disorder, an inflammatory disorder, a hyperattention disorder, and Alzheimer's disease. , Substance abuse, Parkinson's disease, schizophrenia, anxiety, mood disorders or depression, which include administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV) 'or a pharmaceutically acceptable Salt, stuff, amidine or prodrug. 1 Definition of the invention When used throughout this patent specification and the scope of the attached patent application, the following terms have the following meanings: "Fine base," as used herein, means straight or branched. Branched hydrocarbons containing 2 to 10 carbons and at least one carbon-carbon double bond formed by removing two hydrogens. Representative examples of alkenyl groups include, but are not limited to, vinyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl '4-pentenyl, 5-hexenyl, 2- 85228 -126- 200404539 heptyl, 2-methyl-1-heptyl And 3-decanyl. The term "alkoxy" as used herein means an alkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. The alkoxy group represents 2 Examples include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tertiary-butoxy, pentoxy, and hexyloxy. "Alkane" as used herein The term "oxycarbonyl" means an alkoxy group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of alkoxycarbonyl groups include Not limited to methoxycarbonyl, ethoxycarbonyl, and tertiary-butoxycarbonyl. The term "alkoxysulfonyl" as used herein means an alkoxy group, as defined herein, as defined herein. The sulfofluorenyl group is added to the group of the parent molecule. Representative examples of oxysulfonyl groups include, but are not limited to, methoxysulfanyl, ethoxysulfanyl, and propoxyquinol. In this article The term "alkyl" is used to mean a straight or branched chain hydrocarbon containing from 1 to 10 carbon atoms. Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl , Isopropyl, n-butyl, second-butyl, isobutyl, third-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2, 2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl. The term "alkylcarbonyl" as used herein , Means an alkyl group, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Representative examples of alkylcarbonyl groups include, but are not limited to, ethanyl, 1-ketopropyl, 2,2-dimethyl-1-ketopropyl, 1-ketobutyl, and 1-ketopentyl . The term "alkylcarbonyloxy" as used herein means an alkylcarbonyl group as defined herein 85228 -127- 200404539, which is attached to the parent molecular moiety through an oxygen atom. Representative examples of alkylcarbonyloxy include, but are not limited to, ethenyloxy, ethylcarbonyloxy, and tert-butylcarbonyloxy. '' Alkylene π-The word means a divalent group derived from a straight or branched chain hydrocarbon of 1 to 10 carbon atoms. Examples are &lt; 氐-, -012 &lt; ^ 12_, -01 (013)-, -ch (ch2ch3)-, -ch2ch2ch2-, and -ch2ch2ch2ch2-〇 π alkylsulfinylpyridine π-words as used herein , Means a sulphur group as defined herein, appended to the parent molecular moiety through a sub-acid group as defined herein. Representative examples of alkylsulfinylene include, but are not limited to, methylidene and ethylidene. The term "alkylsulfonyl" as used herein means an alkyl group, as defined herein, appended to the parent molecular moiety through a secondary group, as defined herein. Representative examples of alkylsulfonyl include, but are not limited to, methylsulfonyl and ethylsulfonyl. The term "alkylthio" as used herein means an alkyl group, as defined herein, appended to the parent molecular moiety through a sulfur atom. Representative examples of alkylthio include, but are not limited to, methylthio, ethylthio, tertiary-butylthio, and hexylthio. The term "alkynyl" as used herein means a straight or branched chain hydrocarbon group containing 2 to 10 carbon atoms and containing at least one carbon-carbon parameter. Representative examples of alkynyl include, but are not limited to, ethylene, 1-propenyl, 2-propenyl, 3-butynyl, 2-pentynyl, and 1-butynyl. As used herein, πarylπ-word system means phenyl or bicyclic fused ring system or tricyclic fused ring system, in which one or more fused ring systems are phenyl. 85228 -128- 200404539 An example of a double% fused ring system is a phenyl group fused to another phenyl group or to a cycloalkyl group, where the cycloalkyl system is selected from cyclopentane, cyclohexane ring Heptane or cyclooctane. An example of a tricyclic fused ring system is a bicyclic fused ring system fused to a phenyl group. Representative examples of aryl groups include, but are not limited to, anthracenyl, blue sesame hydrocarbon, Chai Ji, 5,6,7,8_tetrahydronaphthyl, 5,6,7,8_tetrahydroberberyl, 1, 2,3,4-tetrahydronaphthyl, (1SH, 2,3,4_tetrahydro_ 丨 _naphthyl, (1,2,3 4tetrahydrophenyl-naphthyl, hydrogeninyl, indenyl, 3-Dihydro-1H-indenyl '2,3-dihydro-1H-inden-5-yl, 1-fluorenyl, 2-fluorenyl, and phenyl. The aryl group of the present invention is 0, 1, 2 , 3, 4 or 5 substituents, the substituents are independently selected from the group consisting of alkoxy, alkenyl, alkyl, alkylsulfinylfluorenyl, alkylfluorenyl, alkylthio, alkynyl, alkoxycarbonyl, Alkylcarbonyl, alkylcarbonyloxy I-based, cyano, formamyl, thiol, alkynyl, alkynyl, mesityl, hydroxyalkyl, mercapto, methylenedioxy, nitro, -NZiz2, (Heart heart) carbonyl and (NZgZ4) sulfonyl. The aryl group of the present invention may be further substituted with another aryl or aralkyl group as defined herein, wherein the aryl part of the other aryl or aralkyl group Is substituted with 0, 1, 2, 3, 4 or 5 substituents independently selected from alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl Carbothio, alkynyl, alkoxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxyl, methyl, methyl, sulfonyl, alkynyl, meridyl, alkyl, mercapto, methylene Dioxy, fluorenyl, -NZlZ2, (NZ3Z4 weaving group and (NZA) continuation SS group. Representative examples include, but are not limited to, 13-benzodioxolene-5-yl, 3-benzylphenyl , 1,1L biphenyl groups, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-bromo-3-methylphenyl, 4-bromo-2-methylphenyl , 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-amino-4-fluorophenyl, 4-chloro-3-methoxyphenyl, 3-85228 -129- 200404539 chlorine 2-methylphenyl, 2-chloro-5-methylphenyl, 2-chloro-6-methylphenyl, 4-chloro-2,6-dimethylphenyl, 3- Chloro-4-fluorophenyl, 5-chloro-2-methylphenyl, 4-chloro-3-methylphenyl, 3-chloro-4-methylphenyl, 2-chloro- 5-trifluoromethylphenyl, 3-chloro-4-trifluoromethoxyphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2,3-dibromo Methyl-5-methylphenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,6-dichloro-3-methylphenyl, 2,6-Diethyl Phenyl, 3,4-difluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 3,5-dimethoxyphenyl, 2,5-dimethoxy Phenyl, 2,3-dimethylphenyl, 2,6-dimethylphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 3,4-dimethyl Phenyl, 3- (dimethylamino) phenyl, 3-ethoxyphenyl, 4- (ethoxycarbonyl) phenyl, 3-ethylphenyl, 2-ethyl · 6-methylphenyl, 2 -Fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-fluoro-5-methylphenyl, 4-fluoro-3-methylphenyl, 4-fluoro-2-methyl Phenyl, 4-fluoro-3-trifluoromethylphenyl, 3-fluoro-5-trifluoromethylphenyl, 2-fluoro-5-trifluoromethylphenyl, 2-fluoro-3 -Trifluoromethylphenyl, 4-iodomethylphenyl, 3-isopropoxyphenyl, 3-isopropylphenyl, 2-isopropyl-6-methylphenyl, 2- Methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-methoxy-6-methylphenyl, 3-methoxy-2-methylphenyl, 3-methylbenzene Methyl, 2-methylphenyl, 'methylphenyl, 5-methyl winter nitrophenyl, 4-methyl-3-trifluoromethylphenyl, 3-methylthiophenyl, 2-nitro Phenyl, 3-nitrophenyl, 4-nitrophenyl, 2,4,6- Bromo-3-methylphenyl, pentafluorophenyl, 3- (second-butyl) phenyl, 2,4,6-trichlorophenyl, 2,4,6-trifluorobenzyl, 2 _Trifluoromethylphenyl, 3-trifluoromethylphenyl '4-trifluoromethylphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxy Phenyl, 3,4,5-trimethoxyphenyl and 3-vinylphenyl. The term &quot; aralkyl, &quot; as used herein, means an aryl 85228-130-200404539 group, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Aralkyl Representative examples include, but are not limited to, phenylmethyl, phenylphenylethyl, 3-phenylpropyl, and 3- (2-methylphenyl) propyl. As used herein, "aryl continued" The term "group" means an aryl group, as defined herein, appended to the parent molecular moiety through a sulfofluorenyl group, as defined herein. Representative examples of arylsulfonyl groups include, but are not limited to, benzenesulfonyl The term "fluorenyl, 2-methylbenzenesulfonyl, 2-nitrophenylsulfonyl, and 3-nitrophenylsulfonyl" as used herein means the term "sulfonylsulfonyl", which means as An aralkyl group as defined herein is appended to the parent molecular moiety through a sulfofluorenyl group as defined herein. Representative examples of arylsulfonyl groups include, but are not limited to, (phenylmethyl) sulfonyl, (2-phenylethyl) continyl, and (3-phenylpropyl) phenyl. The term "carbonyl" as used herein means a -C (O)-group. The term "'carboxy" as used herein means the -C02H group. The term "pi cyano" as used herein means the -CN group. The term "cycloalkyl" as used herein means a monocyclic, bicyclic, or tricyclic ring system. An example of a monocyclic ring system is a saturated cyclic hydrocarbon group containing 3 to 8 carbon atoms. Examples of monocyclic ring systems include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. An example of a bicyclic ring system is a bridged monocyclic ring system in which two non-adjacent carbon atoms of a monocyclic ring are connected by an alkylene bridge group between one and three other carbon atoms ( _CH2 ·, -CH2CH2 •, and -CH2CH2CH2-). Representative examples of bicyclic ring systems include, but are not limited to, bicyclo [3 · 1 · 1] heptane, bicyclo [2.2.1] heptane, bicyclo [2.2.2] octane, bicyclo [3.2 .2] nonane, bicyclic ρ.3.1] nonane and bicyclo [4 · 2 · 1] nonane. An example of a tricyclic ring system is a bicyclic ring system, 85228 -131- 200404539 where two non-adjacent carbon atoms of a bicyclic ring are bonded via a bond between one and three carbon atoms or an alkylene group. Bridge base connection (_CH2-, _CH2CH2- and one CH2 CH2 CH2-). Representative examples of tricyclic ring systems include, but are not limited to, tricyclo [3.3.1.03,7] nonane and tricyclo [3 · 3.1.13,7] decane (goldenyl). The cycloalkyl system of the present invention is substituted with 0, 1, 2, 3, or 4 substituents, and the substituents are independently selected from alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, Alkylthio, alkynyl, alkoxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, alkyl, cyano, methylamido, i-prime, alkoxy, alkyl, hydroxy, hydroxyalkyl, fluorenyl, Nitro, -NZ〗 Z2, (NZ3Z4) carbonyl or (NZ3Z4) sulfofluorenyl. Representative examples of cycloalkyl substituted with 0, 1, 2, 3, or 4 substituents include, but are not limited to, 2-methylcyclohexyl, 2-cyanocyclohexyl, and 2-methoxycyclohexyl. As used herein, the term "fluoroalkylene" means at least one fluoride atom (-F), appended to the parent molecular moiety through an alkylene group as defined herein. Representative examples of fluoroalkylene are -CH (F)-, -CH (F) CH2-, -COF) 2 CH2-, -CH (F) CH (F)-, -CH (CF3)- , -CH (CH2CF3)-and -CH2CH2CH2CH (F)-. As used herein, the term "n-methylamino" means a _C (〇) h group. As used herein, the term "pi halo" or "halogen" means _α, -Br, -I, or -F. The term "ni alkoxy" as used herein means at least one halogen, as defined herein, appended to the parent molecular moiety through an alkoxy group, as defined herein. Representative of halooxy Examples include, but are not limited to, 2-fluoro small chloroethoxy, chloromethoxy, 2-fluoroethoxy, trifluoromethoxy, and pentafluoroethoxy. 85228 -132- 200404539, \ The term "self-burning group" as used in this article means at least-as in this article-my self-prime, 纟 '^ alkyl group as defined herein is appended to the parent molecular moiety 圏. ㈣ group Representative examples include, but are not limited to, chloromethyl, 2-fluoroethyl, Zfluoromethyl, pentafluoroethyl, and 2.chlorofluoropentyl. "Heterocycles" as used herein Or "heterocyclic" term, which means a monocyclic cloth-like or a% -like mounting system. An example of a monocyclic ring system is any &gt; or weak / have atom, independently selected from oxygen, nitrogen and sulfur; or 5-, 6- or 7-member%, containing one, two or three heteroatoms, where The heteroatom system is independently selected from nitrogen, oxygen, and sulfur. 5-membered rings have ~ 2 double bonds, while 6 • and 7_membered rings have 0_3 double bonds. Representative examples of monocyclic ring systems include, but are not limited to, monoazatetrafluorenyl, monoazaheptanyl, aziridinyl, diazaheptenyl, 3-dioxofluorenyl, Oxaloxanyl, disulfanuranyl, sulfanyl, imidyl, dihydroimidazolyl, tetrahydroimidazolyl, isothiazolyl, isoxazoline, isopyrimidyl, xingyin, Iso-dihydrozine ton-based, isotetrahydro $. Soryl, morpholinyl, carbohydrazyl, dihydrogenyl, dioxoyl, dioxoyl, carbohydrazyl, dihydrocarbyl, tetrahydrooxazolyl, hexahydropyridyl, hexahydro Pyridyl, piperanyl, pyridyl, pyrazolyl, dihydropyrazolyl, tetrahydropyrazolyl, pyridyl, pyrimidinyl, dacrotyl, pyrrolyl, dihydropyrrolyl, tetrahydropyrrolyl, Tetrahydrofuranyl, tetrahydro, sedenyl, tetraphenyl, tetrazolyl, fardiazolyl, farlyturyl, dartolyl, farjunyl, Pselenyl, Pselto, Phenoyl, thiomorpholine, thiomorpholine 1,1-dioxide (thiomorpholine minus), thioalkanoyl, trisyl, trisyl, and trithiouranyl. An example of a bicyclic ring system is any of the monocyclic ring systems described above, fused to a phenyl, cyclohexyl, cyclopentyl or another monocyclic heterocyclic ring. Representative examples of bicyclic ring 85228-133-200404539 systems, including but not limited to, for example, benzimidazolyl, benzodioxolyl, benzo0, benzophenoyl, benzotrisialyl , Benzoyl, Benzyl, Benzoyl, Benzothionyl, Pyridyl, Oxazolyl, Benzolyl, 2,3-Dihydroindolyl, Indyl Base, pyridinyl, isobenzofuranyl, isobenzofluorenyl, isobutyryl, isofluorenyl, perylene, piperanopyryl, quinolinyl, quinolyl, quinoxaline Group, quinazolinyl, tetrahydroisofluorinyl, tetrahydroquinolinyl, and thiopiperanylpyridinyl. An example of a two-percent frame system is any of the bicyclic ring systems described above, fused to a phenyl, cyclohexyl, cyclopentyl, or another monocyclic heterocyclic ring. Representative examples of tricyclic ring systems include, but are not limited to, acridinyl, carbazolyl, carbolinyl, dibenzo [b, d] furanyl, dibenzofluorenyl, naphtho [2,3 VII] p Fang, Ping and [2,3 VII] cephenyl, bell whistle base, pharyngeal p well base, phryngyl base, p cynyl base, p cynyl base and u mountain base. The heterocyclic system of the present invention is substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from the group consisting of alkoxy, alkenyl, alkynyl, alkynyl, alkynyl, alkynyl, and alkylthio. Alkynyl, alkynyl, alkoxycarbonyl, alkcarbonyl, alkcarbonyloxy, carboxyl, cyano, formamyl, sulfone, alkoxy, alkyl, hydroxy, alkyl, thiol, nitro,- NZiZ, (NZ3Z4) carbonyl and (NZ3Z4) sulfofluorenyl. The heterocyclic group of the present invention may be further substituted with another heterocyclic group as defined herein, wherein the other heterocyclic group is substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from Alkoxy, alkenyl, alkyl, alkylsulfinyl, sulfanyl, dithio, thiol, decyl, oxyfluorenyl, carbonyl, carbonyloxy, alkyl, cyano, formic acid Base, pixel, iSalkenyl, alkynyl, hydroxy, hydroxyalkyl, mercapto, nitro, -NZiZ2, (NZ3Z4) carbonyl and (nz3z4) 85228 -134- 200404539 sulfonyl. Representative examples include, but are not limited to, 1,3-dimethylbiol-5-yl, 5-fluoro-1,3-benzyl-2-ol, 1-methyl-1H-benzimidyl Spit _2_yl, 6_chloro-based dextrin-2 · yl and 4-p than bite-2_ylhexahydro; hu-1-yl. As used herein, the term "heterocycloalkyl" means a heterocycle, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein. Representative examples of heterocycloalkyl include, but are not limited to, pyridyl methyl, 2-p denselyl-2-ylpropyl, and 4-p-pyridin-2-ylhexahydrogen. base. The term "heterocyclic carbonyl" as used herein means a heterocyclic ring, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. Pyridin-3-ylcarboxy, lin-3-ylcarbonyl and 4-pyridin-2-ylhexahydrocarbylpyridylmethylcarbonyl. The term "π hydroxyl" as used herein means an -OH group. The term "hydroxyalkyl" as used herein means at least one hydroxyl group as defined herein, as defined herein The alkyl group is added to the parent molecular moiety. Representative examples of hexadecyl include, but are not limited to, methyl, 2-chiethyl, 3-hydroxypropyl, 2-ethylpiperidyl, and 2,4-dihydroxybutyl. The term "π-hydroxyalkylene group" as used herein means at least one hydroxyl group, as defined herein, appended to the parent molecular moiety through a hypoalkylene group, as defined herein. Examples are _CH2CH (OH) CH2-, -CH (CH2 OH) ...- CH (CH2 CH2 OH) _ and -CH2 CH2 CH (OH) C ^^ The term "mercapto" as used herein means It is referred to as the _SH group. The term "methylenedioxy," as used herein, means -0CH20- group, wherein the oxygen atom of the methyleneoxy group passes through two adjacent carbon atoms. Group attached to the parent molecular moiety. Representative examples include, but are not limited to, 1,3-benzobis 85228 -135- 200404539 oxopenhen-5-yl. The term "nitro," as used herein, means the -no2 group. The term "nitrogen protecting group," as used herein, is intended to protect the amine group to prevent undesired during the synthetic procedure Reactive group. Nitrogen protecting groups include carbamates, amidines, N-fluorenyl derivatives and imine derivatives. Preferred nitrogen protecting groups are ethenyl, benzamidine, benzyl, fluorenyloxycarbonyl (Cbz), formamyl, benzenesulfonyl, trimethylethylsulfonyl, and tert-butoxycarbonyl (B. c), tert-butylethylfluorenyl, trifluoroethylfluorenyl and triphenylmethyl (trityl). As used herein, the term -NZi Z2 ,, means two groups Z! And Z2, which are attached to the parent molecular moiety through a nitrogen atom. Zι and Z2 are each independently selected from hydrogen, alkyl, carbonyl, alkylsulfonyl, aryl, aralkyl, aralkyl continuation group, arylsulfonyl, formamyl, heterocycle, heterocycle Alkyl and heterocycloalkylcarbonyl. Z! And Z2 are each independently selected from hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl and formamyl. Representative examples of -NZi Z2 include, but are not limited to, amine, methylamine, dimethylamino, acetamido, (ethylamido) (methyl) amino, and (methanesulfonyl) amino. As used herein, the term Π-NZ3 Zn4 π means two groups, z3 and Z4 ′ which are attached to the parent molecular moiety through a nitrogen atom. Z3 and Z4 are each independently selected from hydrogen, alkyl, aryl or aralkyl. Representative examples of -NZ3Z4 include, but are not limited to, amino, methylamino, dimethylamino, ethylmethylamino, phenylamino, (phenylmethyl) moonyl, (2-phenylethyl) Group) amino group, (phenyl) (methyl) amino group and diethylamino group. As used herein, the term '(NZS Z4) alkenyl' means -NZgZ4, as defined herein, appended to the parent molecular moiety through an alkyl group, as defined herein, 85228 -136- 200404539 . Representative examples of (NZ3Z4) alkyl include, but are not limited to, aminomethyl, (dimethylamino) methyl, and (methylamino) methyl. As used herein, the term "((ZZ3Z4) carbonyl)" means -NZsZ4, as defined herein, appended to the parent molecular moiety through a carbonyl group, as defined herein. (A representative example of NZ3Z0 carbonyl, Including but not limited to aminocarbonyl, (methylamino) carbonyl, (dimethylamino) carbonyl, (phenylmethylamino) carbonyl, ((phenyl) (methyl) amino) fluorenyl, (phenyl (Amino) carboxyl, (ethylmethylamino) carbonyl and (diethylamino) carboxyl. The term "(NZ; Z4) continyl" as used herein means "as defined herein" -NZ3 Z4, attached to the parent molecular moiety through a continuation group as defined herein. (NZ; Z4) Representative examples of fluorenyl groups, including, but not limited to, aminosulfonyl, (methylamino) Continue fluorenyl, (dimethylamino) Continue fluorenyl, (phenylmethylamino) Continue

、（苯基胺基）磺醯基及（乙基甲胺基）續醯基。, (Phenylamino) sulfofluorenyl and (ethylmethylamino) continuous fluorenyl.

性起功能障礙或早线。 於本文中使用之”Sexual dysfunction or early line. Used in this article "

包括但不限於女 乞血、性感不快 及陰道瘦攣。 陰道充血、This includes, but is not limited to, female begging blood, sexual unhappiness, and vaginal spasms. Vaginal congestion,

，其中有不對稱或對掌 85228 200404539 中心存在。此等立體異構物為flR”或nS’’，依環繞對掌性碳原 子之取代基組態而定。於本文中使用之nR’f與'fSn術語，係為 如在IUPAC 1974關於段落E，基本立體化學，Pure Appl. Chem·， 1976, 45 : 13-30建議中所定義之組態。本發明意欲涵蓋各種立 體異構物及其混合物，且明確地包含在本發明之範圍内。 立體異構物包括對掌異構物與非對映異構物，及對掌異構 物或非對映異構物之混合物。特定言之，在式（III)或式（IV) 化合物之-L2-B連接點之立體化學，其中X:為一個鍵結，且X2 為CRDRE，可獨立為（R)或（S)之任一個。在式（III)或式（IV)化 合物之-L2-B連接點之立體化學，其中X!為CRBR〇，且X2為一 個键結，可獨立為（R)或（S)之任一個。在式（III)或式（IV)化合 物之-L2-B連接點之立體化學，其中&amp;為CRbRc，且X2為CRdRe ，可獨立為（R)或（S)之任一個。本發明化合物之個別立體異 構物可以合成方式製自含有不對稱或對掌中心之市購可得 起始物質，或藉由製備消旋混合物，接著為一般熟諳此項 技藝者所習知之解析。此等解析方法之實例為⑴使對掌異 構物之混合物連接至對掌性輔助劑，藉再結晶或層析分離 所形成之非對映異構物混合物，及自輔助劑釋出光學上純 之產物，（2)光學對掌異構物混合物在對掌性層析管柱上之 直接分離，或（3)非對映異構物鹽之形成，接著為非對映異 構物鹽其中一個之選擇性再結晶作用。 本發明化合物係由ACD/ChemSketch第5.0版（由先進化學發展 公司，Toronto, ON，Canada所開發）命名，或給予顯示與ACD命名 法一致之名稱。 85228 -138- 200404539 本發明之較佳化合物包括： 2-[4·(2-甲氧苯基）-1-六氫吡畊基]-N_(3_甲基苯基）乙醯胺； 2-[4-(2_氰基苯基）小六氫吡喷基]甲基苯基）乙醯胺； Ν-(3-甲基苯基）-2-[4-(2-嘧啶基）-1-六氫吡畊基]乙醯胺； N-(3-甲基苯基）-2-[4-(2-吡啶基）_1_六氫吡畊基]乙醯胺； 2-[4-(3-氰基_2_吡啶基&gt;1_六氫井基]_n_(3_甲基苯基）乙醯胺； N-(3-甲基苯基）-2-[4-(2-甲基苯基）小六氫p比p井基]乙酸胺； N-(3-甲基苯基）-2-[4-(2-硝基苯基）_1_六氫p比p井基]乙酿胺； _ 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(3_硝基苯基）乙醯胺； 2-[4-(3_氰基-2-吡啶基）小六氫吡畊基;|-N-[3-(三氟甲基）苯基]乙 醯胺； N-(3-甲基苯基）-2-(4-苯基-1-六氫吡畊基）乙醯胺； N-(3-氰基苯基）-2_[4-(3-氰基-2-峨淀基）-1-六氫咐1 p井基]乙酿胺； N-(4-溴基-3-甲基苯基）-2-[4-(2-氯基苯基）-1-六氫u比p井基]乙醯 胺； 2-[4-(2-氣基苯基）-1-7^鼠卩比p井基]-N-苯基乙酿胺； 2-[4-(3-薇基比淀基）-1-ττ氮峨p井基]冬基乙驢胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(4-氟苯基）乙醯胺； 2-[4-(3-氯基-2-ρ比淀基）-1·ή氣外17井基]-N-(3,5-二甲基苯基）乙酿 胺； 2-[4-(3-氰基-2-吡啶基）-1-六氫吡畊基]-N-(2,3-二甲基苯基）乙醯 胺； 2_[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-(2-甲基苯基）乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-(2,5-二甲基苯基）乙醯 85228 -139- 200404539 胺； N-(3-氯苯基）-2-[4-(3-氰基-2_p比淀基）-1-六氫p比呼基]乙酿胺； N-(3-氯基-4-氟苯基）-2-[4-(3·«氣基-2-p比淀基）-1_六氫批呼基]乙 醯胺； 2-[4-(3-氰基-2-外1：淀基）-l-：r;氫峨呼基]_N-(3,4,5-三甲氧基苯基） 乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν_[4·氟基-3-(三氟甲基） 苯基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-[3-氟基-5-(三氟甲基） 苯基]乙醯胺； 2-[4-(3•氰基-2-ρ比淀基）-1-六氫峨_基]-N-[2-氟基-5-(三氟甲基） 苯基]乙醯胺； 2-[4-(3-散基-2»^比淀基）-1-六氫说p井基]-N-[2-氟基-3-(三氟甲基） 苯基]乙醯胺； 2·[4-(3-氰基-2-峨淀基）-1_六氫峨啡基]-N_(4-|t基-3-甲基苯基） 乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν_(2·氟苯基）乙醯胺； 2-[4-(3-氣基-2-ρ比淀基氯ρ比呼基]-Ν-(2-甲氧苯基）乙酸胺； 2-[4-(3-氰基-2-吡啶基&gt;1-六氫吡畊基]-Ν-(2-硝基苯基）乙醯胺； 2-[4-(3-氣基-2-ρ比淀基）小六氮ρ比啡基]-Ν-[2-(三氣甲基）苯基]乙 醯胺； Ν_冬基-2-[4·(2-β比淀基）-l-：r?氯口比p井基]乙酸胺； N-(3-甲基苯基）-2-[4-(1，3-嘧唑-2-基）小六氫吡畊基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-(4·甲基苯基）乙醯胺； 200404539 2-[4-(2-甲氧苯基）-1-六氩吡啶基]-N-(3-甲基笨基）乙醯胺； 2-[4-(2-氟苯基）-1-六氫吡啶基]-N-(3-甲基苯基）乙醯胺； N-(3-甲基苯基）-2-[4-(2-甲基苯基）小六氫吡啶基]乙醯胺； 2-[4-(3-氟苯基）小六氫吡啶基]-N-(3-甲基苯基）乙醯胺； N-(3-甲基苯基）-2-[4-(6-酮基-1(6H)-嗒畊基）-1-六氫吡啶基]乙醯 胺； N-(2,6-二甲基苯基）-2-[4-(2-嘧吩基）-1-六氫吡啶基]乙醯胺； Ν-(2,5·二甲基苯基）-2-[4-(2-嘧吩基）-1-六氫吡啶基]乙醯胺； N-(2-甲基苯基）-2-[4-(2-嘧吩基）-1-六氫吡啶基]乙醯胺； N-(3-氯基-4-氟苯基）-2-[4-(2-嘧吩基）-1-六氫吡啶基]乙醯胺； N-(4-&gt;臭苯基）-2-[4-(2-ρ比淀基）-1-ττ鼠批淀基]乙酸胺， Ν-(2,6-二甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2-硝基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； N-(3-硝基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； Ν·(2,4-二氟苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2,5-二甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2-甲基苯基）-2-[4-(2·吡啶基）-1-六氫吡啶基]乙醯胺； N_(4-甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡啶基]-N-[3-(三氟甲基）苯基]乙醯胺； 4-({[4-(2-吡啶基）-1-六氫吡啶基]乙醯基}胺基）苯甲酸乙酯； N-(3-氯基-4-甲基苯基）-2-[4-(2·吡啶基）小六氫吡啶基]乙醯胺； N-(2-氰基苯基）-2-[4-(2-吡啶基&gt;1-六氫吡啶基]乙醯胺； N-(3-氯苯基）-2_[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）-1-六氫吡啶基]-N-(3-甲基苯基）乙醯胺； 85228 -141- 200404539 N-(3-甲基苯基）-2-(4-苯基-3,6-二氫-1(2H)-吡啶基）乙醯胺； 2-(3'6’-二氫·2,4’_聯吡啶-Γ(2Ή)-基）-N-(3_甲基苯基）乙醯胺； 2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）-N-(2,6-二甲基苯基）乙醯胺； 2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）-N_(2-硝基苯基）乙醯胺； 2-(3’，6’-二氫-2,4’_聯吡啶-Γ(2Ή)-基）-Ν·(3-硝基苯基）乙醯胺； 2-(3f，6’_二氫_2,4^聯吡啶·Γ(2Ή)-基）-Ν-(4·氟苯基）乙醯胺； Ν-(2,4·二氟苯基）-2-(3’，6’-二氫·2,4’·聯吡啶·Γ(2Ή)_基）乙醯胺； 2-(3'6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-(2,5-二甲基苯基）乙醯胺； · 2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）-Ν-(2_甲基苯基）乙醯胺； Ν-環己基-2-(3’，仏二氫_2,4’·聯吡啶-；Γ(2Ή)-基）乙醯胺； 2-(3’，6’-二氫·2,4’_聯吡啶_1’(2Ή)_基）-Ν_(4-甲基苯基）乙醯胺； 2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)·基）-Ν-[3-(三氟甲基）苯基]乙醯胺； 4-[(3f，6’-二氫-2,4f-聯吡啶-1’(2Ή)-基乙醯基）胺基]苯甲酸乙酯； Ν-[2-氯基-5-(三氟甲基）苯基]-2-(3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基） 乙醯胺； Ν-(3-氯基-4-甲基苯基）-2-(3f，6’_二氫-2^-聯吡啶-Γ(2Ή)-基）乙醯· 胺； Ν-(2-氰基苯基）-2-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； Ν-(3-氯苯基）-2-(3f，6’·二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； Ν-(3-氯基-4-氟苯基）-2-(3’，6f-二氫-2,4’-聯吡啶-Γ(2Ή)_基）乙醯胺； 2-(3、6’-二氫-2,4’-聯吡啶-1’(2Ή)-基)-Ν-[4-(三氟甲氧基）苯基]乙醯 胺； 2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基)-Ν-[2_(三氟甲基）苯基]乙醯胺； Ν-(4-氯苯基）-2-(3’，6’-二氫-2,4f-聯吡啶-1’(2Ή)-基）乙醯胺； 85228 -142- 200404539 N-(2,3-二氯苯基）-2·(3’，6’-二氫 _2,4’_聯吡啶-Γ(2Ή)-基）乙醯胺； 斗(3,5-二氯苯基）-2-(3'6’-二氫-2,4^聯吡啶-1丫2’11)-基）乙醯胺； 2-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-(4-氟基_2_甲基苯基）乙醯 胺； Ν-(4-氟苯基）-2-[4-(2-吡啶基）_1-六氫吡啶基]乙醯胺； Ν-(3,5-二氯苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； Ν-(2,3-二氯苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡啶基]-N_[2-(三氟甲基）苯基]乙醯胺； N-(3-氯基_4-氣苯基）-2-[4-(2-峨淀基）小7T氯峨淀基]乙酸胺； 2- [4-(2-吡啶基）4-六氫吡啶基]-Ν-[4-(三氟甲氧基）苯基]乙醯胺； 1^環己基-2-(3’，4’，5’,6^四氫-2’11-[2,4’]聯吡啶基-1’-基）乙醯胺； Ν-{[4-(2-氰基苯基）小六氫吡畊基]甲基}-3-甲基苯甲醯胺； 3- 甲基-Ν-{[4-(2-嘧啶基）-1-六氫吡畊基]甲基}苯甲醯胺； 3-甲基-N-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲醯胺； 3-甲基_N-[(4-苯基-1-六氫吡畊基）甲基]苯甲醯胺； N-{[4-(2-甲氧苯基）小六氫吡畊基]甲基}-3-甲基苯甲醯胺； 乂{[4-(2-氣基苯基氫外1： p井基]甲基}-2-甲基苯甲醯胺； N-{[4-(2-氰基苯基）小六氫吡畊基]甲基}-4-甲基苯甲醯胺； N_{[4-(3-氰基-2-吡啶基）-1·六氫吡畊基]甲基}·3-甲基苯甲醯胺； Ν-{[4-(3-氰基苯基）小六氫吡畊基]甲基卜3-甲基苯甲醯胺； Ν-{[4_(3-氰基苯基）小六氫吡畊基]甲基}-2_甲基苯甲醯胺； Ν-{[4-(3-氰基-2-吡啶基)-1-六氫吡畊基]甲基}苯甲醯胺； N-{[4-(3-氰基-2-吡啶基)-1-六氫吡畊基]甲基}_4_甲基苯甲醯胺； N-{[4-(3-氰基-2-吡啶基)-1-六氫吡畊基]甲基卜2-甲基苯甲醯胺； 85228 -143- 200404539 N-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲醯胺； N-{[4-(2-氯苯基）-1-六氫吡畊基]甲基}苯甲醯胺； 3- 氯-N-{[4-(2-氰基苯基）-1-六氫吡畊基]甲基}苯甲醯胺； 4- 氯-N-{[4-(2-甲氧苯基）-1·六氫吡畊基]甲基}苯甲醯胺； 2- 氯-N-{[4-(3-氰基-2-吡啶基）小六氫吡畊基]甲基}苯甲醯胺； N-{[4-(3-氰基-2-吡啶基）小六氫吡畊基]甲基}-2-(三氟甲基）苯 甲醯胺； N-{[4-(2-氰基苯基）小六氫吡畊基]甲基}苯甲醯胺； N-{[4-(2-甲氧苯基）小六氫吡啶基]甲基}各甲基苯甲醯胺； 3- 甲基-N-{[4-(2-吡啶基）小六氫吡啶基]甲基}苯甲醯胺； 3-甲基-N-[(4-苯基·3,6-二氫-1(2H)-吡啶基）甲基]苯甲醯胺； N_(3’，6’_二氫-2,4’-聯吡啶-1·(2Ή)-基甲基）·3_甲基苯甲醯胺； N-(3f，6f-二氫-2/Μ葬吡啶·ΙΘΉ)-基甲基）-3-甲氧基苯甲醯胺； N-(3’，6’-二氫_2,聯吡啶·Γ(2Ή)_基甲基）_3·氟基苯甲醯胺； N-(3’，6f-二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）-3,5_二氟苯甲醯胺； 2-[4-(3-孰基-2-峨淀基）-1-六氫外1： ρ井基]比淀基乙酿胺； 2-(1_{2_[(3-甲基苯基）胺基]_2_酮基乙基}六氫ρ比淀_4_基）π比錠队 氧化物； Ν-(3-甲基苯基）-2-[4-(2-峨淀基）-1-六氫吨淀基]乙驢胺； N-2-金鋼燒基-2-[4-(3-氣基-2-11比淀基）小六氫p比呼基]乙酿胺； 2-[4-(3•氰基-2-外(:淀基）-1-六氫叶ti ρ井基]環己基乙酸胺； 2-[4-(3-氰基-2-外1:淀基）-1_六氫外1：啡基]孙5,6,7,8-四氫-1-蕃基乙 醯胺； 2-(3’，仏二氫-2,4’_聯吡啶-1’(2Ή)-基）-Ν-(4_氟基_2_甲基苯基）乙醯 85228 -144- 200404539 胺； N-{[4-(2-吡啶基）-1-六氫吡啶基]甲基}-3-(三氟甲基）苯甲醯胺； 3.5- 二甲氧基-N-{[4-(2-p比啶基）小六氫吡啶基]甲基}苯甲醯胺； N-{[4-(2-说啶基）小六氫吡啶基]甲基}環己烷羧醯胺； 3,4_二氟-N-{[4-(2-吡啶基）-1-六氫吡啶基]甲基}苯甲醯胺； 3-氯-N-{[4-(2-吡啶基）-1-六氫吡啶基]甲基}苯甲醯胺； 2,3-二甲基-N-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲醯胺； N-(3’，仏二氫-2,4·-聯吡啶-Γ(2Ή)-基甲基）-3-(三氟甲基）苯甲醯胺；_ 3-氯-N-(3’，6f•二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基）苯甲醯胺； Ν-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基）環己烷羧醯胺； Ν·(3’，6’·二氫-2,4f-聯吡啶-Γ(2Ή)-基甲基）-3,4-二氟苯甲醯胺； Ν-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基）-3,5·二甲氧基苯甲醯胺； Ν-(3_甲基苯基）-2-(4_苯基小六氫吡啶基）乙醯胺； 2- (3’，6’_二氫-2,4f-聯吡啶-Γ(2Ή)-基）·Ν-(3_硝基苯基）乙醯胺； Ν-1-金鋼燒基-2-[4-(3-戴基-2-ρ比淀基氯咐ρ井基]乙酸胺； 3- 甲基_Ν·{[2_甲基-4-(2-外1;淀基）-1_ττ鼠ρ比哨1基]甲基}苯甲酿胺；_ Ν-(3-甲基苯基）-2-[2-甲基-4-(2-吡啶基）-1-六氫吡畊基]乙醯胺； 3.5- 二甲基-N-{[4-(2-吡啶基）-1-六氫吡啶基]甲基}苯甲醯胺； N-P1/’-二氫_2,4’_聯吡啶-1’(2Ή)-基甲基）-3,5-二甲基苯甲醯胺； 3-甲基-Ν-[(3-甲基-3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）甲基]苯甲醯 胺； Ν-[(3-氰基-3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）甲基]_3_甲基苯甲醯 胺； Ν-(2,6-二甲基苯基）-2-(3-甲基-3’，6’-二氫·2,4’_聯吡啶-ΐ’(2Ή&gt;基）乙 85228 -145- 200404539 醯胺 ;Ν·(4_氟苯基）-2-(3-甲基-3，，6，-二氫-2,4，-聯吡啶-1，(2Ή)-基）乙醯 胺； Ν-(2,4-二氟苯基）-2-(3-甲基 _3，，6，_二氫-2,4，-聯吡啶-1，(2Ή)-基）乙醯 胺； 2-(3•甲基_3’，6’_二氫_2,4，-聯吡啶·1，(2Ή)_基）-Ν-(2-甲基苯基）乙醯 胺； 2-(3_ 甲基 _3’，6’_二氫-2,4，-聯吡啶-1，(2Ή)-基）_N_[3-(S 氟甲基）苯基] 乙醯胺； N-(3-氯基冰氟苯基甲基_3，，6，_二氫·2,4，_聯吡啶_l，(2，H)_基） 乙醯胺； 2-(3-甲基_3’，6’-二氫_2,4，-聯吡啶·1，(2Ή)-基）-N-[4_(三氟甲氧基）苯 基]乙醯胺； 2-(3-甲基_3’，6’_二氫_2,4，-聯吡啶-1，(2Ή)·基）_N-[2_(三氟甲基）苯基] 乙醯胺； N-(2,3-二氯笨基）-2-(3_甲基-3，，6，二氫-2,4，·聯吡啶氺(2Ή)_基）乙醯 胺； 2-(3-甲基·3’，6,·二氫_2,4，_聯吡啶-1，(2Ή)_基）-Ν_[4-(三氟甲基）苯基] 乙醯胺； 2-[4-(3-氰基|嘧吩基）_3,6_二氫4(2Η)-吡啶基]_Ν_(3_甲基苯基） 乙醯胺； 2_(3_氰基 _3’，6，_二氫 _2,4，_聯吡啶-1，(2Ή)-基）-Ν-(2,6-二甲基苯基）乙 醯胺； 2-(3-氰基_3，，6，_二氫_2,4，_聯吡啶-1，(2Ή)-基）善(4_氟苯基）乙醯胺； 85228 -146- 200404539 2-(3-氰基 _3f，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基）-N-(2,4-二氟苯基）乙醯 胺； 2-(3-氰基-3f,6L二氩_2,4’-聯p比淀-Γ(2Ή)-基）-N-(2-甲基苯基）乙酉蠢 胺； 2-(3-氰基-3’，6’_二氫-2,4f-聯叶1:淀_Γ(2Ή)_基）-N-[3-(三敦甲基）苯基] 乙醯胺； 2-(3-氰基-3’，6’-二氫-2，心聯^:淀-Γ(2Ή)-基）-Ν·[4-(三氟甲氧基）苯 基]乙醯胺； 2-(3-氰基-3，，6，-二氫-2,-聯吡啶-Γ(2Ή)-基）-Ν-[2-(三氟甲基）苯基] 乙醯胺； 2- (3-氰基-3’，6’-二氫聯^:淀-Γ(2Ή)_基）-Ν-(2,3-二氯苯基）乙酿 胺； 3- 甲基-Ν-{[4-(6-酮基-1(6Η)-嗒畊基）小六氫吡啶基]甲基}苯甲 醯胺； N-(3T，6f-二氯-2,4’-聯ρ比淀-1’(2Ή)·基甲基）小金剛燒，三環癸燒羧 醯胺； 3-甲基_Ν-{[4_(1，3-碟唆-2-基）-3,6-二氫-1(2Η)-ρ比淀基]甲基}苯甲 醯胺； 2-[4-(3-氰基-2-吡啶基）-1_六氫吡啡基]孙1，2,3,4_四氫小茶基乙 醯胺； 2-[4_(3-氰基吡啶基）-1_六氫吡畊基；||[(1卟1，2,3,4_四氫小茶 基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）_ι_六氫吡畊基]|[(1吵1，2,3,4_四氫_1_其 基]乙醯胺； 85228 -147- 200404539 N-(2,6-二乙基苯基）-2-[4-(2-ρ比淀基）-1-ττ氣外b淀基]乙S盛胺； 2-[4-(2-吡啶基）-1-六氫吡啶基]-N-(2,4,6-三氟苯基）乙醯胺； N-(4-氯基-2,6-二甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯 胺； 2-[4-(2-?比淀基）-l_：r?氯卩比淀基]_N-(2,4,6-二氣苯基）乙酸胺； N-(2,6-二乙基苯基）-2-(3*，6’_二氮-2,4’-聯 ρ比淀-lf(2’H)-基）乙酿胺； 2-(3’，6’-二氫-2,4f-聯吡啶-Γ(2Ή)-基）-N-(2,4,6-三氟苯基）乙醯胺； N-(4-氯基-2,6-二甲基苯基)-2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）乙 φ 醯胺； 2-(3’，6’-二氫-2,聯吡啶-1’(2Ή)-基）-Ν-(2,4,6_三氯苯基）乙醯胺； Ν-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}-3-(三氟甲基）苯甲醯胺； 3,5-二甲氧基-N-{[4-(24啶基）-1-六氫吡畊基]甲基}苯甲醯胺； N_{[4-(2-吡啶基&gt;1-六氫吡畊基]甲基}環己烷羧醯胺； N-(2,6-二甲基苯基）-2-[4-(2-p比淀基）-1-ττ氣峨p井基]乙龜胺； Ν-(4-氟苯基）-2-[4-(2-吡啶基）-1-六氫吡畊基]乙醯胺； N-(2,4-二氣苯基）-2-[4-(2巧比淀基）-1-六氯p比_基]乙酿胺； _ Ν-(2-甲基苯基）-2-[4-(2-吡啶基）小六氫吡畊基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡畊基]-Ν-[3-(三氟甲基）苯基]乙醯胺； Ν-(3-氯苯基）-2-[4-(2·吡啶基）小六氫吡畊基]乙醯胺； Ν-爷基-2-[4-(2-ρ比淀基）小六氫外1：ρ井基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡畊基]-Ν-[4-(三氟甲氧基）苯基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡畊基]-Ν-[2-(三氟甲基）苯基]乙醯胺； Ν-(4-氯苯基）-2-[4-(2-吡啶基)小六氫吡畊基]乙醯胺； Ν-(2,3-二氯苯基）-2-[4-(2-吡啶基）小六氫吡畊基]乙醯胺； 85228 -148- ii· 〇* --ί 200404539 N-(3,4-二氯苯基）-2-[4-(2-p比淀基）-1-六氫外l：p井基]乙醯胺； 2- [4-(2-p比淀基）小六氫说畊基]-N-[4-(三氟甲基）苯基]乙醯胺； 3- 氯-N-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲醯胺； 4- 氟基-3-甲基-N-{[4-(2-p比淀基）-1-ττ氫p比呼基]甲基}苯甲酸胺； Ν-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）-4-氟基_3_甲基苯甲醯 胺； 3-甲基-N-{[4-(1，3-噚唑-2-基）_3,6-二氫-l(2H)_p比啶基]甲基}苯甲 醯胺； φ 2-甲基-N-[(3-甲基-3’，6’-二氮-2,4’-聯ρ比淀-Γ(2Ή)·基）甲基]苯甲酸 胺； 2-[4-(3-氣基-2-ρ比淀基）-1·ττ氯ρ比淀基]-Ν-(2,6-二甲基苯基）乙酸 胺； Ν-(3-甲基苯基）-2-[4-(3-甲基-2-峨淀基）-1-六氫叶(：ρ井基]乙酸胺； 2-[4-(3-氯基-2-ρ比淀基）-1-六氫外tl ρ井基]-Ν-[4-(三氟甲基）苯基]乙 醯胺； Ν-(2-乙基-6-甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺；籲 Ν-(2-異丙基-6-甲基苯基）-2-[4-(2-峨啶基）小六氫吡啶基]乙醯 胺； Ν·(2-氯基-6-甲基苯基）-2-[4-(2·吡啶基）小六氫吡啶基]乙醯胺； Ν-(2-甲氧基-6-甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯 胺； 2-(3W-二氫-2,4f-聯吡啶-1’(2Ή)-基）_N-(2-乙基-6-甲基苯基）乙醯 胺； 2-(3\6’-二氫-2,聯吡啶-Γ(2Ή)_基）-N-(2-異丙基-6-甲基苯基）乙 85228 -149- 200404539 醯胺； N-(2-氯基各甲基苯基）_2_(3’，6，-二氫-2,4，-聯吡啶-1，(2Ή)-基）乙醯 胺； 2- (3’，6’-二氫-2,聯吡啶-ΐ’(2Ή)-基）-Ν-(2-甲氧基-6-甲基苯基）乙 醯胺； 3- 氯-Ν-[(3-甲基_3’，6’-二氫-2,4，·聯吡啶-1’(2Ή)-基）甲基]苯甲醯胺； 3·氟·Ν-[(3·甲基_3’，6’_二氫_2,4，_聯吡啶-Γ(2Ή)-基）甲基]苯甲醯胺； 3-甲基-N-{[(2S)-2-甲基_4-(2-吡啶基）小六氫吡啡基]甲基}苯甲 _ 醯胺； N-(3-甲基苯基）_2_[(2S)-2-甲基-4-(2-吡啶基）小六氫吡畊基]乙醯 胺； 3-甲基-N-{[(2R&gt;2-甲基-4-(2-吡啶基）小六氫吡畊基]甲基}苯甲 醯胺； N-(3-甲基冬基）-2-[(2R)-2-甲基-4-(2·ρ比淀基氯批p井基]乙酉盡 胺； 3-甲氧基·Ν-[(3-甲基-3’方-二氫-2,4’-聯吡啶-1’(2Ή)_基）甲基]苯甲 籲 醯胺； 4·氟-Ν-[(3-甲基·3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）甲基]苯甲醯胺； 2_(3·氯基J，6’-二氫-2,4’_聯吡啶-1’(2Ή)-基）-Ν-(2,6-二甲基苯基）乙 醯胺 ;2-(3-氯基二氫-2,聯吡啶-Γ(2Ή)_基）-Ν-(2_甲基苯基）乙 醯胺； Ν-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)·基甲基）-1-萘甲醯胺； Ν-{[4-(3-^基-2-ρ比淀基）-1-77氮峨p井基]甲基}-3-氟基苯甲酿胺； 85228 -150- 200404539 2-(l_{2-[(4-氟基-2-甲基苯基）胺基]_2_酮基乙基}-4-六氫吡啶基） 吡錠N-氧化物； 2-(1-{2-[(4-氟基-3-甲基苯基）胺基]-2-酮基乙基}-4-六氫吡啶基） 吡錠N-氧化物； 2-(1-{2-[(3-氟苯基）胺基]-2-酮基乙基}-4-六氫吡啶基）吡錠N-氧 化物； 2-(1-{2-[(2-氟基-5-甲基苯基）胺基]-2-酮基乙基}-4-六氫吡啶基） 吡錠N-氧化物； 2_(1-{1-甲基·2-[(3-甲基苯基）胺基]-2_酮基乙基卜4-六氫吡啶基） 吡錠Ν-氧化物； 2- (1-{2-[(4-氟苯基）胺基]-2-酮基乙基}-4-六氫ρ比淀基 &gt;比鍵Ν-氧 化物； 2·(1-{2-[(2-氟苯基）胺基]-2-酮基乙基}-4-六氫吡啶基）吡錠Ν-氧 化物； Ν-(3-甲基苯基）-2-{4-[3-(三氟甲基）-2-吡啶基]小六氫吡畊基}乙 醯胺； N_(3-甲基苯基）-2-{4-[3-(三氟甲基）-2-被啶基]小六氫吡畊基}乙 醯胺； N-(3-甲基苯基）-2-[4-(1，3-嘧唑-2-基）-3,6-二氫吡啶-1(2H)_基]乙醯 胺； N-(3-甲基苯基）-2-(4-^塞吩-2-基-3,6-二氮ρ比淀-1(2H)-基）乙驢胺； 3- 甲基_N-[(4-嘧吩-2-基-3,6-二氫吡啶-1(2H)-基）甲基]苯甲醯胺； 2-(1-{2_[(3-氯苯基）胺基]-2-酮基乙基}六氫吡啶冰基）吡錠N-氧 化物； 85228 -151 - 200404539 2-[4-(l-甲基-1H-味哇-2-基）-3,6-· — 鼠 p比淀-1(2H)_基]-Ν-(3·甲基苯 基）乙醯胺； Ν-(3-甲基苯基）-2-[4-(3-硝基ρ比淀_2_基）7Τ氣ρ比哨 _1_基]乙酿胺； 2-[4-(3-氯基吡啶-2-基）六氫吡畊小基]-Ν-(3-甲基苯基）乙醯胺； 2-(1-{2-酮基-2-[(2,4,6-三溴基-3-甲基苯基）胺基]乙基}六氫吡啶_ 4-基）吡錠Ν-氧化物； 2-{4-[3-(胺基甲基）ρ比淀-2-基]7Τ氫峨ρ井-1-基}_]^-(3_甲基苯基）乙 醯胺； φ 2-[4-(2-異丙氧基苯基）六氫吡畊-1-基]-Ν-(3-甲基苯基）乙醯胺； 2-(4_{2-[(3-甲基苯基）胺基]-2-酮基乙基}六氫ρ比π井-μ基）於驗醯 胺； Ν·(3-甲基苯基）-2-[(2S)-2-甲基-4·ρ比淀-2-基六氫ρ比ρ井-1-基]乙燒 硫醯胺； 2-(1-{[(4-溴基-3-甲基苯甲酸基）胺基]甲基}六氫p比淀_4_基）叶匕 錠N-氧化物； 2-[4-(3-氰基吡啶-2-基）六氫吡畊-1_基]-N-[3_(甲硫基）苯基]乙醯籲 胺； N-(3-第三—丁基苯基）·2-[4-(3-氰基吨咬-2-基）六氫外I： _ -1—基]乙 醯胺； 2-[4-(2-羥苯基）六氫吡畊-1_基]-Ν-(3-甲基苯基）乙醯胺； 2_[4-(3-羥苯基）六氫吡畊-1-基]-Ν_(3-甲基苯基）乙醯胺； 2-[4-(4-羥苯基）六氫吡畊小基]-Ν-(3-甲基苯基）乙醯胺； 2-[4-(2-乙氧苯基）六氫吡畊小基]_Ν_(3-甲基苯基）乙醯胺； Ν-(3-甲基苯基）_2-{4-[2-(甲硯基）苯基]六氫吡畊小基}乙醯胺； 85228 -152- 200404539 2-[4-(2-氟苯基）六氫吡畊-1-基；|-N_(3-甲基苯基）乙醯胺； 2-[冬(3-氰基吡啶-2-基）六氫吡畊-1-基]-N-(3-氟苯基）乙醯胺； Ν·(3_溴苯基）-2-[4-(3-氰基吡啶-2-基）六氫吡畊小基]乙醯胺； Ν-(3_甲基苯基）-2-(4_ρ比淀-2-基六氫峨ρ井-1·基）乙燒硫酸胺； 2-[4-(2-胺基苯基）六氫吡畊-1-基]-Ν-(3-甲基苯基）乙醯胺； Ν-(3-硝基苯基)-2-(4-口比岐-2-基六氫ρ比口井-1-基）乙酉盡胺； 2·[4-(2-氰基苯基）六氫ρ比啡-1-基]孙(3_确基苯基）乙酸胺； Ν-(3-氰基苯基）-2-(4^比淀-2-基六氫吡畊-1-基）乙醯胺； N-(3-氰基苯基）_2-[4-(2-氰基苯基）六氫u比呼小基]乙酸胺； 2-[4_(3-氰基吡啶-2-基）六氫吡畊_1·基]-N-(五氟苯基）乙醯胺； 2-[4-(3-氰基峨啶-2-基）六氫p比畊-1-基]-Ν·(1，3-二甲基-1H-吡唑-5-基）乙醯胺； 乂(3-爷基苯基）-2-[4-(3-氰基峨淀_2-基）六氫ρ比呼_ι_基]乙醯胺； 2-[4-(2-氯苯基）六氫外b ρ井-1-基]-N-(3-甲基苯基）乙酸胺； 2-[4-(3-氰基吡畔-2-基）六氫吡畊-1-基]-N-(3-甲基苯基）乙醯胺； 2-(4_吡啶_2_基六氫吡畊-1_基）-N_(2_{[(4-吡啶-2_基六氫吡畊小 基）乙釅基]胺基}苯基）乙醯胺； N-(3-甲基苯基）-2-(4-p比淀-2-基六氫p比淀小基）乙燒硫酸胺； 2·[4-(1-甲基-1H-咪唑-2-基）六氫吡啶小基]具(3_甲基苯基）乙醯 胺； Ν-(3-甲基苯基）-2-[4-(1，3·隹唆-2-基）六氫峨淀-基]乙酸胺； Ν-(4-破基-3-甲基苯基）-2-(4-吡啶_2_基六氫峨啶小基）乙醯胺； 2-(4-氟基-4-苯基六氫p比淀-1·基）-N-(3_甲基苯基）乙驗胺； 2-[4-(5-羥基吡啶-2-基）六氫吡啶小基]|(3_甲基苯基）乙醯胺； 85228 -153- 200404539 N-(5-氟基-1，3_苯并p塞咬-2-基）-2-[4-(3-甲氧苯基）六氫峨p井-i_基] 乙醯胺； 2-[4-(2-甲氧苯基）六氫吡畊小基]-Ν-(1-甲基-1H-苯并咪唑-2-基） 乙醯胺； N-(3-甲基苯基）_2-[4-(3-甲基ρ塞吩-2-基）-3,6-二氮p比淀-1(2H)基]乙 醯胺； 2-(1-{2-[(3,5-二氯苯基）胺基]-2-酮基乙基}六氫p比淀-4-基）p比鍵 N，氧化物； 2-(1-{2_[(2,3-二氯苯基）胺基]-2-酮基乙基}六氫吡啶_4_基）吡錠 N-氧化物； 2-(1-{2·[(2-甲氧基-6-甲基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡錠Ν-氧化物； 2-{1-[2-(1，Γ-聯苯-3-基胺基）-2-酮基乙基]六氫吡啶-4-基}吡錠Ν_ 氧化物； 2_(1-{2-[(3·乙基苯基）胺基]-2-¾¾基乙基氮ρ比淀-4-基）ρ比鍵Ν- 氧化物； 2-{1-[2-(2,3-二氫-1H-茚-5_基胺基）_2_酮基乙基]六氫吡啶冰基} 外匕鉸N-氧化物； 2-{1_[2_酮基-2-(5,6,7,8-四氫荅-1-基胺基）乙基]六氫吡啶冰基}吡 錠N-氧化物； 2-(1-{2-[(3-異丙氧基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡 錠N-氧化物； 2-(1_{2·[(3,5-二甲基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡 鍵Ν-氧化物； 85228 -154- 200404539 2-(l-{2-[(4-溴基_2_甲基苯基）胺基]_2_酮基乙基}六氫吡啶-4-基） 吡錠N-氧化物； 2-[1-(2-酮基_2_{[3_(三氟甲氧基）苯基]胺基}乙基）六氫吡啶_4_ 基]吡錠N-氧化物； 2-(1-{2-[(5-甲基-2-硝基苯基）胺基]-2-酮基乙基}六氫吡啶冰基） 吡錠N-氧化物； 2-(1-{2-[(2,6-二甲基苯基）胺基]-2·_基乙基}六氫吡啶_4_基风 錠Ν-氧化物； 2-(1-{2-[(2,6-一氯-3-甲基苯基）胺基]-2-酮基乙基}六氫ϊ?比淀_4_ 基）吡錠N-氧化物； 2-{1-[2-(1，3-苯并二氧伍圜晞_5_基胺基）-2-g同基乙基]六氫吡啶_ 4-基}咐鍵N-氧化物； 2-[1-(2-{[3_(甲硫基）苯基]胺基卜2-酮基乙基）六氫吡啶·4_基风 錠Ν-氧化物； 2-(1-{2-[(5-氯基-2-甲基苯基）胺基]_2_酮基乙基}六氫吡啶-4_基） 外匕錠Ν-氧化物； 2-(1-{2-[(2,5-一甲氧基苯基）胺基]-2-酮基乙基}六氫p比淀-4-基） 吡錠N-氧化物； 2-(1-{2-[(3,5-二甲氧基苯基）胺基]_2_酮基乙基}六氫吡啶4-基） 吡錠N-氧化物； 2-[1-(2-{[3-(一甲胺基）苯基]胺基}-2-酮基乙基）六氫π比淀-4-基] 吡錠N-氧化物； 2-(1-{2-[(3_異丙基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡錠 N_氧化物； -155- 85228 200404539 2- (1·{2-[(3-氣基-2-甲基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基） 吡錠Ν-氧化物； 3- 甲基-Ν-[2-(4^比啶-2-基六氫吡畊-1_基）乙基]苯甲醯胺； 2-(1-{[(2,3_二溴基-5-甲基苯甲醯基）胺基]甲基}六氫吡啶_4_基） 吡錠N-氧化物； 2-{1-[(苯甲醯胺基）甲基]六氫吡啶斗基}吡錠N-氧化物； 2·(1-{[(4-氣基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡 錠Ν-氧化物； 2-(1-{[(4-氟基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡 錠Ν-氧化物； 2-[1-({[3-氯基-4-(三氟甲氧基）苯甲醯基]胺基}甲基）六氫吡啶_ 4-基]吡錠N-氧化物； 2-(1-{[(3-乙氧基苯甲醯基）胺基]甲基}六氫吡啶_4_基）吡錠N-氧化物； 2-(1_{[(3,5-二氯苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠N-氧 化物； 2-[1-({[4_甲基各(三氟甲基）苯甲醯基]胺基}甲基）六氫吡啶·4_ 基]吡錠Ν-氧化物； 2-(1-{[(3,4-二甲苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠义氧 化物； 2-(1-{[(3-氯基-4-氟苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠Ν_ 氧化物； 2-(1-{[(吡啶-2-基羰基）胺基]甲基}六氫吡啶-4-基）吡錠Ν_氧化 物； 85228 -156- 200404539 2-(1-{[(3,5-二甲苯甲酸基）胺基]甲基}六氮^1比淀_4-基）^?比鍵]^_氧 化物； 2-(l-{[(3-乙烯基苯甲酿基）胺基]甲基}六氫ρ比淀-4-基）峨錠]sf_ 氧化物； 2-(1-{[(4-溴基-3-甲基苯甲醯基）胺基]甲基卜1，2,3,6-四氫吡啶-4-基 &gt;比锭N-氧化物； 2-{1-[(2_蓁甲醯基胺基）甲基]六氫吡啶-4-基}吡錠N-氧化物； 2-(1-{[(噻吩-2-基羰基）胺基]甲基}六氫吡啶-4-基）吡錠N-氧化 物； 2-[H{[(6-氯基吡啶各基）羰基]胺基}甲基）六氫吡啶冰基]吡錠 N_氧化物； 2-(1_{[(3-氰基苯甲酿基）胺基]甲基}六氫p比淀-4-基）峨錠N-氧 化物； 2·(1-{[(2,3-二溴基-5-甲基苯甲醯基）胺基]甲基}-1，2,3,6-四氫峨 啶-4-基）吡錠N-氧化物； 2-(1-{[(4_溴基苯甲酸基）胺基]甲基}六氫u比淀-4-基 &gt;比錠氧 化物； 2-(H[(3-氣基-4-甲基苯甲醯基）胺基]甲基}六氫吡啶冬基）口比 錠N-氧化物； 2-(1-{[甲基（3-甲基苯甲醯基）胺基]甲基}六氫吡啶斗基）吡錠 N-氧化物； 2-(1-{[(3-硝基苯甲醯基）胺基]甲基}六氫吡啶_4·基）吡錠泎氧 化物； 2-(1-{[(2-氯基-5-甲基苯甲醯基）胺基]甲基}六氫吡啶-4-基）峨 85228 -157- 200404539 錠N-氧化物； 2-(l-{[(3-甲氧基-2-甲基苯甲醯基）胺基]甲基}六氫吡啶冬基） 吡錠N-氧化物； 2·(1·{[(4-氯基_3_甲氧苯甲醯基）胺基]甲基}六氫吡啶冰基）吡 錠Ν-氧化物； Ν-(3-甲基苯基）-2-(3•吡啶基六氫吡啶-1-基）乙醯胺； N-(3-甲基苯基）·2-(3-吡啶-2-基四氫吡咯-1-基）乙醯胺； N-(l-甲基-1Η-苯并咪吐-2-基）-2_[3-(1，3-遠♦ -2-基）六氫峨淀小基] 乙醯胺； N-(l_甲基—1Η-苯并咪唑-2_基）_2-[3-(1，3·嘧唑-2-基）四氫吡咯小基] 乙醯胺； 2-(2-苄基四氫吡咯-1-基）-ν_(3-氟笨基）乙醯胺；及 Ν-(4-氟苯基）-2_(3-遠吩-2_基四氫吡咯_ι_基）乙醯胺； 或其藥學上可接受之鹽、酯類、醯胺類或前體藥物。 本發明之最佳化合物為 2-(1-{[(3-甲基苯甲醯基）胺基]甲基丨冰六氫吡啶基）吡錠仏氧 化物。 縮窵 已被使用於下文圖式與實例之說明文中之縮寫，係為：Ac 為乙醯基；BINAP為2,2’-雙（二苯基膦基）_U’_聯萘基；B〇c為第 三-丁氧羰基；nBuLi為正-丁基鋰；dba為二苯亞甲基丙酮； DME為二甲氧基乙烷；DMF*N，N_二甲基甲醯胺；〇鳩〇為 二甲亞颯；EtOH為乙醇；HPLC為高壓液相層析法；Me〇H為 甲醇；TEA為三乙胺；TFA為三氟醋酸；THF為四氫呋喃；THp 85228 -158- 200404539 為四氫喊喃；TLC為薄層層析法。 本發明化合物之製備 本發明之化合物與方法，伴隨薯下述合出闻i v π r思耆卜口成圖式與實例將更 為明瞭，其係說明一種可藉其製備本發明化合物之方式。 圖式1There are centers of asymmetry or opposite palm 85228 200404539. These stereoisomers are flR "or nS", depending on the configuration of the substituents surrounding the opposite carbon atom. The terms nR'f and 'fSn, as used herein, are as described in the IUPAC 1974 paragraph E, Basic Stereochemistry, Pure Appl.  Chem., 1976, 45: 13-30. The invention is intended to cover various stereoisomers and mixtures thereof, and is expressly included within the scope of the invention. Stereoisomers include paraisomers and diastereomers, and mixtures of paraisomers or diastereomers. In particular, the stereochemistry at the -L2-B junction of a compound of formula (III) or formula (IV), where X: is a bond and X2 is CRDRE, which can be independently (R) or (S) Either. The stereochemistry at the -L2-B junction of the compound of formula (III) or formula (IV), where X! Is CRBR0, and X2 is a bond, which can be independently either (R) or (S). The stereochemistry at the -L2-B junction of the compound of formula (III) or formula (IV), where & is CRbRc and X2 is CRdRe, which may be independently either (R) or (S). Individual stereoisomers of the compounds of the present invention can be prepared synthetically from commercially available starting materials containing asymmetric or palmar centers, or by preparing racemic mixtures, followed by resolutions familiar to those skilled in the art. . An example of such analytical methods is to attach a mixture of parameric isomers to a paragenic adjuvant, to separate the diastereomeric mixture formed by recrystallization or chromatography, and to optically release the adjuvant from the auxiliary Pure product, (2) direct separation of an optical paraisomeric mixture on a palm chromatography column, or (3) formation of a diastereomeric salt, followed by a diastereomeric salt Selective recrystallization of one of them. The compound of the present invention is ACD / ChemSketch No. 5. Version 0 (developed by Advanced Chemical Development Corporation, Toronto, ON, Canada) is named, or given a name consistent with the ACD nomenclature. 85228 -138- 200404539 Preferred compounds of the present invention include: 2- [4 · (2-methoxyphenyl) -1-hexahydropyridyl] -N_ (3-methylphenyl) acetamide; 2 -[4- (2-Cyanophenyl) pyrhexahydropyridyl] methylphenyl) acetamide; Ν- (3-methylphenyl) -2- [4- (2-pyrimidinyl) -1-Hydroxypyridyl] ethanamine; N- (3-methylphenyl) -2- [4- (2-pyridyl) _1_hexahydropyridyl] ethyridamine; 2- [ 4- (3-cyano_2_pyridyl) &gt; 1-hexahydrowellyl] _n_ (3-methylphenyl) acetamidine; N- (3-methylphenyl) -2- [4- (2-methylphenyl) small hexahydro p ratio p well-based] amine acetate; N- (3-methylphenyl) -2- [4- (2-nitrophenyl) _1_hexahydro p ratio p well-based] ethyl amine; _ 2- [4- (3-cyano-2-pyridyl) hexahydropyridyl] -N- (3-nitrophenyl) acetamide; 2- [ 4- (3-Cyano-2-pyridyl) pyrrolidine; | -N- [3- (trifluoromethyl) phenyl] acetamidinium; N- (3-methylphenyl) -2- (4-phenyl-1-hexahydropyridyl) acetamidine; N- (3-cyanophenyl) -2_ [4- (3-cyano-2-gadolide) -1 -Hexahydro, 1 p stilbyl] ethyl amine; N- (4-bromo-3-methylphenyl) -2- [4- (2-chlorophenyl) -1-hexahydro u ratio p Well-based] acetamide 2- [4- (2-Gasylphenyl) -1-7 ^ muridine ratio p-well-based] -N-phenylethylamine; 2- [4- (3-Wisyl than dianyl) -1 -ττnitropyridyl] dongylethynylamine; 2- [4- (3-cyano-2-pyridyl) pyrhydropyridyl] -N- (4-fluorophenyl) acetamidine ; 2- [4- (3-Chloro-2-ρbiydyl) -1 · 17-outer gas base] -N- (3,5-dimethylphenyl) ethylamine; 2- [ 4- (3-cyano-2-pyridyl) -1-hexahydropyridyl] -N- (2,3-dimethylphenyl) acetamidamine; 2_ [4- (3-cyano- 2-Pyridyl) Hexahydropyridyl] -N- (2-methylphenyl) acetamidamine; 2- [4- (3-cyano-2-pyridyl) pyrhydropyridyl] -N- (2,5-dimethylphenyl) acetamidine 85228 -139- 200404539 amine; N- (3-chlorophenyl) -2- [4- (3-cyano-2_p ratio)- 1-hexahydro p-pyridyl] ethyl amine; N- (3-chloro-4-fluorophenyl) -2- [4- (3 · «amino-2-p-pyridyl) -1_ Hexahydropyridyl] acetamidine; 2- [4- (3-cyano-2-exo1: Yodo) -l-: r; hydroethoxyl] _N- (3,4,5-trimethyl (Oxyphenyl) acetofluoramine; 2- [4- (3-cyano-2-pyridyl) hexahydropyridyl] -N_ [4 · fluoroyl-3- (trifluoromethyl) phenyl ] Acetylamine; 2- [4- (3-cyano-2-pyridyl) primary six Pyryl] -N- [3-Fluoro-5- (trifluoromethyl) phenyl] acetamidamine; 2- [4- (3 • cyano-2-ρ bipyridyl) -1-hexa Hydrogenyl_-yl] -N- [2-fluoroyl-5- (trifluoromethyl) phenyl] acetamidamine; 2- [4- (3-pentyl-2 »^ bisyl) -1- Hexahydrogen p-well-based] -N- [2-Fluoro-3- (trifluoromethyl) phenyl] acetamidamine; 2 · [4- (3-cyano-2-gadolide) -1 _Hydroxyerphinyl] -N_ (4- | tyl-3-methylphenyl) acetamidine; 2- [4- (3-cyano-2-pyridyl) pyrhotyl] -N_ (2 · fluorophenyl) acetamidamine; 2- [4- (3-Gasyl-2-ρ than ydoyl chloride ρ-pyhyl] -N- (2-methoxyphenyl) amine; 2- [4- (3-cyano-2-pyridyl) &gt; 1-hexahydropyridyl] -N- (2-nitrophenyl) acetamidamine; 2- [4- (3-amino -2-ρ than yodoyl) small hexanitro ρ than morphinyl] -N- [2- (trifluoromethyl) phenyl] acetamidinium; Ν_dongyl-2- [4 · (2-β ratio (Yodo-based) -l-: r? Chloride than p-well-based] amine; N- (3-methylphenyl) -2- [4- (1,3-pyrazol-2-yl) hexahydro Pyridinyl] ethenylamine; 2- [4- (3-cyano-2-pyridyl) pyrohexylpyridinyl] -N- (4.methylphenyl) ethenylamine; 200404539 2- [ 4- (2-methoxyphenyl) -1-hexahydropyridyl] -N- (3-methyl ) Ethylamine; 2- [4- (2-fluorophenyl) -1-hexahydropyridyl] -N- (3-methylphenyl) acetamide; N- (3-methylphenyl ) -2- [4- (2-methylphenyl) hexahydropyridyl] acetamidine; 2- [4- (3-fluorophenyl) hexahydropyridyl] -N- (3-methyl N- (3-methylphenyl) -2- [4- (6-keto-1 (6H) -pyridyl) -1-hexahydropyridyl] acetamido ; N- (2,6-dimethylphenyl) -2- [4- (2-pyridinyl) -1-hexahydropyridyl] acetamidine; N- (2,5 · dimethylbenzene ) -2- [4- (2-pyridinyl) -1-hexahydropyridyl] acetamidinium; N- (2-methylphenyl) -2- [4- (2-pyridinyl) -1-Hexahydropyridyl] acetamidine; N- (3-chloro-4-fluorophenyl) -2- [4- (2-pyridinyl) -1-hexahydropyridyl] acetamidine ; N- (4- &gt; Styrophenyl) -2- [4- (2-ρ Biydyl) -1-ττMorylyl] amine, N- (2,6-dimethylphenyl ) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidinium; N- (2-nitrophenyl) -2- [4- (2-pyridyl) minor hexahydro Pyridyl] acetamidine; N- (3-nitrophenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; Ν · (2,4-difluoro Phenyl) -2- [4- (2-pyridyl) -1-hexahydropyridine Methyl] acetamidamine; N- (2,5-dimethylphenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidamine; N- (2-methyl Phenyl) -2- [4- (2 · pyridyl) -1-hexahydropyridyl] acetamidamine; N_ (4-methylphenyl) -2- [4- (2-pyridyl) -1 -Hexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- [3- (trifluoromethyl) phenyl] acetamidine; 4- ({[4- (2-pyridyl) -1-hexahydropyridyl] ethenyl} amino) benzoate ethyl; N- (3-chloro-4-methylphenyl) -2- [ 4- (2 · pyridyl) small hexahydropyridyl] acetamidine; N- (2-cyanophenyl) -2- [4- (2-pyridyl &gt; 1-hexahydropyridyl] acetamidine Amine; N- (3-chlorophenyl) -2_ [4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; 2- [4- (3-cyano-2-pyridyl) 1-hexahydropyridyl] -N- (3-methylphenyl) acetamidamine; 85228 -141- 200404539 N- (3-methylphenyl) -2- (4-phenyl-3,6 -Dihydro-1 (2H) -pyridyl) acetamidamine; 2- (3'6'-dihydro · 2,4'_bipyridine-Γ (2Ή) -yl) -N- (3-methyl Phenyl) acetamide; 2- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -yl) -N- (2,6-dimethylphenyl) ethyl Amidine; 2- (3 ', 6'- Dihydro-2,4'-bipyridine-1 '(2Ή) -yl) -N_ (2-nitrophenyl) acetamidamine; 2- (3', 6'-dihydro-2,4'_ Bipyridine-Γ (2Ή) -yl) -N · (3-nitrophenyl) acetamidamine; 2- (3f, 6'_dihydro_2,4 ^ bipyridine · Γ (2Ή) -yl) -N- (4 · fluorophenyl) acetamide; Ν- (2,4 · difluorophenyl) -2- (3 ', 6'-dihydro · 2,4' · bipyridine · Γ (2Ή ) -Yl) acetamidinium; 2- (3'6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N- (2,5-dimethylphenyl) acetamidine Amine; · 2- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -yl) -N- (2-methylphenyl) acetamide; Ν-cyclohexyl -2- (3 ', fluorenedihydro_2,4' · bipyridine-; Γ (2Ή) -yl) acetamidinium; 2- (3 ', 6'-dihydro · 2,4'_bipyridine _1 '(2Ή) _yl) -N_ (4-methylphenyl) acetamidamine; 2- (3', 6'-dihydro-2,4'-bipyridine-1 '(2Ή) · yl ) -N- [3- (trifluoromethyl) phenyl] ethanamidine; 4-[(3f, 6'-dihydro-2,4f-bipyridine-1 '(2Ή) -ylethenyl) Amino] ethyl benzoate; Ν- [2-chloro-5- (trifluoromethyl) phenyl] -2- (3f, 6'-dihydro-2,4'-bipyridine-Γ (2Ή ) -Yl) acetamide; N- (3-chloro-4-methyl Phenyl) -2- (3f, 6'_dihydro-2 ^ -bipyridine-Γ (2Ή) -yl) acetamidine · amine; Ν- (2-cyanophenyl) -2- (3 ' , 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; Ν- (3-chlorophenyl) -2- (3f, 6 '· dihydro-2,4 '-Bipyridine-Γ (2Ή) -yl) acetamide; Ν- (3-chloro-4-fluorophenyl) -2- (3', 6f-dihydro-2,4'-bipyridine- Γ (2Ή) -yl) acetamidinium; 2- (3,6'-dihydro-2,4'-bipyridine-1 '(2Ή) -yl) -N- [4- (trifluoromethoxy ) Phenyl] acetamide; 2- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -yl) -N- [2- (trifluoromethyl) phenyl] Acetamide; Ν- (4-chlorophenyl) -2- (3 ', 6'-dihydro-2,4f-bipyridine-1' (2Ή) -yl) acetamide; 85228 -142- 200404539 N- (2,3-dichlorophenyl) -2 · (3 ', 6'-dihydro_2,4'_bipyridine-Γ (2Ή) -yl) acetamidine; (3,5- Dichlorophenyl) -2- (3'6'-dihydro-2,4 ^ bipyridine-1 ^ 2'11) -yl) acetamide; 2- (3 ', 6'-dihydro-2 , 4'-bipyridyl-Γ (2Ή) -yl) -N- (4-fluoro-2-methylphenyl) acetamidamine; Ν- (4-fluorophenyl) -2- [4- ( 2-pyridyl) _1-hexahydropyridyl] acetamidinium; N- (3,5-dichloro Phenyl) -2- [4- (2-pyridyl) microhexahydropyridyl] acetamidinium; N- (2,3-dichlorophenyl) -2- [4- (2-pyridyl)- 1-hexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N_ [2- (trifluoromethyl) phenyl] acetamidine; N- (3-Chloro-4-phenylphenyl) -2- [4- (2-eodoyl) small 7T chloroeridyl] amine; 2- [4- (2-pyridyl) 4-hexahydro Pyridyl] -N- [4- (trifluoromethoxy) phenyl] acetamidinium; 1 ^ cyclohexyl-2- (3 ', 4', 5 ', 6 ^ tetrahydro-2'11- [ 2,4 '] bipyridyl-1'-yl) acetamidamine; Ν-{[4- (2-cyanophenyl) pyropyryl] methyl} -3-methylbenzidine Amine; 3-methyl-N-{[4- (2-pyrimidinyl) -1-hexahydropyridyl] methyl} benzamide; 3-methyl-N-{[4- (2- Pyridyl) -1-hexahydropyridyl] methyl} benzylamine; 3-methyl_N-[(4-phenyl-1-hexahydropyridyl) methyl] benzylamine; N-{[4- (2-methoxyphenyl) hexahydropyridyl] methyl} -3-methylbenzylamine; 乂 {[4- (2-aminophenylhydrogen outside 1: p-wellyl] methyl} -2-methylbenzylamine; N-{[4- (2-cyanophenyl) pyrhydropyridyl] methyl} -4-methylbenzylamine ; N _ {[4- (3-cyano -2-pyridyl) -1 · hexahydropyridyl] methyl} · 3-methylbenzylamine; Ν-{[4- (3-cyanophenyl) small hexahydropyridyl] methyl Benzyl 3-methylbenzylamine; Ν-{[4_ (3-cyanophenyl) pyralinyl] methyl} -2_methylbenzylamine; Ν-{[4- (3-cyano-2-pyridyl) -1-hexahydropyridyl] methyl} benzamide; N-{[4- (3-cyano-2-pyridyl) -1-hexahydro Pyridinyl] methyl} _4-methylbenzylamine; N-{[4- (3-cyano-2-pyridyl) -1-hexahydropyridinyl] methylbutan-2-methylbenzene Formamidine; 85228 -143- 200404539 N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzidine; N-{[4- (2-chlorophenyl ) -1-hexahydropyridyl] methyl} benzylamine; 3-chloro-N-{[4- (2-cyanophenyl) -1-hexahydropyridyl] methyl} benzyl Chloramine; 4-chloro-N-{[4- (2-methoxyphenyl) -1 · hexahydropyridyl] methyl} benzamide; 2-chloro-N-{[4- (3 -Cyano-2-pyridyl) hexahydropyridyl] methyl} benzylamine; N-{[4- (3-cyano-2-pyridyl) hexahydropyridyl] methyl } -2- (trifluoromethyl) benzamidine; N-{[4- (2-cyanophenyl) pyrrolidine] methyl} benzamide; N-{[4- (2-methoxy Phenyl) Hexahydropyridyl] methyl} each methylbenzylamine; 3-methyl-N-{[4- (2-pyridyl) small hexahydropyridyl] methyl} benzidine ; 3-methyl-N-[(4-phenyl · 3,6-dihydro-1 (2H) -pyridyl) methyl] benzidine; N_ (3 ', 6'_dihydro-2 , 4'-bipyridyl-1 · (2Ή) -ylmethyl) · 3-methylbenzidine; N- (3f, 6f-dihydro-2 / M-pyridine · ΙΘΉ) -ylmethyl) -3-methoxybenzamide; N- (3 ', 6'-dihydro_2, bipyridine · Γ (2Ή) _ylmethyl) _3 · fluorobenzamide; N- (3 ', 6f-dihydro-2,4'-bipyridine-1' (2Ή) -ylmethyl) -3,5-difluorobenzamide; 2- [4- (3-fluorenyl-2- Edianyl) -1-Hexane outside 1: rhoyl] pyridyl ethylamine; 2- (1_ {2 _ [(3-methylphenyl) amino] _2_ketoethyl} hexahydro ρ Biyodo_4_yl) π specific ingot oxide; Ν- (3-methylphenyl) -2- [4- (2-Edianyl) -1-hexahydrotynyl] ethyldonylamine ; N-2-Gold steel sulphuryl-2- [4- (3-Gasyl-2-11 is smaller than yodo) Hexahydro p-pyhyl] ethyl amine; 2- [4- (3 • cyano -2-exo (: Yodo) -1-hexahydro leaf ti ρ well-based] cyclohexylamine acetate; 2- [4- (3-cyano-2-exo 1: Yodo) -1_hexahydroexo 1: Radical] sun 5,6,7,8-tetrahydro-1-benzoylacetamide; 2- (3 ', pyrene dihydro-2,4'_bipyridine-1' (2Ή) -yl) -N -(4-fluoroyl_2_methylphenyl) acetamidine 85228 -144- 200404539 amine; N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} -3- ( Trifluoromethyl) benzamidine; 3. 5-dimethoxy-N-{[4- (2-p than pyridyl) small hexahydropyridyl] methyl} benzimidamine; N-{[4- (2- said pyridyl) small six Hydropyridyl] methyl} cyclohexanecarboxamide; 3,4-difluoro-N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzamide; 3 -Chloro-N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzamide; 2,3-dimethyl-N-{[4- (2-pyridyl ) -1-hexahydropyridyl] methyl} benzidine; N- (3 ', fluorene dihydro-2,4 · -bipyridyl-Γ (2Ή) -ylmethyl) -3- (tri Fluoromethyl) benzamide; _ 3-chloro-N- (3 ', 6f • dihydro-2,4'-bipyridine-Γ (2Ή) -ylmethyl) benzamide; Ν- ( 3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -ylmethyl) cyclohexanecarboxamide; Ν · (3', 6 '· dihydro-2,4f-linked Pyridine-Γ (2Ή) -ylmethyl) -3,4-difluorobenzamide; Ν- (3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -ylmethyl ) -3,5 · dimethoxybenzamide; Ν- (3-methylphenyl) -2- (4-phenyl small hexahydropyridyl) acetamide; 2- (3 ', 6'_dihydro-2,4f-bipyridine-Γ (2Ή) -yl) · N- (3-nitrophenyl) acetamide; Ν-1- 金钢 烧 基 -2- [4- ( 3-Dyki-2-ρ ratio Yodoyl chloride, ytyl] amine acetate; 3-methyl_N · {[2_methyl-4- (2-exo 1; yodo) -1_ττrho pi 1yl] methyl} benzyl Fermented amines; _N- (3-methylphenyl) -2- [2-methyl-4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; 3. 5-dimethyl-N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzidine; N-P1 / '-dihydro_2,4'_bipyridine -1 '(2Ή) -ylmethyl) -3,5-dimethylbenzamide; 3-methyl-N-[(3-methyl-3', 6'-dihydro-2,4 '-Bipyridine-1' (2Ή) -yl) methyl] benzidine; Ν-[(3-cyano-3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή ) -Yl) methyl] -3_methylbenzamide; Ν- (2,6-dimethylphenyl) -2- (3-methyl-3 ', 6'-dihydro · 2,4 '_Bipyridine-fluorenyl' (2 '&gt; yl) ethyl 85228 -145- 200404539 hydrazine; N · (4-fluorophenyl) -2- (3-methyl-3,6, -dihydro-2, 4, -bipyridine-1, (2Ή) -yl) acetamide; Ν- (2,4-difluorophenyl) -2- (3-methyl-3,6, _dihydro-2, 4, -bipyridine-1, (2Ή) -yl) acetamide; 2- (3 • methyl_3 ', 6'_dihydro_2,4, -bipyridine · 1, (2Ή) _yl ) -N- (2-methylphenyl) acetamide; 2- (3_methyl_3 ', 6'_dihydro-2,4, -bipyridine-1, (2 ()-yl) _N_ [ 3- (S fluoromethyl) phenyl] ethanamine; N- (3-chlorobenzylfluorophenylmethyl-3,, 6, _dihydro-2,4, _bipyridine_1, (2 , H)-group) Acetylamine; 2- ( 3-methyl-3 ', 6'-dihydro_2,4, -bipyridine · 1, (2Ή) -yl) -N- [4- (trifluoromethoxy) phenyl] acetamidamine; 2 -(3-methyl_3 ', 6'_dihydro_2,4, -bipyridine-1, (2Ή) · yl) _N- [2_ (trifluoromethyl) phenyl] acetamidine; N -(2,3-dichlorobenzyl) -2- (3-methyl-3,, 6, dihydro-2,4, · bipyridinium (2Ή) _yl) acetamide; 2- (3 -Methyl · 3 ', 6, · dihydro_2,4, _bipyridine-1, (2Ή) _yl) -N_ [4- (trifluoromethyl) phenyl] acetamide; 2- [ 4- (3-cyano | pyriminyl) _3,6_dihydro 4 (2Η) -pyridyl] _N_ (3_methylphenyl) acetamidine; 2_ (3_cyano_3 ', 6 , -Dihydro_2,4, _bipyridine-1, (2Ή) -yl) -N- (2,6-dimethylphenyl) acetamide; 2- (3-cyano-3 ,, 6, _dihydro_2,4, _bipyridine-1, (2Ή) -yl) zine (4-fluorophenyl) acetamide; 85228 -146- 200404539 2- (3-cyano_3f, 6 '_Dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N- (2,4-difluorophenyl) acetamide; 2- (3-cyano-3f, 6L diargon _2,4'-bi-p-pyridine-Γ (2Ή) -yl) -N- (2-methylphenyl) acetamidine; 2- (3-cyano-3 ', 6'_dihydro- 2,4f-Couple 1: Yodo_Γ (2Ή) _base) -N- [3- ( Benzyl) phenyl] acetamidinium; 2- (3-cyano-3 ', 6'-dihydro-2, cardiac ^: Yodo-Γ (2Ή) -yl) -N · [4- ( Trifluoromethoxy) phenyl] ethanamine; 2- (3-cyano-3,, 6, -dihydro-2, -bipyridine-Γ (2Ή) -yl) -N- [2- ( Trifluoromethyl) phenyl] ethanamine; 2- (3-cyano-3 ', 6'-dihydrobi ^: Yodo-Γ (2Ή) _yl) -N- (2,3-dichloro Phenyl) ethanamine; 3-methyl-N-{[4- (6-keto-1 (6Η) -dacrotyl) small hexahydropyridyl] methyl} benzamide; N- ( 3T, 6f-dichloro-2,4'-bi-peptide-1 '(2Ή) · methylmethyl) adamantine, tricyclodecanecarboxamidine; 3-methyl_N-{[4_ ( 1,3-diso-2-yl) -3,6-dihydro-1 (2Η) -ρ ratio yl] methyl} benzamide; 2- [4- (3-cyano-2- Pyridyl) -1_hexahydropyridinyl] sun 1,2,3,4_tetrahydropyroxypyrylamine; 2- [4_ (3-cyanopyryl) -1_hexahydropyridyl ; || [(1p1,2,3,4_tetrahydrosmall tea-based] acetamidinium; 2- [4- (3-cyano-2-pyridyl) _ι_hexahydropyridyl] | [(1 1,2,3,4_tetrahydro_1_ its group) acetamide; 85228 -147- 200404539 N- (2,6-diethylphenyl) -2- [4- (2 -ρ 比比 基) -1-ττ gas outside b dian]] S Amine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- (2,4,6-trifluorophenyl) acetamide; N- (4-chloro-2, 6-dimethylphenyl) -2- [4- (2-pyridyl) small hexahydropyridyl] ethanamine; 2- [4- (2-? Pyridyl) -l_: r? Chlorofluorene Biyodo] _N- (2,4,6-diphenylphenyl) amine; N- (2,6-diethylphenyl) -2- (3 *, 6'_diazo-2,4 '-Biρ Biyodo-lf (2'H) -yl) ethyl amine; 2- (3', 6'-dihydro-2,4f-bipyridine-Γ (2Ή) -yl) -N- ( 2,4,6-trifluorophenyl) acetamide; N- (4-chloro-2,6-dimethylphenyl) -2- (3 ', 6'-dihydro-2,4' -Bipyridine-1 '(2Ή) -yl) ethylφamidamine; 2- (3', 6'-dihydro-2, bipyridine-1 '(2Ή) -yl) -N- (2,4, 6_trichlorophenyl) acetamide; Ν-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} -3- (trifluoromethyl) benzamide; 3 , 5-dimethoxy-N-{[4- (24pyridyl) -1-hexahydropyridyl] methyl} benzamide; N _ {[4- (2-pyridyl &gt; 1- Hexahydropyridyl] methyl} cyclohexanecarboxamide; N- (2,6-dimethylphenyl) -2- [4- (2-p than ydoyl) -1-ττair p [Jingji] Ethylamine; Ν- (4-fluorophenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl ] Acetylamine; N- (2,4-Dioxophenyl) -2- [4- (2Cydroyl) -1-hexachloro p ratio_yl] ethylamine; _N- (2- Methylphenyl) -2- [4- (2-pyridyl) microhexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N -[3- (trifluoromethyl) phenyl] acetamidine; Ν- (3-chlorophenyl) -2- [4- (2 · pyridyl) pyrhydropyridyl] acetamide; Ν -Lyderyl-2- [4- (2-ρ is smaller than yodoyl) outside hexahydro 1: ρ well-based] acetamidinyl; 2- [4- (2-pyridyl) -1-hexahydropyridyl ] -N- [4- (trifluoromethoxy) phenyl] ethanamine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- [2- (trifluoro Methyl) phenyl] acetamidine; Ν- (4-chlorophenyl) -2- [4- (2-pyridyl) pyrhydropyridyl] acetamidine; Ν- (2,3-di Chlorophenyl) -2- [4- (2-pyridyl) pyrihydropyridyl] acetamidine; 85228 -148- ii · 〇 * --ί 200404539 N- (3,4-dichlorophenyl) ) -2- [4- (2-p than Yodoyl) -1-Hexane outside 1: p wells] Ethylamine; 2- [4- (2-p than Yodoyl) Hexahydrogen ] -N- [4- (trifluoromethyl) phenyl] ethanamine; 3-chloro-N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzyl Amidoamine; 4-fluoro-3-methyl-N-{[4- (2 -p than yodoyl) -1-ττ hydrogen p-pyroyl] methyl} benzoic acid amine; N- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -yl (Methyl) -4-fluoro_3-methylbenzidine; 3-methyl-N-{[4- (1,3-oxazol-2-yl) _3,6-dihydro-l ( 2H) _pbipyridyl] methyl} benzidine; φ 2-methyl-N-[(3-methyl-3 ', 6'-diaza-2,4'-bi-p-pyridine-Γ (2Ή) · methyl) methyl] benzoic acid amine; 2- [4- (3-Gas-2--2-pyridyl) -1 · ττchloroρ-pyridyl] -N- (2,6-di Methylphenyl) amine; Ν- (3-methylphenyl) -2- [4- (3-methyl-2-glydyl) -1-hexahydro leaf (: ρ wellyl) amine acetate ; 2- [4- (3-Chloro-2-ρ than ydoyl) -1-hexahydroxyl ρ oxyl] -N- [4- (trifluoromethyl) phenyl] acetamidine; Ν -(2-ethyl-6-methylphenyl) -2- [4- (2-pyridyl) microhexahydropyridyl] acetamidine; N- (2-isopropyl-6-methyl Phenyl) -2- [4- (2-eridinyl) microhexahydropyridyl] acetamidine; Ν · (2-chloro-6-methylphenyl) -2- [4- (2 · Pyridyl) Hexahydropyridyl] acetamidine; N- (2-methoxy-6-methylphenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] ethyl Amidine; 2- (3W-dihydro-2,4f-bipyridine -1 '(2Ή) -yl) _N- (2-ethyl-6-methylphenyl) acetamidamine; 2- (3 \ 6'-dihydro-2, bipyridine-Γ (2Ή) _yl ) -N- (2-isopropyl-6-methylphenyl) ethyl 85228 -149- 200404539 fluorenamine; N- (2-chloroyl methylphenyl) _2_ (3 ', 6, -dihydro -2,4, -bipyridine-1, (2Ή) -yl) acetamide; 2- (3 ', 6'-dihydro-2, bipyridine-ΐ' (2Ή) -yl) -N- ( 2-methoxy-6-methylphenyl) acetamide; 3-chloro-N-[(3-methyl-3 ', 6'-dihydro-2,4, · bipyridine-1' ( 2Ή) -yl) methyl] benzidine; 3 · fluoro · N-[(3 · methyl-3 ', 6'_dihydro_2,4, _bipyridine-Γ (2Ή) -yl) Methyl] benzamide; 3-methyl-N-{[((2S) -2-methyl_4- (2-pyridyl) small hexahydropyridinyl] methyl} benzamide; N- (3-methylphenyl) _2 _ [(2S) -2-methyl-4- (2-pyridyl) pyrihydropyridyl] acetamidine; 3-methyl-N-{[( 2R &gt; 2-methyl-4- (2-pyridyl) pyrihydropyridyl] methyl} benzamide; N- (3-methyl winteryl) -2-[(2R) -2- Methyl-4- (2 · ρ than pyridyl chloride, p-yl] ethylammonium amine; 3-methoxy · N-[(3-methyl-3 'square-dihydro-2,4'-linked Pyridine-1 '(2Ή) _yl) methyl ] Benzylamine; 4 · fluoro-N-[(3-methyl · 3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) methyl] benzidine Amines; 2- (3.chloro-J, 6'-dihydro-2,4'-bipyridine-1 '(2Ή) -yl) -N- (2,6-dimethylphenyl) acetamide; 2- (3-Chlorodihydro-2, bipyridine-Γ (2 _) _ yl) -N- (2-methylphenyl) acetamide; Ν- (3 ', 6'-dihydro-2 , 4'-bipyridine-Γ (2Ή) · methyl] -1-naphthylamidine; Ν-{[4- (3- ^ yl-2-ρ 比基基) -1-77 nitrogen p Jingyi] methyl} -3-fluorobenzylamine; 85228 -150- 200404539 2- (l_ {2-[(4-fluoro-2-methylphenyl) amino] _2_ketoethyl } -4-hexahydropyridyl) pyridinium N-oxide; 2- (1- {2-[(4-fluoro-3-methylphenyl) amino] -2-ketoethyl} -4-hexahydropyridyl) pyridinium N-oxide; 2- (1- {2-[(3-fluorophenyl) amino] -2-ketoethyl} -4-hexahydropyridyl) Pyridinium N-oxide; 2- (1- {2-[(2-fluoro-5-methylphenyl) amino] -2-ketoethyl} -4-hexahydropyridyl) pyridinium N-oxide; 2- (1- {1-methyl · 2-[(3-methylphenyl) amino] -2-ketoethylethyl 4-hexahydropyridyl) pyridinium N-oxide ; 2- (1- {2-[(4-fluoro Aminyl) amino] -2-ketoethyl} -4-hexahydroρ biphenyl group> specific bond N-oxide; 2 · (1- {2-[(2-fluorophenyl) amino group] -2-ketoethyl} -4-hexahydropyridyl) pyridine N-oxide; N- (3-methylphenyl) -2- {4- [3- (trifluoromethyl) -2 -Pyridyl] pyrhexahydropyridyl} acetamidine; N_ (3-methylphenyl) -2- {4- [3- (trifluoromethyl) -2-pyridinyl] pyrhexahydropyridine Phenyl} acetamidine; N- (3-methylphenyl) -2- [4- (1,3-pyrazol-2-yl) -3,6-dihydropyridine-1 (2H) _yl ] Acetylamine; N- (3-methylphenyl) -2- (4- ^ sedien-2-yl-3,6-diazine p-pyridine-1 (2H) -yl) ethynylamine; 3-methyl_N-[(4-pyrimin-2-yl-3,6-dihydropyridine-1 (2H) -yl) methyl] benzidine; 2- (1- {2 _ [( 3-chlorophenyl) amino] -2-ketoethyl} hexahydropyridinyl) pyridine N-oxide; 85228 -151-200404539 2- [4- (l-methyl-1H-weiwa -2-yl) -3,6- · —murine pibiline-1 (2H) _yl] -N- (3 · methylphenyl) acetamide; Ν- (3-methylphenyl)- 2- [4- (3-nitroρ 比比 _2_yl) 7T gasρbi_1_1yl] ethylamine; 2- [4- (3-chloropyridin-2-yl) hexahydro Pycnogenol] -N- (3-methylphenyl) acetamide; 2- (1 -{2-keto-2-[(2,4,6-tribromo-3-methylphenyl) amino] ethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2 -{4- [3- (Aminomethyl) ρBiyodo-2-yl] 7T-hydroepi-1-yl} _] ^-(3-methylphenyl) acetamide; φ 2- [4- (2-isopropoxyphenyl) hexahydropyrine-1-yl] -N- (3-methylphenyl) acetamide; 2- (4_ {2-[(3-methyl Phenyl) amino] -2-ketoethyl} hexahydro ρ than π-well-μ)) in the test amine; Ν · (3-methylphenyl) -2-[(2S) -2-methyl -4 · ρ biyodo-2-yl hexahydroρ ratio ρ well -1-yl] ethanesulfanilamide; 2- (1-{[(4-bromo-3-methylbenzoate) amine [Methyl] methyl} hexahydro p ratio_4_yl) leaf N-oxide; 2- [4- (3-cyanopyridine-2-yl) hexahydropyridine-1_yl] -N -[3_ (methylthio) phenyl] ethanamine; N- (3-tertiary-butylphenyl) · 2- [4- (3-cyanotox-2-yl) hexahydrogen I: _-1-yl] acetamidin; 2- [4- (2-hydroxyphenyl) hexahydropyroxy-1-yl] -N- (3-methylphenyl) acetamidin; 2_ [ 4- (3-hydroxyphenyl) hexahydropyridine-1-yl] -N_ (3-methylphenyl) acetamidamine; 2- [4- (4-hydroxyphenyl) hexahydropyridine small group ] -N- (3-methylphenyl) acetamide; 2- [4- (2 -Ethoxyphenyl) hexahydropyridine] _N_ (3-methylphenyl) acetamide; Ν- (3-methylphenyl) _2- {4- [2- (methylamino) benzene [Yl] hexahydropyridine small group} Ethylamine; 85228 -152- 200404539 2- [4- (2-fluorophenyl) hexahydropyridine-1-yl; | -N_ (3-methylphenyl) Acetylamine; 2- [Winter (3-cyanopyridine-2-yl) hexahydropyridine-1-yl] -N- (3-fluorophenyl) acetamidine; Ν · (3-bromophenyl ) -2- [4- (3-cyanopyridine-2-yl) hexahydropyridyl] ethylacetamide; Ν- (3-methylphenyl) -2- (4-p Hexahydro-1, 2-yl) ethyl amine sulfate; 2- [4- (2-aminophenyl) hexahydropyrine-1-yl] -N- (3-methylphenyl) acetamidine Amines; Ν- (3-nitrophenyl) -2- (4-orbito-2-ylhexahydror than bikoui-1-yl) acetamidine; 2 · [4- (2-cyano Phenyl) hexahydroρ-biffin-1-yl] sun (3-cyclophenyl) acetamide; Ν- (3-cyanophenyl) -2- (4 ^ bidian-2-ylhexahydropyridine Phen-1-yl) acetamidamine; N- (3-cyanophenyl) _2- [4- (2-cyanophenyl) hexahydroupyhvyl] amine; 2- [4_ (3 -Cyanopyridin-2-yl) hexahydropyridine_1 · yl] -N- (pentafluorophenyl) acetamidamine; 2- [4- (3-cyanoeridin-2-yl) hexahydro p Pichen-1-yl] -N · (1,3-dimethyl-1H-pyrazol-5-yl) acetamidinium; hydrazone (3-methylphenyl) -2- [4- (3- Cyanoether _2-yl) hexahydroρbihu_ι_yl] acetamidinium; 2- [4- (2-chlorophenyl) hexahydroexo b ρ-well-1-yl] -N- ( 3-methylphenyl) amine; 2- [4- (3-cyanopyridin-2-yl) hexahydropyrine-1-yl] -N- (3-methylphenyl) acetamidine ; 2- (4_pyridin_2_ylhexahydropyridin-1_yl) -N_ (2 _ {[(4-pyridin-2-ylhexahydropyridinyl) ethenyl] amino} phenyl ) Ethylamine; N- (3-methylphenyl) -2- (4-p-Hydro-2-ylhexahydrop-Hydro-small) Ethyl ammonium sulfate; 2 · [4- (1-methyl -1H-imidazol-2-yl) hexahydropyridine small group] with (3-methylphenyl) acetamidamine; N- (3-methylphenyl) -2- [4- (1,3 · Fluoren-2-yl) hexahydroeodo-yl] amine; N- (4-alkyl-3-methylphenyl) -2- (4-pyridin-2-ylhexahydroeridine small group) Acetylamine; 2- (4-Fluoro-4-phenylhexahydrop-pyridine-1 · yl) -N- (3-methylphenyl) ethenamine; 2- [4- (5-hydroxy Pyridin-2-yl) hexahydropyridine small group] | (3-methylphenyl) acetamidamine; 85228 -153- 200404539 N- (5-fluoro-1,3-benzobenzopyridine-2- ) -2- [4- (3-methoxybenzene Yl) hexahydropyridine-i_yl] acetamide; 2- [4- (2-methoxyphenyl) hexahydropyracyl] -N- (1-methyl-1H-benzimidazole -2-yl) acetamidamine; N- (3-methylphenyl) _2- [4- (3-methylρ sedien-2-yl) -3,6-diazepine p ratio -1 ( 2H) yl] acetamidinium; 2- (1- {2-[(3,5-dichlorophenyl) amino] -2-ketoethyl} hexahydro p ratio yodo-4-yl) p ratio Bond N, oxide; 2- (1- {2 _ [(2,3-dichlorophenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1- {2 · [(2-methoxy-6-methylphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2 -{1- [2- (1, Γ-biphenyl-3-ylamino) -2-ketoethyl] hexahydropyridin-4-yl} pyridine N_ oxide; 2_ (1- {2- [(3 · Ethylphenyl) amino] -2-¾¾ethylethyl ρ ratio lake 4-yl) ρ ratio bond N-oxide; 2- {1- [2- (2,3-di Hydrogen-1H-inden-5_ylamino) _2_ketoethyl] hexahydropyridylicel} outer N-oxide; 2- {1_ [2_keto-2- (5,6, 7,8-tetrahydropyridin-1-ylamino) ethyl] hexahydropyridinyl} pyridine N-oxide; 2- (1- {2-[(3-isopropoxyphenyl) amine Yl] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1_ {2 · [(3,5-dimethylphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 85228 -154- 200404539 2- (l- {2-[(4-Bromo_2_methylphenyl) amino] _2_ketoethyl} hexahydropyridin-4-yl) pyridinium N-oxidation Compounds; 2- [1- (2-keto_2 _ {[3_ (trifluoromethoxy) phenyl] amino} ethyl) hexahydropyridine_4-yl] pyridine N-oxide; 2- ( 1- {2-[(5-methyl-2-nitrophenyl) amino] -2-ketoethyl} hexahydropyridinyl) pyridine N-oxide; 2- (1- {2 -[(2,6-dimethylphenyl) amino] -2 · _ylethyl} hexahydropyridine_4_ylwind ingot N-oxide; 2- (1- {2-[(2, 6-monochloro-3-methylphenyl) amino] -2-ketoethyl} hexahydropyridine_4_yl) pyridine N-oxide; 2- {1- [2- (1 , 3-benzodioxofluoren-5-ylamino) -2-g isopropylethyl] hexahydropyridin-4-yl} bond N-oxide; 2- [1- (2- { [3_ (methylthio) phenyl] amino group 2-ketoethyl) hexahydropyridine · 4-based wind ingot N-oxide; 2- (1- {2-[(5-chloro-2 -Methylphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) N-oxide; 2- (1- {2-[(2,5-monomethoxy) Phenyl) Pyridyl] -2-ketoethyl} hexahydrop-pyridyl-4-yl) pyridinium N-oxide; 2- (1- {2-[(3,5-dimethoxyphenyl) amino ] _2_ketoethyl} hexahydropyridine 4-yl) pyridinium N-oxide; 2- [1- (2-{[3- (monomethylamino) phenyl] amino} -2-one Methyl ethyl) hexahydroπ ratio lake 4-yl] pyridinium N-oxide; 2- (1- {2-[(3_isopropylphenyl) amino] -2-ketoethyl} Hexahydropyridin-4-yl) pyridine N_oxide; -155- 85228 200404539 2- (1 · {2-[(3-Gas-2-methylphenyl) amino] -2-one Ethyl} hexahydropyridin-4-yl) pyridinium N-oxide; 3-methyl-N- [2- (4 ^ pyridin-2-ylhexahydropyridine-1_yl) ethyl] benzene Formamidine; 2- (1-{[(2,3-dibromo-5-methylbenzylidene) amino] methyl} hexahydropyridin-4-yl) pyridinium N-oxide; 2- {1-[(benzylamino) methyl] hexahydropyridinyl} pyridine N-oxide; 2 · (1-{[(4-amino-3-methylbenzyl) ) Amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1-{[((4-fluoro-3-methylbenzyl) amino) amino] methyl} Hexahydropyridin-4-yl) pyridine N-oxide; 2- [1-({[3-Chloro-4- (trifluoromethoxy) benzylidene] amino} methyl ) Hexahydropyridine 4-yl] pyridine N-oxide; 2- (1-{[((3-ethoxybenzyl) amino) methyl] hexahydropyridine 4-yl) pyridine N-oxide; 2- (1 _ {[(3,5-dichlorobenzyl) amino] methyl] hexahydropyridin-4-yl) pyridine N-oxide; 2- [1- ( {[4-Methyl (trifluoromethyl) benzylidene] amino} methyl) hexahydropyridine · 4-yl] pyridine N-oxide; 2- (1-{[(3,4- Xylolyl) amino] methyl] hexahydropyridin-4-yl) pyridinium oxide; 2- (1-{[((3-chloro-4-fluorobenzyl) amino) amino] Methyl} hexahydropyridin-4-yl) pyridine N_ oxide; 2- (1-{[(pyridin-2-ylcarbonyl) amino] methyl} hexahydropyridin-4-yl) pyridine N_ Oxides; 85228 -156- 200404539 2- (1-{[((3,5-xylylcarboxylate) amino] methyl] hexazine ^ 1 than lake_4-yl) ^? Specific bond] ^ _ oxidation Compounds; 2- (l-{[(3-vinylbenzyl) amino] methyl} hexahydroρ biden-4-yl) eodanium] sf_ oxide; 2- (1-{[( 4-bromo-3-methylbenzyl) amine] methyl] 1,2,3,6-tetrahydropyridin-4-yl &gt; specific N-oxide; 2- {1- [ (2-Methenylamino) methyl] hexahydropyridin-4-yl} pyridine N-oxidation ; 2- (1-{[(thiophen-2-ylcarbonyl) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- [H {[(6-chloropyridine each Group) carbonyl] amino} methyl) hexahydropyridinyl] pyridine N_oxide; 2- (1 _ {[((3-cyanobenzoyl) amino] methyl} hexahydrop-pyridine) -4-yl) Eodonium N-oxide; 2 · (1-{[((2,3-dibromo-5-methylbenzylidene) amino] methyl} -1,2,3, 6-tetrahydroeridin-4-yl) pyridine N-oxide; 2- (1-{[((4-bromobenzoate) amino] methyl} hexahydrou-pyridine-4-yl &gt; &gt;; Ingot oxide; 2- (H [(3-Gas-4-methylbenzylidene) amino] methyl] hexahydropyridolyl) ratio ingot N-oxide; 2- (1 -{[Methyl (3-methylbenzyl) amino] methyl} hexahydropyridinyl) pyridine N-oxide; 2- (1-{[(3-nitrobenzyl ) Amino] methyl} hexahydropyridin-4-yl) pyridine hydrazone oxide; 2- (1-{[((2-chloro-5-methylbenzyl) amino) amino] methyl} hexa Hydropyridin-4-yl) E 85228 -157- 200404539 Ingot N-oxide; 2- (l-{[((3-methoxy-2-methylbenzyl) amino) methyl] hexahydro] Pyridyl) Pyridinium N-oxide; 2 · (1 · {[(4-chloro_3 _Methoxybenzylidene) amino] methyl} hexahydropyridyl) pyridine N-oxide; N- (3-methylphenyl) -2- (3 • pyridylhexahydropyridine-1 -Yl) acetamide; N- (3-methylphenyl) · 2- (3-pyridin-2-yltetrahydropyrrole-1-yl) acetamide; N- (l-methyl-1fluorene- Benzimid-2-yl) -2_ [3- (1,3-distant ♦ -2-yl) hexahydroeodolide small group] acetamidamine; N- (l_methyl-1fluorene-benzimidazole -2_yl) _2- [3- (1,3 · pyrazol-2-yl) tetrahydropyrrole small group] acetamidine; 2- (2-benzyltetrahydropyrrole-1-yl) -ν_ ( 3-fluorobenzyl) acetamide; and N- (4-fluorophenyl) -2_ (3-telephen-2-yltetrahydropyrrole_yl_yl) acetamide; or a pharmaceutically acceptable Salts, esters, amidines or prodrugs. The most preferred compound of the present invention is 2- (1-{[(3-methylbenzyl) amino] methyl] methylhexahydropyridyl) pyridinesulfonium oxide. Abbreviations have been used in the abbreviations in the illustrations of the following figures and examples, as: Ac is ethenyl; BINAP is 2,2'-bis (diphenylphosphino) _U'_binapyl; B. c is the third-butoxycarbonyl group; nBuLi is n-butyllithium; dba is diphenylmethyleneacetone; DME is dimethoxyethane; DMF * N, N-dimethylformamide; 〇 is dimethyl sulfoxide; EtOH is ethanol; HPLC is high pressure liquid chromatography; MeOH is methanol; TEA is triethylamine; TFA is trifluoroacetic acid; THF is tetrahydrofuran; THp 85228 -158- 200404539 is four Hydrogen chant; TLC is thin layer chromatography. Preparation of the compound of the present invention The compound and method of the present invention will be made clearer with the accompanying drawings and examples of the following formula, which illustrate a way by which the compound of the present invention can be prepared. Schema 1

CI a-nh2 ⑴ + γ-Β「CI a-nh2 ⑴ + γ-Β 「

Na〇H, CH2CI2, RT 或 甲苯，回流 A痛丫、 〇 (2) (2)Na〇H, CH2CI2, RT or toluene, reflux A pain, 〇 (2) (2)

iP「2EtN,曱苯，加熱 或 Na2C03) DMF, RT 或 K2C〇3,甲笨，RTiP 「2EtN, toluene, heating or Na2C03) DMF, RT or K2C〇3, methylbenzene, RT

A-NH HN^ 或 、B (3)A-NH HN ^ or, B (3)

、B 通式⑹化合物，其中A、Z、B及…均如式①中之定義， 其可按圖式1中所述製成。可將通式⑴之胺類以氯化溴乙醯 、氫氧化鈉，在譬如但不限於甲苯或二氯甲烷之溶劑中處 理，以提供通式（2)化合物。可將通式⑺化合物以通式⑶或（4) 或（5)芡胺處理，於鹼存在下，譬如但不限於二異丙基乙胺 、碳酸鈉或碳酸鉀，在譬如但不限於甲苯或N，N_二甲基甲醯 胺之溶劑中進行，以提供通式⑹化合物。 85228 200404539 圖式2Compounds of the general formula ⑹, B, in which A, Z, B and ... are as defined in formula (1), which can be prepared as described in formula (1). The amines of the general formula IX may be treated with bromoacetamidine chloride and sodium hydroxide in a solvent such as, but not limited to, toluene or dichloromethane to provide the compound of the general formula (2). Compounds of general formula VII can be treated with general formula (3) or (4) or (5) amines in the presence of a base such as, but not limited to, diisopropylethylamine, sodium carbonate, or potassium carbonate, such as but not limited to toluene Or N, N-dimethylformamide in a solvent to provide a compound of general formula VII. 85228 200404539 Scheme 2

⑹ 〇⑹ 〇

酸 ^ 或 一氣化亞硫醯 BM 或 (9)一 l^L-B ⑶ 3〇2^lg〇2N(C2H5)2 (10)〇HAcid ^ or mono-gasified thionyl BM or (9) -l ^ L-B ⑶ 302 ^ lg〇2N (C2H5) 2 (10) 〇H

(11) 去除保護(11) Remove protection

(11) ηΐ^ (4) Β 通式（5)與（4)化合物，其中β係如式①中之定義，可按圖式 2中所述製成。通式⑻之六氫&lt;相，可㈣獲得或使用熟 W此蟄者所已知之標準方法製成，其中ρ為氮保護基，譬如 但不限於(CH3)3C〇2C-或C6H5CH2〇2C_，可將其以通式(9)化合 物處理’其中Μ為Li、MgBr、Mga、HZn，以提供通式⑽ 化t物。可將通式（10)化合物以Burgess試劑、三氯化亞硫酿 或酸處理，譬如但不限於硫酸或三氟醋酸，以提供通式⑴） 之二氫吡啶。可將通式⑼之二氫吡啶，使用一般熟諳此藝 者所已知之標準方法去除保護，以提供通式(4)與(5)化合物。 圖式3(11) ηΐ ^ (4) B Compounds of the general formulae (5) and (4), wherein β is as defined in formula (1), and can be prepared as described in formula (2). The hexahydro &lt; phase of the general formula ㈣ can be obtained or prepared by standard methods known to those skilled in the art, where ρ is a nitrogen protecting group, such as but not limited to (CH3) 3C〇2C- or C6H5CH2〇2C_ It can be treated with a compound of the general formula (9) 'wherein M is Li, MgBr, Mga, HZn to provide a halogenated t compound of the general formula. The compound of general formula (10) can be treated with Burgess reagent, sulfurous chloride or acid, such as but not limited to sulfuric acid or trifluoroacetic acid to provide dihydropyridine of general formula IX). Dihydropyridines of the general formula (I) can be removed by standard methods known to those skilled in the art to provide protection of the compounds of the general formulae (4) and (5). Scheme 3

A「X 或 hetX, Pd(0)A 「X or hetX, Pd (0)

去除保護HNRemove protection HN

(14) (14) X = Br 或 I Ar=芳基 Het =雜環(14) (14) X = Br or I Ar = aryl Het = heterocyclic

(11) 芳基或雜環 Β B(〇R)2(11) aryl or heterocyclic group B B (〇R) 2

85228 -160- 200404539 通式（4)與（5)化合物，其中B係如式①中之定義，可按圖式 3中所述製成。通式⑻之六氫吡啶酮，可市購獲得或使用熟 諳此藝者所已知之標準方法製成，其中P為氮保護基，譬如 但不限於（CHACO，-或C^CH^C-，可將其以Tf2Nph處理 ，以提供通式（13)之三氟甲烷磺酸酯。可將通式（13)之三氟 甲虼％酸酯可以二硼烷品吶可酯處理，以提供通式（Μ)之硼 烷。可將通式（14)之硼烷以ArX或HetX，於抑⑼觸媒存在下 處理，以提供通式（11)化合物。可將通式（π)化合物，使用一 般熟諳此藝者所已知之標準方法去除保護，以提供通式⑷ 與（5)化合物。 圖式485228 -160- 200404539 Compounds of general formulae (4) and (5), where B is as defined in formula ①, and can be prepared as described in formula 3. The hexahydropyridone of the general formula ⑻ can be obtained commercially or prepared using standard methods known to those skilled in the art, wherein P is a nitrogen protecting group, such as but not limited to (CHACO,-or C ^ CH ^ C-, It can be treated with Tf2Nph to provide the trifluoromethanesulfonate of the general formula (13). The trifluoromethane% acid ester of the general formula (13) can be treated with diborane pinaconate to provide Borane of formula (M). Borane of formula (14) can be treated with ArX or HetX in the presence of a catalyst to provide a compound of formula (11). A compound of formula (π) can be Protection is removed using standard methods known to those skilled in the art to provide compounds of the general formula ⑷ and (5). Scheme 4

ΗΗ

〇 〇 Pb(〇Ac)4〇 〇 Pb (〇Ac) 4

Λ Η 07)Λ Η 07)

(3) (16)(3) (16)

鹼Alkali

逋式（18)化合物 可按圖式4中所述製成。 《疋我 、式（16)又鉍，可市購獲得或使 此蟄者已知之標準方法製成，可將其The compound of formula (18) can be prepared as shown in Figure 4. "I, formula (16) and bismuth are commercially available or made by a standard method known to this person.

與酷酸銅(Π)處理，在譬如但不限 A 加熱，以提供通式(17)之酷酸酿。可：:中進：： 通式⑶或(4)或(5)之胺與鹼處理，嬖如但二艮於m 譬如但不限於乙腈之溶 ；二乙胺、 j中進订’以提供通式（18)化合物。 85228 -161 - 200404539 圖式5 〇 ΗΝΓ ΗΝΓ (3) α^νη2 (20) +It is treated with copper acid (II) and heated at, for example, but not limited to, A to provide the acid acid of the general formula (17). Available :: Zhongjin :: Amines and bases of the general formula (3) or (4) or (5) are treated with amines such as but not in m such as but not limited to acetonitrile; diethylamine and j are ordered to provide Compounds of general formula (18). 85228 -161-200404539 Scheme 5 〇 ΗΝΓ ΗΝΓ (3) α ^ νη2 (20) +

或 Β (4) ΗΝOr Β (4) ΗΝ

^Η2〇)π^ Η2〇) π

B 〇 λΑ μ 、tr Η (18) 又 •Β ， (5) 通式（18)化合物，其 、 Ζ、Β及…均如式（Τ) φ 士 a產 可按圖式5中所述製成。 （）中&lt;疋我： 使用-般熟諳此藝者已。广、(2〇)之驢胺類’可市購獲得3 驗處理，譬如但不法製成，可將其以”，劑中進行，並加埶， …、以&amp;供通式（18)化合物。【實施方式】 下述實例係意欲作為太恭 、 為本發明 &lt; 說明，並非限制其範圍，如 在隨又所附（申請專利範圍中所界定者。 貴例1 棊1·Ν·(3•甲某主玉）乙醯脖 實例1Α 丄3-甲基苽某R _脸 將3-甲基苯胺(Α_，15綱升，141·8毫莫耳）在观氯氧化 鈉水溶液（200毫升）中，於室溫下，以氯化溴乙醯（sigma，丨25〇 宅升，152·0耄莫耳）在二氯甲烷（2〇〇毫升）中之溶液處理。3〇 分鐘後，分離液層，並將水相以另一份二氯甲烷萃取。將 有機相合併，以IN HC1水溶液洗滌，脫水乾燥讲七s〇4)，過 濾，並使濾液在減壓下濃縮，提供16.69克（52%產率）標題化 合物，為白色固體。1 H NMR (300 MHz, DMSO_d6) 5 2.28 (s，3H)，4.01 85228 -162- 200404539 (s，2H)，6.91 (d，1H，J=7.5 Hz)，7.20 (dd，1H，J=7.5, 7·5 Ηζ)，7·36 (d，1H，J=8.8 Hz)，7.42 (s，1H)，10.28 (br s，1H); MS (DCI/NH3) m/e 228/230 (M+H)+ ; 245/ 247 (M+NH4)+.B 〇λΑ μ, tr Η (18) and • B, (5) Compounds of the general formula (18), which, Z, B and ... are as shown in formula (T) φ can be produced as described in Figure 5 to make. () In &lt; 疋 Me: use-as familiar with this artist already. Cantonese (20) donkey amines are commercially available and can be tested for 3 times. For example, if they are not made, they can be treated with "" in the agent, and then added with…, with &amp; for the general formula (18) [Embodiment] The following examples are intended to be too respectful and to illustrate the present invention &lt; not to limit its scope, as attached herewith (as defined in the scope of patent application. 贵 例 1 棊 1 · Ν · (3 • A certain main jade) Ethyl Neck Example 1 Α 3-methyl cyanide R _ face will be 3-methylaniline (A_, 15 liters, 141.8 millimoles) in aqueous sodium oxychloride solution ( 200 ml), at room temperature, treated with a solution of bromoacetammonium chloride (sigma, 250 liters, 152.0 mol) in dichloromethane (200 ml). 30 minutes After that, the liquid layer was separated, and the aqueous phase was extracted with another portion of dichloromethane. The organic phases were combined, washed with an IN HC1 aqueous solution, dried and dried, and filtered, and the filtrate was concentrated under reduced pressure. Provided 16.69 g (52% yield) of the title compound as a white solid. 1 H NMR (300 MHz, DMSO_d6) 5 2.28 (s, 3H), 4.01 85228 -162- 200404539 (s, 2H), 6. 91 (d, 1H, J = 7.5 Hz), 7.20 (dd, 1H, J = 7.5, 7 · 5 Ηζ), 7.36 (d, 1H, J = 8.8 Hz), 7.42 (s, 1H), 10.28 (br s, 1H); MS (DCI / NH3) m / e 228/230 (M + H) +; 245/247 (M + NH4) +.

實例IB 2-「4·(2-甲氣笨基M-六氫吡畊基甲某苽某仏醯脸 將1-(2-甲氧苯基）六氫吡畊（Aldrich，1.50克，7.80毫莫耳）與 N，N-二異丙基乙胺（2.0毫升）在甲苯（30毫升）中，以得自實例 1A之產物（1.12克’ 4.90毫莫耳）處理’並於60°C下加熱18小時 。使混合物冷卻至室溫’轉移至分液漏斗，並以飽和碳酸 氫鈉水溶液洗務。使有機相脫水乾燥（Na2 S04)，過滤，並使 濾液在減壓下濃縮。使殘留物於矽膠上藉急騾式層析純化（ 以85%己烷：醋酸乙酯，然後以50%己烷：醋酸乙酯溶離） ，提供1.39克（83%產率）標題化合物，為黃色油。iHNMR (300 MHz，DMSO-d6) (5 2·28 (s，3H)，2·67 (m，4H)，3·03 (m，4H)，3.17 (s，2H)， 3.77 (s，3Η)，6·89 (m，5Η)，7.18 (dd，1Η，J=7.8, 7·8 Ηζ)，7·44 (m，2Η)，9·64 (br s， 1H) ； MS (DCI/NH3) m/e 340 (M+H)+. HC1鹽：白色固體；熔點 80°C(分解）；iHNMRpOOMHADMSOO 5 2·30 (s，3H)，3.11 (br s，2H)，3·46 (br s，4H)，3.60 (br s5 2H)，3.80 (s5 3H)， 4.25 (br s，2H)，6.95 (m，5H)，7·24 (dd，1H，J= 7.4, 7.4 Hz)，7.44 (m，2H)，10.52 (br s，0.5H)，10.82 (br s，0.5H);對 C2 〇 H2 5 N3 02 · 0.90 HC1 之分析計算 值：C，64.53 ; H，7·01 ; N，11.29.實測值：C，64.38 ; H，6.83 ; N，11.17. 實例2 2-「4-(2-氰基苯基）-1-六氫外井基1-Ν-Γ3-甲基苯基）乙酸胺 按照實例1B中所述之程序，以1_(2_氰基苯基）六氫吡畊（Chess) 85228 -163- 200404539 取代1-(2-甲氧苯基）六氫吡畊，提供標題化合物（92%產率）， g&amp;g&amp;°1HNMR(300MHz，DMSO-d6)5 2.28(s，3H)，2.73(m，4H)， 3.21 (s，2H)，3.23 (m，4H)，6.88 (br d，1H，J=7.5 Hz)，7.10 (ddd，1H，&gt;7.5, 7.5， 0.7 Hz)，7.19 (m，2H)，7.44 (m，2H)，7.61 (ddd，1H，J=7.5, 7_5, 1.7 Hz)，7.70 (dd5 1H，J=7.8,1·7 Hz)，9·68 (br s，1H) ; MS (DCI/NH3) m/e 335 (M+H)+ · 順丁晞二酸鹽：白色固體，熔點168-170°C ; iHNMRQOOMHz， DMSO-d6) 5 2.30 (s，3H)，3.21 (br s5 4H)，3.37 (bi* s，4H)，3·82 (br s，2H)，6·13 (s，2H)，6·93 (br d，1H，J=7.4 Hz)，7·18 (m，3H)，7·42 (m，2H)，7.64 (ddd，1H，J= φ 7.5, 7.5, 1.4 Hz)，7.74 (dd，1H，J=7.8, 1.7 Hz)，10.15 (br s，1H); 對 C2〇H22N40 · 1.0 C4H404之分析計算值：C, 63.99; H，5.82; N，12.44. 實測值：C, 63.80 ; H，5.80 ; N，12.21. 實例3 N-(3-甲基苯基）-2-「4-(2·口密淀基氮p比呼基1乙酸月安 按照實例1B中所述之程序，以1-(2-嘧啶基）六氫吡畊（EMKA-Chemie)取代1_(2_甲氧苯基）六氫吡畊，提供標題化合物(70%產 率），為白色固體。熔點 113-116°C ; iHNMRGOOMHz’DMSOO # 5 2·28 (s，3H)，2.57 (m，4H)，3·17 (s，2H)，3.80 (m，4H)，6.62 (dd，1H，J=4.8， 4.8 Hz)，6.88 (br d，1H，J=7.4 Hz)，7.18 (dd，1H，J=7.8, 7.8 Hz)，7.46 (m，2H)， 8.36(d，2H，J=4.7Hz)，9.67(brs，1H) ; MS (DCI/NH3) m/e 312 (M+H)+ ； 對(：171121&gt;150 之分析計算值：c，65.57; H，6.80; N，22.49.實測值 :C，65.39 ; H，6.77 ; N，22.56. 實例4 N-(3-甲基笨基V2-「4-(2-吡啶基VI-六氫吡畊基1乙醯胺 按照實例1B中所述之程序，以1-(2-吡啶基）六氫吡畊（Aldrich) 85228 -164- 200404539 取代1-(2-甲氧苯基）六氫吡畊，提供標題化合物（65%產率）， 為白色固體。熔點 126-127°C ; 1H NMR (300 MHz，DMSO-d6) δ 2·27 (s， 3H)，2·60 (m，4H)，3.17 (s，2H)，3_55 (m，4H)，6.63 (ddd，1H，J=6.7, 4.7, 0.6 Hz)， 6.82 (d，1H，J=8.8 Hz)，6.88 (br d，1H，J=7.8 Hz)，7.18 (dd，1H，J=6.7, 4.7, 0·6 Hz)，7.46 (m，2H)，7.52 (ddd，1H，J=8.8, 7.1，2·0 Hz)，8.11 (m，1H)，9·67 (br s， 1H); MS(DCI/NH3)m/e311(M+H)+ ;對 C18H22N40 之分析計算值 :C，69.65 ; H，7·14 ; N，18.05.實測值：C，69.72 ; H，7.09 ; N，18.22. 實例5 · 2-[4-(3-氰基-2-吡啶某VI-六氫吡畊基甲基笨基）乙醯胺 按照實例1B中所述之程序，以2-(1-六氫吡啡基）菸鹼腈（Chess) 取代1-(2-甲氧苯基）六氫吡畊，提供標題化合物（64%產率）， 為白色固體。熔點 99-100°C ; 1H NMR (300 MHz，DMSO_d6) 5 2.28 (s， 3H)，2.68 (m，4H)，3_19 (s，2H)，3.68 (m，4H)，6.88 (br d，1H，J=7.8 Hz)，6.93 (dd5 1H5 J=7.85 4.8 Hz)5 7.18 (dd5 1H5 J=7.5? 7.5 Hz)? 7.44 (br d? 1H? J=8.2 Hz)? 7.47 (br s，1H)，8.07 (dd’lH，J=7.8, 2.0 Hz)，8.42 (dd，1H，J=5.1，2.0 Hz)，9.68 ( brs，1H) ; MS(DCI/NH3)m/e336(M+H)+ ;對 C19H21N50 之分析計 鲁 算值：C，68.04 ; H，6·31 ; N，20·88_ 實測值：C，68.19 ; H，6·36 ; N，21.15. 實例6 N-(3-甲基苯基）-244-(2-甲基笨某VI-六氫吡畊基1乙醯胺 按照實例1B中所述之程序，以1-(2-甲基苯基）六氫吡畊 (EMKAChemie)取代1-(2-甲氧苯基）六氫吡啩，提供標題化合物 (75% 產率），為白色固體。熔點 i〇4_l〇6°C ; WNMRpOOMHz， DMSO-d6) δ 2.24 (s3 3Η)5 2.28 (s? 3Η)5 2.69 (m? 4Η)5 2.91 (m? 4Η), 3.19 (s5 2H)5 6.88 (br d5 1H? J=7.4 Hz)5 6.95 (dd5 1H? J=7.1, 7.1 Hz), 7.05 (m? 1H)? 7.17 85228 -165- 200404539 (m，3H)，7.45(m,2H)，9.64(brs，lH) ; MS (DCI/NH3) m/e 324 (M+H)+ ； 對 C2〇H25N30之分析計算值：c，74.27; Η，7·79; Ν，12·99·實測值 :C，74.34 ; Η，7·85 ; Ν，12.91. 實例7 N-G-甲某茉某V2-|~4-(2-硝基苯某Μ-六氫吡畊基1乙醯胺 按照實例1Β中所述之程序，以1-(2-硝基苯基）六氫吡畊 (EMKA Chemie)取代1-(2-甲氧苯基）六氫外1：畊，提供標題化合物 (91% 產率），為橘色油。1 H NMR (300 MHz，DMS(M6) 5 2.28 (s，3H)， 2.66 (m? 4H)? 3.07 (m, 4H)5 3.18 (s5 2H)? 6.88 (br d5 1H, J=7.8 Hz)? 7.13 (ddd? 1H，J=8.5, 7.1，1_0 Hz)，7.18 (dd，1H，J=7.8, 7.8 Hz)，7.35 (dd，1H，J=8.1，1·0 Hz)，7.45 (m，2H)，7.59 (ddd，1H，J=8.1，7.1，1.3 Hz)，7.79 (dd，1H，J=8.l·，1·7 Hz)? 9.66 (br s? 1H) ； MS (DCI/NH3) m/e 355 (M+H)+. 順丁烯二酸鹽：黃色固體；熔點172_175。〇;對c19H22N403 · 1.0C4H4O4之分析計算值：c，58.72; H，5.57; Ν，11·91·實測值： C，58.38 ; Η，5.49 ; Ν，11.64. 實例8 ^[4-(3-氰基-2-吡啶基）-1-六氫吡畊基ι_Ν_(3-硝基苯基）乙醯胺 將2-(1-六氫吡畊基）_3_吨啶甲腈（64〇毫克，3.40毫莫耳）與Ν，Ν-二異丙基乙胺（1.0毫升）在甲苯（15毫升）中，於室溫下，以Ν-氯基乙醯基-3-硝基苯胺（Lancaster，610毫克，2.84毫莫耳）處 理’並和反應物在90 C下加熱18小時。使混合物冷卻至室溫 ’轉移至分液漏斗，並以飽和碳酸氫鈉水溶液洗滌。使有 機相脫水乾燥（Na2S04)，過濾，並使濾液在減壓下濃縮。使 殘留物於矽膠上藉急,驟式層析純化（以85%己烷：醋酸乙酯 85228 -166- 200404539 溶離），提供256毫克（25%產率）標題化合物，為淡黃褐色固 體。熔點 143-145°C ; 1H NMR (300 MHz，DMSO-d6) (5 2.69 (m，4H)，3.27 (s，2H)，3.70 (m，4H)，6.93 (dd，1H，J=7.4, 5·0 Hz)，7·61 (dd，1H，J=8.1，8.1 Hz)， 7.93 (br d，1H，J=8.2 Hz)，8.06 (dd，2H，J=7.8, 7.8 Hz)，8.42 (m，1H)，8.70 (br s， 1H)，10.28 (br s，1H) ; MS (DCI/NH3) m/e 367 (M+H)+ ;對 q 8 H! 8 N6 03 之分析計算值：C，59.01; H，4.95 ; N，22.94.實測值：C，59.31; H，5.25 ;N，22.66· 實例9 · 氰基-2-吡啶基VI-六氫吡畊基l-N43-(三氟甲基）苯某1 乙醯胺 按照實例8中所述之程序，以N-氯基乙醯基-3·(三氟甲基）苯 胺取代N_氯基乙醯基-3-硝基苯胺，提供標題化合物（84%產率） ，為黃色油。1H NMR (300 MHz，DMSO-d6 ) δ 2.69 (m，4H)，3.25 (s，2H)， 3.69 (m，4Η)，6.93 (dd，1Η，J=7.8, 4·7 Ηζ)，7·41 (br d，1Η，J=7.8 Ηζ)，7·56 (dd， 1H，J=7.8, 7.8 Hz)，7.90 (br d，1H，J=8.4 Hz)，8·07 (dd，1H，JN7.8, 2·1 Hz)，8_15 (br s，1H)，8.42 (dd，1H，J=4.7, L7 Hz)，10.11 (br s，1H) ; MS (DCI/NH3) m/e Φ 390 (M+H)+. 順丁烯二酸鹽：黃褐色固體；熔點157_158°c ; iHNMR(300 MHz， DMSO-d6) 5 3.07 (br s，4H)，3.73 (br s，2H)，3.79 (br s，4H)，6·15 (s，2H)，7.00 (dd，1H，J=7.4, 4.7 Hz)，7.46 (br d，1H，J=7.8 Hz)，7.59 (dd，1H，J=7.8, 7.8 Hz)， 7.85 (br d，1H，J=8.2 Hz)，8.13 (m，2H)，8.45 (dd，1H，J=4.7, 2.0 Hz)，10.48 (br s， 1H);對 Α9Η18Ρ3Ν5Ο·1.0(：4Η4Ο4 之分析計算值：C，54.56; Η，4·39 ;Ν，13.86.實測值：C，54.30 ; Η，4·42 ; Ν，13.42. 實例10 85228 -167 &gt; 200404539 N-(3-甲基笨基）-2-(4-笨基-1_六氫吡畊基）乙醯胺 按照實例1B中所述之程序，以1-苯基六氫吡畊（Aldrich)取 代1-(2-甲氧苯基）六氫吡畊，提供標題化合物（86%產率），為 白色固體。熔點 120-12rc ; iHNMRpOOMHADMSO·^) 52.27(s， 3H)，2.66 (m，4H)，3.17 (s, 2H)，3·20 (m，4H)，6·77 (dd, 1H，J=7.1，7·1 Ηζ)，6·88 (br d，1H，J=7.5 Hz)，6·94 (d，2H，J=7.8 Hz)，7.21 (m，3H)，7·44 (m，2H)，9.65 (brs，lH); MS(DCI/NH3)m/e310(M+H)+ ;對（：191123^0 之分析計 算值：C，73_76 ; H，7.49 ; N，13·58.實測值：C，73.73 ; H，7.50 ; N，13.64. 實例11 N-(3-氰某茉某V2-『4-(3-氰基-2-吡啶基VI-六氫吡畊基1乙醯胺 按照實例8中所述之程序，以N-氯基乙醯基-3-氰基苯胺 (Maybridge)取代N-氯基乙醯基-3-硝基苯胺，提供標題化合物（60 % 產率），為無色油。1HNMR(300MHz，DMSO-d6)52.68(m，4H)， 3.25 (s，2H)，3.69 (m，4H)，6.92 (dd，1H，J=7.5, 5.1 Hz)，7.52 (m，2H)，7_94 (m， 1H)，8.07 (m，1H)，8_15 (m，1H)，8·41 (m，1H)，10.10 (br s，1H); MS (DCI/NH3) m/e 347(M+H)+. 順丁烯二酸鹽：白色固體；熔點166-167°C ; iHNMRpOOMHz， DMSO-d6) 6 3_04 (br s，4H)，3.69 (br s，2H)，3.78 (br s，4H)，6_16 (s，2H)，6.99 (dd，1H，J=7.5, 4.6 Hz)，7.58 (m，2H)，7.89 (m，1H)，8·12 (m，2H)，8.45 (dd，1H， J=4.7, 2.0 Hz)，10.46 (br s，1H);對 Ci 9 Η! 8 N6 O · 1.0C4 H4 04 之分析計 算值：C，59·73 ; H，4·79 ; N，18.17·實測值：C，59·73 ; H，4·81; N，18·45· 實例12 Ν-(4-溴基-3-甲基笨基）-244-(2-氰基笨基VI-六氫吡畊基1乙醯胺Example IB 2- "4- (2-methylbenzyl M-hexahydropyridine, a certain face, 1- (2-methoxyphenyl) hexahydropyridine (Aldrich, 1.50 g, 7.80 Mmol) with N, N-diisopropylethylamine (2.0 ml) in toluene (30 ml), treated with the product from Example 1A (1.12 g '4.90 mmol) and at 60 ° C Heat for 18 hours under cooling. Allow the mixture to cool to room temperature and transfer to a separatory funnel and wash with saturated aqueous sodium bicarbonate solution. The organic phase is dried (Na2S04), filtered, and the filtrate is concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (isolated with 85% hexane: ethyl acetate and then 50% hexane: ethyl acetate) to provide 1.39 g (83% yield) of the title compound as yellow Oil. IHNMR (300 MHz, DMSO-d6) (5 2 · 28 (s, 3H), 2.67 (m, 4H), 3.03 (m, 4H), 3.17 (s, 2H), 3.77 (s , 3Η), 6.89 (m, 5Η), 7.18 (dd, 1Η, J = 7.8, 7 · 8 Ηζ), 7.44 (m, 2Η), 9.64 (br s, 1H); MS ( DCI / NH3) m / e 340 (M + H) +. HC1 salt: white solid; melting point 80 ° C (decomposition); iHNMRpOOMHADMSOO 5 2 · 30 (s, 3H), 3.11 (br s, 2H), 3.46 (br s, 4H), 3.60 (br s5 2H), 3.80 (s5 3H), 4.25 (br s, 2H), 6.95 (m, 5H), 7 24 (dd, 1H, J = 7.4, 7.4 Hz), 7.44 (m, 2H), 10.52 (br s, 0.5H), 10.82 (br s, 0.5H); for C2 〇H2 5 N3 02 · 0.90 HC1 Analytical calculated values: C, 64.53; H, 7.01; N, 11.29. Found: C, 64.38; H, 6.83; N, 11.17. Example 2 2- "4- (2-cyanophenyl)- 1-Hexahydro Outeryl 1-N-Γ3-methylphenyl) acetic acid Follow the procedure described in Example 1B with 1_ (2_cyanophenyl) hexahydropyridine (Chess) 85228 -163- 200404539 Substituted 1- (2-methoxyphenyl) hexahydropyridine to provide the title compound (92% yield), g & g & ° 1HNMR (300MHz, DMSO-d6) 5 2.28 (s, 3H), 2.73 ( m, 4H), 3.21 (s, 2H), 3.23 (m, 4H), 6.88 (br d, 1H, J = 7.5 Hz), 7.10 (ddd, 1H, &gt; 7.5, 7.5, 0.7 Hz), 7.19 ( m, 2H), 7.44 (m, 2H), 7.61 (ddd, 1H, J = 7.5, 7_5, 1.7 Hz), 7.70 (dd5 1H, J = 7.8, 1. · 7 Hz), 9.68 (br s, 1H); MS (DCI / NH3) m / e 335 (M + H) + · maleic acid salt: white solid, melting point 168-170 ° C; iHNMR QOOMHz, DMSO-d6) 5 2.30 (s, 3H), 3.21 (br s5 4H), 3.37 (bi * s, 4H), 3.82 (br s, 2H), 6.13 (s, 2H), 6 · 93 (br d, 1H, J = 7.4 Hz), 7.18 (m, 3H), 7.42 (m, 2H), 7.64 (ddd, 1H, J = φ 7.5, 7.5, 1.4 Hz), 7.74 (dd, 1H, J = 7.8, 1.7 Hz), 10.15 (br s, 1H); Analytical calculated value for C20H22N40 · 1.0 C4H404: C, 63.99; H, 5.82; N, 12.44. Found: C, 63.80; H, 5.80; N, 12.21. Example 3 N- (3-methylphenyl) -2- "4- (2. Methylpentyl nitrogen p-Hydroxyl 1 acetic acid Yuean as described in Example 1B The procedure was to replace 1- (2-methoxyphenyl) hexahydropyridine with 1- (2-pyrimidinyl) hexahydropyridine (EMKA-Chemie) to provide the title compound (70% yield) as a white solid. Melting point 113-116 ° C; iHNMRGOOMHz'DMSOO # 5 2 · 28 (s, 3H), 2.57 (m, 4H), 3.17 (s, 2H), 3.80 (m, 4H), 6.62 (dd, 1H, J = 4.8, 4.8 Hz), 6.88 (br d, 1H, J = 7.4 Hz), 7.18 (dd, 1H, J = 7.8, 7.8 Hz), 7.46 (m, 2H), 8.36 (d, 2H, J = 4.7Hz), 9.67 (brs, 1H); MS (DCI / NH3) m / e 312 (M + H) +; Analytical calculation for (: 171121 &gt; 150: c, 65.57; H, 6.80; N, 22.49 .Measured values: C, 65.39; H, 6.77; N, 22.56. Example 4 N- (3-methylbenzyl V2- "4- (2-pyridyl VI-hexahydropyridyl 1 acetamidine according to the example Procedure described in 1B, 1- (2-pyridyl) hexahydropyridine (Aldrich) 85228 -164- 200404539 replacing 1- (2-methoxyphenyl) hexahydropyridine to provide the title compound (65% Yield) as a white solid. Melting point 126-127 ° C; 1H NMR (300 MHz, DMSO-d6) δ 2.27 (s, 3H), 2.60 (m, 4H), 3.17 (s, 2H) , 3_55 (m, 4H), 6.63 (ddd, 1H, J = 6.7, 4.7, 0.6 Hz), 6.82 (d, 1H, J = 8.8 Hz), 6.88 (br d, 1H, J = 7.8 Hz), 7.18 (dd, 1H, J = 6.7, 4.7, 0.6 Hz), 7.46 (m, 2H), 7.52 (ddd, 1H, J = 8.8, 7.1, 2.0 Hz) 8.11 (m, 1H), 9.67 (br s, 1H); MS (DCI / NH3) m / e311 (M + H) +; Analysis and calculation of C18H22N40: C, 69.65; H, 7.14; N, 18.05. Found: C, 69.72; H, 7.09; N, 18.22. Example 5 2- [4- (3-cyano-2-pyridine VI-hexahydropyridylmethylbenzyl) ethyl Amidine was replaced with 2- (1-hexahydropyridinyl) nicotinonitrile (Chess) in accordance with the procedure described in Example 1B to provide the title compound (64 % Yield) as a white solid. Melting point 99-100 ° C; 1H NMR (300 MHz, DMSO_d6) 5 2.28 (s, 3H), 2.68 (m, 4H), 3_19 (s, 2H), 3.68 (m, 4H), 6.88 (br d, 1H, J = 7.8 Hz), 6.93 (dd5 1H5 J = 7.85 4.8 Hz) 5 7.18 (dd5 1H5 J = 7.5? 7.5 Hz)? 7.44 (br d? 1H? J = 8.2 Hz )? 7.47 (br s, 1H), 8.07 (dd'lH, J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 5.1, 2.0 Hz), 9.68 (brs, 1H); MS (DCI / NH3 ) m / e336 (M + H) +; Analytical calculation of C19H21N50: C, 68.04; H, 6.31; N, 20 · 88_ Found: C, 68.19; H, 6.36; N, 21.15. Example 6 N- (3-methylphenyl) -244- (2-methylbenzyl VI-hexahydropyridyl 1 acetamide The procedure described in Example 1B, replacing 1- (2-methoxyphenyl) hexahydropyridine with 1- (2-methylphenyl) hexahydropyrine (EMKAChemie), provided the title compound (75% yield ), As a white solid. Melting point i04_106 ° C; WNMRpOOMHz, DMSO-d6) δ 2.24 (s3 3Η) 5 2.28 (s? 3Η) 5 2.69 (m? 4Η) 5 2.91 (m? 4Η), 3.19 (s5 2H) 5 6.88 (br d5 1H? J = 7.4 Hz) 5 6.95 (dd5 1H? J = 7.1, 7.1 Hz), 7.05 (m? 1H)? 7.17 85228 -165- 200404539 (m, 3H), 7.45 (m, 2H), 9.64 (brs, lH); MS (DCI / NH3) m / e 324 (M + H) +; Analytical calculated value for C20H25N30: c, 74.27; Η, 7.79; Ν, 12.99 · measured Value: C, 74.34; Thallium, 7.85; N, 12.91. Example 7 NG-methyl molybdenum V2- | ~ 4- (2-nitrobenzene molybdenum M-hexahydropyridyl 1 acetamide according to the example The procedure described in 1B, replacing 1- (2-methoxyphenyl) hexahydro with 1- (2-nitrophenyl) hexahydropyridine (EMKA Chemie) 1: Till, providing the title compound (91% Yield) as an orange oil. 1 H NMR (300 MHz, DMS (M6) 5 2.28 (s, 3H), 2.66 (m? 4H)? 3.07 (m, 4H) 5 3.18 (s5 2H)? 6.88 ( br d5 1H, J = 7.8 Hz)? 7.13 (ddd? 1H, J = 8.5, 7.1, 1_0 Hz), 7.18 (dd, 1H, J = 7.8, 7.8 Hz), 7.35 (dd, 1H, J = 8.1, 1 · 0 Hz), 7.45 (m, 2H), 7.59 (ddd, 1H, J = 8.1, 7.1, 1.3 Hz), 7.79 (dd, 1H, J = 8.l ·, 1.7 Hz)? 9.66 ( br s? 1H); MS (DCI / NH3) m / e 355 (M + H) +. Maleic acid salt: yellow solid; melting point 172-175. 〇; Analysis calculated for c19H22N403 · 1.0C4H4O4: c, 58.72; H , 5.57; N, 11.91. Found: C, 58.38; Hf, 5.49; N, 11.64. Example 8 ^ [4- (3-cyano-2-pyridyl) -1-hexahydropyridyl ι_Ν_ (3-Nitrophenyl) acetamidinium 2- (1-Hexahydropyridyl) _3-t-pyridinecarbonitrile (64 mg, 3.40 mmol) with Ν, Ν-diisopropylethylamine (1.0 ml) in toluene (15 ml) at room temperature with N-chloroethylfluorenyl-3-nitroaniline (Lancaster, 610 mg, 2.84 mmol) and reacted at 90 ° C. Heated at C for 18 hours. The mixture was allowed to cool to room temperature 'and transferred to a separatory funnel and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic phase was dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (dissolved with 85% hexane: ethyl acetate 85228-166-200404539) to provide 256 mg (25% yield) of the title compound as a pale yellow-brown solid. Melting point 143-145 ° C; 1H NMR (300 MHz, DMSO-d6) (5 2.69 (m, 4H), 3.27 (s, 2H), 3.70 (m, 4H), 6.93 (dd, 1H, J = 7.4, 5.0 Hz), 7.61 (dd, 1H, J = 8.1, 8.1 Hz), 7.93 (br d, 1H, J = 8.2 Hz), 8.06 (dd, 2H, J = 7.8, 7.8 Hz), 8.42 (m, 1H), 8.70 (br s, 1H), 10.28 (br s, 1H); MS (DCI / NH3) m / e 367 (M + H) +; Analysis and calculation of q 8 H! 8 N6 03 Value: C, 59.01; H, 4.95; N, 22.94. Found: C, 59.31; H, 5.25; N, 22.66. Example 9 · Cyano-2-pyridyl VI-hexahydropyridyl 1-N43- (Trifluoromethyl) benzyl 1 acetamidine According to the procedure described in Example 8, the N-chloroethylamido-3 · (trifluoromethyl) aniline was substituted for N_chloroethanyl-3- Nitroaniline, providing the title compound (84% yield) as a yellow oil. 1H NMR (300 MHz, DMSO-d6) δ 2.69 (m, 4H), 3.25 (s, 2H), 3.69 (m, 4Η), 6.93 (dd, 1Η, J = 7.8, 4 · 7 Ηζ), 7.41 (br d, 1Η, J = 7.8 Ηζ), 7.56 (dd, 1H, J = 7.8, 7.8 Hz), 7.90 (br d, 1H, J = 8.4 Hz), 8.07 (dd, 1H, JN7.8, 2.1 Hz), 8_15 (br s, 1H), 8.42 (dd, 1H, J = 4.7, L7 Hz), 10.11 (br s, 1H); MS (DCI / NH3) m / e Φ 390 (M + H) +. Maleic acid salt: tan solid; melting point 157_158 ° c; iHNMR (300 MHz, DMSO-d6 ) 5 3.07 (br s, 4H), 3.73 (br s, 2H), 3.79 (br s, 4H), 6.15 (s, 2H), 7.00 (dd, 1H, J = 7.4, 4.7 Hz), 7.46 (br d, 1H, J = 7.8 Hz), 7.59 (dd, 1H, J = 7.8, 7.8 Hz), 7.85 (br d, 1H, J = 8.2 Hz), 8.13 (m, 2H), 8.45 (dd, 1H, J = 4.7, 2.0 Hz), 10.48 (br s, 1H); Analytical calculated value for A9Η18P3Ν5Ο · 1.0 (: 4Η4〇4: C, 54.56; Η, 4.39; N, 13.86. Found: C, 54.30 Η, 4.42; Ν, 13.42. Example 10 85228 -167 &gt; 200404539 N- (3-methylbenzyl) -2- (4-benzyl-1_hexahydropyridyl) acetamidine according to The procedure described in Example 1B, replacing 1- (2-methoxyphenyl) hexahydropyridine with 1-phenylhexahydropyridine (Aldrich) provided the title compound (86% yield) as a white solid. Melting point 120-12rc; iHNMRpOOMHADMSO · ^) 52.27 (s, 3H), 2.66 (m, 4H), 3.17 (s, 2H), 3.20 (m, 4H), 6.77 (dd, 1H, J = 7.1 , 7 · 1 Ηζ), 6.88 (br d, 1H, J = 7.5 Hz), 6.94 (d, 2H, J = 7.8 Hz), 7.21 (m, 3H), 7.44 (m, 2H ), 9.65 (brs, lH); MS (DCI / NH3) m / e310 (M + H) +; Analytical calculation for (: 191123 ^ 0: C, 73_76; H, 7.49; N, 13.58. Measured value: C, 73.73; H, 7.50; N, 13.64. Example 11 N- (3-Cyanomozine V2- "4- (3-cyano-2-pyridyl VI-hexahydropyracyl 1B Amidine was replaced by N-chloroethylfluorenyl-3-cyanoaniline (Maybridge) according to the procedure described in Example 8 to provide the title compound (60% yield Ratio), is a colorless oil. 1HNMR (300MHz, DMSO-d6) 52.68 (m, 4H), 3.25 (s, 2H), 3.69 (m, 4H), 6.92 (dd, 1H, J = 7.5, 5.1 Hz), 7.52 (m, 2H), 7_94 (m, 1H), 8.07 (m, 1H), 8_15 (m, 1H), 8.41 (m, 1H), 10.10 (br s, 1H); MS (DCI / NH3 ) m / e 347 (M + H) +. Maleic acid salt: white solid; melting point 166-167 ° C; iHNMRpOOMHz, DMSO-d6) 6 3_04 (br s, 4H), 3.69 (br s , 2H), 3.78 (br s, 4H), 6_16 (s, 2H), 6.99 (dd, 1H, J = 7.5, 4.6 Hz), 7.58 (m, 2H), 7.89 (m, 1H), 8 · 12 (m, 2H), 8.45 (dd, 1H, J = 4.7, 2.0 Hz), 10.46 (br s, 1H); Analytical calculation for Ci 9 Η! 8 N6 O · 1.0C4 H4 04: C, 59 · 73; H, 4.79; N, 18.17. Found: C, 59.73; H, 4.81; N, 18.45. Example 12 N- (4-bromo-3-methylbenzyl) -244- (2-Cyanobenzyl VI-hexahydropyridyl 1 acetamide

實例12A 85228 -168- 200404539 溴基-3-甲某苯某、己_ 將4-溴基-3_甲基苯胺（10.08克，5418毫莫耳）在汹氫氧化鈉 (200毫升）中，以氯化溴乙醯（5 〇〇毫升，6〇·8毫莫耳）在二氣 甲：ki (200愛升）中之溶液逐滴處理。Μ分鐘後，分離液層。 將有機相以1N鹽酸洗滌，脫水乾燥，過濾，並使濾 液在減壓下濃縮，提供11.75克（71% )標題化合物，為黃褐色 固體。1H NMR (300 MHz，CDC13) 5 2.39 (s，3H)，4.01 (s，2H)，7.23 (m，1H)， 7.44 (d，1H，J=2.4 Hz)，7·49 (d，1H，J=8.8 Hz)，8.07 (br s，1H); MS (DCI/NH3) m/e306 (M+H)+.Example 12A 85228 -168- 200404539 Bromo-3-methylbenzene, hexamethyl-4-bromo-3-methylaniline (10.08 g, 5418 mmol) in sodium hydroxide (200 ml), It was treated dropwise with a solution of acetamidine bromide (500 ml, 60.8 mmol) in dichloromethane: ki (200 liters). After M minutes, the layers were separated. The organic phase was washed with 1N hydrochloric acid, dried over water, filtered, and the filtrate was concentrated under reduced pressure to provide 11.75 g (71%) of the title compound as a tan solid. 1H NMR (300 MHz, CDC13) 5 2.39 (s, 3H), 4.01 (s, 2H), 7.23 (m, 1H), 7.44 (d, 1H, J = 2.4 Hz), 7.49 (d, 1H, J = 8.8 Hz), 8.07 (br s, 1H); MS (DCI / NH3) m / e306 (M + H) +.

實例12B 漠基-3_甲基笨基）_2-『4-(2-氰基茉基）-1-六氫p比p井基i乙驢胺 將得自實例12A之產物（3.51克，11·4毫莫耳）與N，N-二異丙 基乙胺（2.50毫升）在甲苯（50毫升）中，以1-(2-氰基苯基）六氫 外匕啡（Chess，2.90克，15.5毫莫耳）處理，並將反應混合物於90 °C下加熱18小時。使混合物冷卻至室溫，並轉移至具有醋酸 乙酉3與水之分液漏斗。將有機相以飽和碳酸氫鈉水溶液洗 務，脫水乾燥（Na2S04)，過濾，並使濾液在減壓下濃縮。使 殘留物於矽膠上藉急驟式層析純化，提供3.66克（77% )標題 化合物，為黃色固體。熔點 143-145°C ; 1H NMR (300 MHz，DMSO-d6) 5 2·32 (s，3H)，2·72 (m，4H)，3.22 (m，6H)，7.10 (ddd，1H，J=7.4, 7.4, 0.6 Hz)， 7·19 (d，1H，8.1 Hz)，7.49 (m，2H)，7.61 (m，1H)，7.65 (d，1H，J=2.1 Hz)，7.70 (dd，1H，J=7.8, 1·7 Hz)，9.82 (br s，1H) ; MS (DCI/NH3) m/e 413/415 (M+H)+ ;對(^2〇11218故40 之分析計算值：C,58.12; Η，5·12; N，13.56·實 測值：C，58.13 ; Η，5·07 ; N，13.54· 85228 -169- 200404539 實例13 ^ιί4-(2-氰基苯基VI-六氫p比畊基1-N_笨基乙醯胺 按照實例12B中所述之程序，以2-氯苯基乙醯胺（Maybridge) 取代得自實例12A之產物，提供標題化合物p9%產率），為 黃色固體，熔點 137-138X： ; iHNMRpOOMHz’DMSOd 52.73(m， 4H)，3.22 (m，6H)，7·08 (m，2H)，7·19 (d，1H，J=8_5 Hz)，7.30 (m，2H)，7·63 (m， 2H)，7.70 (dd，1H，J=7_8, 1.7 Hz)，9.76 (br s，1H) ; MS (DCI/NH3) m/e 321 (M+H)+ ;對 Cl 9H2〇N40 之分析計算值：c，Ή·23 ; H，6.29 ; N，17.49· φ 實測值：C，70.92 ; H，6·34 ; N，17_34. 實例14 2-14-(3-氰基-2-峨淀基）-1-六藎，外井基Ί-Ν-苯基乙酸胺 按照實例8中所述之程序，以2-氯苯基乙醯胺（Maybridge) 取代N-氯基乙醯基-3-硝基苯胺，提供標題化合物（52%產率） ，為白色固體。熔點 110-112°C ; iHNMRpOOMHADMSO-db) 5 2.68 (m? 4H)? 3.21 (s? 2H)? 3.68 (m, 4H)5 6.93 (dd? 1H5 J=7.8? 4.7 Hz)? 7.06 (dd, 1H，J=7.8, 7.8 Hz)，7·31 (dd，2H，J=7.8, 7.8 Hz)，7.64 (dd，2H，J=8.8,1.4 Hz)， ❿ 8·07 (dd，1H，J=7.8, 2·0 Hz)，8·42 (dd，1H，J=4.8, 1.7 Hz)，9.76 (br s，1H) ; MS (DCI/NH3)m/e322(M+H)+ ;對C18H19N50之分析計算值：C，67.27 ;Η，5·96; Ν，21·79·實測值：C，67.21; Η，5·77; Ν，21·59· 實例15 2-「4-(3-氰某-2-吡啶基VI-六氫吡畊基氟苯基）乙醯胺 按照實例8中所述之程序，以N-氯基乙驗基-4-氟苯胺（Avocado) 取代N-氯基乙醒基-3-硝基苯胺，提供標題化合物（91%產率） ，為白色固體。熔點 98-100°C ; iHNMRpOOMHADMSOO 5 2.68 85228 -170- 200404539 (m，4H)，3·20 (s，2H)，3.68 (m，4H)，6.92 (dd，1H，J=7.5, 4·8 Hz)，7.15 (m，2H)， 7.67 (m，2H)，8_07 (dd，1H，J=7.8, 2.0 Hz)，8.41 (dd，1H，J=4.8, 1.7 Hz)，9.83 (br s，1H) ; MS (DCI/NH3) m/e 340 (M+H)+ ;對 q 8 H! 8 FN5 O 之分析 計算值：C，63.71 ; H，5·35; N，20.64·實測值：C，63.57 ; Η，5·32; N，20.79· 實例16 氰基比淀基）-1-六氫咏p井基l-N-(3,5-二甲基笨基）乙酸胺Example 12B Molyl-3_methylbenzyl) _2- [4- (2-cyanamosyl) -1-hexahydro p ratio p stilbenzyl acetoline will be obtained from the product of Example 12A (3.51 g, 11.4 mmol) and N, N-diisopropylethylamine (2.50 ml) in toluene (50 ml) with 1- (2-cyanophenyl) hexahydroexorphine (Chess, 2.90 G, 15.5 mmol), and the reaction mixture was heated at 90 ° C for 18 hours. The mixture was allowed to cool to room temperature and transferred to a separatory funnel with acetamidine acetate 3 and water. The organic phase was washed with a saturated aqueous sodium bicarbonate solution, dried (Na2S04), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel to provide 3.66 g (77%) of the title compound as a yellow solid. Melting point 143-145 ° C; 1H NMR (300 MHz, DMSO-d6) 5 2 · 32 (s, 3H), 2.72 (m, 4H), 3.22 (m, 6H), 7.10 (ddd, 1H, J = 7.4, 7.4, 0.6 Hz), 7.19 (d, 1H, 8.1 Hz), 7.49 (m, 2H), 7.61 (m, 1H), 7.65 (d, 1H, J = 2.1 Hz), 7.70 (dd , 1H, J = 7.8, 1 · 7 Hz), 9.82 (br s, 1H); MS (DCI / NH3) m / e 413/415 (M + H) +; Analysis of (^ 2〇11218 and 40) Calculated: C, 58.12; Thallium, 5.12; N, 13.56. Found: C, 58.13; Tranquility, 5.07; N, 13.54. 85228 -169- 200404539 Example 13 ^ ιί 4- (2-cyanobenzene Benzyl VI-hexahydro p-pyridyl 1-N-benzylacetamide Following the procedure described in Example 12B, the product obtained from Example 12A was replaced with 2-chlorophenylacetamide (Maybridge) to provide the title compound p9% yield), as a yellow solid, melting point 137-138X:; iHNMR pOOMHz'DMSOd 52.73 (m, 4H), 3.22 (m, 6H), 7.08 (m, 2H), 7.19 (d, 1H, J = 8_5 Hz), 7.30 (m, 2H), 7.63 (m, 2H), 7.70 (dd, 1H, J = 7_8, 1.7 Hz), 9.76 (br s, 1H); MS (DCI / NH3) m / e 321 (M + H) +; Analytical calculation for Cl 9H20N40: c, Ή · 23; H, 6.29; N, 17.49 · φ real Measured value: C, 70.92; H, 6.34; N, 17_34. Example 14 2-14- (3-cyano-2-erodoyl) -1-hexamidine, outer well-based fluorene-N-phenyl Ammonium acetate Substituted N-chloroethynyl-3-nitroaniline with 2-chlorophenylacetamidine (Maybridge) according to the procedure described in Example 8 to provide the title compound (52% yield), white Solid. Melting point 110-112 ° C; iHNMRpOOMHADMSO-db) 5 2.68 (m? 4H)? 3.21 (s? 2H)? 3.68 (m, 4H) 5 6.93 (dd? 1H5 J = 7.8? 4.7 Hz)? 7.06 ( dd, 1H, J = 7.8, 7.8 Hz), 7.31 (dd, 2H, J = 7.8, 7.8 Hz), 7.64 (dd, 2H, J = 8.8, 1.4 Hz), ❿ 8.07 (dd, 1H , J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 4.8, 1.7 Hz), 9.76 (br s, 1H); MS (DCI / NH3) m / e322 (M + H) + ; Analysis and calculation for C18H19N50: C, 67.27; Η, 5.96; Ν, 21 · 79 ·, Measured value: C, 67.21; Η, 5.77; Ν, 21 · 59 · Example 15 2- "4- (3-Cyano-2-pyridyl VI-hexahydropyridylfluorophenyl) acetamidine was replaced with N-chloroethoxy-4-fluoroaniline (Avocado) according to the procedure described in Example 8. N-chloroethoxy-3-nitroaniline provided the title compound (91% yield) as a white solid. Melting point 98-100 ° C; iHNMRpOOMHADMSOO 5 2.68 85228 -170- 200404539 (m, 4H), 3.20 (s, 2H), 3.68 (m, 4H), 6.92 (dd, 1H, J = 7.5, 4 · 8 Hz), 7.15 (m, 2H), 7.67 (m, 2H), 8_07 (dd, 1H, J = 7.8, 2.0 Hz), 8.41 (dd, 1H, J = 4.8, 1.7 Hz), 9.83 (br s, 1H); MS (DCI / NH3) m / e 340 (M + H) +; Analytical calculated values for q 8 H! 8 FN5 O: C, 63.71; H, 5.35; N, 20.64 · Measured values: C, 63.57; Hf, 5.32; N, 20.79. Example 16 Cyanopyridyl) -1-hexahydropyridyl 1N- (3,5-dimethylbenzyl) amine

實例16A 2-氯_N-(3,5-二甲墓笨基）乙醯胺 將3,5-二甲苯胺（Acros，10.50毫升，84.05毫莫耳）在2N氫氧 化鈉（200毫升）中，以氯化氯乙醯（Acros，10.00毫升，125.7毫 莫耳）在二氯甲烷（200毫升）中之溶液逐滴處理。18小時後， 分離液層。將有機相以1Ν鹽酸洗務，脫水乾燥（Nh S〇4 )，過 濾，並使濾液在減壓下濃縮，提供15·64克（94% )標題化合物 ，為白色固體。1 H NMR (300 MHz，DMSO-d6) δ 2.24 (s，6Η)，4.21 (s，2Η)， 6.73 (s，1Η)，7.20 (s，2Η)，10.11 (bi: s，1Η) ; MS (DCI/NH3) m/e 198 (Μ+Η)+.Example 16A 2-Chloro_N- (3,5-dimethylbenzylbenzyl) acetamidine 3,5-dimethyltoluidine (Acros, 10.50 ml, 84.05 mmol) in 2N sodium hydroxide (200 ml) The solution was treated dropwise with a solution of chloroacetamidine (Acros, 10.00 ml, 125.7 mmol) in dichloromethane (200 ml). After 18 hours, the layers were separated. The organic phase was washed with 1N hydrochloric acid, dried (Nh S04), filtered, and the filtrate was concentrated under reduced pressure to provide 15.64 g (94%) of the title compound as a white solid. 1 H NMR (300 MHz, DMSO-d6) δ 2.24 (s, 6Η), 4.21 (s, 2Η), 6.73 (s, 1Η), 7.20 (s, 2Η), 10.11 (bi: s, 1Η); MS (DCI / NH3) m / e 198 (Μ + Η) +.

實例16B 244-(3-氰基-2-ττ比淀基M-六氫外1：畊基l-N-(3,5-二甲基茉基）乙驢胺 按照實例8中所述之程序，以得自實例16Α之產物，取代Ν-氣基乙醒基-3-硝基苯胺’提供標題化合物（63%產率），為白 色固體。熔點 139-140°C ; 1H NMR (300 MHz，DMSO-d6 ) δ 2·23 (s，6Η)， 2.70 (m，4Η)，3.18 (s，2Η)，3.68 (m，4Η)，6·70 (br s，1Η)，6.93 (dd，1Η，J=7.8， 4.7 Hz)，7.28 (br s，2H)，8.07 (dd，1H，J=7.8, 2.0 Hz)，8.42 (dd，1H，J=4.7, 2.0 Hz)，9·60 (br s，1H) ; MS (DCI/NH3) m/e 350 (M+H)+ ;對 C2 〇 H2 3 N5 O 之 85228 -171- 200404539 分析計算值·· c，68.74 ; Η，6·63 ; N，20.04.實測值：c，68.56 ; H，6.56 ;N，20.05. 實例17 -2-外I：症某VI-六氫吡畊基i_N_(2,3-二甲某I某）乙醯胺Example 16B 244- (3-Cyano-2-ττ is more than ytyl M-hexahydro 1: Gynyl 1N- (3,5-dimethyl molyl) ethynylamine Follow the procedure described in Example 8, Substitution of the product from Example 16A with N-aminoethoxy-3-nitroaniline 'provided the title compound (63% yield) as a white solid. Melting point 139-140 ° C; 1H NMR (300 MHz, DMSO-d6) δ 2 · 23 (s, 6Η), 2.70 (m, 4Η), 3.18 (s, 2Η), 3.68 (m, 4Η), 6.70 (br s, 1Η), 6.93 (dd, 1Η) , J = 7.8, 4.7 Hz), 7.28 (br s, 2H), 8.07 (dd, 1H, J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 4.7, 2.0 Hz), 9.60 (br s, 1H); MS (DCI / NH3) m / e 350 (M + H) +; 85228-171-200404539 for C2 0H2 3 N5 O · c, 68.74; Η, 6.63; N, 20.04. Measured values: c, 68.56; H, 6.56; N, 20.05. Example 17 -2-External I: Syndrome VI-Hydroxypyridyl i_N_ (2,3-dimethyl-1, I-1) Acetate amine

實例17AExample 17A

1_氯-Ν-α3-二甲甚笨基）乙醯胺 按照實例16Α中所述之程序，以2,3-二甲苯胺取代3,5-二甲 苯胺’提供標題化合物（96%產率），為白色固體。1 ηNMR (300 MHz, DMSO_d6) 5 2·07 (s，3Η)，2.24 (s，3Η)，4.28 (s5 2Η)，7.07 (m，3Η)， 9.70 (br s? 1H) ； MS (DCI/NH3) m/e 198 (M+H)+.1-Chloro-N-α3-dimethylxylbenzyl) acetamide Following the procedure described in Example 16A, substituting 2,3-xylylamine for 3,5-xylylamine 'provided the title compound (96% yield Ratio) as a white solid. 1 ηNMR (300 MHz, DMSO_d6) 5 2 · 07 (s, 3Η), 2.24 (s, 3Η), 4.28 (s5 2Η), 7.07 (m, 3Η), 9.70 (br s? 1H); MS (DCI / H NH3) m / e 198 (M + H) +.

實例17B 2-[4-_(3_-氰基-2-吡啶某）-1-六氫吡畊基i_n/2,3-二甲某笨基）乙醯胺 按照實例8中所述之程序，以得自實例ι7Α之產物取代怍氯 基乙醯基-3-硝基苯胺，提供標題化合物（32%產率），為白色 固體。熔點 124-126°C ; iHNMRpOOMH^DMSO-dJc^.UCOH)， 2.26 (s，3H)，2_72 (m，4H)，3·21 (s，2H)，3·69 (m，4H)，6.94 (dd，1H，J=7.8,4·8 Hz)，6.99 (br d，1H，J=7.4 Hz)，7.07 (dd，1H，J=7.4, 7.4 Hz)，7.45 (to d，1H，J= 7.8 Hz)3 8.08 (dd? 1H? J=7.85 2.0 Hz)5 8.42 (dd? 1H5 4.85 2.1 Hz)? 9.42 (br s? 1H) ;MS(DCI/NH3)m/e350(M+H)+ ;對(：2()1123^[50· 0.10 H20之分析 計算值·· C，68.39 ; Η, 6·66 ; N，19,94.實測值：C，68β74 ; H，6.58 ; N，19.56· 實例18 2-f4-(3-氣基-2·^比淀基JL p比井基甲基笨基）乙酸胺Example 17B 2- [4 -_ (3_-Cyano-2-pyridine) -1-hexahydropyridyl i_n / 2,3-dimethyl-benzyl) acetamidamine Follow the procedure described in Example Substituting chlorochloroethylfluoren-3-nitroaniline with the product obtained from Example ι7A provided the title compound (32% yield) as a white solid. 124-126 ° C; iHNMRpOOMH ^ DMSO-dJc ^ .UCOH), 2.26 (s, 3H), 2-72 (m, 4H), 3.21 (s, 2H), 3.69 (m, 4H), 6.94 (dd, 1H, J = 7.8, 4 · 8 Hz), 6.99 (br d, 1H, J = 7.4 Hz), 7.07 (dd, 1H, J = 7.4, 7.4 Hz), 7.45 (to d, 1H, J = 7.8 Hz) 3 8.08 (dd? 1H? J = 7.85 2.0 Hz) 5 8.42 (dd? 1H5 4.85 2.1 Hz)? 9.42 (br s? 1H); MS (DCI / NH3) m / e350 (M + H) +; Analytical calculation of (: 2 () 1123 ^ [50 · 0.10 H20 ·· C, 68.39; Η, 6.66; N, 19,94. Found: C, 68β74; H, 6.58; N, 19.56 · Example 18 2-f4- (3-Gasyl-2 · ^ pyridyl JL p than Jingylmethylbenzyl) amine

實例18A 85228 -172- 200404539 2-氯-N-(2-甲某笨基）乙醯胺 按照實例16A中所述之程序，以2-甲基苯胺取代3,5-二甲苯 胺，提供標題化合物（90%產率），為白色固體。iHNMRpOOMHz， DMSO-d6) 5 2·20 (s，3H)，4.30 (s，2H)，7.16 (m，3H)，7.38 (d，1H，J=7.8 Hz), 9.63 (br s，1H) ; MS (DCI/NH3) m/e 184 (M+H)+ ·Example 18A 85228 -172- 200404539 2-Chloro-N- (2-methylbenzyl) acetamidine Follow the procedure described in Example 16A to replace 3,5-xylylamine with 2-methylaniline to provide the title Compound (90% yield) as a white solid. iHNMRpOOMHz, DMSO-d6) 5 2 · 20 (s, 3H), 4.30 (s, 2H), 7.16 (m, 3H), 7.38 (d, 1H, J = 7.8 Hz), 9.63 (br s, 1H); MS (DCI / NH3) m / e 184 (M + H) + ·

實例18B 244-(3-氰基_2-吡啶基)-1•六氫吡畊基甲基笨基）乙醯胺 按照實例8中所述之程序，以得自實例18A之產物取代N-氯 籲 基乙醯基-3-硝基苯胺，提供標題化合物（58%產率），為淡黃 色固體。熔點 123-125°C ; 1H NMR (300 MHz，DMSO-d6) 5 2.25 (s，3H)， 2.73 (m，4H)，3.22 (s，2H)，3.69 (m，4H)，6.94 (dd，1H，J=7.8, 4·8 Hz)，7.06 (ddd， 1H，J=7.4, 7.4, 1.0 Hz)，7.17 (d，1H，J=7_8 Hz)，7.21 (dd，1H，8.5, 8·5 Hz)，7·75 (d，1H，J=7.8 Hz)，8.08 (dd，1H，J=7.8, 1·7 Hz), 8·42 (dd，1H，J=5.0, 1·7 Hz)， 9.42 (br s，1H) ; MS (DCI/NH3) m/e 336 (M+H)+ ;對 Q 9 H2 i N5 0 · 0.20 H2 O 之分析計算值：C，67.32 ; H，6.36 ; N，20.66·實測值：C，67.29 ;H，6·23 ; N，20.66. φ 實例19 2二[4-(3-氰基-2-吡啶基M-六氫吡畊基1-Ν-(2,5-二甲基笨基）乙醯胺 實例19Α 1 氯-Ν-(2,5-二甲某苽基）乙醯胺 按照實例16Α中所述之程序，以2,5-二甲苯胺取代3,5-二甲 苯胺，提供標題化合物（89%產率），為白色固體。iHNMR (300 MHz，DMSO-d6) 5 2.14 (s，3H)，2.24 (s，3H)，4.28 (s，2H)，6.93 (d，1H， J=7.8 Hz)，7·10 (d，1H，J=7.8 Hz)，7·20 (s，1H)，9.57 (br s，1H); MS (DCI/NH3) 85228 -173- 200404539 m/el98 (M+H)+.Example 18B 244- (3-cyano_2-pyridyl) -1 • hexahydropyridylmethylbenzyl) acetamidine Following the procedure described in Example 8, substituting N- with the product from Example 18A Chloroethoxy-3-nitroaniline provided the title compound (58% yield) as a pale yellow solid. Melting point 123-125 ° C; 1H NMR (300 MHz, DMSO-d6) 5 2.25 (s, 3H), 2.73 (m, 4H), 3.22 (s, 2H), 3.69 (m, 4H), 6.94 (dd, 1H, J = 7.8, 4 · 8 Hz), 7.06 (ddd, 1H, J = 7.4, 7.4, 1.0 Hz), 7.17 (d, 1H, J = 7_8 Hz), 7.21 (dd, 1H, 8.5, 8 · 5 Hz), 7.75 (d, 1H, J = 7.8 Hz), 8.08 (dd, 1H, J = 7.8, 1 · 7 Hz), 8.42 (dd, 1H, J = 5.0, 1 · 7 Hz ), 9.42 (br s, 1H); MS (DCI / NH3) m / e 336 (M + H) +; Analytical calculated value for Q 9 H2 i N5 0 · 0.20 H2 O: C, 67.32; H, 6.36 N, 20.66. Found: C, 67.29; H, 6.23; N, 20.66. Φ Example 19 2bis [4- (3-cyano-2-pyridylM-hexahydropyridyl 1-N -(2,5-Dimethylbenzyl) acetamidamine Example 19A 1 Chloro-N- (2,5-dimethyl certain amidyl) acetamidamine Follow the procedure described in Example 16A with 2,5- Xylylamine replaced 3,5-xylylamine to provide the title compound (89% yield) as a white solid. IHNMR (300 MHz, DMSO-d6) 5 2.14 (s, 3H), 2.24 (s, 3H), 4.28 (s, 2H), 6.93 (d, 1H, J = 7.8 Hz), 7.10 (d, 1H, J = 7.8 Hz), 7.20 (s, 1H), 9.57 (br s, 1H); MS (DCI / NH3) 85228 -17 3- 200404539 m / el98 (M + H) +.

實例19B 2-「4-(3-氰基-2-吡啶基H-六氫吡p井基1_Ν-Γ2.5-二甲基笨墓）乙醯胺 按照實例8中所述之程序，以實例19Α取代Ν-氯基乙醯基-3-硝基苯胺，提供標題化合物（34%產率），為白色固體。熔點 106-108〇C ； 1H NMR (300 MHz? DMSO-d6) δ 2.19 (s? 3H)? 2.26 (s, 3H)5 2.72 (m，4H)，3.20 (s，2H)，3.69 (m，4H)，6.87 (d，1H，J=7.4 Hz)，6.94 (dd，1H，J=7.5， 4.8 Hz)，7.10 (d，1H，J=7.8 Hz)，7.59 (br s，1H)，8.08 (dd，1H，J=7.8, 2.0 Hz)， φ 8.42 (dd，1H，J=4.7, 2·0 Hz)，9.35 (br s，1H) ; MS (DCI/NH3) m/e 350 (M+H)+ ;對 C2 〇 H2 3 N5 O · 0.20 H2 O 之分析計算值：C，68·04; H，6.68; N，19.84. 實測值：C，67.89 ; H，6.54 ; N，19.88. 實例20 氣苯基）-244-(3-氣基-2-p比淀基VI-六氮t?比啡基1乙酿胺 按照實例8中所述之程序，以3-氯-N-(氯基乙醯基）苯胺 (Maybridge)取代N-氯基乙醯基-3-硝基苯胺，提供標題化合物（79 %產率），為淡黃褐色固體。熔點108-109°C ; iHNMRQOOMHz， # DMSO-d6) d 2.68 (m，4H)，3.23 (s，2H)，3.69 (m，4H)，6.93 (dd，1H，J=7.8, 4.8 Hz)，7·12 (m，1H)，7.34 (dd，1H，J=8.1，8.1 Hz)，7.57 (m，1H)，7.86 (m，1H)， 8.07 (dd，1H，J=7.8, 2.0 Hz)，8.42 (dd，1H，J=4.7, 2.0 Hz)，9.96 (br s，1H) ; MS (DCI/NH3) m/e 356 (M+H)+ ;對 Ci 8 Hi 8 C1N5 O 之分析計算值：c，60.76 ;H，5.10 ; N，19·68·實測值：C，60.71 ; H，5.09 ; N，19.58· 實例21 N-(3-氯基-4-氟笨基V2-『4-(3-氰某-2-吡啶基M-六氫吡畊某1 乙醯胺 85228 -174- 200404539 按照實例8中所述之程序，以3-氯-N-(氯基乙醯基）-4-敷苯胺 (Maybridge)取代N-氯基乙醯基-3-硝基苯胺，提供標題化合物（39 %產率），為淡黃褐色固體。熔點137-140°C ; iHNMRpOOMHz， DMSO-d6) 5 2.67 (m5 4H)，3·22 (s，2H)，3.69 (m，4H)，6·93 (dd，1H，J=7.5, 4·8 Hz)，7·37 (dd，1H，J=9.1，9_1 Hz)，7.61 (ddd，1H，J=9.2, 4.5, 2·8 Hz)，7·98 (dd， 1H，J=7.2, 2.8 Hz)，8.07 (dd，1¾ J=7.8, 2.0 Hz)，8.41 (dd，1H，J=4.8, 1.7 Hz)， 9.98 (br s，1H) ; MS (DCI/NH3) m/e 374 (M+H)+ ;對 q 8 % 7 C1FN5 0 之 分析計算值·· C，57.84 ; H，4.58 ; N，18.73.實測值：C，57.98 ; H，4·42 ;N, 18.65. 實例22 2-[4-(3-氰基-2-吡啶基）-1-六氫吡畊基ΐ-Ν-(3·4,5-三甲氣某笨基） 乙醯胺Example 19B 2- "4- (3-Cyano-2-pyridyl H-hexahydropyridinyl 1-N-Γ2.5-dimethylbenzyl) acetamidine Following the procedure described in Example 8, Example 19A Substituted N-chloroethynyl-3-nitroaniline to provide the title compound (34% yield) as a white solid. Melting point 106-108 ° C; 1H NMR (300 MHz? DMSO-d6) δ 2.19 (s? 3H)? 2.26 (s, 3H) 5 2.72 (m, 4H), 3.20 (s, 2H), 3.69 (m, 4H), 6.87 (d, 1H, J = 7.4 Hz), 6.94 (dd, 1H, J = 7.5, 4.8 Hz), 7.10 (d, 1H, J = 7.8 Hz), 7.59 (br s, 1H), 8.08 (dd, 1H, J = 7.8, 2.0 Hz), φ 8.42 (dd, 1H , J = 4.7, 2.0 Hz), 9.35 (br s, 1H); MS (DCI / NH3) m / e 350 (M + H) +; Analysis and calculation of C2 〇H2 3 N5 O · 0.20 H2 O Value: C, 68 · 04; H, 6.68; N, 19.84. Found: C, 67.89; H, 6.54; N, 19.88. Example 20 Phenylphenyl) -244- (3-amino-2-p ratio Yodo VI-Hexaline t-Biffinyl 1 Ethylamine Follow the procedure described in Example 8 to replace N-chloroethyridyl with 3-chloro-N- (chloroethylethenyl) aniline (Maybridge) -3-nitroaniline provided the title compound (79% yield) as a pale yellow-brown solid. 108-109 ° C; iHNMRQOOMHz, # DMSO-d6) d 2.68 (m, 4H), 3.23 (s, 2H), 3.69 (m, 4H), 6.93 (dd, 1H, J = 7.8, 4.8 Hz), 7 12 (m, 1H), 7.34 (dd, 1H, J = 8.1, 8.1 Hz), 7.57 (m, 1H), 7.86 (m, 1H), 8.07 (dd, 1H, J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 4.7, 2.0 Hz), 9.96 (br s, 1H); MS (DCI / NH3) m / e 356 (M + H) +; Analytical calculation for Ci 8 Hi 8 C1N5 O : C, 60.76; H, 5.10; N, 19.68. Found: C, 60.71; H, 5.09; N, 19.58. Example 21 N- (3-Chloro-4-fluorobenzyl V2- "4- (3-cyano-2-pyridyl M-hexahydropyroxy 1 ethylacetamide 85228 -174- 200404539 Follow the procedure described in Example 8 using 3-chloro-N- (chloroethylacetamido)- 4-Aniline (Maybridge) substituted N-chloroethanyl-3-nitroaniline to provide the title compound (39% yield) as a pale yellow-brown solid. Melting point 137-140 ° C; iHNMRpOOMHz, DMSO-d6) 5 2.67 (m5 4H), 3.22 (s, 2H), 3.69 (m, 4H), 6.93 (dd, 1H, J = 7.5, 4 · 8 Hz), 7.37 (dd, 1H, J = 9.1, 9_1 Hz), 7.61 (ddd, 1H, J = 9.2, 4.5, 2 · 8 Hz), 7.98 (dd, 1H, J = 7.2, 2.8 Hz), 8.07 (dd, 1¾ J = 7.8, 2.0 Hz), 8.41 (dd, 1H, J = 4.8, 1.7 Hz), 9.98 (br s, 1H); MS (DCI / NH3) m / e 374 ( M + H) +; Analytical calculations for q 8% 7 C1FN50 0 · C, 57.84; H, 4.58; N, 18.73. Found: C, 57.98; H, 4.42; N, 18.65. Example 22 2- [4- (3-cyano-2-pyridyl) -1-hexahydropyridylpyridinium-N- (3,4,5-trimethylbenzyl) acetamide

實例22A _2-氯-N-(3,4,5_三甲氧基笨基）乙酸胺 將3,4,5-三甲氧基苯胺（Aldrich，4.06克，22.2毫莫耳）與氯化 氯乙醯（2·60毫升，32·7毫莫耳）在甲苯（50毫升）中，於i〇〇°c下 加熱24小時。使混合物冷卻至室溫，及在減壓下移除揮發 性物質。使殘留物溶於甲苯中，並濃縮（3χ)，以移除微量起 始氯化醯，及放置在高真空下，提供5.26克（91% )標題化合 物，為淡褐色固體。1 H NMR (500 MHz，DMSO-d6) δ 3.62 (s，3Η)，3.74 (s，6Η)，4·21 (s，2Η)，6.96 (s，2Η)，10.19 (br s，1Η) ; MS (DCI/NH3) m/e 260 (M+H)+.Example 22A _2-Chloro-N- (3,4,5_trimethoxybenzyl) amine acetate Thorium (2.60 ml, 32.7 mmol) was heated in toluene (50 ml) at 100 ° C for 24 hours. The mixture was allowed to cool to room temperature and the volatile materials were removed under reduced pressure. The residue was dissolved in toluene and concentrated (3x) to remove traces of starting rhenium chloride, and placed under high vacuum to provide 5.26 g (91%) of the title compound as a light brown solid. 1 H NMR (500 MHz, DMSO-d6) δ 3.62 (s, 3Η), 3.74 (s, 6Η), 4.21 (s, 2Η), 6.96 (s, 2Η), 10.19 (br s, 1Η); MS (DCI / NH3) m / e 260 (M + H) +.

實例22B g-「4-(3-氰基-2-吡啶某VI-六氫吡畊基1-Ν-α4,5-三甲氲某茉基） 85228 -175- 200404539 乙醯胺 按照實例8中所述之程序，以實例22A取代N-氯基乙醯基-3-硝基苯胺，提供標題化合物（69%產率），為淡黃褐色固體。 熔點 123-124°C ; iHNMRpOOMHADMSOOSZ^CmJHU.lVs， 2H)，3·61 (s，3H)，3.69 (m，4H)，3.74 (s，6H)，6.93 (dd，1H，J=7.8, 4·7 Hz)，7.07 (s，2H)，8.07 (dd，1H，J=7.4, L7 Hz)，8.42 (dd，1H，J=4.8, 2.1 Hz)，9.67 (br s，1H) ;MS(DCI/NH3)m/e412(M+H)+ ;對C21H25N50之分析計算值： C，61.30 ; H，6·12 ; N，17·02·實測值：C，6L27 ; H，6·08 ; N，16.95. ❿ 實例23 l『4-(3-氰基-2-吡啶基&gt;1-六氫吡啡基1-N44-氣基-3-(三氟甲某）苯Example 22B g- "4- (3-cyano-2-pyridine VI-hexahydropyridyl 1-N-α4,5-trimethylammonium molyl) 85228 -175- 200404539 Acetylamine according to Example 8 The procedure described, substituting Example 22A for N-chloroethylfluoren-3-nitroaniline provided the title compound (69% yield) as a pale yellow-brown solid. Melting point 123-124 ° C; iHNMRpOOMHADMSOOSZ ^ CmJHU. lVs, 2H), 3.61 (s, 3H), 3.69 (m, 4H), 3.74 (s, 6H), 6.93 (dd, 1H, J = 7.8, 4.7 Hz), 7.07 (s, 2H) , 8.07 (dd, 1H, J = 7.4, L7 Hz), 8.42 (dd, 1H, J = 4.8, 2.1 Hz), 9.67 (br s, 1H); MS (DCI / NH3) m / e412 (M + H ) +; Analysis and calculation of C21H25N50: C, 61.30; H, 6.12; N, 17.02. Measured value: C, 6L27; H, 6.08; N, 16.95. ❿ Example 23 l 『4- (3-cyano-2-pyridyl) 1-hexahydropyridinyl 1-N44-amino-3- (trifluoromethyl) benzene

基1乙醯胺 實例23A 2-氯_N-(4-氟基-3-三說甲基笨基）乙醯胺 按照實例16A中所述之程序，以4-氟基-3-(三氟甲基）苯胺 (Acros)取代3,5-二甲苯胺，提供標題化合物（79%產率），為白 色固體。1 H NMR (300 MHz，DMSO-d6) 5 4.29 (s，2H)，7.50 (dd，1H，J=9.8， φ 9·8 Hz)，7.85 (m5 1H)，8·08 (dd，1H，J=6.5, 2·7 Hz)，10.64 (br s，1H)·Example 1A Ethylamine 23A 2-Chloro-N- (4-Fluoro-3-trisylmethylbenzyl) acetamidine Following the procedure described in Example 16A, Fluoromethyl) aniline (Acros) replaced 3,5-xylylamine to provide the title compound (79% yield) as a white solid. 1 H NMR (300 MHz, DMSO-d6) 5 4.29 (s, 2H), 7.50 (dd, 1H, J = 9.8, φ 9 · 8 Hz), 7.85 (m5 1H), 8.08 (dd, 1H, J = 6.5, 2 · 7 Hz), 10.64 (br s, 1H) ·

實例23B 氰基_2_吡啶基&gt;1-六氫吡畊某UK-氟基-3-(三氟甲U苯 基1乙醯脖 按照實例8中所述之程序，以得自實例μα之產物取代N—氯 基乙醯基各硝基苯胺，提供標題化合物（47%產率），為白色 固體。熔點 120-122°C ; iHNMR (300 MHz，DMSO-d6 )5 2.68 (m，4H)， 3.24 (s，2H)，3·69 (m，4H)，6·93 (dd，1H，&gt;8.1，5·1 Hz)，7·48 (dd，1H，J=10.2， 85228 -176- 200404539 10·2 Hz)，7.97 (m，1Η)，8·07 (dd，1H，J=7.1，2·0 Hz)，8.16 (dd，1H，J=6.8, 2·7Example 23B Cyano-2-pyridyl &gt; 1-Hydroxypyryl UK-Fluoro-3- (trifluoromethyl Uphenyl 1 ethyl ether) Follow the procedure described in Example 8 to obtain from Example μα The product replaced the N-chloroethanyl nitroaniline to provide the title compound (47% yield) as a white solid. Melting point 120-122 ° C; iHNMR (300 MHz, DMSO-d6) 5 2.68 (m, 4H), 3.24 (s, 2H), 3.69 (m, 4H), 6.93 (dd, 1H, &gt; 8.1, 5.1 Hz), 7.48 (dd, 1H, J = 10.2, 85228 -176- 200404539 10 · 2 Hz), 7.97 (m, 1Η), 8.07 (dd, 1H, J = 7.1, 2.0 Hz), 8.16 (dd, 1H, J = 6.8, 2 · 7

Hz)，8.42 (dd，1H，J=4.8, 2·0 Hz)，10·1 (br s，1H) ; MS (DCI/NH3)m/e 408 (M+H)+;對 C19H17F4N50之分析計算值：c，56.02; Η，4·21; N，17.19. 實測值：C，55.94 ; H，4.14 ; N，17.31. 實例24 2K.3-氰基-2-吡啶基)-1-六氫吡畊基1-N43-氟基-5-(三氟甲基）茉 基1乙醯胺 實例24A · 2-氯-N-(3-氟基-5-三氟甲某苯基）乙酸胺 按照實例16A中所述之程序，以3-氟基-5-(三氟甲基）苯胺 (Oakwood)取代3,5-二甲苯胺，提供標題化合物（79%產率），為 白色固體。1 H NMR (300 MHz，CDC13) 5 4.22 (s，2H)，7.14 (m，1H)，7.49 (br s，1H)，7·76 (ddd，1H，J=10.1，2.0, 2·0 Hz)，8.37 (br s，1H)·Hz), 8.42 (dd, 1H, J = 4.8, 2.0 Hz), 10 · 1 (br s, 1H); MS (DCI / NH3) m / e 408 (M + H) +; Analysis of C19H17F4N50 Calculated: c, 56.02; Hf, 4.21; N, 17.19. Found: C, 55.94; H, 4.14; N, 17.31. Example 24 2K.3-Cyano-2-pyridyl) -1-Hex Hydropyridyl 1-N43-fluoro-5- (trifluoromethyl) mosyl-1 acetamido Example 24A · 2-Chloro-N- (3-Fluoro-5-trifluoromethylphenyl) acetic acid The amine was substituted for 3,5-xylylamine with 3-fluoro-5- (trifluoromethyl) aniline (Oakwood) according to the procedure described in Example 16A to provide the title compound (79% yield) as a white solid . 1 H NMR (300 MHz, CDC13) 5 4.22 (s, 2H), 7.14 (m, 1H), 7.49 (br s, 1H), 7.76 (ddd, 1H, J = 10.1, 2.0, 2.0 Hz ), 8.37 (br s, 1H) ·

實例24B 氰基..:2-吡啶基&gt;1-六氫吡畊基ι_Ν_β_蠢基_5_(三氟甲某）苽 基&quot;I乙醯脖 · 按照實例8中所述之程序，以得自實例24A之產物取代N-氯 基乙醯基-3-硝基苯胺，提供標題化合物（41%產率），為白色 固體。熔點 108-110°C ; WNMRpOO MHz, DMSO-d6 )δ2·68 (m，4H)， 3.26 (s，2H)，3·70 (m，4H)，6_93 (dd，1H, J=7.8, 4.7 Hz)，7.36 (m，1H)，7·93 (m， 2H)，8.08 (dd，1H，7·7, 2·0 Hz)，8.42 (dd，1H，J=4.7, 2.0 Hz)，10.28 (br s，1H); MS(DCI/NH3)m/e408(M+H)+ ;對 C19H17F4N50之分析計算值： C，56.02 ; H，4.21; Ν，17·19.實測值：c，56.17 ; Η，4·11; N，17.43. 實例25 85228 -177- 200404539 2-「4-(3-氰基-2_吡啶基Η-六氫吡畊基氟基-5-(三氟甲某1苯Example 24B Cyano: 2-pyridyl &gt; 1-hexahydropyridyl ι_Ν_β_ 笨 基 _5_ (trifluoromethyl) fluorenyl &quot; I ethyl hydrazine · According to the procedure described in Example 8, Substitution of N-chloroethanyl-3-nitroaniline with the product from Example 24A provided the title compound (41% yield) as a white solid. Melting point: 108-110 ° C; WNMRpOO MHz, DMSO-d6) δ2 · 68 (m, 4H), 3.26 (s, 2H), 3.70 (m, 4H), 6_93 (dd, 1H, J = 7.8, 4.7 Hz), 7.36 (m, 1H), 7.93 (m, 2H), 8.08 (dd, 1H, 7.7, 2.0 Hz), 8.42 (dd, 1H, J = 4.7, 2.0 Hz), 10.28 (br s, 1H); MS (DCI / NH3) m / e408 (M + H) +; Analytical calculated value for C19H17F4N50: C, 56.02; H, 4.21; Ν, 17.19. Found: c, 56.17 Η, 4.11; N, 17.43. Example 25 85228 -177- 200404539 2- "4- (3-cyano-2-pyridylfluorene-hexahydropyridylfluoro-5- (trifluoromethyl) 1 benzene

基1乙醯胺 實例25A 2-氯氟基·5-(三氟甲基）苽某）乙醯脍 按照實例22Α中所述之程序，以2-氟基-5-(三氟甲基）苯胺 (Acros)取代3,4,5-三甲氧基苯胺，提供標題化合物（66%產率） ，為黃褐色固體。111丽11(3001^出，〇]^〇-(16)(5 4.40(8,211)，7.58 (m，2H)，8.38 (dd，1H，JN7.4, 2.0 Hz)，10.42 (br s，1H).Example 1A Ethylamine 25A 2-Chlorofluoro · 5- (trifluoromethyl) (a certain) acetamidine According to the procedure described in Example 22A, 2-fluoro-5- (trifluoromethyl) Aniline (Acros) replaced 3,4,5-trimethoxyaniline to provide the title compound (66% yield) as a tan solid. 111 Li 11 (3001 ^ out, 〇) ^ 〇- (16) (5 4.40 (8,211), 7.58 (m, 2H), 8.38 (dd, 1H, JN7.4, 2.0 Hz), 10.42 (br s, 1H ).

實例25B 2-f4-(3-氰基-2_p比症基）-1-六氫咐^井基氟基-5_(三氟甲某）苯 基1乙醯胺 按照實例8中所述之程序，以得自實例25A之產物取代N-氯 基乙醒基-3-硝基苯胺’提供標題化合物（61 %產率），為白色 固體。熔點 130-133°C ; iHNMRpOOMHADMSO-dJc^JVmJH)， 3·31 (s5 2H)，3.67 (m，4H)，6·94 (dd，1H，J=7.8, 5·1 Hz)，7.56 (m，2H)，8.08 (dd, 1H，J=7.5, 2.1 Hz)，8.42 (m，2H)，9.91 (br s，1H) ； MS (DCI/NH3) m/e 408 (M+H)+;對(：191117?4^0 之分析計算值:C，56.02; H，4.21; N，17.19. 實測值：C，55.88 ; H，4.14; N，17.15. 實例26 M4-(3-氰某冬吡啶基&gt;l-_六氫吡畊基l-N-「2-氣某-3-(三氣甲基）苯Example 25B 2-f4- (3-cyano-2_p-pyridyl) -1-hexahydrocarbazylfluoro-5_ (trifluoromethyl) phenyl 1acetamidine Follow the procedure described in Example 8 Substitution of N-chloroethoxy-3-nitroaniline with the product from Example 25A provided the title compound (61% yield) as a white solid. 130-133 ° C; iHNMRpOOMHADMSO-dJc ^ JVmJH), 3.31 (s5 2H), 3.67 (m, 4H), 6.94 (dd, 1H, J = 7.8, 5.1 Hz), 7.56 (m , 2H), 8.08 (dd, 1H, J = 7.5, 2.1 Hz), 8.42 (m, 2H), 9.91 (br s, 1H); MS (DCI / NH3) m / e 408 (M + H) +; Analytical calculated values for (: 191117? 4 ^ 0: C, 56.02; H, 4.21; N, 17.19. Found: C, 55.88; H, 4.14; N, 17.15. Example 26 M4- (3-cyanogen Pyridyl &gt; l-_hexahydropyridyl lN- "2-Gas-3- (trigasmethyl) benzene

基1乙酸胺 實例26A 2-氳-N-(2-氟基-3-三氟甲基笨某）乙醯胺 按照實例22A中所述之程序，以2-氟基-3-(三氟甲基）苯胺 85228 -178- 200404539 (Acros)取代3,4,5-三甲氧基苯胺，提供標題化合物（72%產率） ，為白色固體。1 H NMR (300 MHz，DMSO_d6) 6 4.39 (m，2H)，7.41 (dd， 1H，J=8.2, 8·2 Hz)，7.57 (dd，1H，J=6.5 Hz)，8·18 (dd，1H，J=7.1 Hz)，10.37 (br s， 1H).Example 1A amine acetate 26A 2-fluorenyl-N- (2-fluoro-3-trifluoromethylbenzyl) acetamidine Follow the procedure described in Example 22A with 2-fluoro-3- (trifluoro Methyl) aniline 85228-178-200404539 (Acros) substituted 3,4,5-trimethoxyaniline to provide the title compound (72% yield) as a white solid. 1 H NMR (300 MHz, DMSO_d6) 6 4.39 (m, 2H), 7.41 (dd, 1H, J = 8.2, 8.2 Hz), 7.57 (dd, 1H, J = 6.5 Hz), 8.18 (dd , 1H, J = 7.1 Hz), 10.37 (br s, 1H).

實例26B 2-[4_(3_氰基-2-吡淀基H-六氫吡畊某1-N42-氟基-3-(三氟甲某）革 基1乙醯胺 按照實例8中所述之程序，以得自實例26A之產物取代N_氯 鲁 基乙醯基各硝基苯胺，提供標題化合物（66%產率），為白色 固體。熔點 118-121°C ; iHNMRpOOMHiDMSOOc^mCmJH)， 3·30 (s，2H)，3.68 (m，4H)，6.94 (dd，1H，J=7.5,4.8 Hz)，7.40 (dd，1H，J=8.1， 8.1 Hz)，7.54 (m，1H), 8·08 (dd，1H，J=7.8, 2.0 Hz)，8.23 (dd5 1H，J=8.5, 8·5 Hz)， 8.42 (dd? 1H5 J=5.1? 2.1 Hz)? 9.90 (br s5 1H) ； MS (DCI/NH3) m/e 408 (M+H)+ ;對心9!^7?4：^…之分析計算值：c，56.02 ; H，4.21; N，17.19.實 測值：C，55.82 ; H，4_20; N，17.18. 實例27 · 2-[~4_(3-氰基-2-p比淀基H-六氫井基氟基_3_甲基笨基）Example 26B 2- [4_ (3-Cyano-2-pyridinyl H-hexahydropyridine 1-N42-fluoro-3- (trifluoromethyl) glyme 1 acetamido) according to Example 8 The procedure described describes the replacement of N-chloroluluylacetamidinyl nitroaniline with the product from Example 26A to provide the title compound (66% yield) as a white solid. Melting point 118-121 ° C; iHNMRpOOMHiDMSOOc ^ mCmJH) , 3.30 (s, 2H), 3.68 (m, 4H), 6.94 (dd, 1H, J = 7.5, 4.8 Hz), 7.40 (dd, 1H, J = 8.1, 8.1 Hz), 7.54 (m, 1H ), 8 · 08 (dd, 1H, J = 7.8, 2.0 Hz), 8.23 (dd5 1H, J = 8.5, 8 · 5 Hz), 8.42 (dd? 1H5 J = 5.1? 2.1 Hz)? 9.90 (br s5 1H); MS (DCI / NH3) m / e 408 (M + H) +; Analytical calculated value for center 9! ^ 7? 4: ^ ...: c, 56.02; H, 4.21; N, 17.19. Measured value : C, 55.82; H, 4_20; N, 17.18. Example 27 · 2- [~ 4_ (3-cyano-2-p ratio HYDROXYHYDROXYFLUORYL_3_METHYLBENYL)

乙醯胺 實例27A 2-氯-N-(4-氟基-3_甲基笨基）乙醯胺 按照貫例16A中所述之程序’以4-氟基-3-甲基苯胺（Lancaster) 取代3,5-二甲苯胺，提供標題化合物（83%產率），為白色固 體。1HNMR(300MHz，DMSO-d6)(52.21(d，3H，J=2.1Hz)，4_23(s，2H)， 7.10 (dd，1H，J=9_2, 9·2 Ηζ)，7·40 (m，1H)，7.49 (dd，1H，J=7.1，2_4 Hz)，10.25 85228 -179- 200404539 (br s，1H) ; MS (DCI/NH3) m/e 219 (M+NH4)+ ·Acetylamine Example 27A 2-Chloro-N- (4-fluoro-3_methylbenzyl) acetamidamine Follow the procedure described in Example 16A 'with 4-fluoro-3-methylaniline (Lancaster ) In place of 3,5-xylylamine to provide the title compound (83% yield) as a white solid. 1HNMR (300MHz, DMSO-d6) (52.21 (d, 3H, J = 2.1Hz), 4_23 (s, 2H), 7.10 (dd, 1H, J = 9_2, 9 · 2 Ηζ), 7.40 (m, 1H), 7.49 (dd, 1H, J = 7.1, 2_4 Hz), 10.25 85228 -179- 200404539 (br s, 1H); MS (DCI / NH3) m / e 219 (M + NH4) + ·

實例27B 氰基-2-吡啶某VI-六氫吡畊基氟基各甲某茉基） 乙醯胺 按照實例8中所述之程序，以得自實例27A之產物取代N-氯 基乙醯基-3-硝基苯胺，提供標題化合物（67%產率），為淡黃 褐色固體。熔點 111_113°C; iHNMRpOOMH^DMSOO 52.21(d，3H， J=1.7 Hz)，2.67 (m，4H)，3·19 (s，2H)，3.68 (m，4H)，6.93 (dd，1H，J=7.6, 4.8 Hz)， 7.07 (dd，1H，J=9.2, 9.2 Hz)，7.49 (m，1H)，7.55 (m，1H), 8.07 (dd，1H，J=7.5， 2.1 Hz)，8·41 (dd，1H，J=4.7, 2.0 Hz)，9.74 (br s，1H); MS (DCI/NH3) m/e 354 (M+H)+ ;對 Q 9H2〇FN5 O 之分析計算值：C，64·57; H，5.70; N，19.82· 實測值：C，64.34 ; H，5·73 ; N，19.83. 實例28Example 27B Cyano-2-pyridine VI-hexahydropyridylfluoromethyl methyl molybdenyl) Acetylamine Follow the procedure described in Example 8 to replace N-chloroacetamidine with the product from Example 27A 3-nitroaniline to provide the title compound (67% yield) as a pale yellow-brown solid. Melting point: 111-113 ° C; iHNMRpOOMH ^ DMSOO 52.21 (d, 3H, J = 1.7 Hz), 2.67 (m, 4H), 3.19 (s, 2H), 3.68 (m, 4H), 6.93 (dd, 1H, J = 7.6, 4.8 Hz), 7.07 (dd, 1H, J = 9.2, 9.2 Hz), 7.49 (m, 1H), 7.55 (m, 1H), 8.07 (dd, 1H, J = 7.5, 2.1 Hz), 8 · 41 (dd, 1H, J = 4.7, 2.0 Hz), 9.74 (br s, 1H); MS (DCI / NH3) m / e 354 (M + H) +; Analytical calculated value for Q 9H2〇FN5 O : C, 64 · 57; H, 5.70; N, 19.82 · Found: C, 64.34; H, 5.73; N, 19.83. Example 28

IzPK3-氰基-2〜比淀基）-1-六氫峨畊某氟苯基）乙醯胺 實例28A 2-氯_N-(2-氟苯某）乙醯胺 按照實例22A中所述之程序，以2-氟苯胺（Aldrich)取代3,4,5-三甲氧基苯胺，提供標題化合物（88%產率），為白色固體。 1H NMR (300 MHz，DMSO-d6) 5 4.35 (s，2H)，7.23 (m，3H)，7.87 (m，1H)， 10.17 (br s，1H) ; MS (DCI/NH3) m/e 188 (M+H)+ ·IzPK3-cyano-2 ~ bitoyl) -1-Hexahydrogeno, a fluorophenyl) acetamide example 28A 2-chloro_N- (2-fluorophenyl) acetamide as described in Example 22A The procedure replaced 3,4,5-trimethoxyaniline with 2-fluoroaniline (Aldrich) to provide the title compound (88% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) 5 4.35 (s, 2H), 7.23 (m, 3H), 7.87 (m, 1H), 10.17 (br s, 1H); MS (DCI / NH3) m / e 188 (M + H) + ·

實例28B ^ίΙΑΑ-2-d基H-六氲吡畊基氟笨基）乙醯胺 按照實例8中所述之程序，以得自實例28A之產物取代N-氯 基乙醯基各硝基苯胺，提供標題化合物（42%產率），為白色 85228 -180 - 200404539 固體。熔點 78-79°C ; 1H NMR (300 MHz，DMSO-d6) 5 2.71 (m，4H)，3.27 (s，2H)，3.67 (m，4H)，6.94 (dd，1H，J=7.8, 4.8 Hz)，7.18 (m，2H)，7.26 (m，1H)， 7.98 (m，1H)，8_08 (dd，1H，J=7.8, 2.0 Hz)，8.42 (dd，1H，J=5.1，2.1 Hz)，9.65 (br s，1H) ; MS (DCI/NH3) m/e 340 (M+H)+ ;對 q 88 FN5 O 之分析 計算值：C，63.70 ; H，5·35 ; N，20.64·實測值：C，63.48 ; H，5.32 ; N? 20.54. 實例29 2-「4-(3-氰基-2-吡啶基VI-六氫吡畊某甲氣笨基）乙醯胺 ·Example 28B ^ ΙΑΑ-2-dylH-hexapyridinylfluorobenzyl) acetamide Following the procedure described in Example 8, substituting the N-chloroacetamidinyl nitro group with the product from Example 28A Aniline provided the title compound (42% yield) as a white 85228 -180-200404539 solid. 78-79 ° C; 1H NMR (300 MHz, DMSO-d6) 5 2.71 (m, 4H), 3.27 (s, 2H), 3.67 (m, 4H), 6.94 (dd, 1H, J = 7.8, 4.8 Hz), 7.18 (m, 2H), 7.26 (m, 1H), 7.98 (m, 1H), 8_08 (dd, 1H, J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 5.1, 2.1 Hz ), 9.65 (br s, 1H); MS (DCI / NH3) m / e 340 (M + H) +; Analytical calculated values for q 88 FN5 O: C, 63.70; H, 5.35; N, 20.64 · Measured values: C, 63.48; H, 5.32; N? 20.54. Example 29 2- "4- (3-Cyano-2-pyridyl VI-hexahydropyridine, a methylbenzyl) acetamidine ·

實例29A 2-氯甲氣苽基）乙醯胺 按照實例22A中所述之程序，以2-甲氧基苯胺（Acros)取代 3,4,5-三甲氧基苯胺，提供標題化合物（83%產率），為褐色固 體。1 H NMR (300 MHz，DMSO-d6) 5 3.85 (s，3H)，4·38 (s5 2H)，6·92 (m，1H)， 7.08 (m，2Η)，7.91 (d，1Η，J=7.8 Ηζ)，9.48 (br s，1Η) ; MS (DCI/NH3) m/e 200 (M+H)+. 實例29B · 2-『4-(3-氣基-2-p比淀基風峨？井基甲氧苯基）乙酿胺 按照實例8中所述之程序，以得自實例29A之產物取代N-氯 基乙醯基-3-硝基苯胺，提供標題化合物（34%產率），為白色 固體。熔點 174-175°C ; WNMR(300MHz，DMSO-d6)(5 2.71 (m，4H)， 3.22 (s，2H)，3·70 (m，4H)，3.88 (s，3H)，6.96 (m, 2H)，7·07 (m，2H)，8·10 (dd， 1H，J=7.8, 2.1 Hz), 8.21 (d，1H，J=7.8 Hz)，8.44 (dd，1H，4.7, 1.7 Hz)，9.73 (br s， 1H); MS(DCI/NH3)m/e 352 (M+H)+ ;對(：19112:^502之分析計算值 :C，64.94 ; H，6·02 ; N，19.93·實測值·· c，64·70 ; H，5·95 ; N，19·71· 85228 -181 - 200404539 實例30 、 % 2-「4-(3-氰基-2-#b咬基）-1_六氫17比喷基1-Ν-(2-硝基苯基）乙醯胺Example 29A 2-Chloromethylammonium) acetamidine Following the procedure described in Example 22A, replacing 3,4,5-trimethoxyaniline with 2-methoxyaniline (Acros) provided the title compound (83% Yield) as a brown solid. 1 H NMR (300 MHz, DMSO-d6) 5 3.85 (s, 3H), 4.38 (s5 2H), 6.92 (m, 1H), 7.08 (m, 2Η), 7.91 (d, 1Η, J = 7.8 Ηζ), 9.48 (br s, 1Η); MS (DCI / NH3) m / e 200 (M + H) +. Example 29B · 2- 『4- (3-Gas-2-p ratio Fang? Jingi methoxyphenyl) ethyl amine Follow the procedure described in Example 8 to replace the N-chloroethenyl-3-nitroaniline with the product from Example 29A to provide the title compound (34% Yield) as a white solid. 174-175 ° C; WNMR (300MHz, DMSO-d6) (5 2.71 (m, 4H), 3.22 (s, 2H), 3.70 (m, 4H), 3.88 (s, 3H), 6.96 (m , 2H), 7.07 (m, 2H), 8.10 (dd, 1H, J = 7.8, 2.1 Hz), 8.21 (d, 1H, J = 7.8 Hz), 8.44 (dd, 1H, 4.7, 1.7 Hz), 9.73 (br s, 1H); MS (DCI / NH3) m / e 352 (M + H) +; Analytical calculation for (: 19112: ^ 502: C, 64.94; H, 6.02; N, 19.93 · Measured value · c, 64 · 70; H, 5.95; N, 19 · 71 · 85228 -181-200404539 Example 30,% 2- "4- (3-cyano-2- # b Bentyl) -1_hexahydro 17 is better than pentyl 1-N- (2-nitrophenyl) acetamide

實例30A 2-氧-N-(2·硝基笨基）乙驢胺 按照實例22A中所述之程序，以2-硝基苯胺（Aldrich)取代 3,4,5-三甲氧基苯胺，提供標題化合物（94%產率），為黃色固 體。1 H NMR (300 MHz, DMSO-d6) δ 4.38 (s，2H)，7.41 (dd(UH, J=8.1， 7.1，1.7 Hz)，7.77 (m，2H)，8.03 (dd，1H，J=8.2, 1·4 Hz)，10.68 (br s，1H) ; MS φ (DCI/NH3) m/e 232 (M+NH4 )+.Example 30A 2-oxo-N- (2 · nitrobenzyl) ethynylamine Follow the procedure described in Example 22A to replace 3,4,5-trimethoxyaniline with 2-nitroaniline (Aldrich) to provide The title compound (94% yield) as a yellow solid. 1 H NMR (300 MHz, DMSO-d6) δ 4.38 (s, 2H), 7.41 (dd (UH, J = 8.1, 7.1, 1.7 Hz), 7.77 (m, 2H), 8.03 (dd, 1H, J = 8.2, 1.4 Hz), 10.68 (br s, 1H); MS φ (DCI / NH3) m / e 232 (M + NH4) +.

實例30B 2-[4-(3_氰基-2·^比症基）小六氫p比喷基硝基笨基）乙酸胺 按照實例8中所述之程序，以得自實例30A之產物取代N-氯 基乙醯基-3-硝基苯胺，提供標題化合物（39%產率），為黃色 固體。熔點 134-136°C ; ΑΝΜΙΙβΟΟΜΗζ,ΟΜβΟ^^^Ζπΐ：!!!〆!!)， 3.29 (s，2Η)，3.72 (m，4Η)，6.96 (dd，1Η，J=7.8, 4.8 Ηζ)，7.32 (ddd，1Η，J=8.5， 7.1，1.4 Hz)，7.78 (ddd, 1H，J=8.8, 7.4, 1.6 Hz)，8.10 (dd，1H，J=7.8, 2.1 Hz)， ® 8.20 (dd，1H，J=8.2, 1.4 Hz)，8.44 (dd，1H，J=5.1，2.0 Hz)，8.61 (dd，1H，J=8.5， 1.4 Hz)，11.55 (br s，1H); MS (DCI/NH3) m/e 367 (M+H)+ ;對 C! 8 印 8 N6 O 之分析計算值·· C，59.01; H，4·95 ; N，22.94·實測值：C，58.87; H，5.01 ;N，23.08· 實例31 gi4-(3-氰基选淀基)-1-六氫吡畊基三氟甲某彳笨基i乙醯胺 按照實例8中所述之程序，以N_氯基乙醯基_2_(三氟甲基）苯 胺(Apollo)取代N-氯基乙醯基-3_硝基苯胺，提供標題化合物（47 85228 -182- 200404539 % 產率），為無色油。1H NMR (300 MHz，DMSO_d6) 5 2.74 (m，4H)， v 3.27 (s? 2H)? 3.65 (m5 4H)? 6.97 (dd5 1H? J=7.5? 4.8 Hz)? 7.36 (dd? 1H5 J=7.8? 7.8 Hz)，7·69 (d，1H，J=7.5 Hz)，7.73 (dd，1H，J=8.1，8·1 Hz)，8.10 (dd，1H，J= 8.1，2.0 Hz)，8.21 (d，1H，J=8.5 Hz)，8.44 (dd，1H，J=4.7, 2.3 Hz)，9.89 (br s，1H) ;MS (DCI/NH3) m/e 390 (M+H)+ ·順丁 缔二酸鹽：白色固體，熔 點 143-145 C ;對 8F3N50 · 1.0 C4H4O4 之分析計算值·· C，54.65 ;Η，4·39; N，13.86·實測值：C，54.61 ; Η，4·32; N，13.83. 實例32 · Ν-苯基-2-〖4-(2-外(：淀基Μ-六氫ρ比咕基1乙酸胺 將Ν-氯基乙醯苯胺（0.5克，2.95毫莫耳）、1-(2-吡啶基）六氫 吡畊（0.72克，4.42毫莫耳）及N，N-二異丙基乙胺（1.03毫升，5.9 毫莫耳）在甲苯中合併，並於回流下加熱過夜。使混合物冷 卻至室溫，過濾，並使濾液在減壓下濃縮。使殘留物於矽 膠上藉急驟式管柱層析純化（以60%醋酸乙酯：己烷溶離）， 提供400毫克（46%產率）’標題化合物，為吸濕性白色固體 。iHNMR(300 MHz，CDC13) 6 2.60 (m，4H)，3.18 (s，2H)，3.55 (m，4H)， # 6.65 (dd，1H，J=12, 6 Hz)，6.85 (d，1H，J=9 Hz)，7.05 (t，1H，J=6 Hz)，7.3 (t，2H， J=9 Hz)，7.51 (ddd5 1H，J=9, 7.5, 3 Hz) 7.68 (d，2H，J=9 Hz) 8.1 (dd，1H，J=6， 3Hz)9.75(brs，lH); MS(DCI/NH3)m/e297(M+H)+ ;對€17112〇凡0 之分析計算值：C，68.89; H，6·80; N，18.90·實測值：C，68.97; H, 6.87 ;N，19.01· 實例33 N-(3-甲基苯基）-2-「4-(l，3-碟嗤-2-基VI-六氫比喷基1乙酿胺 實例33Α 85228 -183- 200404539 2-獻甲基苯基）乙醯胺 將3-甲基苯胺（1克，9.3毫莫耳）在2N氫氧化鈉水溶液（30毫 升）中，於室溫下，以氯化氯乙醯（0.82毫升，10.27毫莫耳）在 二氯甲烷中之溶液逐滴處理。18小時後，以水使反應混合 物淬滅，並分離液層。將有機相以IN HC1水溶液洗滌，並以 MgS04脫水乾燥，過濾，且使濾液在減壓下濃縮，提供丨.3克 (76%)標題化合物，為白色固體。1HNMR(300MHz，CDCl3)(J 2.35 (s5 3H)? 4.20 (s? 2H)5 7.00 (s? 1H)5 7.22 (m5 1H)? 7.35-7.45 (m5 2Ά\ 8.15 (br s? 1H) ； MS (DCI/NH3) m/e 201 (M+NH4)+. 實例33B 1-(1,3-4唑-2_基）六氫吡畊 按照J· Med· Chem· 1996, 39(7)，1431中所述之程序，以提供標題 化合物。使2-溴基嘧唑（3克，18.3毫莫耳）與六氫吡畊（3.15克 ，36.6毫莫耳）之混合物，在正-丁醇中回流18小時。使反應 混合物冷卻至室溫，及在減壓下濃縮。將殘留物以10% K2C〇3 水溶液處理，並以醋酸乙酯萃取。使有機相以MgS〇4脫水乾 燥，過濾，並使濾液在減壓下濃縮，提供2.7克（87% )標題化 合物，為褐色油，直接使用在下一步驟中，無需進一步純 化。1 H NMR (300 MHz，CDC13) 5 2.99 (m，4H)，3.47 (m，4H)，6.57 (d，1H， J=4.5 Hz)? 7.20 (d9 1H5 J=4.5 Hz) ； MS (DCI/NH3) m/e 170 (M+H)+.Example 30B 2- [4- (3-Cyano-2.pyridinyl) Hexahydrop.Phenylnitrobenzyl) amine. The procedure described in Example 8 was used to obtain the product from Example 30A Substitution of N-chloroethanyl-3-nitroaniline provided the title compound (39% yield) as a yellow solid. Melting point 134-136 ° C; ΑΝΜΙΙβΟΟΜΗζ, ΟΜβΟ ^^^ ππΐ: !!! 〆 !!), 3.29 (s, 2Η), 3.72 (m, 4Η), 6.96 (dd, 1Η, J = 7.8, 4.8 Ηζ) , 7.32 (ddd, 1Η, J = 8.5, 7.1, 1.4 Hz), 7.78 (ddd, 1H, J = 8.8, 7.4, 1.6 Hz), 8.10 (dd, 1H, J = 7.8, 2.1 Hz), ® 8.20 ( dd, 1H, J = 8.2, 1.4 Hz), 8.44 (dd, 1H, J = 5.1, 2.0 Hz), 8.61 (dd, 1H, J = 8.5, 1.4 Hz), 11.55 (br s, 1H); MS ( DCI / NH3) m / e 367 (M + H) +; Analytical calculated value for C! 8 and 8 N6 O · C, 59.01; H, 4.95; N, 22.94 · Measured value: C, 58.87; H, 5.01; N, 23.08. Example 31 gi4- (3-cyanoselective) -1-hexahydropyridyltrifluoromethane, stilbenzyl, acetamidine, and the procedure described in Example 8, using N-chloroethylfluorenyl-2_ (trifluoromethyl) aniline (Apollo) replaces N-chloroethylfluorenyl-3-nitroaniline to provide the title compound (47 85228 -182- 200404539% yield), as Colorless oil. 1H NMR (300 MHz, DMSO_d6) 5 2.74 (m, 4H), v 3.27 (s? 2H)? 3.65 (m5 4H)? 6.97 (dd5 1H? J = 7.5? 4.8 Hz)? 7.36 (dd? 1H5 J = 7.8? 7.8 Hz), 7.69 (d, 1H, J = 7.5 Hz), 7.73 (dd, 1H, J = 8.1, 8.1 Hz), 8.10 (dd, 1H, J = 8.1, 2.0 Hz), 8.21 (d, 1H, J = 8.5 Hz), 8.44 (dd, 1H, J = 4.7, 2.3 Hz), 9.89 (br s, 1H); MS (DCI / NH3) m / e 390 (M + H) + · Maleic acid salt: white solid, melting point 143-145 C; Analytical calculated value for 8F3N50 · 1.0 C4H4O4 · · C, 54.65; Η, 4.39; N, 13.86 · Measured value: C, 54.61; Η 4.32; N, 13.83. Example 32 · N-phenyl-2- [4- (2-exo (: Yodo-M-hexahydro-p-pyridyl-1 acetic acid amine N-chloroethyl aniline aniline ( 0.5 g, 2.95 millimoles), 1- (2-pyridyl) hexahydropyrine (0.72 g, 4.42 millimoles) and N, N-diisopropylethylamine (1.03 ml, 5.9 millimoles) Combine in toluene and heat under reflux overnight. The mixture was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (60% ethyl acetate) Ester: hexane dissociation), For 400 mg (46% yield) of the 'title compound as a hygroscopic white solid. IHNMR (300 MHz, CDC13) 6 2.60 (m, 4H), 3.18 (s, 2H), 3.55 (m, 4H), # 6.65 (dd, 1H, J = 12, 6 Hz), 6.85 (d, 1H, J = 9 Hz), 7.05 (t, 1H, J = 6 Hz), 7.3 (t, 2H, J = 9 Hz), 7.51 (ddd5 1H, J = 9, 7.5, 3 Hz) 7.68 (d, 2H, J = 9 Hz) 8.1 (dd, 1H, J = 6, 3Hz) 9.75 (brs, lH); MS (DCI / NH3) m / e297 (M + H) +; Analytical calculated values for € 17,112 and 0: C, 68.89; H, 6.80; N, 18.90. Found: C, 68.97; H, 6.87; N, 19.01. Example 33 N- (3-Methylphenyl) -2- "4- (l, 3-Difluoren-2-yl VI-hexahydrobipentyl 1 ethyl amine Example 33A 85228 -183- 200404539 2- Methylphenyl) acetamidine 3-methylaniline (1 g, 9.3 mmol) in 2N aqueous sodium hydroxide (30 ml) at room temperature with chloroacetamidine (0.82 ml, 10.27 mmol) was treated dropwise in methylene chloride. After 18 hours, the reaction mixture was quenched with water and the layers were separated. The organic phase was washed with aqueous IN HC1 solution, dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure to provide 1.3 g (76%) of the title compound as a white solid. 1HNMR (300MHz, CDCl3) (J 2.35 (s5 3H)? 4.20 (s? 2H) 5 7.00 (s? 1H) 5 7.22 (m5 1H)? 7.35-7.45 (m5 2Ά \ 8.15 (br s? 1H); MS (DCI / NH3) m / e 201 (M + NH4) +. Example 33B 1- (1,3-4azole-2_yl) hexahydropyridine according to J. Med. Chem. 1996, 39 (7), The procedure described in 1431 to provide the title compound. A mixture of 2-bromopyrimazole (3 g, 18.3 mmol) and hexahydropyrine (3.15 g, 36.6 mmol) in n-butanol The mixture was refluxed for 18 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was treated with a 10% K2CO3 aqueous solution and extracted with ethyl acetate. The organic phase was dried over MgS04 and filtered The filtrate was concentrated under reduced pressure to provide 2.7 g (87%) of the title compound as a brown oil, which was used directly in the next step without further purification. 1 H NMR (300 MHz, CDC13) 5 2.99 (m, 4H ), 3.47 (m, 4H), 6.57 (d, 1H, J = 4.5 Hz)? 7.20 (d9 1H5 J = 4.5 Hz); MS (DCI / NH3) m / e 170 (M + H) +.

實例33C N-(3-甲基苯基）-2-「4-(1，3&lt;塞也-2-基H-六氫外井某1乙酿胺 將得自實例33A之產物（〇·2克，1.18毫莫耳）、得自實例33B 之產物（0_25克，1.48毫莫耳）及Ν，Ν-二異丙基乙胺（〇·4ΐ毫升， 85228 -184- 200404539 2·3毫莫耳）在甲苯（25毫升）中合併，並於回流下加熱過夜。 使反應物冷卻至室溫，過濾，並使濾液在減壓下濃縮。使 殘留物於矽膠上藉管柱層析純化（以50%醋酸乙酯：己烷溶 離），提供0.08克（22% )所要之物質，為白色固體。熔點151-153 °C ; iHNMR(300 MHz，DMSO-d6) 6 2.28 (s，3H), 2.65 (m，4H)，3.20 (s， 2H)，3.48 (m，4H)，6.85 (m，2H)，7·18 (m，2H)，7·48 (m，2H), 9.65 (s，1H); MS(DCI/NH3)m/e317(M+H)+ ;對 C16H2〇N4OS 之分析計算值： C，60.73 ; H，6.37 ; N，17.71.實測值：C，60.66 ; H，6·24 ; N，17.35. 實例34 2__「4-(3-氰基-2-p比淀基)-1-六氫外b畊基甲基笨某）乙醯胺Example 33C N- (3-methylphenyl) -2- "4- (1,3 &lt; Seil-2-yl H-hexahydrogenide 1 ethyl amine will be obtained from the product of Example 33A (〇 · 2 grams, 1.18 millimoles), the product from Example 33B (0-25 grams, 1.48 millimoles), and N, N-diisopropylethylamine (0.4 milliliters, 85228 -184- 200404539 2.3 millimoles Mol) was combined in toluene (25 ml) and heated under reflux overnight. The reaction was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel. (Dissolved in 50% ethyl acetate: hexane) to provide 0.08 g (22%) of the desired substance as a white solid. Melting point 151-153 ° C; iHNMR (300 MHz, DMSO-d6) 6 2.28 (s, 3H ), 2.65 (m, 4H), 3.20 (s, 2H), 3.48 (m, 4H), 6.85 (m, 2H), 7.18 (m, 2H), 7.48 (m, 2H), 9.65 ( s, 1H); MS (DCI / NH3) m / e317 (M + H) +; Analytical calculation for C16H2ON4OS: C, 60.73; H, 6.37; N, 17.71. Found: C, 60.66; H , 6.24; N, 17.35. Example 34 2 __ "4- (3-cyano-2-p ratio of yodoyl) -1-hexahydroexo-b-methyl-benzyl) acetamide

實例34A 2_氯-N-(4-甲基苯基）乙醯胺 按照實例33A中所述之程序，以4_甲基苯胺取代3-甲基苯 胺，提供白色固體。1H NMR (300 MHz，CDC13) 5 2.30 (s, 3H)，4.20 (s， 2H)，7·15 (d，2H，J=9 Hz)，7.41 (m，2H)，8.15 (br s，1H) ; MS (DCI/NH3) m/e 201 (M+NH4)+.Example 34A 2-Chloro-N- (4-methylphenyl) acetamide Following the procedure described in Example 33A, 3-methylaniline was replaced with 4-methylaniline to provide a white solid. 1H NMR (300 MHz, CDC13) 5 2.30 (s, 3H), 4.20 (s, 2H), 7.15 (d, 2H, J = 9 Hz), 7.41 (m, 2H), 8.15 (br s, 1H ); MS (DCI / NH3) m / e 201 (M + NH4) +.

實例34B 氰基-2-吡啶基&gt;1-六氫吡畊某甲某苯基）乙醯胺 將得自實例34A之產物（0_4克，2.18毫莫耳）、1-(2-氰基吡啶 基）六氫吡畊（0·62克，3.3毫莫耳）及n，N-二異丙基乙胺（0.76毫 升’ 4.36耄莫耳）在甲苯（50耄升）中，於回流下加熱。is小時 後，使反應混合物冷卻至室溫，過濾，並使濾液在減壓下 濃縮。使殘留物於矽膠上藉管柱層析純化（以6〇%醋酸乙酯 :己烷溶離），提供0.51克（70% )所要之物質，為黃色油。 85228 -185- 200404539 1H NMR (300 ΜΗζ? CDC13) 5 2.30 (s，3Η), 2.80 (m，4Η)，3·25 (s，2Η)，3·80 · (m，4H)，6·80 (dd，1H，J=12, 6 Hz)，7.12 (d，2H，J=9 Hz)，7.48 (d，2H，J=9 Hz)， 7.80 (dd，1H，J=9, 3 Hz)，8.38 (dd，1H，J=6, 3 Hz)，9.10 (bi: s，1H); MS (DCI/NH3)m/e 336 (M+H)+ ;順丁烯二酸鹽：獲得為灰白色粉 末；熔點 156-158°C ;對 C23H25N505 *0.20H20之分析計算值·· C，60.70 ; Η，5·63 ; N，15.39·實測值：c，60·33 ; H，5.55 ; N，15.10· 實例35 1-[4_(2-甲氧苯基)小六氫咐淀基ΐ-Ν-(3·甲基笨某）乙酸胺 · 將4-(2-甲氧苯基）六氫吡啶(2〇〇毫克，1毫莫耳）、得自實例ία 之產物（228毫克，1毫莫耳）及N，N-二異丙基乙胺（0.185毫升， 11晕莫耳）在甲苯（8毫升）中，於60°C下搅拌18小時。將反應 混合物倒入水（30毫升）中，並以醋酸乙酯（3〇毫升）萃取。將 有機層以鹽水（2x 30毫升）洗滌，以MgS04脫水乾燥，過濾， 並使濾液在減壓下濃縮。使殘留物於矽膠上藉急驟式層析 純化（以二氯甲烷：甲醇溶離，9·5 : 〇·5)，提供標題化合物 ，177 毫克（52.3% )。1H NMR (300 MHz，DMSO-d6) δ 1.71 (m，4Η)，2.28 φ (m，5Η)，2·89 (m，1Η)，2·96 (m，2Η)，3·13 (s，2Η)，3·78 (s，3Η)，6·91 (m，3Η)， 7.20 (m，3Η)，7.45 (m，2Η)，8.69 (s，1Η) ; MS (DCI/NH3) m/e 339 (Μ+Η)+ · 對 c21H26N202 之分析計算值：c，74.52 ; H，7.74 ; N，8.28·實測值 :C，74.23，H，7.71，N，8.26. 實例36 Μι(β_甲基苯基）-2-「4-(2-吡啶基M-六氫吡啶某1乙醯胺Example 34B Cyano-2-pyridyl &gt; 1-hexahydropyridine, methyl, phenyl) acetofluoramine will be obtained from the product of Example 34A (0-4 g, 2.18 mmol), Pyridyl) Hexahydropyrene (0.62 g, 3.3 mmol) and n, N-diisopropylethylamine (0.76 ml '4.36 mol) in toluene (50 liter) under reflux heating. After 1 hour, the reaction mixture was cooled to room temperature, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (dissolved with 60% ethyl acetate: hexane) to provide 0.51 g (70%) of the desired substance as a yellow oil. 85228 -185- 200404539 1H NMR (300 ΜΗζ? CDC13) 5 2.30 (s, 3Η), 2.80 (m, 4Η), 3.25 (s, 2Η), 3.80 · (m, 4H), 6.80 (dd, 1H, J = 12, 6 Hz), 7.12 (d, 2H, J = 9 Hz), 7.48 (d, 2H, J = 9 Hz), 7.80 (dd, 1H, J = 9, 3 Hz) , 8.38 (dd, 1H, J = 6, 3 Hz), 9.10 (bi: s, 1H); MS (DCI / NH3) m / e 336 (M + H) +; maleate: obtained as Off-white powder; melting point 156-158 ° C; analytical calculated value for C23H25N505 * 0.20H20 · C, 60.70; Η, 5.63; N, 15.39 · measured: c, 60 · 33; H, 5.55; N, 15.10 · Example 35 1- [4_ (2-Methoxyphenyl) HexahydrohydrochlorideYodoyl-N- (3 · methylbenzyl) amine Pyridine (200 mg, 1 mmol), the product from Example α (228 mg, 1 mmol) and N, N-diisopropylethylamine (0.185 ml, 11 hamol) in toluene (8 ml) and stirred at 60 ° C for 18 hours. The reaction mixture was poured into water (30 ml) and extracted with ethyl acetate (30 ml). The organic layer was washed with brine (2 x 30 mL), dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (dichloromethane: methanol, 9.5: 0.5) to provide the title compound, 177 mg (52.3%). 1H NMR (300 MHz, DMSO-d6) δ 1.71 (m, 4Η), 2.28 φ (m, 5Η), 2.89 (m, 1Η), 2.96 (m, 2Η), 3.13 (s, 2Η), 3.78 (s, 3Η), 6.91 (m, 3Η), 7.20 (m, 3Η), 7.45 (m, 2Η), 8.69 (s, 1Η); MS (DCI / NH3) m / e 339 (Μ + Η) + · Analysis and calculation of c21H26N202: c, 74.52; H, 7.74; N, 8.28. Found: C, 74.23, H, 7.71, N, 8.26. Example 36 Μι (β_ 甲Phenyl) -2- "4- (2-pyridyl M-hexahydropyridine 1 ethylacetamide

實例36A ϋ基_4-(2-ρ比症基六氫p比途複酸字西皆 85228 -186 - 200404539 將2-溴基吡呢（〇·47〇毫升，5毫莫耳）在THF (20毫升）中，於-60 C下’以己烷中之n-BULi 1.6M (5.2毫升，5.2毫莫耳）逐滴處 理。於-60 C下攪拌30分鐘後，將反應混合物以4_酮基+六氫 叶匕呢羧酸爷酯（1.14克，4·9毫莫耳）在THF (10毫升）中慢慢處 理。於-60°C下再攪拌15分鐘後，以飽和水溶液使反應 混合物淬滅，使其溫熱至室溫，並在二氯甲烷中萃取。將 有機物質合併，於MgS04上脫水乾燥，過濾，並使濾液在減 壓下濃縮。使殘留物於矽膠上藉急騾式層析純化（以己烷： 醋酸乙酯溶離，1: 1)，提供標題化合物（4〇〇毫克，27%產率） 。1H NMR (300 MHz，DMSO-d6) 51.54 (m，2H)，2.05 (m，2H)，3.25 (m，2H)， 3.95 (m，2H)，5.11 (s，2H)，5.35 (s，1H)，7·25 (m，1H)，7.35 (m，5H)，7.68 (m， 1H)，7·79 (m，1H)，8.5 (m，1H) ; MS (DCI/NH3) m/e 313 (M+H)+ ·Example 36A fluorenyl_4- (2-ρ-pyridylhexahydro-p-pyridoxate, sigme 85228 -186-200404539 2-bromopyran (0.470 ml, 5 mmol) in THF (20 ml), n-BULi 1.6M (5.2 ml, 5.2 mmol) in hexane was treated dropwise at -60 C. After stirring at -60 C for 30 minutes, the reaction mixture was stirred at 4 ° C. _ Keto + Hexahydrodane carboxylate (1.14 g, 4.9 mmol) was slowly treated in THF (10 ml). After stirring for another 15 minutes at -60 ° C, a saturated aqueous solution was used. The reaction mixture was quenched, allowed to warm to room temperature, and extracted in dichloromethane. The organic materials were combined, dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure. The residue was placed on silica gel. Purification by flash chromatography (isolated with hexane: ethyl acetate, 1: 1) provided the title compound (400 mg, 27% yield). 1H NMR (300 MHz, DMSO-d6) 51.54 (m , 2H), 2.05 (m, 2H), 3.25 (m, 2H), 3.95 (m, 2H), 5.11 (s, 2H), 5.35 (s, 1H), 7.25 (m, 1H), 7.35 ( m, 5H), 7.68 (m, 1H), 7.79 (m, 1H), 8.5 (m, 1H); MS (DCI / NH3) m / e 313 (M + H) + ·

實例36B 1!&gt;6’-二氫-2,4’-聯吡啶-1丫2’11)-複酸芊酯 使得自實例36A之產物（400毫克，1·28毫莫耳）在二氯化亞 硫醯（6毫升）中回流3小時，使其冷卻至室溫，及在減壓下 濃縮。將殘留物以冰與40%氫氧化鈉水溶液處理，然後在二 氯甲烷中萃取，以鹽水洗滌，脫水乾燥，過濾，並 使濾液於減壓下濃縮，提供標題化合物（332毫克）。Example 36B 1! &Gt; 6'-Dihydro-2,4'-bipyridine-1α 2'11) -fluorenate diacetate so that the product from Example 36A (400 mg, 1.28 mmol) Sulfuryl chloride (6 ml) was refluxed for 3 hours, allowed to cool to room temperature, and concentrated under reduced pressure. The residue was treated with ice and a 40% aqueous sodium hydroxide solution, and then extracted with dichloromethane, washed with brine, dehydrated and dried, filtered, and the filtrate was concentrated under reduced pressure to provide the title compound (332 mg).

實例36C 2-(4-7^氫卩比咬基V比症 將得自實例36B之產物於60 psi及50°C下，以10% Pd/C (250毫 克）處理40小時，提供標題化合物（150毫克，88%產率）。 MS (DCI/NH3) m/e 163 (M+H)+. 85228 -187- 200404539Example 36C 2- (4-7 ^ Hydroxypyridine V ratio syndrome) The product from Example 36B was treated at 60 psi and 50 ° C with 10% Pd / C (250 mg) for 40 hours to provide the title compound. (150 mg, 88% yield). MS (DCI / NH3) m / e 163 (M + H) +. 85228 -187- 200404539

實例36D Νι(3-甲基苯棊）:2-|&quot;4-(2·^比啶某VI-六氫峨咬某1乙醯脖 將得自實例36C之產物（2〇〇毫克，1毫莫耳）、得自實例1A 之產物（228耄克，1毫莫耳）及ν，Ν·二異丙基乙胺（0.185毫升， 1.1毫莫耳）在甲苯（8毫升）中，於60°C下，擾拌18小時。將反 應混合物倒入水（30毫升）中，並以醋酸乙酯（2〇毫升）萃取。 將有機層以鹽水（2 X 30毫升）洗滌，以MgS04脫水乾燥，過濾 ’並使濾液在減壓下濃縮。使殘留物於矽膠上藉急騾式層 析純化（以醋酸乙酯：乙醇溶離，9.2 : 0.8)，提供標題化合 物（169 毫克，55% )。1H NMR (300 MHz，DMSO_d6 ) 5 1.83 (m，4H)，2.24 (m，5H)，2·64 (m，lH)，2·98 (m，2H)，3.12 (s，2H)，6·88 (d，1H，J=6 Hz)，7·20 (m， 2H)，7·30 (d，1H，J=6 Hz)，7.45 (d，2H，J=6 Hz)，7.71 (m，1H)，8.51 (m，1H)， 9.59 (br s，1H); MS (DCI/NH3) m/e 310 (M+H)+ ·對 q 9 H2 3 N3 Ο · 0.15H2 O 之分析計算值·· C，73.12 ; H，7·52 ; N，13.46.實測值：C，72.72, H，7_24，N，13.28. 實例37 2-[4-(2-氟笨基VI-六氫吡啶基甲基笨基）乙醯胺 按照實例35中所述之程序，以4-(2-氟苯基）六氫吡啶取代4-(2-甲氧苯基）六氫吡啶（89毫克，80.9%產率），提供標題化合物（89 毫克，80.9% 產率）。iHNMRpOOMHADMSac^) δ 1.72(m，2H)， 1.85 (m，2H)，2·29 (m，5H)，2.51 (m，1H)，2·80 (m，1H)，2·97 (m，2H)，3.12 (s， 2H)，6.88 (d，1H，J=6 Hz)，7.19 (m，4H)，7·42 (m，3H)，9.61 (br s，1H) ； MS (DCI/NH3)m/e 327 (M+H)+.對 C2〇H23FN20 之分析計算值：C，73.59 ;H，7.10; N，8.58.實測值：C，73.49, H，6.97, N，8.30. 85228 -188- 200404539 實例38 N-(3-甲基笨基）-244-(2-甲基苯基）-1-六i p比途基1乙酸胺 按照實例35中所述之程序，以4-(2-甲基苯基）六氫吡啶取代 4-(2-甲氧苯基）六氫吡啶，提供標題化合物（65毫克，87.8%產 率）。1H NMR (300 MHz，DMSO-d6) 3 1.72 (m，2H)，1.79 (m，2H)，2.29 (m， 8H)，2.69 (m，1H)，2.97 (m，2H)，3·12 (s，2H)，6·88 (d，1H，J=6 Hz)，7_13 (m， 4H)，7.28 (d，1H，J=6 Hz)，7.47 (m，2H)，9.61 (br s，1H) ; MS (DCI/NH3) m/e 323 (M+H)+ ·對 C2 丨 H2 6N2 O 之分析計算值：C，78.22; H，8·13; N，8.69· 實測值：C，77.86, H，8.12, N，8.51. 實例39 2-「4-(3-氟茉基VI-六氫吡唸某l-N-(3-甲基笨基）乙醯胺 按照實例35中所述之程序，以4-(3-氟苯基）六氫吡啶取代4-(2-甲乳麥基）六氮外b淀’提供標題化合物（68毫克，61 ·8%產率） 。1H NMR (300 MHz，DMSO-d6) (5 1.75 (m，4Η)，2.29 (m，5Η)，2.55 (m，1Η)， 2·96 (m，2H)，3.12 (s，2H)，6·88 (d，1H，J=6 Hz)，7.01 (m，1H)，7.14 (m，3H)， 7·35 (m，1H)，7.45 (m，2H)，9·61 (br s，1H) ; MS (DCI/NH3) m/e 327 (M+H)+ · 實例40 N-(3-甲基笨基V2-「4-(6-酮基客畊基）-1-六氫吡啶某1乙醯胺Example 36D Νι (3-methylphenylhydrazone): 2- | &quot; 4- (2 · ^ pyridine VI-hexahydroepine bite 1 ethyl ether neck will be obtained from the product of Example 36C (200 mg, 1 mmol), the product from Example 1A (228 g, 1 mmol) and ν, N · diisopropylethylamine (0.185 ml, 1.1 mmol) in toluene (8 ml), Stir for 18 hours at 60 ° C. Pour the reaction mixture into water (30 mL) and extract with ethyl acetate (20 mL). Wash the organic layer with brine (2 X 30 mL) and MgS04 Dehydrated, filtered, and concentrated the filtrate under reduced pressure. The residue was purified by flash chromatography on silica gel (isolated with ethyl acetate: ethanol, 9.2: 0.8) to provide the title compound (169 mg, 55% ). 1H NMR (300 MHz, DMSO_d6) 5 1.83 (m, 4H), 2.24 (m, 5H), 2.64 (m, 1H), 2.98 (m, 2H), 3.12 (s, 2H), 6.88 (d, 1H, J = 6 Hz), 7.20 (m, 2H), 7.30 (d, 1H, J = 6 Hz), 7.45 (d, 2H, J = 6 Hz), 7.71 (m, 1H), 8.51 (m, 1H), 9.59 (br s, 1H); MS (DCI / NH3) m / e 310 (M + H) + · For q 9 H2 3 N3 〇 · 0.15H2 O Minute Calculated ·· C, 73.12; H, 7.52; N, 13.46. Found: C, 72.72, H, 7_24, N, 13.28. Example 37 2- [4- (2-Fluorobenzyl VI-hexahydro Pyridylmethylbenzyl) acetamidinide Follow the procedure described in Example 35 to replace 4- (2-methoxyphenyl) hexahydropyridine with 4- (2-fluorophenyl) hexahydropyridine (89 mg, 80.9% yield) to provide the title compound (89 mg, 80.9% yield). IHNMRpOOMHADMSac ^) δ 1.72 (m, 2H), 1.85 (m, 2H), 2.29 (m, 5H), 2.51 (m, 1H), 2.80 (m, 1H), 2.97 (m, 2H), 3.12 (s, 2H), 6.88 (d, 1H, J = 6 Hz), 7.19 (m, 4H), 7.42 (m, 3H), 9.61 (br s, 1H); MS (DCI / NH3) m / e 327 (M + H) +. Analytical calculated value for C20H23FN20: C, 73.59; H, 7.10; N, 8.58. Found: C, 73.49, H, 6.97, N, 8.30. 85228 -188- 200404539 Example 38 N- (3-methylbenzyl) -244- (2-methylphenyl) -1-hexap Bityl 1 amine acetate was substituted for 4- (2-methoxyphenyl) hexahydropyridine by 4- (2-methylphenyl) hexahydropyridine following the procedure described in Example 35 to provide the title compound (65 mg , 87.8% yield). 1H NMR (300 MHz, DMSO-d6) 3 1.72 (m, 2H), 1.79 (m, 2H), 2.29 (m, 8H), 2.69 (m, 1H), 2.97 (m, 2H), 3.12 ( s, 2H), 6.88 (d, 1H, J = 6 Hz), 7_13 (m, 4H), 7.28 (d, 1H, J = 6 Hz), 7.47 (m, 2H), 9.61 (br s, 1H); MS (DCI / NH3) m / e 323 (M + H) + · Analytical calculation for C2 丨 H2 6N2 O: C, 78.22; H, 8.13; N, 8.69. Measured value: C, 77.86, H, 8.12, N, 8.51. Example 39 2- "4- (3-Fluoramosyl VI-hexahydropyridine 1N- (3-methylbenzyl) acetamidine is as described in Example 35 Procedure to replace 4- (2-methyllactyl) hexazide with 4 (3-fluorophenyl) hexahydropyridine to provide the title compound (68 mg, 61.8% yield). 1H NMR ( 300 MHz, DMSO-d6) (5 1.75 (m, 4Η), 2.29 (m, 5Η), 2.55 (m, 1Η), 2.96 (m, 2H), 3.12 (s, 2H), 6.88 ( d, 1H, J = 6 Hz), 7.01 (m, 1H), 7.14 (m, 3H), 7.35 (m, 1H), 7.45 (m, 2H), 9.61 (br s, 1H); MS (DCI / NH3) m / e 327 (M + H) + · Example 40 N- (3-methylbenzyl V2- "4- (6-ketokeenyl) -1-hexahydropyridine 1 Acetamide

實例40A 4-(6-酮基-1Γ6Η)-塔畊基VI-六氤吡啶叛酸第三-丁酯 將4-溴基-1-六氫吡啶羧酸第三—丁酯（1〇〇克，3 78毫莫耳）在 DMF (20毫升）中，以k2C03(523毫克，3.78毫莫耳）與3(2H)_嗒 畊酮（340毫克，3.78毫莫耳）處理，然後於45°C下加熱60小時 。使反應混合物冷卻至室溫，倒入水（8〇毫升）中，並以醋酸 85228 -189- 200404539 乙酯（80毫升）萃取。將有機層以鹽水（3 x 50毫升）洗滌，以 MgS04脫水乾燥，過濾，並使濾液在減壓下濃縮。使殘留物 於矽膠上藉急驟式層析純化（以己烷：醋酸乙酯溶離，3 : 1) ，提供標題化合物（180毫克，17%產率）。iHNMRQOOMHz， DMSO-d6) 1.41 (s，9H)，1·66 (m，4H)，2.91 (m，2H)，4.05 (m，2H)，4.96 (m， 1H)，ό·93 (dd，1H，J=1.5, 9.0 Hz)，7.39 (dd，1H，J=3.0, 9.0 Hz)，7.95 (dd，1H，J= 3.0, 9.0 Hz) ； MS (DCI/NH3) m/e 280 (M+H)+.Example 40A 4- (6-Keto-1Γ6Η) -Taragenyl VI-hexapyridine tertiary-butyl ester 4-bromo-1-hexahydropyridinecarboxylic acid third-butyl ester (100%) G, 3 78 mmol) in DMF (20 ml), treated with k2C03 (523 mg, 3.78 mmol) and 3 (2H) -dacrotonone (340 mg, 3.78 mmol), then at 45 Heated at 60 ° C for 60 hours. The reaction mixture was cooled to room temperature, poured into water (80 ml), and extracted with ethyl acetate 85228-189-200404539 (80 ml). The organic layer was washed with brine (3 x 50 ml), dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (isolated with hexane: ethyl acetate, 3: 1) to provide the title compound (180 mg, 17% yield). iHNMRQOOMHz, DMSO-d6) 1.41 (s, 9H), 1.66 (m, 4H), 2.91 (m, 2H), 4.05 (m, 2H), 4.96 (m, 1H), · 93 (dd, 1H , J = 1.5, 9.0 Hz), 7.39 (dd, 1H, J = 3.0, 9.0 Hz), 7.95 (dd, 1H, J = 3.0, 9.0 Hz); MS (DCI / NH3) m / e 280 (M + H) +.

實例40B 2-(4-六氤吡啶某）—3(2HV嗒畊酮 使得自實例40A之產物（180毫克，0.6毫莫耳）在二氯甲烷（5 毫升）中冷卻至0°C，並以三氟醋酸（TFA) (0·46毫升，6毫莫耳） 處理。在〇°C下揽拌3小時後，使反應混合物溫熱至室溫，且 再攪拌3小時。使反應混合物在減壓下濃縮，並將殘留物與 甲苯（2x30毫升）共沸，提供標題化合物，gTFA鹽（18〇毫克） 。1H NMR (300 MHz，DMSO-d6) 5 2.05 (m，4H)，3· 14 (m，2H)，3.4 (m，2H)， 5·〇8 (m，1H)，6.97 (dd，1H，J=1.5, 9·0 Hz)，7.43 (dd，1H，J=3.0, 9.0 Hz)，8.0 (dd， 1H，J=3.0, 9.0 Hz)，8.36 (br s，1H)，8.70 (br s，1H) ; (MS (DCI/NH3) m/e 180 (M+H)+.Example 40B 2- (4-Hexapyridine) -3 (2HV dacrodone) The product from Example 40A (180 mg, 0.6 mmol) was cooled to 0 ° C in dichloromethane (5 ml), and Treated with trifluoroacetic acid (TFA) (0.46 ml, 6 mmol). After stirring at 0 ° C for 3 hours, the reaction mixture was allowed to warm to room temperature and stirred for another 3 hours. Concentrated under reduced pressure and the residue was azeotroped with toluene (2x30 mL) to provide the title compound, gTFA salt (180 mg). 1H NMR (300 MHz, DMSO-d6) 5 2.05 (m, 4H), 3 · 14 (m, 2H), 3.4 (m, 2H), 5.08 (m, 1H), 6.97 (dd, 1H, J = 1.5, 0.9 Hz), 7.43 (dd, 1H, J = 3.0, 9.0 Hz), 8.0 (dd, 1H, J = 3.0, 9.0 Hz), 8.36 (br s, 1H), 8.70 (br s, 1H); (MS (DCI / NH3) m / e 180 (M + H) +.

實例40C 基苯基&gt;2-「4_(6-酮基·丄(6H)-塔畊基vi_六氫吡啶某Ί乙醯脖 將以TFA鹽得自實例40Β之產物（8〇毫克，〇·27毫莫耳）、得 自貫例1A之產物（0.062克，0.27毫莫耳）及k2C〇3(〇113克，〇·81 *莫耳）在甲苯（8毫升）中合併，並於室溫下攪拌18小時。將 反應混合物倒入水（30毫升）中，並以醋酸乙酯（2〇毫升）萃取 85228 -190- 200404539 。將有機層以鹽水（2 x 30毫升）洗滌，以MgS04脫水乾燥，過 、 濾’並使滤液在減壓：下濃縮。使殘留物藉急驟式層析純化 ，使用醋酸乙酯··乙醇，9·7 : 0.3，提供標題化合物，89毫 克（100% 產率）。1H NMR (300 MHz，DMSO-d6) (J1.74 (m，2Η), 2.01 (m， 2H)，2.29 (s，3H)，2.35 (m，2H)，3.0 (m，2H)，3.15 (s，2H)，4·78 (m，1H)，6.88 (d， 1H，J=7.5 Hz)，6.93 (dd，1H，J=1.5, 9.0 Hz)，7.19 (t，1H，J=7.5 Hz)，7.38 (dd，1H， J=3.0, 9.0 Hz)，7.43 (d，2H，J=7.5 Hz)，7.98 (dd，1H，J=3.0, 9.0 Hz)，9.31 (br s， 1H) ； MS (DCI/NH3) m/e 327 (M+H)+. 邐 實例41 N-(296&quot;一甲基本基V2-f4-(2_p塞吩基）-1-穴氮p比淀基1乙酸胺 使4-(2^塞吩基）六氫17比淀鹽酸鹽（22毫克，0.11毫莫耳）、2-氯 -N-(2,6-二甲基苯基）乙醯胺（24毫克，0.12毫莫耳）及碳酸鈉（50 毫克）在N，N-二甲基甲醯胺：水（2: 1，2毫升）中，於環境溫 度下，振盪18小時。使所形成之混合物在減壓下濃縮。使 殘留物藉預備之HPLC純化，提供標題化合物，為三氟醋酸 鹽（30 毫克，62% 產率）。1H NMR (300 MHz，DMSO-d6 ) 5 2.00 (m，2H)， # 2.19 (s, 6H)5 2.20 (m? 2H)? 3.15-3.30 (m? 3H)? 3.60 (m? 2H)3 4.22 (s5 2H), 6.97 (m，1H)，7_00 (m，1H)，7.16 (m，3H)，7.40 (d，lH，J=3 Hz)，9.85 (br s，1H)，9·95 (s，1H) ; MS (ESI APCI+) m/e 329 (M+H)+. 實例42 基笨某V244-(2-啶吩基H-六氫吡啶基1乙醯胺 按照實例41中所述之程序，以2-氯-Ν-(2,5-二甲基苯基）乙醯 胺取代2-氯-Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（35毫 克，72% 產率）。iHNMR(300MHz，DMSO-d6) 5 2.00(m，2H)，2.19(s， 85228 -191- 200404539 3H)，2·20 (m，2H)，2.25 (s，3H)，3·18-3·30 (m，3H)，3.60 (m，2H)，4.20 (s，2H)， 6.97 (m，1H)，7·00 (m，2H)，7.18 (d，1H，J=6 Hz)，7.22 (s，1H)，7.40 (d，1H，J= 3 Hz)，9.80 (br s，1H)，9.90 (s，1H) ; MS (ESI APCI+) m/e 329 (M+H)+ · 實例43 N-(2-甲基笨基V2-「4-(2-嘧吩基M-六氫吡啶某1乙醯胺 按照實例41中所述之程序，以2-氯-N-(2-甲基苯基）乙醯胺取 代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（30毫克， 64% 產率）。1H NMR (300 MHz, DMSO_d6 ) 5 2.00 (m，2H)，2·20 (m，2H)， φ 2.22 (s，3H)，3.18-3.30 (m，3H)，3·60 (m，2H)，4.20 (s，2H)，6.97 (m，1H)，7.00 (m，1H)，7_18 (m，1H)，7·22 (m，1H)，7·28 (m，1H)，7.40 (m，2H)，9.82 (br s，1H)， 10.00 (s，1H) ; MS (ESI APCI+) m/e 315 (M+H)+ · 實例44 N-(3_氯基·4-氣苯基-2_|~4-(2-碟吩基Vl-六淀基1乙醯胺 按照實例41中所述之程序，以2-氯_Ν_(3-氯基-4-氟苯基）乙醯 胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（29毫 克，57% 產率）。1H NMR (300 MHz，DMSO_d6) 5 2.00 (m，2H)，2.20 (m， # 2H)，3.18-3.30 (m，3H)，3·60 (m，2H)，4·20 (s，2H)，6.97 (m5 1H)，7.00 (m，1H)， 7.42 (m，3H)，7_95 (d，1H，J=3 Hz)，9.90 (br s，1H)，10.75 (br s，1H); MS (ESI APCI+) m/e 353 (M+H)+. 實例45 溴笨基）-2-「4-(2_?比淀基）_1-六氤7比喊基i乙酸胺 使得自實例36C之產物（鹽酸鹽，20毫克，〇·ι〇毫莫耳）、N_ (4-溴苯基）-2-氯乙驗胺（27愛克，0.11毫莫耳）及碳酸鈉（5〇毫克） 在DMF ·水（2 : 1，2耄升）中，於環境溫度下，振盪18小時 85228 -192- 200404539 。將所形成之混合物傾析，及在減壓下濃縮。使殘留物藉 · 預備之HPLC純化，提供標題化合物，為三氟醋酸鹽（34毫克 ，70.9% 產率）。1H NMR (500 MHz，DMSO-d6) 6 2.10 (m，4H)，3.02 (m， 1H)，3.26 (m，2H)，3.62 (m，2H)，4·21 (s，2H)，7·28 (m，2H)，7.56 (m，4H)，7.82 (t，1H，J=6 Hz)，8.26 (d，1H，J=6 Hz)，9.90 (br s，1H)，10.20 (br s5 1H) ； MS (ESI APCI+) m/e 373 (M-H)+. 實例46 N-(2,6-二甲基苯基）-2-f4-(2-外(：淀基）-1 ·六氫比淀基1乙酸胺 · 按照實例45中所述之程序，以2-氯-N-(2,6-二甲基苯基）乙醯 胺取代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（31毫克，70.3 % 產率）。iHNMRGOOMHADMSO-c^) 5 2.10(m，4H)，2.18(s，6H)， 3·02 (m，1H)，3·31 (m，2H)，3.62 (m，2H), 4.25 (s，2H)，7.12 (m，3H)，7.32 (t，1Η， J=4 Hz)，7.28 (d，1H，J=6 Hz)，7.82 (t，1H，J=6 Hz)，8·66 (d，1H，J=4 Hz)，9.90 (br s，1H)，9·98 (s，1H) ; MS (ESI APCI+) m/e 324 (M+H)+ · 實例47 N_(2-硝基苯基比淀基）-l-7T氨p比淀基1乙驢胺 按照實例45中所述之程序，以2-氯_N-(2-硝基苯基）乙醯胺取 代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（43毫克，90% 產率）。iHNMRpOOMI^DMSOddi^-lOCm/HXS^CnUHXS.Sl (m，2H)，3·62 (m，2H)，4.25 (s，2H)，7·22 (m，2H)，7.45 (t，1H，J=4 Hz)，7.65 (m， 1H)，7.80 (m，2H)，8·01 (d，1H，J=6 Hz)，8.58 (d，1H，J=4 Hz)，10.00 (br s5 1H)， 11.02 (s，1H) ; MS (ESI APCI+) m/e 341 (M+H)+ · 實例48 N-G-硇暮苯某）-244-(2-吡啶基）_1-六氫吡啶基1乙醯胺 85228 -193- 200404539 按照實例45中所述之程序，以2-氯-N-(3-硝基苯基）乙醯胺取 代N-(4-溴苯基）-2_氯乙醯胺，提供標題化合物（25毫克，55% 產率）。iHNMRGOOMHADMSO-ddM.lOCm/Hp.f^CnUEQJJl (m，2H)，3.62 (m，2H)，4.25 (s，2H)，7.38 (m，2H)，7.70 (t，1H，J=6 Hz)，7.82 (t， 1H，J=4 Hz)，7.92 (d，1H，J=6 Hz)，9.02 (d，1H，J=4 Hz)，8_58 (d，1H，J=4 Hz)， 8.65 (s，1H)，10.00 (br s，1H)，11.12 (s，1H); MS (ESI APCI+) m/e 341 (M+H)+ · 實例49 N-(2,4-二氟笨基）-244-(2-外1：淀基）小六氫外1:淀基1乙酸胺 按照實例45中所述之程序，以2-氯-N-(2,4-二氟苯基）乙醯胺 取代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（26毫克，59 % 產率）。！HNMR(500 MHz，DMSO-d6) δ 2.08(m，4H)，3.02 (m，lH)， 3·31 (m，2H)，3.62 (m5 2H)，4.20 (s，2H)，7·15 (m，1H)，7·28 (m5 3H)，7·82 (m， 2H)，8.58 (d，1H，J=4 Hz)，9·92 (br s，1H)，10.52 (s，1H); MS (ESI APCI+) m/e 332 (M+H)+. 實例50 N-(2,5-二甲基苯基峨淀基）-1-六氫外[：淀基1乙酸胺 按照實例45中所述之程序，以2-氯-N-(2,5-二甲基苯基）乙醯 胺取代N-(4-溪苯基）-2-氯乙驗胺’提供標題化合物（12.2毫克， 28% 產率）。iHNMRpOOMHzJMSOOi^.KKmJI^^lSGdH)， 2.28 (s，3H)，3.05 (m，1H)，3.31 (m，2H)，3.65 (m，2H)，4.25 (s，2H)，6.98 (d，1H， J=6 Hz)，7_15 (d，1H，J=6 Hz)，7·22 (s，1H)，7.38 (m，2H)，7.82 (t，1H，J=4 Hz)， 8.58 (d，1H，J=4 Hz)，9.90 (br s，1H)，9.98 (s，1H) ; MS (ESI APCI+) m/e 324 (M+H)' 實例51 85228 194- 200404539 N-(2-甲某苽某V2-「4-(2-吡啶基Μ-六i,吡啶基1乙醯胺 按照實例45中所述之程序，以2-氯-N-(2-甲基苯基）乙醯胺取 代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（16毫克，37% 產率）。iHNMR(500MHz，DMSOd6)(5 2.10(m，4H)，2.12(s，3H)，3.05 (m，1H)，3.28 (m，2H)，3.65 (m，2H)，4·22 (s，2H)，7·10 (m，3H)，7.42 (m，3H)， 7.85 (t，1H，J=4 Hz)，8.58 (d，1H，J=4 Hz)，9.90 (br s，1H)，9.98 (s，1H) ; MS (ESI APCI+) m/e 310 (M+H)+. 實例52 N-(4-甲基笨基比淀基氮p比淀基1乙酸胺 按照實例45中所述之程序，以2-氯-N-(4_f基苯基）乙醯胺取 代Ν_(4·溴苯基）-2-氣乙醯胺，提供標題化合物（29毫克，68% 產率）。1H NMR (500 MHz，DMSO-d6) 5 2_10 (m5 4H)，2.32 (s，3H)，3·05 (m，1Η)，3·28 (m，2Η)，3·65 (m，2Η)，4·22 (s，2Η)，7·18 (d，2Η，J=6 Ηζ)，7·38 (t， 1H，J=4 Hz)，7·42 (d，1H，J=4 Hz)，7·50 (d，2H，J=6 Hz)，7.85 (t，1H，J=4 Hz)， 8.58 (d，1H，J=4 Hz)，9.90 (br s，1H)，10.55 (s，1H) ; MS (ESI APCI+) m/e 310 (M+H)' 實例53 2-『4-(2-吡啶基VI-六氫吡啶基三氟甲基）茉基1乙醯胺 按照實例45中所述之程序，以2-氯-N_(3-三氟甲基苯基）乙醯 胺取代N_(4_溴苯基）-2-氯乙醯胺，提供標題化合物（34毫克，71 % 產率）。1H NMR (500 MHz，DMSOd6) 5 2.05 (m，4H)，2.95 (m，1H)， 3·28 (m，2H)，3.65 (m，2H)，4.12 (s，2H)，7·22 (t，1H，J=4 Hz)，7·35 (d，1H，J= 4 Hz)，7.42 (d，1H，J=4 Hz)，7.60 (t，1H，J=4 Hz)，7.75 (t，1H，J=4 Hz)，7.85 (d5 1H，J=4 Hz)，8.12 (s，1H)，8·52 (d，1H，J=4 Hz)，9.95 (br s，1H)，10.75 (to s，1H) 200404539 ;MS (ESI APCI+) m/e 364 (M+H)+ · · 實例54 4-川4-(2-吡啶某VI-六氫吡啶基1乙醯基丨胺某）笨甲酸乙酯 按照實例45中所述之程序，以4-[(氯基乙醯基）胺基]苯甲酸 乙酯取代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（30毫克 ，62% 產率）。1H NMR (500 MHz，DMSO-d6) δ 1.28 (t，3H，J=4 Hz)，1.98 (m，6H)，2.41 (m，2H)，2·72 (m，1H)，3.01 (m，2H)，3.20 (s，2H)，4.28 (dd，2H， J=4,4 Hz)，7.22 (t，1H，J=3 Hz)，7.30 (d，1H，J=4 Hz)，7.78 (m，3H)，7.95 (d，2H， φ J=3 Hz)，8·55 (s，1H)，9·90 (br s，1H)，10.55 (br s，1H) ; MS (ESI APCI+) m/e 368 (M+H)+. 實例55 N-(3-氯基_4-甲基笨基V2-「4-(2-吡啶基）小六新.吡啶基1乙醯胺 按照實例45中所述之程序，以2-氯-Ν·(3-氯基-4-甲基苯基）乙 醯胺取代Ν-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（33毫克 ，72% 產率）。1H NMR (500 MHz，DMSO-d6) 6 2.02 (m，5H)，2.28 (s，3H)， 2.91 (m，1H)，3·28 (m，3H)，4.02 (s，2H)，7.22 (t，1H，J=4 Hz)，7·35 (d，1H，J= # 4 Hz)，7.45 (d，1H，J=4 Hz)，7.75 (t，2H，J=4 Hz)，7.80 (s，1H)，8.52 (d，1H，J= 4 Hz)，9_95 (br s，1H)，10.75 (br s，1H) ; MS (ESI APCI+) m/e 344 (M+H)+ · 實例56 Ν·(2-氰基苯基V2-「4-(2·吡啶基VI-六氫吡啶基1乙醯胺 按照實例45中所述之程序，以2-氯-N-(2-氰基苯基）乙醯胺取 代Ν·(4-溴苯基）-2•氣乙醯胺，提供標題化合物（27毫克，63% 產率）。1H NMR (500 MHz，DMSO-d6) 5 2.02 (m5 4Η)，2.91 (m，1Η)，3.28 (m，2H)，3_65 (m，2H)5 4.22 (s，2H)，7.22-7.45 (m，3H)，7.75-7.85 (m，4H)，8·52 85228 -196- 200404539 (m5 1H)5 9.95 (br s? 1H)5 10.85 (br s, 1H) ； MS (ESI APCI+) m/e 321 (M+H)+. - 實例57 N-(3_氯笨某）-244-(2-4淀基H-六氫p比淀基1乙酸胺 按照實例45中所述之程序，以2-氯-N-(3-氯苯基）乙醯胺取代 N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（16毫克’ 36%產 率）。1H NMR (500 MHz，DMSO-d6) 5 2.05 (m，4H)，2_98 (m，3H)，3.65 (m， 2H)，4.02 (s，2H)，7·22 (t，1H，J=4 Hz)，7·35 (d，1H，J=4 Hz)，7.42 (d，1H，J=4Example 40C-based phenyl group> 2- "4- (6-keto · fluorene (6H) -taragenyl vi_hexahydropyridine, ethyl acetone) The product of Example 40B (80 mg, 0.027 millimoles), the product obtained from Example 1A (0.062 g, 0.27 millimoles), and k2C03 (〇113 grams, 0.81 * mole) were combined in toluene (8 mL), and Stir at room temperature for 18 hours. Pour the reaction mixture into water (30 ml) and extract with ethyl acetate (20 ml) 85228 -190- 200404539. Wash the organic layer with brine (2 x 30 ml), It was dehydrated and dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure: The residue was purified by flash chromatography using ethyl acetate · ethanol, 9.7: 0.3 to provide the title compound, 89 mg ( 100% yield). 1H NMR (300 MHz, DMSO-d6) (J1.74 (m, 2Η), 2.01 (m, 2H), 2.29 (s, 3H), 2.35 (m, 2H), 3.0 (m , 2H), 3.15 (s, 2H), 4.78 (m, 1H), 6.88 (d, 1H, J = 7.5 Hz), 6.93 (dd, 1H, J = 1.5, 9.0 Hz), 7.19 (t, 1H, J = 7.5 Hz), 7.38 (dd, 1H, J = 3.0, 9.0 Hz), 7.43 (d, 2H, J = 7.5 Hz), 7.98 (dd, 1H , J = 3.0, 9.0 Hz), 9.31 (br s, 1H); MS (DCI / NH3) m / e 327 (M + H) +. Example 41 N- (296 &quot; monomethyl radical V2-f4- (2-p-sedenyl) -1-hole nitrogen p-pyridyl 1 acetic acid makes 4- (2 ^ sedenyl) hexahydro 17-pyridine hydrochloride (22 mg, 0.11 mmol), 2-chloro- N- (2,6-dimethylphenyl) acetamide (24 mg, 0.12 mmol) and sodium carbonate (50 mg) in N, N-dimethylformamide: water (2: 1, 2 ml), shaking at ambient temperature for 18 hours. The resulting mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to provide the title compound as trifluoroacetate (30 mg, 62% yield Rate). 1H NMR (300 MHz, DMSO-d6) 5 2.00 (m, 2H), # 2.19 (s, 6H) 5 2.20 (m? 2H)? 3.15-3.30 (m? 3H)? 3.60 (m? 2H ) 3 4.22 (s5 2H), 6.97 (m, 1H), 7_00 (m, 1H), 7.16 (m, 3H), 7.40 (d, lH, J = 3 Hz), 9.85 (br s, 1H), 9 · 95 (s, 1H); MS (ESI APCI +) m / e 329 (M + H) +. Example 42 Benzyl V244- (2-pyridinyl H-hexahydropyridyl 1 acetamidine) according to Example 41 Procedure described in 2-chloro-N- (2,5-dimethylphenyl) acetamide Substituting 2-chloro -Ν- (2,6- dimethylphenyl) acetyl amine to provide the title compound (35 mg, 72% yield). iHNMR (300 MHz, DMSO-d6) 5 2.00 (m, 2H), 2.19 (s, 85228 -191- 200404539 3H), 2.20 (m, 2H), 2.25 (s, 3H), 3.18-3 · 30 (m, 3H), 3.60 (m, 2H), 4.20 (s, 2H), 6.97 (m, 1H), 7.0 (m, 2H), 7.18 (d, 1H, J = 6 Hz), 7.22 (s, 1H), 7.40 (d, 1H, J = 3 Hz), 9.80 (br s, 1H), 9.90 (s, 1H); MS (ESI APCI +) m / e 329 (M + H) + · Examples 43 N- (2-methylbenzyl V2- "4- (2-pyridinyl M-hexahydropyridine-1 acetamidine) Follow the procedure described in Example 41 with 2-chloro-N- (2- Methylphenyl) acetamide replaced 2-chloro-N- (2,6-dimethylphenyl) acetamide to provide the title compound (30 mg, 64% yield). 1H NMR (300 MHz, DMSO_d6 ) 5 2.00 (m, 2H), 2.20 (m, 2H), φ 2.22 (s, 3H), 3.18-3.30 (m, 3H), 3.60 (m, 2H), 4.20 (s, 2H) , 6.97 (m, 1H), 7.00 (m, 1H), 7_18 (m, 1H), 7.22 (m, 1H), 7.28 (m, 1H), 7.40 (m, 2H), 9.82 (br s, 1H), 10.00 (s, 1H); MS (ESI APCI +) m / e 315 (M + H) + · Example 44 N- (3_chloro group 4-4-phenylphenyl-2_ | ~ 4- ( 2-Disc phenyl Vl-hexanoyl 1 acetamidamine Following the procedure described in Example 41, 2-Chloro-N- (3-chloro-4-fluorophenyl) acetamide replaced 2-chloro-N- (2,6-dimethylphenyl) acetamide to provide the title compound (29 mg, 57 % Yield). 1H NMR (300 MHz, DMSO_d6) 5 2.00 (m, 2H), 2.20 (m, # 2H), 3.18-3.30 (m, 3H), 3.60 (m, 2H), 4.20 (s, 2H), 6.97 (m5 1H), 7.00 (m, 1H), 7.42 (m, 3H), 7_95 (d, 1H, J = 3 Hz), 9.90 (br s, 1H), 10.75 (br s ， 1H); MS (ESI APCI +) m / e 353 (M + H) +. Example 45 Bromobenzyl) -2- "4- (2_? Bitoyl) _1-hexamidine 7-methylaminoacetate The product from Example 36C (hydrochloride, 20 mg, 0.00 mmol), N_ (4-bromophenyl) -2-chloroethionamine (27 gram, 0.11 mmol) and carbonic acid Sodium (50 mg) was shaken in DMF · water (2: 1, 2 liters) at ambient temperature for 18 hours 85228 -192- 200404539. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide the title compound as trifluoroacetate (34 mg, 70.9% yield). 1H NMR (500 MHz, DMSO-d6) 6 2.10 (m, 4H), 3.02 (m, 1H), 3.26 (m, 2H), 3.62 (m, 2H), 4.21 (s, 2H), 7 · 28 (m, 2H), 7.56 (m, 4H), 7.82 (t, 1H, J = 6 Hz), 8.26 (d, 1H, J = 6 Hz), 9.90 (br s, 1H), 10.20 (br s5 1H); MS (ESI APCI +) m / e 373 (MH) +. Example 46 N- (2,6-dimethylphenyl) -2-f4- (2-Exo (: Yodo) -1 · Six Hydroxylamino 1 acetic acid. Substitute N- (4-bromophenyl) -2 with 2-chloro-N- (2,6-dimethylphenyl) acetamide according to the procedure described in Example 45. -Chlorhexidine to provide the title compound (31 mg, 70.3% yield). IHNMRGOOMHADMSO-c ^) 5 2.10 (m, 4H), 2.18 (s, 6H), 3.02 (m, 1H), 3. · 31 (m, 2H), 3.62 (m, 2H), 4.25 (s, 2H), 7.12 (m, 3H), 7.32 (t, 1Η, J = 4 Hz), 7.28 (d, 1H, J = 6 Hz ), 7.82 (t, 1H, J = 6 Hz), 8.66 (d, 1H, J = 4 Hz), 9.90 (br s, 1H), 9.98 (s, 1H); MS (ESI APCI +) m / e 324 (M + H) + · Example 47 N_ (2-nitrophenyl ratio) -l-7T ammonia p ratio 1 ethylammonium amine Follow the procedure described in Example 45, using 2- Chloro_N- (2-nitrophenyl) acetamide substituted N- (4-bromophenyl 2-chloro-acetyl-amine to provide the title compound (43 mg, 90% yield). iHNMRpOOMI ^ DMSOddi ^ -lOCm / HXS ^ CnUHXS.Sl (m, 2H), 3.62 (m, 2H), 4.25 (s, 2H), 7.22 (m, 2H), 7.45 (t, 1H, J = 4 Hz), 7.65 (m, 1H), 7.80 (m, 2H), 8.01 (d, 1H, J = 6 Hz), 8.58 (d, 1H, J = 4 Hz), 10.00 (br s5 1H ), 11.02 (s, 1H); MS (ESI APCI +) m / e 341 (M + H) + · Example 48 NG-Cyclophenyl) -244- (2-pyridyl) _1-hexahydropyridyl 1 Acetylamine 85228 -193- 200404539 Follow the procedure described in Example 45 to replace N- (4-bromophenyl) -2-chloroethyl with 2-chloro-N- (3-nitrophenyl) acetamidamine Phenamine provides the title compound (25 mg, 55% yield). iHNMRGOOMHADMSO-ddM.lOCm / Hp.f ^ CnUEQJJl (m, 2H), 3.62 (m, 2H), 4.25 (s, 2H), 7.38 (m, 2H), 7.70 (t, 1H, J = 6 Hz), 7.82 (t, 1H, J = 4 Hz), 7.92 (d, 1H, J = 6 Hz), 9.02 (d, 1H, J = 4 Hz), 8_58 (d, 1H, J = 4 Hz), 8.65 ( s, 1H), 10.00 (br s, 1H), 11.12 (s, 1H); MS (ESI APCI +) m / e 341 (M + H) + · Example 49 N- (2,4-difluorobenzyl) -244- (2-Ex1: Yodo) Phenylhexahydroex 1: Yodo1 Ammonium Acetate Follow the procedure described in Example 45 with 2-chloro-N- (2,4-difluorophenyl) ethyl Amidine replaced N- (4-bromophenyl) -2-chloroacetamidine to provide the title compound (26 mg, 59% yield). !! HNMR (500 MHz, DMSO-d6) δ 2.08 (m, 4H), 3.02 (m, 1H), 3.31 (m, 2H), 3.62 (m5 2H), 4.20 (s, 2H), 7.15 ( m, 1H), 7.28 (m5 3H), 7.82 (m, 2H), 8.58 (d, 1H, J = 4 Hz), 9.92 (br s, 1H), 10.52 (s, 1H) ; MS (ESI APCI +) m / e 332 (M + H) +. Example 50 N- (2,5-Dimethyphenylelidelide) -1-Hexane [[Yodoyl 1 acetic acid according to example The procedure described in 45, substituting 2-chloro-N- (2,5-dimethylphenyl) acetamide for N- (4-brookphenyl) -2-chloroethanamine 'provides the title compound ( 12.2 mg, 28% yield). iHNMRpOOMHzJMSOOi ^ .KKmJI ^^ SGdH), 2.28 (s, 3H), 3.05 (m, 1H), 3.31 (m, 2H), 3.65 (m, 2H), 4.25 (s, 2H), 6.98 (d, 1H, J = 6 Hz), 7_15 (d, 1H, J = 6 Hz), 7.22 (s, 1H), 7.38 (m, 2H), 7.82 (t, 1H, J = 4 Hz), 8.58 (d, 1H, J = 4 Hz), 9.90 (br s, 1H), 9.98 (s, 1H); MS (ESI APCI +) m / e 324 (M + H) 'Example 51 85228 194- 200404539 N- (2-A A certain V2- "4- (2-pyridyl M-hexai, pyridyl 1 acetamidine, according to the procedure described in Example 45, with 2-chloro-N- (2-methylphenyl) acetamidine Amine substituted N- (4-bromophenyl) -2-chloroacetamidine to provide the title compound (16 mg, 37% yield). IHNMR (500 MHz, DMSOd6) (5 2.10 (m, 4H), 2.12 (s , 3H), 3.05 (m, 1H), 3.28 (m, 2H), 3.65 (m, 2H), 4.22 (s, 2H), 7.10 (m, 3H), 7.42 (m, 3H), 7.85 (t, 1H, J = 4 Hz), 8.58 (d, 1H, J = 4 Hz), 9.90 (br s, 1H), 9.98 (s, 1H); MS (ESI APCI +) m / e 310 (M + H) +. Example 52 N- (4-methylbenzylidene than p-nitrogen p-pyridyl 1 amine acetate Follow the procedure described in Example 45 using 2-chloro-N- (4-fylphenyl) ethyl Amido substituted N_ (4-bromophenyl ) -2-Gastilamine to provide the title compound (29 mg, 68% yield). 1H NMR (500 MHz, DMSO-d6) 5 2_10 (m5 4H), 2.32 (s, 3H), 3.05 ( m, 1Η), 3.28 (m, 2Η), 3.65 (m, 2Η), 4.22 (s, 2Η), 7.18 (d, 2Η, J = 6 Ηζ), 7.38 ( t, 1H, J = 4 Hz), 7.42 (d, 1H, J = 4 Hz), 7.50 (d, 2H, J = 6 Hz), 7.85 (t, 1H, J = 4 Hz), 8.58 (d, 1H, J = 4 Hz), 9.90 (br s, 1H), 10.55 (s, 1H); MS (ESI APCI +) m / e 310 (M + H) 'Example 53 2- 『4- ( 2-Pyridyl VI-hexahydropyridyl trifluoromethyl) mosyl 1 acetamidinide Substituted with 2-chloro-N_ (3-trifluoromethylphenyl) acetamidine according to the procedure described in Example 45. N_ (4-bromophenyl) -2-chloroacetamidamine provided the title compound (34 mg, 71% yield). 1H NMR (500 MHz, DMSOd6) 5 2.05 (m, 4H), 2.95 (m, 1H), 3.28 (m, 2H), 3.65 (m, 2H), 4.12 (s, 2H), 7.22 ( t, 1H, J = 4 Hz), 7.35 (d, 1H, J = 4 Hz), 7.42 (d, 1H, J = 4 Hz), 7.60 (t, 1H, J = 4 Hz), 7.75 ( t, 1H, J = 4 Hz), 7.85 (d5 1H, J = 4 Hz), 8.12 (s, 1H), 8.52 (d, 1H, J = 4 Hz), 9.95 (br s, 1H), 10.75 (to s, 1H) 200404539; MS (ESI APCI +) m / e 364 (M + H) + · Example 54 4-Chloro 4- (2-pyridine VI-hexahydropyridyl 1 ethylfluorenylamine (A) Ethyl benzylformate was replaced with N- (4-bromophenyl) -2-chloroacetamidine by ethyl 4-[(chloroethylacetamido) amino] benzoate according to the procedure described in Example 45. Provide the title compound (30 mg, 62% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.28 (t, 3H, J = 4 Hz), 1.98 (m, 6H), 2.41 (m, 2H), 2.72 (m, 1H), 3.01 (m, 2H), 3.20 (s, 2H), 4.28 (dd, 2H, J = 4, 4 Hz), 7.22 (t, 1H, J = 3 Hz), 7.30 (d, 1H, J = 4 Hz), 7.78 ( m, 3H), 7.95 (d, 2H, φ J = 3 Hz), 8.55 (s, 1H), 9.90 (br s, 1H), 10.55 (br s, 1H); MS (ESI APCI +) m / e 368 (M + H) +. Example 55 N- (3-Chloro-4-methylbenzyl V2- "4- (2-pyridyl) small six new. Pyridyl 1 acetamidine according to the example Procedure described in 45, substituting 2-chloro-N · (3-chloro-4-methylphenyl) acetamide for N- (4-bromophenyl) -2-chloroacetamide, providing the title Compound (33 mg, 72% yield). 1H NMR (500 MHz, DMSO-d6) 6 2.02 (m, 5H), 2.28 (s, 3H), 2.91 (m, 1H), 3.28 (m, 3H ), 4.02 (s, 2H), 7.22 (t, 1H, J = 4 Hz), 7.35 (d, 1H, J = # 4 Hz), 7.45 (d, 1H, J = 4 Hz), 7.75 ( t, 2H, J = 4 Hz), 7.80 (s, 1H), 8.52 (d, 1H, J = 4 Hz), 9_95 (br s, 1H), 10.75 (br s, 1H); MS (ESI APCI +) m / e 344 (M + H) + Example 56 Ν (2-cyanophenyl V2- "4- (2.pyridyl VI-hexa Pyridyl 1 acetamidinide Follow the procedure described in Example 45 to replace N · (4-bromophenyl) -2 · aziridine with 2-chloro-N- (2-cyanophenyl) acetamide. Provide the title compound (27 mg, 63% yield). 1H NMR (500 MHz, DMSO-d6) 5 2.02 (m5 4Η), 2.91 (m, 1Η), 3.28 (m, 2H), 3_65 (m, 2H) ) 5 4.22 (s, 2H), 7.22-7.45 (m, 3H), 7.75-7.85 (m, 4H), 8.52 85228 -196- 200404539 (m5 1H) 5 9.95 (br s? 1H) 5 10.85 ( br s, 1H); MS (ESI APCI +) m / e 321 (M + H) +.-Example 57 N- (3_chlorobenzyl) -244- (2-4H-Hp Amine 1 acetate Follow the procedure described in Example 45 to replace N- (4-bromophenyl) -2-chloroacetamide with 2-chloro-N- (3-chlorophenyl) acetamide to provide the title Compound (16 mg '36% yield). 1H NMR (500 MHz, DMSO-d6) 5 2.05 (m, 4H), 2_98 (m, 3H), 3.65 (m, 2H), 4.02 (s, 2H), 7.22 (t, 1H, J = 4 Hz), 7.35 (d, 1H, J = 4 Hz), 7.42 (d, 1H, J = 4

Hz)，7.60 (t，1H，J=4 Hz)，7.75 (t，1H，J=4 Hz)，7.85 (d，1H，J=4 Hz)，8.12 (s， φ 1H)，8.52 (d，1H，J=4 Hz)，9·95 (br s，1H), 10.75 (br s，1H) ; MS (ESI APCI+) m/e 330 (M+H)' 實例58 244-(3-氰基-2-吡啶基VI-六氫吡啶基甲基笨基）乙醯胺Hz), 7.60 (t, 1H, J = 4 Hz), 7.75 (t, 1H, J = 4 Hz), 7.85 (d, 1H, J = 4 Hz), 8.12 (s, φ 1H), 8.52 (d , 1H, J = 4 Hz), 9.95 (br s, 1H), 10.75 (br s, 1H); MS (ESI APCI +) m / e 330 (M + H) 'Example 58 244- (3-cyanide 2-pyridyl VI-hexahydropyridylmethylbenzyl) acetamidamine

實例58A 4-{|T三氟甲某）墙醯基1氣基丨-3,6-二氫-U2HV吡啶羧酸芊酯 標題化合物係根據J. Org· Chem· 1998, 63, 8320中所述之程序製 成。將4-酮基-1-六氫吡啶羧酸苄酯（0.5克，2.1毫莫耳）與N-苯 鲁 基三氟甲烷磺醯亞胺（1.15克，3.2毫莫耳）在四氫呋喃（10毫升） 中，於-78°C下，以六甲基二矽氮化鋰（2_14毫升，2.1毫莫耳） 處理。於-78°C下4小時後，以水使混合物反應淬滅，並以大 為過量之乙醚萃取（3x)。將含醚層合併，以硫酸鈉脫水乾燥 ，過濾，並使滤液在減壓下濃縮。使殘留物於急驟式矽膠 上層析（20%醋酸乙酯：己烷），提供標題化合物（0.471克， % 產率）。1H NMR (300 MHz，CDC13) 5 2.47 (m，2H)，3·72 (m，2H)，4.13 (m，2H)，5·16 (s，2H)，5.78 (br m，1H)，7.36 (m，5H); 85228 -197- 200404539 MS (ESI) m/e 366 (M+H)+.Example 58A 4- {| Ttrifluoromethane) fluorenyl 1-gas group 丨 -3,6-dihydro-U2HV pyridinecarboxylic acid methyl ester The title compound is according to J. Org · Chem · 1998, 63, 8320 The procedure described is made. Benzyl 4-keto-1-hexahydropyridinecarboxylate (0.5 g, 2.1 mmol) with N-benzyl trifluoromethanesulfonylimide (1.15 g, 3.2 mmol) in tetrahydrofuran (10 Ml), at -78 ° C, treated with lithium hexamethyldisilazide (2-14 ml, 2.1 mmol). After 4 hours at -78 ° C, the mixture was quenched with water and extracted with a large excess of ether (3x). The ether-containing layers were combined, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. Chromatography of the residue on flash silica gel (20% ethyl acetate: hexane) provided the title compound (0.471 g,% yield). 1H NMR (300 MHz, CDC13) 5 2.47 (m, 2H), 3.72 (m, 2H), 4.13 (m, 2H), 5.16 (s, 2H), 5.78 (br m, 1H), 7.36 (m, 5H); 85228 -197- 200404539 MS (ESI) m / e 366 (M + H) +.

實例58B 4_-(4,4,5,5-四甲基-1，3,2-二氣硼伍圜-2-某 V3.6-二邀二UgM)： 吡啶羧酸芊酿 標題化合物係根據Tetrahedron Lett. 2000,41 3705中所述之程序 製成。將雙（品吶可基）二硼烷（338毫克，1.33毫莫耳）、醋酸 鉀（356毫克，3.63毫莫耳）、[1，Γ·雙（二苯基膦基）二環戊二烯 鐵]二氯鈀（II)(PdCl2 dppf ; 30毫克，0.04毫莫耳）及1，Γ-雙（二苯基 膦基）二環戊二烯鐵（20毫克，0.04毫莫耳）合併，並以得自實 例58Α之產物（440毫克，1.21毫莫耳）在已脫氣之1，4-二氧陸圜 (7毫升）中處理。將反應混合物於8〇°C下加熱16小時，使其 冷卻至23°C，以水稀釋，並以二氯甲烷萃取（3x)。將二氯甲 燒萃液合併，以硫酸鈉脫水乾燥，過濾，並使濾液在減壓 下濃縮。使殘留物於急騾式矽膠上層析（20%醋酸乙酯：己 烷），提供標題化合物（323毫克，78%產率）。1H NMR (300 MHz， CDC13) 5 1.25 (s，12H)，2·24 (m，2H)，3.52 (dd，2H，J=5.7, 5.7 Hz)，4.03 (dd， 2H，J=3,6 Hz)，5.14 (s，2H)，6.46 (br m，1H)，7.32 (m，5H) ; MS (ESI) m/e 344 (M+H)'Example 58B 4 _- (4,4,5,5-tetramethyl-1,3,2-dioxoborohydride-2-V3.6-diisopropyl UgM): pyridinecarboxylic acid was used to prepare the title compound Prepared according to the procedure described in Tetrahedron Lett. 2000, 41 3705. Bis (pinacyl) diborane (338 mg, 1.33 mmol), potassium acetate (356 mg, 3.63 mmol), [1, Γ · bis (diphenylphosphino) dicyclopentane Ironene] Dichloropalladium (II) (PdCl2 dppf; 30 mg, 0.04 mmol) and 1, Γ-bis (diphenylphosphino) dicyclopentadiene iron (20 mg, 0.04 mmol) And treated with the product from Example 58A (440 mg, 1.21 mmol) in degassed 1,4-dioxolane (7 ml). The reaction mixture was heated at 80 ° C for 16 hours, allowed to cool to 23 ° C, diluted with water, and extracted with dichloromethane (3x). The dichloromethane extracts were combined, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. Chromatography of the residue on flash silica gel (20% ethyl acetate: hexane) provided the title compound (323 mg, 78% yield). 1H NMR (300 MHz, CDC13) 5 1.25 (s, 12H), 2.24 (m, 2H), 3.52 (dd, 2H, J = 5.7, 5.7 Hz), 4.03 (dd, 2H, J = 3,6 Hz), 5.14 (s, 2H), 6.46 (br m, 1H), 7.32 (m, 5H); MS (ESI) m / e 344 (M + H) '

實例58C 1A^3’，6’-二氫 _2,4’_聯吡啶酸芊酯 4,4,5,5_四甲某-1A2- 二氧硼伍圜-2-醇複合物 將得自實例58B之產物（200毫克，0.58毫莫耳）、碳酸鉀(241 毫克，1.75毫莫耳）、PdCl2dppf(29毫克，0.035毫莫耳）及2-氯 基各氰基吡啶（85毫克，〇·61毫莫耳），在已脫氣之N，N-二甲 85228 -198- 200404539 基甲驢胺（4毫升）中合併。將反應混合物於8〇。〇下加熱16小 時’使其冷卻至23°C，以水、二氯甲烷稀釋，並分離液層。 以二氯甲烷萃取（2x)水相。將所有二氯甲烷相合併，以硫酸 鈉脫水乾燥，過滤，並使濾液在減壓下濃縮。使殘留物於 急騾式矽膠上層析（50%醋酸乙酯：己烷），提供標題化合物 ’足夠純，以在進一步反應中繼續進行(323毫克，78%產率） 。1H NMR (300 MHz，CDC13) 5 1.13 (s，12H)，2.74 (br s，2H)，3.75 (dd，2H， J=6 Hz)，4.26 (m，2H)，5.19 (s，2H)，6·57 (br m，1H)，7.32 (m，6H)，7.98 (dd，1H， J=1.8, 7.8 Hz), 8.76 (dd，1H，J=l-8, 4.5 Hz) ; MS (ESI) m/e 320 (M+H)+ ·Example 58C 1A ^ 3 ', 6'-dihydro_2,4'_bipyridinate phosphonate 4,4,5,5_tetramethyl-1A2-dioxoborofluoren-2-ol complex will give Product from Example 58B (200 mg, 0.58 mmol), potassium carbonate (241 mg, 1.75 mmol), PdCl2dppf (29 mg, 0.035 mmol) and 2-chloroisocyanopyridine (85 mg, 0.61 mmol), combined in degassed N, N-dimethyl 85228-198-200404539 methdonylamine (4 ml). The reaction mixture was heated at 80. It was heated at 0 ° C for 16 hours and allowed to cool to 23 ° C, diluted with water and dichloromethane, and the liquid layer was separated. The aqueous phase was extracted (2x) with dichloromethane. All dichloromethane phases were combined, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. Chromatography of the residue on flash silica gel (50% ethyl acetate: hexane) provided the title compound 'which was sufficiently pure to proceed in a further reaction (323 mg, 78% yield). 1H NMR (300 MHz, CDC13) 5 1.13 (s, 12H), 2.74 (br s, 2H), 3.75 (dd, 2H, J = 6 Hz), 4.26 (m, 2H), 5.19 (s, 2H), 6.57 (br m, 1H), 7.32 (m, 6H), 7.98 (dd, 1H, J = 1.8, 7.8 Hz), 8.76 (dd, 1H, J = l-8, 4.5 Hz); MS (ESI ) m / e 320 (M + H) + ·

實例58D 2-(4-六氫吡啶基）菸鹼腈 使Η?之穩定液流於23°C下，起泡經過得自實例58C之產物（70 毫克，0.15毫莫耳）、Pd/C (5毫克）及乙醇（2毫升）之經攪拌溶 液，歷經24小時。停止H2起泡，並使N2起泡經過，歷經數 分鐘。使反應混合物通過矽藻土，並使濾液在減壓下濃縮 ’提供標題化合物，足夠純，以進行至進一步反應（3〇毫克） 。MS(ESI)m/el88(M+H)+.Example 58D 2- (4-Hexahydropyridyl) nicotinonitrile allowed a stable solution of rhenium to flow at 23 ° C and foamed through the product from Example 58C (70 mg, 0.15 mmol), Pd / C (5 mg) and ethanol (2 ml) over a period of 24 hours. Stop H2 foaming and let N2 foam through for several minutes. The reaction mixture was passed through diatomaceous earth and the filtrate was concentrated under reduced pressure to provide the title compound, which was sufficiently pure to proceed to a further reaction (30 mg). MS (ESI) m / el88 (M + H) +.

實例58EExample 58E

M4-(3-氰基-2-吡啶基M-六j,吡啶某1-Ν-Π-甲基笨基）乙醯脖 將仔自實例58D之產物、得自實例1A之產物（37毫克，0.16 毫莫耳）、N，N_二異丙基乙胺（31毫克，0.24毫莫耳）及甲苯（3 毫升）合併，並於60°C下加熱。16小時後，使混合物冷卻至23 C ’及在減壓下濃縮。使殘留物藉薄層層析法純化（7%酷酸 乙酯：己烷），提供標題化合物（9毫克，17%產率）。iHNMR 85228 -199- 200404539 (400 MHz，DMSO-d6 ) 5 1.79 (br d，2H，J=12 Ηζ)，2·02 (m，2H)，2.27 (s，3H)， . 2.32 (m，2H)，3_04 (m，3H)，3·16 (s，2H)，6.88 (bd，1H，J=8 Hz), 7.18 (dd，1H，J= 7.2, 7·2 Hz)，7.45 (m，3H)，8.26 (dd，1H，J=l，2 Hz)，8·82 (dd，1H，J=l，4.4 Hz)， 9.58 (s5 1H) ； MS (APCI/ESI) m/e 335 (M+H)+. 實例59 N-(3_甲基笨基V2-(4-笨基-3,6-二氤-U2HV吡啶基）乙醯胺 按照實例35中所述之程序，以4_苯基-1，2,3,6-四氫吡啶鹽酸 鹽取代4-(2_甲氧苯基）六氫吡啶，提供標題化合物（180毫克， 0 39% 產率）。1H NMR (300 MHz, DMSO-d6) 5 2.27 (s，3H)，2.55 (m，2H)， 2.78 (t，2H，J=6 Hz)，3·26 (m，4H)，6.18 (m，1H)，6·88 (m, 1H)，7·17 (t，1H，J= 7.5 Hz)，7.25 (m，1H)，7.35 (m，2H)，7.45 (m，4H)，9.64 (s，1H); MS (DCI/NH3) !11^307如+11)+.對€2()1122^0.0.101120之分析計算值：（：，77.94 ;H，7.26 ; N，9.09·實測值：C，77·72, H，7.28, N9.03. 實例60 2-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-N-(3-甲基笨基）乙醯胺 按照實例35中所述之程序，以r，2’，3’，心四氫-2,4’_聯吡啶鹽酸 _ 鹽（Saari，W_S.等人；J. Med_ Chem. 1984, 27, 1182)取代 4-(2-甲氧苯基） 六氫吡啶，提供標題化合物（210毫克，53.8%產率）。iHNMR (300 MHz，DMSO-d6) 5 2.27 (s，3H)，2.65 (m，2H)，2·78 (t，2H，J=6 Hz)，3.25 (s? 3.30 (m? 2H)? 6.71 (m? 1H)5 6.88 (m51H). 7.18 (t? 1H? J=7.5 Hz)5 7.23 (m，1H)，7.45 (m5 2H)，7.55 (d，1H，J=9 Hz)，7.75 (m，1H)，8.53 (m，1H)，9.64 (br s，1H) ; MS (DCI/NH3) m/e 308 (M+H)+.對 q 9 H2 12N3 O · 0.30 H2 O 之分析計算值：C，72.96 ; H，6·96 ; N，13.43.實測值·· 72.73, H，6.57， N? 13.47. 85228 200- 200404539 實例61 - 2_(3’，6’_二氮-2,4’-聯p比淀-1’(2Ή)-基）-N-(2,6-二甲基苯基）乙硫脖 將Γ，2\3’，6’-四氫-2,聯吡啶鹽酸鹽（22毫克，0.11毫莫耳）、2-氯-Ν-(2,6-二甲基苯基）乙酸胺（24毫克，0.12毫莫耳）及碳酸納 (50毫克）在DMF:水(2: 1，2毫升）中合併，並於環境溫度下 振盪18小時。使混合物在減壓下濃縮。使殘留物藉預備之 HPLC純化，提供標題化合物，為三氟醋酸鹽（43毫克，90% 產率）。1H NMR (300 MHz，DMSO-d6) 5 2.20 (s，6Η)，2·96 (br s，2Η)，3.43- φ 3·63 (m，2Η)，4.03-4.20 (m，2Η)，4·39 (s，2Η)，6·72 (br s，1Η)，7·12 (m，3Η)， 7·38 (m，1H)，7.62 (d，1H，J=6 Hz)，7·82 (m，1H)，8.59 (m，1H)，10.00 (m，1H)， 10.40 (br s5 1H) ； MS (ESI APCI+) m/e 322 (M+H)+. 實例62 ·二氫-2,4’-聯吡啶-l’(2’HV基硝基苯基）乙醯胺 按照實例61中所述之程序，以2-氯-N-(2-硝基苯基）乙醯胺取 代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（27毫克， 54% 產率）。1H NMR (300 MHz，DMSO-d6) 5 2_93 (br s，2H)，3·40·3·70 # (m，2H)，4.00-4.20 (m，2H)，4·38 (s，2H)，6.75 (br s，1H)，7·38 (m，1H)，7·48 (t， 1H，J=6 Hz)，7·62 (m，2H)，7·80 (t，1H，J=6 Hz)，7·88 (t，1H，J=6 Hz)，8.03 (m， 1H)，8.60 (br s，1H)，10.44 (br s，1H)，10.98 (br s，1H) ; MS (ESI APCI+) m/e 339 (M+H)+. 實例63 二氫-2,4’-聯吡啶-Γ(2Ή)-基VN-(3,硝某茉某）乙醯胺 按照實例61中所述之程序，以2-氯-N-(3-硝基苯基）乙醯胺取 代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（48毫克， 85228 -201 - 200404539 97% 產率）。1H NMR (300 MHz, DMSO-d6 ) 5 2.96 (br s，2H)，3.45-3.75 (m，. 2H)，4.05-4.20 (m，2H)，4_38 (s，2H)，6_75 (br s，1H)，7.38 (m，1H)，7.66 (m，2H)， 7.89 (m，2H)，8.00 (d，1H，J=6 Hz)，8.60 (m，1H)，8.63 (br s，1H)，10.45 (br s， 1H)，11.08 (br s，1H) ; MS (ESI APCI+) m/e 339 (M+H)+ · 實例64 2_(3’，6’_二氤_2,4’·聯吡啶-Γ(2Ή)-基VN-(4-氟笨基）乙醯胺 按照實例61中所述之程序，以2-氯-N-(4-氟苯基）乙醯胺取代 2-氯·Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（40毫克，86 φ % 產率）。1H NMR (300 MHz，DMSO-d6) 5 2.96 (br s，2Η)，3.45-3.75 (m， 2H)，4.004.20 (m，2H)，4.35 (s，2H)，6.72 (br s，1H)，7·22 (t，2H，J=7 Hz)，7.38 (m，1H)，7·63 (m，3H)，7.82 (m，1H)，8·60 (m，1H)，10.38 (br s，1H)，10.62 (br s， 1H) ； MS (ESI APCI+) m/e 312 (M+H)+. 實例65 泳(2,4-二氯苽某&gt;2-(3’,6’-二氫-2,4’-聯吡啶-1’(2’《〇-基）乙醯胺 按照實例61中所述之程序，以2-氣-N-(2,4_二氟苯基）乙醯胺 取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（45毫克 _ ，92% 產率）。1H NMR (300 MHz，DMSO-d6) δ 2.95 (br s，2H)，3.45-3.70 (m，2H)，4.004.20 (m，2H)，4·35 (s，2H)，6·74 (br s，1H)，7.18 (t，1H, J=7 Hz)， 7.36 (m，2H)，7.63 (m，1H)，7·85 (m，2H)，8.60 (m，1H)，10.40 (br s，1H)，10.45 (br s? 1H) ； MS (ESI APCI+) m/e 330 (M+H)+. 實例66 2-(3’万-二氫-2,嫵吡啶-1Ϊ2Ή)-基）_N-(2,5_二甲基笨基）乙醯胺 按照實例61中所述之程序，以氯-N_(2,5-二甲基笨基）乙醯 胺取代2-氯-N-(2,6-二甲基苯基）乙酿胺’提供標題化合物（28毫 85228 -202- 200404539 克，59% 產率）。1H NMR (300 MHz，DMSO-d6 ) 5 2.20 (s，3H)，2·25 (s， - 3H)，2.95 (br s，2H)，3.45-3.70 (m，2H)，4.00-4.20 (m，2H)，4·35 (s，2H)，6·74 (bf s，1H)，7.00 (d，1H，J=7 Hz)，7·18 (d，1H，J=7 Hz)，7.22 (s，1H)，7.38 (m5 1H)， 7.63 (d，1H，J=7 Hz)，7.82 (m，1H)，8.60 (m，1H)，9·92 (br s，1H)，10_35 (br s， 1H) ； MS (ESI APCI+) m/e 322 (M+H)+. 實例67 2-(3f，6f-二氤-2A-聯吡啶-Γ(2Ή)_基甲基笨基）乙醯胺 按照實例61中所述之程序，以2-氯-N-(2-甲基苯基）乙醯胺取 _ 代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（30毫克， 65% 產率）。1H NMR (300 MHz，DMSO-d6) 5 2.25 (s，3H)，2_95 (br s，2H)， 3.45-3.70 (m，2H)，4.00-4.20 (m，2H)，4.35 (s，2H)，6.75 (br s，1H)，7.18 (m，1H)， 7.22 (m，1H)，7.28 (m，1H)，7.38 (m，1H)，7.43 (d，1H，J=7 Hz)，7.63 (d，1H，J= 7 Hz)，7.82 (m，1H)，8.60 (m，1H)，9.96 (br s，1H)，10.35 (br s，1H); MS (ESI APCI+) m/e 308 (M+H)+. 實例68 N-環己基-2-(3f，6’-二氫-2,4’-聯吡啶-1’(2Ή)·基）乙醯胺 · 按照實例61中所述之程序，以2-氯-Ν-環己基乙醯胺取代2-氯_Ν-(2,6·二甲基苯基）乙醯胺，提供標題化合物（20毫克，44 % 產率）。iHNMRpOOMHz’DMSOO 6 l.l(M.35(m，5H)，1.60-1.80 (m，5H)，2.95 (br s，2H)，3.45-3.70 (m，3H)，4_00_4·20 (m，2H)，4.35 (s，2H)， 6·68 (to s，1H)，7.38 (m, 1H)，7.63 (d，1H，J=7 Hz)，7.82 (m，1H)，8.42 (d，1H， J=7 Hz)，8·60 (m，1H)，10.25 (br s，1H) ; MS (ESI APCI+) m/e 300 (M+H)+ · 實例70 2-(3’.6f-二新.-2,4’-聯吡啶-1Ϊ2Ή)-基VN-(4-甲基笨基）乙醯胺 85228 -203 - 200404539 按照實例61中所述之程序，以2-氯-N-(4-甲基苯基）乙醯胺取 代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（26毫克， 56% 產率）。1H NMR (300 MHz，DMSO-d6) 6 2.24 (s，3H)，2.95 (br s，2H)， 3.45-3.70 (m，2H)，4.00-4.20 (m，2H)，4.35 (s，2H)，6.74 (br s，1H)，7.19 (d，2H， J=7 Hz), 7·38 (m，1H)，7.49 (d，2H，J=7 Hz)，7_63 (d，1H，J=7 Hz)，7.82 (m，1H)， 8.60 (m，1H)，10.35 (br s，1H)，10.45 (br s，1H) ； MS (ESI APCI+) m/e 308 (M+H)+ · 實例71 2_(3\6’-二氤-2,4’·聯吡啶·Γ(2Ή)_基）三氣甲某）笨基1乙醯胺 按照實例61中所述之程序，以2-氯-N-[3_(三氟甲基）苯基]乙 醯胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（47 毫克，90% 產率）。111丽11(300以出，〇]^3〇-(16)(52.95扣8,211)，3.45-3.70 (m，2H)，4.00-4.20 (m，2H)，4·35 (s，2H)，6.74 (br s，1H)，7.38 (m，1H)， 7.49 (d，1H，J=6 Hz)，7.63 (m，2H)，7·79 (d，1H，J=6 Hz)，7.82 (m，1H)，8·08 (s， 1H)，8.60 (m，1H)，10.45 (br s，1H)，10.98 (br s，1H); MS (ESI APCI+) m/e 362 (M+H)' 實例72 4-『(3’,6’-二氫·2,4’_聯吡啶基乙醯基）胺基1笨甲酸乙酯 按照實例61中所述之程序，以乙基4-[(氯基乙醯基）胺基]苯 甲酸酯取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物 (51 毫克，97% 產率）。iHNMRpOOMHz’DMSO-dd ά 1.35(t，3H，J= 7 Hz)，2.95 (br s，2H)，3.45-3.70 (m，2H)，4.00-4.20 (m，2H)，4.22 (q，2H，J=7 Hz)，4.36 (s，2H)，6.74 (br s，1H)，7.38 (m，1H)，7.62 (d，1H，J=6 Hz)，7.74 (d， 2H，J=8 Hz)，7.82 (m，1H), 7.98 (d，2H，J=8 Hz)，8.60 (m，1H)，10.40 (br s，1H)， 200404539 10.92 (br s? 1H) ； MS (ESI APCI+) m/e 366 (M+H)+. 實例73 N-「2-氣基-5-(三氟甲某）笨基l-2-(3，,6，-二氫·2,4，·聯吡啶-Γ(2Ή)-基） 乙醯胺 按照實例61中所述之程序，以2-氯-N-[2-氯基-5-(三氟甲基） 苯基]乙醯胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化 合物（18 毫克，32% 產率）。1H NMR (300 MHz，DMSO-d6) 5 2.95 (br s， 2H)，3.45-3.70 (m，2H)，4.00-4.20 (m，2H)，4·35 (s，2H)，6.73 (br s5 1Η)，7.38 (m， 1H), 7.63 (m? 2H)? 7.82 (m, 2H), 8.22 (s? 1H)? 8.60 (m? 1H)? 10.40 (br s? 1H)? 10.50 (br s5 1H) ； MS (ESI APCI+) m/e 396 (M+H)+. 實例74 N-(3-氯基-4-甲基苯基V2-(3’,6’-二氤-2,4f-聯吡啶基）乙醯胺 按照實例61中所述之程序，以2-氯-Ν-(3-氯基-4-甲基苯基）乙 醯胺取代2-氯_Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（44 毫克，88% 產率）。41^^(3001^1^03^80-(16)(5 2.28(3,311),2.95 (br s5 2H)，3.45-3.75 (m，2H)，4.00-4.20 (m，2H)，4.30 (s，2H)，6·73 (br s，1H)， 7.38 (m，3Η)，7.63 (d，1Η，J=6 Ηζ)，7·80 (s，1Η)，7·83 (m，1Η)，8.60 (m，1Η)， 10.38 (br s，1H)，10.63 (br s，1H) ; MS (ESI APCI+) m/e 342 (M+H)+ · 實例75 y-(2-氰基笨基V2-(3’,6’-二氫-2,聯吡啶-1Η’(2Ήν基）乙醯胺 按照實例61中所述之程序，以2-氯-Ν-(2-氰基苯基）乙醯胺取 代2-氣-Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（46毫克， 97% 產率）。1H NMR (300 MHz，DMSO-d6) 5 2.95 (br s，2Η)，3.45-3.75 (m， 2H)? 4.00-4.20 (m9 2H)? 4.40 (s? 2H), 6.75 (br s? 1H)? 7.38 (m? 1H)? 7.42 (t? 1H? 85228 -205- 200404539 J=6 Hz)，7.63 (m，2H)，7·78 (m，1H)，7.83 (m，1H)，7.88 (m，1H)，8_60 (m，1H)， - 10.42 (br s，1H)，10.93 (br s，1H) ; MS (ESI APCI+) m/e 319 (M+H)+ · 實例76 迕(3_氣苯某二氫-2,4f-聯吡啶-Γ(2Ή)-基）乙醯胺 按照實例61中所述之程序，以2-氯-Ν-(3-氯苯基）乙醯胺取代 2-氯-Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（42毫克，86 % 產率）。1H NMR (300 MHz，DMSO-d6) δ 2·95 (br s，2Η)，3.45-3.75 (m， 2H)，4.00-4.20 (m，2H)，4.34 (s，2H)，6.75 (br s，1H)，7.20 (d，1H，J=6 Hz)，7.38 φ (m，1H)，7.42 (m，2H)，7.63 (d，1H，J=6 Hz)，7.80 (s，1H)，7.83 (m，1H)，8·60 (m， 1H), 10.40 (br s，1H)，10.80 (br s，1H) ; MS (ESI APCI+) m/e 328 (M+H)+. 實例77 N-(3-氯基-4_氣笨墓V2_(3f，6f-二氫-2,4’-聯吡啶基）乙醯胺 按照實例61中所述之程序，以2-氯-N-(3_氯基-4-氟苯基）乙醯 胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（43毫 克，85% 產率）。iHNMRpOOMHADMSO-ddSl^O^rsJHXS.AS· 3.75 (m，2H)，4·00_4·20 (m，2H)，4·38 (s，2H)，6.73 (br s，1H)，7.38 (m，1H)， # 7.43 (m，2H)，7.63 (d，1H，J=6 Hz)，7·83 (m，1H)，7.92 (d，1H，J=5 Hz)，8·60 (m， 1H)，10.38 (br s，1H)，10.83 (br s，1H) ; MS (ESI APCI+) m/e 346 (M+H)+ · 實例78 2-(3’，6f-二氫-2,4’-聯吡啶基VN44-(三氟甲氣基）笨基1乙醯胺 按照實例61中所述之程序，以2-氯-N-[4-(三氟甲氧基）苯基] 乙醯胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物 (44 毫克，81% 產率）。1H NMR (300 MHz，DMSO-d6) 5 2.95 (bi* s，2H)， 3·45_3.75 (m，2H)，4.00-4.20 (m，2H)，4.35 (s，2H)，6·73 (br s，1H)，7·38 (m，1H)， 85228 -206- 200404539 7.41 (d，2H，J=7 Ηζ)，7·63 (d，1H，J=6 Hz)，7·73 (d，2H，J=7 Hz)，7.84 (m，1H)， - 8.60 (m，1H)，10.40 (br s，1H)，10.80 (br s，1H) ； MS (ESI APCI+) m/e 378 (M+H). · 實例79 2-(3’,心二氫-聯吡啶-1’(2Ήν基三氟甲某）笨某1乙醯胺 按照實例61中所述之程序，以2-氯-N-[2-(三氟甲基）苯基]乙 醯胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（41 毫克，78% 產率）。iHNMRpOOMHADMSOO (5 2.95(brs，2H)， φ 3.45-3.75 (m，2Η)，4.00瞻4·20 (m，2Η)，4.35 (s，2Η)，6.73 (br s，1Η)，7.38 (m，1Η)， 7·50·7·70 (m5 3H)，7.80-7.90 (m，3H)，8.60 (m，1H)，10_40 (s5 1H)，10.43 (br s， 1H) ； MS (ESI APCI+) m/e 362 (M+H)+. 實例80 N-(4-氯笨基V2-(3’，6’_二氫-2,4’-聯吡啶基）乙醯胺 按照實例61中所述之程序，以2-氯-Ν-(4-氯苯基）乙醯胺取代 2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（39毫克，80 % 產率）。1H NMR (300 MHz，DMSO-d6) 6 2.95 (br s，2H)，3.45-3.75 (m， 籲 2H)，4.00-4.20 (m，2H)，4·30 (s，2H)，6.73 (br s，1H)，7·38 (m，1H)，7·44 (d，2H， J=7 Hz)5 7.63 (m，3H)，7.83 (m，1H)，8.60 (m，1H)，10.40 (br s，1H)，10.63 (s， 1H) ; MS (ESI APCI+) m/e 328 (M+H)+ · 實例81 N_(2.3-二翕.^:某 V2-(3’,6’-二氫 _2,4f-聯吡啶 _r(2fHV基）乙醯胺 按照實例61中所述之程序，以2-氯·Ν-(2,3-二氯苯基）乙醯胺 取代2-氯-Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（37毫克 ，70% 產率）。1H NMR (300 MHz，DMSO-d6) (5 2.95 (br s5 2Η)，3.45-3.75M4- (3-cyano-2-pyridyl M-hexaj, pyridine 1-N-Π-methylbenzyl) acetamidine was obtained from the product of Example 58D, the product from Example 1A (37 mg (0.16 mmol), N, N-diisopropylethylamine (31 mg, 0.24 mmol) and toluene (3 ml) were combined and heated at 60 ° C. After 16 hours, the mixture was cooled to 23 C 'and concentrated under reduced pressure. The residue was purified by thin layer chromatography (7% ethyl acetate: hexane) to provide the title compound (9 mg, 17% yield). iHNMR 85228 -199- 200404539 (400 MHz, DMSO-d6) 5 1.79 (br d, 2H, J = 12 Ηζ), 2.02 (m, 2H), 2.27 (s, 3H),. 2.32 (m, 2H ), 3_04 (m, 3H), 3.16 (s, 2H), 6.88 (bd, 1H, J = 8 Hz), 7.18 (dd, 1H, J = 7.2, 7.2 Hz), 7.45 (m, 3H), 8.26 (dd, 1H, J = 1, 2 Hz), 8.82 (dd, 1H, J = 1, 4.4 Hz), 9.58 (s5 1H); MS (APCI / ESI) m / e 335 ( M + H) +. Example 59 N- (3-Methylbenzyl V2- (4-benzyl-3,6-difluorenyl-U2HV pyridyl) acetamidamine Follow the procedure described in Example 35 to 4 -Phenyl-1,2,3,6-tetrahydropyridine hydrochloride substituted 4- (2-methoxyphenyl) hexahydropyridine to provide the title compound (180 mg, 0 39% yield). 1H NMR ( 300 MHz, DMSO-d6) 5 2.27 (s, 3H), 2.55 (m, 2H), 2.78 (t, 2H, J = 6 Hz), 3.26 (m, 4H), 6.18 (m, 1H), 6.88 (m, 1H), 7.17 (t, 1H, J = 7.5 Hz), 7.25 (m, 1H), 7.35 (m, 2H), 7.45 (m, 4H), 9.64 (s, 1H) ; MS (DCI / NH3)! 11 ^ 307 such as +11) +. Analytical calculated value for € 2 () 1122 ^ 0.0.101120: (:, 77.94; H, 7.26; N, 9.09. Found: C, 77 · 72, H, 7.28, N9.03. Example 60 2- (3 ' , 6'-Dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N- (3-methylbenzyl) acetamidamine Following the procedure described in Example 35, using r, 2 ' , 3 ', cardiotetrahydro-2,4'_bipyridine hydrochloride_ salt (Saari, W_S. Et al .; J. Med_ Chem. 1984, 27, 1182) replacing 4- (2-methoxyphenyl) hexahydro Pyridine, provided the title compound (210 mg, 53.8% yield). IHNMR (300 MHz, DMSO-d6) 5 2.27 (s, 3H), 2.65 (m, 2H), 2.78 (t, 2H, J = 6 Hz), 3.25 (s? 3.30 (m? 2H)? 6.71 (m? 1H) 5 6.88 (m51H). 7.18 (t? 1H? J = 7.5 Hz) 5 7.23 (m, 1H), 7.45 (m5 2H) , 7.55 (d, 1H, J = 9 Hz), 7.75 (m, 1H), 8.53 (m, 1H), 9.64 (br s, 1H); MS (DCI / NH3) m / e 308 (M + H) +. Analysis and calculation of q 9 H2 12N3 O · 0.30 H2 O: C, 72.96; H, 6.96; N, 13.43. Measured value · 72.73, H, 6.57, N? 13.47. 85228 200- 200404539 Example 61-2_ (3 ', 6'_diaza-2,4'-bi-p-pyridine-1' (2Ή) -yl) -N- (2,6-dimethylphenyl) ethylsulfide , 2 \ 3 ', 6'-tetrahydro-2, bipyridine hydrochloride (22 mg, 0.11 mmol), 2-chloro-N- (2,6-dimethylphenyl) amine (24 Nothing , 0.12 mmol) and sodium carbonate (50 mg) in DMF: water (2: 1, 2 mL) were combined and shaken at ambient temperature for 18 hours. The mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to provide the title compound as trifluoroacetate (43 mg, 90% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.20 (s, 6Η), 2.96 (br s, 2Η), 3.43- φ 3.63 (m, 2Η), 4.03-4.20 (m, 2Η), 4 · 39 (s, 2Η), 6.72 (br s, 1Η), 7 · 12 (m, 3Η), 7.38 (m, 1H), 7.62 (d, 1H, J = 6 Hz), 7 · 82 (m, 1H), 8.59 (m, 1H), 10.00 (m, 1H), 10.40 (br s5 1H); MS (ESI APCI +) m / e 322 (M + H) +. Example 62 · Dihydro- 2,4'-bipyridine-l '(2'HV-based nitrophenyl) acetamidamine Follow the procedure described in Example 61 with 2-chloro-N- (2-nitrophenyl) acetamidamine Substitution of 2-chloro-N- (2,6-dimethylphenyl) acetamidine provided the title compound (27 mg, 54% yield). 1H NMR (300 MHz, DMSO-d6) 5 2_93 (br s, 2H), 3.40 · 3 · 70 # (m, 2H), 4.00-4.20 (m, 2H), 4.38 (s, 2H) , 6.75 (br s, 1H), 7.38 (m, 1H), 7.48 (t, 1H, J = 6 Hz), 7.62 (m, 2H), 7.80 (t, 1H, J = 6 Hz), 7.88 (t, 1H, J = 6 Hz), 8.03 (m, 1H), 8.60 (br s, 1H), 10.44 (br s, 1H), 10.98 (br s, 1H); MS (ESI APCI +) m / e 339 (M + H) +. Example 63 Dihydro-2,4'-bipyridine-Γ (2Ή) -based VN- (3, nitramidine) acetamidine according to the example The procedure described in 61 replaces 2-chloro-N- (2,6-dimethylphenyl) acetamide with 2-chloro-N- (3-nitrophenyl) acetamide to provide the title compound (48 mg, 85228-201-200404539 97% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.96 (br s, 2H), 3.45-3.75 (m, .2H), 4.05-4.20 (m, 2H), 4_38 (s, 2H), 6_75 (br s, 1H), 7.38 (m, 1H), 7.66 (m, 2H), 7.89 (m, 2H), 8.00 (d, 1H, J = 6 Hz), 8.60 (m, 1H), 8.63 (br s, 1H) , 10.45 (br s, 1H), 11.08 (br s, 1H); MS (ESI APCI +) m / e 339 (M + H) + · Example 64 2_ (3 ', 6'_ 二 氤 _2,4' Bipyridyl-Γ (2Ή) -yl VN- (4-fluorobenzyl) acetamidamine Substituted 2 with 2-chloro-N- (4-fluorophenyl) acetamidine according to the procedure described in Example 61 -Chloro-N- (2,6-dimethylphenyl) acetamide, which provided the title compound (40 mg, 86 φ% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.96 (br s, 2Η), 3.45-3.75 (m, 2H), 4.004.20 (m, 2H), 4.35 (s, 2H), 6.72 (br s, 1H), 7.22 (t, 2H, J = 7 Hz), 7.38 (m, 1H), 7.63 (m, 3H), 7.82 (m, 1H), 8.60 (m, 1H), 10.38 (br s, 1H), 10.62 (br s, 1H); MS ( ESI APCI +) m / e 312 (M + H) +. Example 65 Swim (2,4-dichlorofluorene)> 2- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2 '<0-yl) acetamidin was performed according to the procedure described in Example 61. Replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide with 2-gas-N- (2,4-difluorophenyl) acetamide to provide the title compound (45 mg_ , 92% yield). 1H NMR (300 MHz, DMSO-d6) δ 2.95 (br s, 2H), 3.45-3.70 (m, 2H), 4.004.20 (m, 2H), 4.35 (s, 2H), 6.74 (br s, 1H), 7.18 (t, 1H, J = 7 Hz), 7.36 (m, 2H), 7.63 (m, 1H), 7.85 (m, 2H), 8.60 ( m, 1H), 10.40 (br s, 1H), 10.45 (br s? 1H); MS (ESI APCI +) m / e 330 (M + H) +. Example 66 2- (3'10,000-dihydro-2 , Pyridine-1Ϊ2Ή) -yl) _N- (2,5_dimethylbenzyl) acetamidine Follow the procedure described in Example 61 with chloro-N_ (2,5-dimethylbenzyl) ethyl Amidine substituted 2-chloro-N- (2,6-dimethylphenyl) ethylamine 'provided the title compound (28 mmol 85228-202-200404539 g, 59% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.20 (s, 3H), 2.25 (s, -3H), 2.95 (br s, 2H), 3.45-3.70 (m, 2H), 4.00-4.20 (m , 2H), 4.35 (s, 2H), 6.74 (bf s, 1H), 7.00 (d, 1H, J = 7 Hz), 7.18 (d, 1H, J = 7 Hz), 7.22 (s, 1H), 7.38 (m5 1H), 7.63 (d, 1H, J = 7 Hz), 7.82 (m, 1H), 8.60 (m, 1H), 9.92 (br s, 1H), 10_35 ( br s, 1H); MS (ESI APCI +) m / e 322 (M + H) +. Example 67 2- (3f, 6f-difluorene-2A-bipyridine-Γ (2Ή) _ylmethylbenzyl) Acetylamine Follow the procedure described in Example 61 to replace 2-chloro-N- (2,6-dimethylphenyl) with 2-chloro-N- (2-methylphenyl) acetamidine Acetamide provides the title compound (30 mg, 65% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.25 (s, 3H), 2_95 (br s, 2H), 3.45-3.70 (m, 2H), 4.00-4.20 (m, 2H), 4.35 (s, 2H) , 6.75 (br s, 1H), 7.18 (m, 1H), 7.22 (m, 1H), 7.28 (m, 1H), 7.38 (m, 1H), 7.43 (d, 1H, J = 7 Hz), 7.63 (d, 1H, J = 7 Hz), 7.82 (m, 1H), 8.60 (m, 1H), 9.96 (br s, 1H), 10.35 (br s, 1H); MS (ESI APCI +) m / e 308 (M + H) +. Example 68 N-cyclohexyl-2- (3f, 6'-dihydro-2,4'-bipyridine-1 '(2 () · yl) acetamide The procedure described describes the replacement of 2-chloro-N- (2,6 · dimethylphenyl) acetamidine with 2-chloro-N-cyclohexylacetamide to provide the title compound (20 mg, 44% yield) . iHNMRpOOMHz'DMSOO 6 ll (M.35 (m, 5H), 1.60-1.80 (m, 5H), 2.95 (br s, 2H), 3.45-3.70 (m, 3H), 4_00_4 · 20 (m, 2H), 4.35 (s, 2H), 6.68 (to s, 1H), 7.38 (m, 1H), 7.63 (d, 1H, J = 7 Hz), 7.82 (m, 1H), 8.42 (d, 1H, J = 7 Hz), 8.60 (m, 1H), 10.25 (br s, 1H); MS (ESI APCI +) m / e 300 (M + H) + · Example 70 2- (3'.6f- 二 新.-2,4'-bipyridine-1Ϊ2Ή) -yl VN- (4-methylbenzyl) acetamidine 85228 -203-200404539 Follow the procedure described in Example 61 using 2-chloro-N- (4 -Methylphenyl) acetamide replaced 2-chloro-N- (2,6-dimethylphenyl) acetamide to provide the title compound (26 mg, 56% yield). 1H NMR (300 MHz, DMSO-d6) 6 2.24 (s, 3H), 2.95 (br s, 2H), 3.45-3.70 (m, 2H), 4.00-4.20 (m, 2H), 4.35 (s, 2H), 6.74 (br s, 1H), 7.19 (d, 2H, J = 7 Hz), 7.38 (m, 1H), 7.49 (d, 2H, J = 7 Hz), 7_63 (d, 1H, J = 7 Hz), 7.82 ( m, 1H), 8.60 (m, 1H), 10.35 (br s, 1H), 10.45 (br s, 1H); MS (ESI APCI +) m / e 308 (M + H) + · Example 71 2_ (3 \ 6'-Difluorene-2,4 '· bipyridine · Γ (2Ή) _yl) Acetyloyl) benzyl 1 acetamide was replaced with 2-chloro-N- [3_ (trifluoromethyl) phenyl] acetamide in accordance with the procedure described in Example 61. 6-Dimethylphenyl) acetamide, which provided the title compound (47 mg, 90% yield). 111 Li 11 (out of 300, 0) ^ 3 0- (16) (52.95 deducted 8,211), 3.45-3.70 (m, 2H), 4.00-4.20 (m, 2H), 4.35 (s, 2H), 6.74 (br s, 1H), 7.38 (m, 1H), 7.49 (d, 1H, J = 6 Hz), 7.63 (m, 2H), 7.79 (d, 1H, J = 6 Hz), 7.82 ( m, 1H), 8.08 (s, 1H), 8.60 (m, 1H), 10.45 (br s, 1H), 10.98 (br s, 1H); MS (ESI APCI +) m / e 362 (M + H ) 'Example 72 4-"(3', 6'-Dihydro · 2,4'-bipyridylethylfluorenyl) amino 1 ethylbenzylformate Follow the procedure described in Example 61, using ethyl 4- [(Chloroethylamido) amino] benzoate substituted 2-chloro-N- (2,6-dimethylphenyl) acetamidine to provide the title compound (51 mg, 97% yield). iHNMRpOOMHz'DMSO-dd ά 1.35 (t, 3H, J = 7 Hz), 2.95 (br s, 2H), 3.45-3.70 (m, 2H), 4.00-4.20 (m, 2H), 4.22 (q, 2H, J = 7 Hz), 4.36 (s, 2H), 6.74 (br s, 1H), 7.38 (m, 1H), 7.62 (d, 1H, J = 6 Hz), 7.74 (d, 2H, J = 8 Hz ), 7.82 (m, 1H), 7.98 (d, 2H, J = 8 Hz), 8.60 (m, 1H), 10.40 (br s, 1H), 200404539 10.92 (br s? 1H); MS (ESI APCI +) m / e 366 (M + H) +. Example 73 N-``2- Carbo-5- (trifluoromethyl) benzyl l-2- (3,, 6, -dihydro · 2,4, · bipyridine-Γ (2Ή) -yl) Acetylamine is as described in Example 61 The procedure described is to replace 2-chloro-N- (2,6-dimethylphenyl) ethane with 2-chloro-N- [2-chloro-5- (trifluoromethyl) phenyl] acetamidamine Amidine, providing the title compound (18 mg, 32% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.95 (br s, 2H), 3.45-3.70 (m, 2H), 4.00-4.20 (m, 2H), 4.35 (s, 2H), 6.73 (br s5 1Η), 7.38 (m, 1H), 7.63 (m? 2H)? 7.82 (m, 2H), 8.22 (s? 1H)? 8.60 (m 1H)? 10.40 (br s? 1H)? 10.50 (br s5 1H); MS (ESI APCI +) m / e 396 (M + H) +. Example 74 N- (3-chloro-4-methylbenzene V2- (3 ', 6'-difluorene-2,4f-bipyridyl) acetamidinium was prepared according to the procedure described in Example 61 with 2-chloro-N- (3-chloro-4-methyl Phenyl) acetamide replaced 2-chloro-N- (2,6-dimethylphenyl) acetamide to provide the title compound (44 mg, 88% yield). 41 ^^ (3001 ^ 1 ^ 03 ^ 80- (16) (5 2.28 (3,311), 2.95 (br s5 2H), 3.45-3.75 (m, 2H), 4.00-4.20 (m, 2H), 4.30 (s , 2H), 6.73 (br s, 1H), 7.38 (m, 3Η), 7.63 (d, 1Η, J = 6 Ηζ), 7.80 (s, 1Η), 7.83 (m, 1Η) , 8.60 (m, 1Η), 10.38 (br s, 1H), 10.63 (br s, 1H); MS (ESI APCI +) m / e 342 (M + H) + · Example 75 y- (2-cyanobenzyl V2- (3 ', 6'-dihydro-2, bipyridine-1Η' (2Ήνyl) acetamidamine Follow the procedure described in Example 61, using 2-chloro-N- (2-cyanophenyl ) Acetamide to replace 2-Ga-N- (2,6-dimethylphenyl) acetamide, to provide the title compound (46 mg, 97% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.95 (br s, 2Η), 3.45-3.75 (m, 2H)? 4.00-4.20 (m9 2H)? 4.40 (s? 2H), 6.75 (br s? 1H)? 7.38 (m? 1H)? 7.42 (t 1H? 85228 -205- 200404539 J = 6 Hz), 7.63 (m, 2H), 7.78 (m, 1H), 7.83 (m, 1H), 7.88 (m, 1H), 8_60 (m, 1H) ,-10.42 (br s, 1H), 10.93 (br s, 1H); MS (ESI APCI +) m / e 319 (M + H) + · Example 76 迕 (3_Gabenzene dihydro-2,4f- Bipyridine-Γ (2Ή) -yl) acetamidinium was as described in Example 61 Procedure to replace 2-chloro-N- (2,6-dimethylphenyl) acetamide with 2-chloro-N- (3-chlorophenyl) acetamide to provide the title compound (42 mg, 86% Yield). 1H NMR (300 MHz, DMSO-d6) δ 2.95 (br s, 2Η), 3.45-3.75 (m, 2H), 4.00-4.20 (m, 2H), 4.34 (s, 2H), 6.75 (br s, 1H), 7.20 (d, 1H, J = 6 Hz), 7.38 φ (m, 1H), 7.42 (m, 2H), 7.63 (d, 1H, J = 6 Hz), 7.80 (s , 1H), 7.83 (m, 1H), 8.60 (m, 1H), 10.40 (br s, 1H), 10.80 (br s, 1H); MS (ESI APCI +) m / e 328 (M + H) +. Example 77 N- (3-Chloro-4_Gaben Tomb V2_ (3f, 6f-dihydro-2,4'-bipyridyl) acetamidine Follow the procedure described in Example 61, using 2- Chloro-N- (3-chloro-4-fluorophenyl) acetamide replaced 2-chloro-N- (2,6-dimethylphenyl) acetamide to provide the title compound (43 mg, 85% Yield). iHNMRpOOMHADMSO-ddSl ^ O ^ rsJHXS.AS · 3.75 (m, 2H), 4.00_4 · 20 (m, 2H), 4.38 (s, 2H), 6.73 (br s, 1H), 7.38 (m, 1H ), # 7.43 (m, 2H), 7.63 (d, 1H, J = 6 Hz), 7.83 (m, 1H), 7.92 (d, 1H, J = 5 Hz), 8.60 (m, 1H ), 10.38 (br s, 1H), 10.83 (br s, 1H); MS (ESI APCI +) m / e 346 (M + H) + · Example 78 2- (3 ', 6f-dihydro-2,4 '-Bipyridyl VN44- (trifluoromethylamino) benzyl 1 acetamidine Followed the procedure described in Example 61 with 2-chloro-N- [4- (trifluoromethoxy) phenyl] ethyl Amidine replaced 2-chloro-N- (2,6-dimethylphenyl) acetamidide to provide the title compound (44 mg, 81% yield). 1H NMR (300 MHz, DMSO-d6) 5 2.95 ( bi * s, 2H), 3.45_3.75 (m, 2H), 4.00-4.20 (m, 2H), 4.35 (s, 2H), 6.73 (br s, 1H), 7.38 (m, 1H), 85228 -206- 200404539 7.41 (d, 2H, J = 7 Ηζ), 7.63 (d, 1H, J = 6 Hz), 7.73 (d, 2H, J = 7 Hz), 7.84 ( m, 1H),-8.60 (m, 1H), 10.40 (br s, 1H), 10.80 (br s, 1H); MS (ESI APCI +) m / e 378 (M + H). · Example 79 2- ( 3 ', cardiodihydro-bipyridine-1' (2Ήν-based trifluoromethyl) Benzoamine was replaced with 2-chloro-N- [2- (trifluoromethyl) phenyl] acetamidin by the procedure described in Example 61. Methylphenyl) acetamidamine to provide the title compound (41 mg, 78% yield). IHNMRpOOMHADMSOO (5 2.95 (brs, 2H), φ 3.45-3.75 (m, 2Η), 4.00 pm 4.20 (m, 2Η), 4.35 (s, 2Η), 6.73 (br s, 1Η), 7.38 (m, 1Η), 7.50 · 7 · 70 (m5 3H), 7.80-7.90 (m, 3H), 8.60 (m, 1H), 10_40 (s5 1H), 10.43 (br s, 1H); MS (ESI APCI +) m / e 362 (M + H) +. Example 80 N- (4-chlorobenzyl V2- (3 ', 6 '_Dihydro-2,4'-bipyridyl) acetamide Following the procedure described in Example 61, 2-chloro-N- (4-chlorophenyl) acetamide was substituted for 2-chloro-N- (2,6-dimethylphenyl) acetamide, which provided the title compound (39 mg, 80% yield). 1H NMR (300 MHz, DMSO-d6) 6 2.95 (br s, 2H), 3.45-3.75 (m, 2H), 4.00-4.20 (m, 2H), 4.30 (s, 2H), 6.73 (br s, 1H), 7.38 (m, 1H), 7.44 (d, 2H, J = 7 Hz) 5 7.63 (m, 3H), 7.83 (m, 1H), 8.60 (m, 1H), 10.40 (br s, 1H), 10.63 (s, 1H); MS (ESI APCI +) m / e 328 (M + H) + · Example 81 N_ (2.3- 二 翕. ^: Some V2- (3 ', 6' -Dihydro_2,4f-bipyridine_r (2fHV group) acetamidinide Follow the procedure described in Example 61 to replace 2 with 2-chloro · N- (2,3-dichlorophenyl) acetamide -Chloro-N- (2,6-dimethylphenyl) acetamide, which provided the title compound (37 mg, 70% yield). 1H NMR (300 MHz, DMSO-d6) (5 2.95 (br s5 2Η ), 3.45-3.75

85228 -207- 200404539 (m5 2H)5 4.00-4.20 (m? 2H)? 4.40 (s? 2H)? 6.73 (br s? 1H)? 7.38 (m, 1H)5 7.42 (t? - 1H，J=7 Hz)，7.58 (d，1H，J=7 Hz)，7.64 (d，1H，J=7 Hz)，7.72 (d，1H，J=7 Hz)， 7.83 (m，1H)，8_60 (m，1H), 10.40 (s，1H), 10_43 (br s，1H) ; MS (ESI APCI+) m/e 363 (M+H)+. 實例82 N-G·5-二事.苯某V2-(3\6’-二氫_2,肛聯吡啶_1’(2Ή)-基）乙醯胺 按照實例61中所述之程序，以2-氯-Ν-(3,5-二氯苯基）乙醯胺 取代2-氯-Ν-(2,6-二甲基苯基）乙醯胺，提供標題化合物（31毫克 φ ，59% 產率）。1H NMR (300 MHz，DMSOd6) 5 2.95 (br s，2Η)，3.45-3.75 (m，2H)，4.00-4.20 (m，2H)，4·34 (s，2H)，6·73 (br s5 1H)，7.38 (m，1H)5 7.40 (s， 1H)，7·63 (m，3H)，7.83 (m，1H)，8.60 (m，1H)，10.40 (br s5 1H)，10.90 (s，1H) ；MS (ESI APCI+) m/e 363 (M+H)+. 實例83 2-(3’,6’-二氫_2,4’-聯吡啶_1丫2’印-基）-化(4-氟基-2_甲基苯基）乙醯胺 按照實例61中所述之程序，以2-氯-N-(4-氟基-2-甲基苯基）乙 醯胺取代2-氯-N-(2,6-二甲基苯基）乙醯胺，提供標題化合物（34 φ 毫克，70% 產率）。iHNMRpOOMHADMSO-ddc^JiHsdH)，〗％ (br s，2H)，3.43-3.63 (m，2H)，4.03-4.20 (m，2H)，4.39 (s，2H), 6·72 (br s，1H)， 7.10 (m，2H)，7.38 (m，1H)，7.43 (m，1H)，7.64 (d，1H，J=7 Hz)，7.84 (m，1H)， 8.60 (m，1H)，10.00 (m，1H)，10.40 (br s，1H); MS (ESI APCI+) m/e 326 (M+H)+ · 實例84 N-(4_氟笨基）-2-「4-(2·吡啶基Μ·六氫吡啶基1乙醯胺 按照實例45中所述之程序，以2-氯-Ν-(4-氟苯基）乙醯胺取代 Ν-(4-溴苯基&gt;2-氯乙醯胺，提供標題化合物（57.5毫克，59%產85228 -207- 200404539 (m5 2H) 5 4.00-4.20 (m? 2H)? 4.40 (s? 2H)? 6.73 (br s? 1H)? 7.38 (m, 1H) 5 7.42 (t?-1H, J = 7 Hz), 7.58 (d, 1H, J = 7 Hz), 7.64 (d, 1H, J = 7 Hz), 7.72 (d, 1H, J = 7 Hz), 7.83 (m, 1H), 8_60 (m , 1H), 10.40 (s, 1H), 10_43 (br s, 1H); MS (ESI APCI +) m / e 363 (M + H) +. Example 82 NG · 5-Two things. Benzene V2- (3 \ 6'-Dihydro_2, anthrapyridine_1 '(2Ή) -yl) acetamidin. Follow the procedure described in Example 61, using 2-chloro-N- (3,5-dichlorophenyl) Acetamide replaced 2-chloro-N- (2,6-dimethylphenyl) acetamide to provide the title compound (31 mgφ, 59% yield). 1H NMR (300 MHz, DMSOd6) 5 2.95 (br s, 2Η), 3.45-3.75 (m, 2H), 4.00-4.20 (m, 2H), 4.34 (s, 2H), 6.73 (br s5 1H), 7.38 (m, 1H) 5 7.40 (s, 1H), 7.63 (m, 3H), 7.83 (m, 1H), 8.60 (m, 1H), 10.40 (br s5 1H), 10.90 (s , 1H); MS (ESI APCI +) m / e 363 (M + H) +. Example 83 2- (3 ', 6'-dihydro_2,4'-bipyridine_1γ2'in-yl) -(4-Fluoro-2-methylphenyl) ethanamine Following the procedure described in Example 61, 2-chloro-N- (4-fluoro-2-methylphenyl) ethanamine was used Substitution of 2-chloro-N- (2,6-dimethylphenyl) acetamidine provided the title compound (34 φ mg, 70% yield). iHNMRpOOMHADMSO-ddc ^ JiHsdH),% (br s, 2H), 3.43-3.63 (m, 2H), 4.03-4.20 (m, 2H), 4.39 (s, 2H), 6.72 (br s, 1H) , 7.10 (m, 2H), 7.38 (m, 1H), 7.43 (m, 1H), 7.64 (d, 1H, J = 7 Hz), 7.84 (m, 1H), 8.60 (m, 1H), 10.00 ( m, 1H), 10.40 (br s, 1H); MS (ESI APCI +) m / e 326 (M + H) + · Example 84 N- (4_fluorobenzyl) -2- "4- (2 · pyridine M. hexahydropyridyl 1 acetamidine Follow the procedure described in Example 45 to replace N- (4-bromophenyl) with 2-chloro-N- (4-fluorophenyl) acetamide. 2- Chlorhexidine, providing the title compound (57.5 mg, 59% yield

85228 -208 - 200404539 率）。1H NMR (500 MHz，DMSO-d6) 5 2.15 (m，4H)，3.01 (m，1H)，3.26 (m， - 2H)，3.65 (m，2H)，4.18 (s，2H)，7_22 (m，2H)，7.35 (m，2H)，7.58 (m，2H)，7·82 (m，1H)，8.60 (m，1H)，9.95 (br s，1H)，10.65 (br s，1H) ； MS (ESIAPCI+) m/e314(M+H)+. 實例85 N-(3,5-二氯笨基）-244-(2-吡啶基）-1-六氫吡啶基1乙醯胺 按照實例45中所述之程序，以2-氯-N-(4-氟苯基）乙醯胺取代 N-(4-&gt;臭苯基）-2-氯乙縫胺’提供標題化合物（18.5毫克，39%產 率）。1H NMR (500 MHz，DMSO-d6) 5 1 ·85 (m，2H)，1.95 (m，2H)，2.25 (m， 2H)，2.68 (m，1H)，2.95 (m，2H)，3·20 (s，2H)，7.20 (m，1H)，7.30 (m，2H)，7.75 (m，2H)，7·82 (s，2HX 8.52 (s5 1H)，10.05 (br s5 1H) ； MS (ESI APCI+) m/e 365 (M+H)+. 實例86 N-(2,3-二氯苯基）-2-「4·(2-ρ比淀基）-1-六氮？比淀基1乙酸胺 按照實例45中所述之程序，以2-氣-Ν·(2,3-二氯苯基）乙醯胺 取代Ν-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（18毫克，38 # % 產率）。iHNMRpOOMHz’DMSO-c^) ά 1.90(m，4H)，2.42(m，2H)， 2.75 (m，1H)，3.05 (m，2H)，3.28 (s，2H)，7.22 (t，1H，J=3 Hz)，7.30 (d，1H，J= 3 Hz)，7_42 (m，3H)，7.75 (t，1H，J=3 Hz)，8.25 (s，1H)，8.50 (s，1H)，10.18 (br s， 1H) ； MS (ESI APCI+) m/e 365 (M+H)+. 實例87 244-(2-吡啶某VI-六氫吡啶基三顧，甲基）笨基1乙醯胺 按照實例45中所述之程序，以2-氣-Ν-[2·(三氟甲基）苯基]乙 醯胺取代Ν-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（22毫克 85228 -209- 200404539 ，46% 產率）。iHNMRpOOMHADMSOO 5 1.85(m，4H)，2.41 (m， - 2H)，2.72 (m，1H)，3.01 (m，2H)，3.20 (s，2H)，7·22 (t，1H，J=3 Hz)，7·30 (d，1Η， J=3 Hz)，7·38 (m，1H)，7.72 (m，4H)，8.25 (br s，1H)，8·50 (s，1H)，9.98 (br s，1H) ；MS (ESI APCI+) m/e 364 (M+H)+. 實例88 N_(3_氯基-4-氟笨墓V2-「4-(2-吡啶基）-1-六氫吡啶基1乙醯胺 按照實例45中所述之程序，以2-氯-N-(3-氯基-4-氟苯基）乙醯 胺取代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（19毫克，43 φ % 產率）。1H NMR (500 MHz，DMSO-d6) 5 1.95 (m，4H)，2.41 (m，2H)， 2·72 (m，1H)，3.01 (m，2H)，3·20 (s，2H)，7·25 (t，1H，J=3 Hz)，7·30 (d，1H， 3 Hz)，7.40 (t，1H，J=3 Hz)，7.55 (s，1H)，7.75 (t，1H，J=3 Hz)，7.95 (t，1H，J=3 Hz)，8.45 (s，1H)，9.90 (br s，1H)，10.35 (br s，1H) ; MS (ESI APCI+) m/e 348 (M+H)' 實例89 2-14-(2-吡啶基）-1-六氫吡啶某i-N-「4—(三氟甲氣基）笨基i乙醯胺 按照實例45中所述之程序，以2_氯_N-[4_(三氟甲氧基）苯基]_ 乙醯胺取代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（21毫 克，43% 產率）。1H NMR (500 MHz，DMSO-d6) 61.91 (m，4H)，2·41 (m， 2H)，2.65 (m，lH)，3.05 (m，2H)，3.20 (s，2H)，7.12 (m，1Η)，7.25 (m，3Η)，7·85 (m，4H)，8.50 (s，1H)，9.90 (br s，1Η) ; MS (ESI APCI+) m/e 380 (M+H)+ · 實例90 攻_環己基-2-(3’,4’,5’,6’-四氤_2，11-「2.4，1聯吡啶基-1，-基）乙醯胺 按照實例45中所述之程序，以2-氯-N-環己基乙醯胺取代N-(4-溴苯基）-2-氯乙醯胺，提供標題化合物（49毫克，53%產率）。85228 -208-200404539 rate). 1H NMR (500 MHz, DMSO-d6) 5 2.15 (m, 4H), 3.01 (m, 1H), 3.26 (m,-2H), 3.65 (m, 2H), 4.18 (s, 2H), 7_22 (m , 2H), 7.35 (m, 2H), 7.58 (m, 2H), 7.82 (m, 1H), 8.60 (m, 1H), 9.95 (br s, 1H), 10.65 (br s, 1H); MS (ESIAPCI +) m / e314 (M + H) +. Example 85 N- (3,5-dichlorobenzyl) -244- (2-pyridyl) -1-hexahydropyridyl 1 acetamidine according to example The procedure described in 45, substituting N- (4- &gt; styphenyl) -2-chloroethanamide 'with 2-chloro-N- (4-fluorophenyl) acetamidine provided the title compound (18.5 mg , 39% yield). 1H NMR (500 MHz, DMSO-d6) 5 1 · 85 (m, 2H), 1.95 (m, 2H), 2.25 (m, 2H), 2.68 (m, 1H), 2.95 (m, 2H), 3. · 20 (s, 2H), 7.20 (m, 1H), 7.30 (m, 2H), 7.75 (m, 2H), 7.82 (s, 2HX 8.52 (s5 1H), 10.05 (br s5 1H); MS ( ESI APCI +) m / e 365 (M + H) +. Example 86 N- (2,3-dichlorophenyl) -2- "4 · (2-ρbidianyl) -1-hexazine? Bidian Substituted 1-amine acetic acid according to the procedure described in Example 45, replacing N- (4-bromophenyl) -2-chloroacetamidamine with 2-gas-N · (2,3-dichlorophenyl) acetamide Provide the title compound (18 mg, 38 #% yield). IHNMRpOOMHz'DMSO-c ^) ά 1.90 (m, 4H), 2.42 (m, 2H), 2.75 (m, 1H), 3.05 (m, 2H) , 3.28 (s, 2H), 7.22 (t, 1H, J = 3 Hz), 7.30 (d, 1H, J = 3 Hz), 7_42 (m, 3H), 7.75 (t, 1H, J = 3 Hz) , 8.25 (s, 1H), 8.50 (s, 1H), 10.18 (br s, 1H); MS (ESI APCI +) m / e 365 (M + H) +. Example 87 244- (2-pyridine VI- Hexahydropyridyl tripeptide, methyl) benzyl 1 acetamidinium. Follow the procedure described in Example 45, substituting 2-amino-N- [2. (trifluoromethyl) phenyl] acetamide for N- ( 4-bromophenyl) -2-chloroethyl Amidine to provide the title compound (22 mg 85228-209-200404539, 46% yield). IHNMRpOOMHADMSOO 5 1.85 (m, 4H), 2.41 (m,-2H), 2.72 (m, 1H), 3.01 (m, 2H) ), 3.20 (s, 2H), 7.22 (t, 1H, J = 3 Hz), 7.30 (d, 1Η, J = 3 Hz), 7.38 (m, 1H), 7.72 (m, 4H), 8.25 (br s, 1H), 8.50 (s, 1H), 9.98 (br s, 1H); MS (ESI APCI +) m / e 364 (M + H) +. Example 88 N_ (3_ Chloro-4-fluorobenzyl V2- "4- (2-pyridyl) -1-hexahydropyridyl 1 acetamidine Follow the procedure described in Example 45 using 2-chloro-N- (3-chloro Substituted N- (4-bromophenyl) -2-chloroacetamidinyl with 4-fluorophenyl) ethanilamide to provide the title compound (19 mg, 43 φ% yield). 1H NMR (500 MHz, DMSO-d6) 5 1.95 (m, 4H), 2.41 (m, 2H), 2.72 (m, 1H), 3.01 (m, 2H), 3.20 (s, 2H), 7.25 (t, 1H, J = 3 Hz), 7.30 (d, 1H, 3 Hz), 7.40 (t, 1H, J = 3 Hz), 7.55 (s, 1H), 7.75 (t, 1H , J = 3 Hz), 7.95 (t, 1H, J = 3 Hz), 8.45 (s, 1H), 9.90 (br s, 1H), 10.35 (br s, 1H); MS (ESI APCI +) m / e 348 (M + H) 'Example 89 2-14- (2-pyridyl) -1-hexahydropyridine iN- "4- (trifluoromethylamino) benzyl i acetamide as described in Example 45 Procedure to replace N- (4-bromophenyl) -2-chloroacetamidine with 2-chloro_N- [4_ (trifluoromethoxy) phenyl] _acetamidine to provide the title compound (21 mg , 43% yield). 1H NMR (500 MHz, DMSO-d6) 61.91 (m, 4H), 2.41 (m, 2H), 2.65 (m, 1H), 3.05 (m, 2H), 3.20 (s , 2H), 7.12 (m, 1Η), 7.25 (m, 3Η), 7.85 (m, 4H), 8.50 (s, 1H), 9.90 (br s, 1Η); MS (ESI APCI +) m / e 380 (M + H) + · Example 90 Attack_cyclohexyl-2- (3 ', 4', 5 ', 6'-tetrafluorene_2,11- "2.4,1 bipyridyl-1, -yl) Acetylamine followed the procedure described in Example 45 using 2-chloro-N-cyclohexyl As acetamide substituted N- (4- bromophenyl) -2-chloro-acetyl-amine to provide the title compound (49 mg, 53% yield).

85228 -210- 200404539 1H NMR (500 MHz，DMSO-d6) 3 1.10-1.35 (m，6H)，1·55 (m，1H)，1.70 (m， · 2H)，1·79 (m，2H)，2.08 (m，4H)，2.98 (m，1H)，3.18 (m，2H)，3.68 (m，2H)，3.88 (s，2H)，7.38 (m，2H)，7.82 (t，1H，J=4 Hz)，8.45 (d，1H，J=4 Hz)，8.58 (d，1H， 3 Hz)，9.70 (br s，1H) ; MS (ESI APCI+) m/e 302 (M+H)+ · 實例91 N-{「4-(2-氰基苯基）-1-六氳比p井基1甲基}-3-甲基苯甲酸胺85228 -210- 200404539 1H NMR (500 MHz, DMSO-d6) 3 1.10-1.35 (m, 6H), 1.55 (m, 1H), 1.70 (m, · 2H), 1.79 (m, 2H) , 2.08 (m, 4H), 2.98 (m, 1H), 3.18 (m, 2H), 3.68 (m, 2H), 3.88 (s, 2H), 7.38 (m, 2H), 7.82 (t, 1H, J = 4 Hz), 8.45 (d, 1H, J = 4 Hz), 8.58 (d, 1H, 3 Hz), 9.70 (br s, 1H); MS (ESI APCI +) m / e 302 (M + H) + · Example 91 N-{"4- (2-Cyanophenyl) -1-hexamidine p-pyryl 1methyl} -3-methylbenzoate

實例91A 赌酸[(3-甲基笨甲醯基）胺某1甲酯 ·Example 91A Glyceric acid [(3-methylbenzylidene) amine 1 methyl ester ·

將N-(3-甲基苯甲醯基）甘胺酸（1〇克，51.7毫莫耳）、四醋酸 鉛（25.25克，56.94毫莫耳）及醋酸銅⑼單水合物（〇·94克，5.17 毫莫耳）在甲苯中合併，並於回流下加熱過夜。使反應混合 物冷卻至室溫，經過矽藻土過漉，並使濾液在減壓下濃縮 。使殘留物於矽膠上藉急騾式管柱層析純化（以25%醋酸乙 酯/己烷溶離），提供標題化合物（7.95克，74%產率）。1H NMR (300 MHz，CDC13) 5 2.10 (s，3Η)，2_40 (s，3Η)，5.45 (d5 2Η，J=9 Ηζ)，7.35 (m， 2H)，7.55 (m，1H)，7.62 (s，1H) ; MS (DCI/NH3) m/e 208 (M+H)+ · _N- (3-methylbenzyl) glycine (10 g, 51.7 mmol), lead tetraacetate (25.25 g, 56.94 mmol) and copper acetate monohydrate (0.94 g (5.17 mmol), combined in toluene and heated under reflux overnight. The reaction mixture was allowed to cool to room temperature, passed through celite, and the filtrate was concentrated under reduced pressure. The residue was purified on silica gel by flash column chromatography (isolated with 25% ethyl acetate / hexane) to provide the title compound (7.95 g, 74% yield). 1H NMR (300 MHz, CDC13) 5 2.10 (s, 3Η), 2_40 (s, 3Η), 5.45 (d5 2Η, J = 9 Ηζ), 7.35 (m, 2H), 7.55 (m, 1H), 7.62 ( s, 1H); MS (DCI / NH3) m / e 208 (M + H) + · _

實例91B Μ·4-(2-氰基苯基）六氫吡畊-1-基甲某甲基笨甲醯胺 將得自實例91A之產物（4.00克，19.2毫莫耳）、1-(2-氰基苯 基）六氫外I：畊（3.6克，19.2毫莫耳）及三乙胺（5.3毫升，38·4毫莫 耳）在乙腈（100毫升）中合併，並於室溫下攪拌過夜。使反應 混合物在減壓下濃縮，並使殘留物於矽膠上藉急驟式管柱 層析純化（以醋酸乙酯溶離），提供標題化合物，為無色油（2·85 克 ’ 44% 產率）。1H NMR (3〇〇 MHz，CDC13) 5 2.40 (s，3Η)，2_90 (m，4Η)， 85228 -211- 200404539 3.25 (m，4H)，4.45 (d，2H，J=6 Hz)，6.66 (br s，1H)，7_0 (m，2H)，7·35 (m，2H)， 7.48 (m，1H)，7.55 (m，2H)，7.58 (s，1H) ; MS (DCI/NH3 ) m/e 335 (M+H)+ · 順丁烯二酸鹽：熔點 131-133°C ;對 C24H26N405 . 0.30H20 之分 析計算值：C，63·23 ; H，5.88 ; N，12.29.實測值：C，63.04 ; H，5.74 ;N，12.05· 實例92 3-甲基-N]「4-(2-嘧啶基VI-六氫吡畊基1甲基}笨甲醯胺 按照實例91B中所述之程序，以1-(2-嘧啶基）六氫吡畊取代1- _ (2-氰基苯基）六氫吡畊，提供標題化合物，為無色油。1HNMR (300 MHz，CDC13) 5 2.40 (s，3H)，2.75 (m，4H)，3.88 (m，4H)，4.44 (d，2H，J= 6 Hz)，6.50 (t，1H，J=4.5 Hz)，6.7 (br s，1H)，7.32 (d，2H，J=6 Hz)，7.55 (m，1H)， 7.65 (s，1H)，8.30 (d，2H，J=6 Hz) ; MS (DCI/NH3) m/e 312 (M+H)+ ·順丁 烯-二酸鹽：獲得為白色粉末（0.31克）；熔點163-165°C ;對 C2iH25N505之分析計算值：C，:59.01 ; Η，5·90 ; N，16.38.實測值 :C，59·05 ; Η，5.93 ; Ν，16.31· 實例93 · 3-甲基峨淀基VI-六氫？比ρ井基1甲某}笨甲驗胺 按照實例91Β中所述之程序，以1-(2-吡啶基）六氫峨畊取代1-(2-氣基苯基氯峨p井’提供標題化合物，為灰白色殘留物。 1H NMR (300 MHz，CDC13) 5 2.40 (s，3H)，2.75 (m5 4H)，3.60 (m，4H)，4.40 (d，2H，J=6 Hz)，6·58 (br s，1H)，6·65 (m，2H)，7·32 (d，2H，J=6 Hz)，7.40-7.55 (m，2H)，7.55 (s5 1H)，8.2 (m，1H) ; MS (DCI/NH3) m/e 311 (M+H)+ ;順丁 烯二酸鹽：灰白色固體；熔點141-143°C ;對(：2211261\[405之分 析計算值：C，61.96 ; H，6.15; N，13.14.實測值：C，61.78 ; Η，6·08 85228 -212- 200404539 ;Ν，13·09· 實例94 3-甲基-Ν-ΙΥ4-苯基-1-六氫吡畊基）甲某1苯甲醯胺 按照實例91Β中所述之程序，以1_苯基六氫吡畊取代1-(2-氰 基苯基）六氫吡畊，提供標題化合物，為無色油。iHNMR(300 MHz，CDC13) 5 2.40 (s，3H)，2·82 (m，4H)，3.21 (m5 4H)，4.44 (d，2H，J=6 Hz)， 6.60 (br s，1H)，6.82-6.95 (m，3H)，7·20 (m，2H)，7.35 (d，2H，J=6 Hz)，7.58 (m， 1H)7.63(s，1H); MS(DCI/NH3)m/e310(M+H)+ ;順丁晞二酸鹽： 獲得為灰白色粉末；熔點145_147°C ;對C23H27N305之分析計 算值：C，64.93 ; Η，6·40 ; N，9.88.實測值：C，6屯83 ; H，6.38 ; N，9.89· 實例95 Μ_-_{[4-(2•甲氧苯基Η-六氫吡畊基1甲基丨-3-甲某笨甲醯胺 實例95Α 醋酸「(3-氯基笨甲醯基）胺某1甲酯 按照實例91Α中所述之程序，以Ν-(3-氯基苯甲醯基）甘胺酸 取代Ν-(3-甲基苯甲醯基）甘胺酸，提供標題化合物。 修 實例95Β Μ-{「4-(2-甲氣笨基VI-六氫峨喷基1甲基丨_3-甲基苯甲酸胺 按照實例91Β中所述之程序，以得自實例95Α之產物取代 得自實例91Α之產物，並以1-(2-甲氧苯基）六氫吡畊取代1-(2-氰基苯基）六氫吡畊，提供標題化合物（1.95克）。iHNMR (300 MHz，CDC13) 5 2.90 (m，4H)，3.15 (m，4H)，3.85 (s，3H)，4.45 (d，2H，J= 6 Hz)，6·55 (bi· s，1H)，6.84 (d，1H，J=7.5 Hz)，6.9-7.15 (m，3H)，7.40 (t，1H，J= 7.5 Hz)，7.5 (m，1H)，7.68 (m，1H) 7.8 (t，1H，J=3 Hz) ； MS (DCI/NH3) m/e 85228 -213- 200404539 360 (M+H)+ ;順丁稀二酸鹽：褐色粉末；溶點i39_i42°C ;對 C2 3 H26C1N306之分析計算值：C，57.61 ; Η, 5·55 ; ν，8·76·實測值 :C，57.26 ; Η，5.65 ; Ν，8.69. 實例96 Ν-{[4-(2-氰基苯基）-1-六氫ρ比ρ井基1甲基丨_2-甲_^苯甲酸胺Example 91B M · 4- (2-cyanophenyl) hexahydropyrine-1-ylformamethylbenzidine. The product obtained from Example 91A (4.00 g, 19.2 mmol), 1- ( 2-cyanophenyl) hexahydrogen I: Teng (3.6 g, 19.2 mmol) and triethylamine (5.3 ml, 38.4 mmol) were combined in acetonitrile (100 ml) and allowed to stand at room temperature Stir overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica gel (isolated with ethyl acetate) to provide the title compound as a colorless oil (2.85 g '44% yield) . 1H NMR (300MHz, CDC13) 5 2.40 (s, 3Η), 2_90 (m, 4Η), 85228 -211- 200404539 3.25 (m, 4H), 4.45 (d, 2H, J = 6 Hz), 6.66 (br s, 1H), 7_0 (m, 2H), 7.35 (m, 2H), 7.48 (m, 1H), 7.55 (m, 2H), 7.58 (s, 1H); MS (DCI / NH3) m / e 335 (M + H) + · Maleic acid: Melting point 131-133 ° C; Analytical calculated value for C24H26N405. 0.30H20: C, 63 · 23; H, 5.88; N, 12.29. Measured Values: C, 63.04; H, 5.74; N, 12.05. Example 92 3-methyl-N] "4- (2-pyrimidinyl VI-hexahydropyridyl 1methyl} benzimidamine according to Example 91B The procedure described replaces 1- (2-cyanophenyl) hexahydropyridine with 1- (2-pyrimidinyl) hexahydropyridine to provide the title compound as a colorless oil. 1HNMR (300 MHz, CDC13) 5 2.40 (s, 3H), 2.75 (m, 4H), 3.88 (m, 4H), 4.44 (d, 2H, J = 6 Hz), 6.50 (t, 1H, J = 4.5 Hz), 6.7 (br s , 1H), 7.32 (d, 2H, J = 6 Hz), 7.55 (m, 1H), 7.65 (s, 1H), 8.30 (d, 2H, J = 6 Hz); MS (DCI / NH3) m / e 312 (M + H) + · maleic acid-di-acid salt: obtained as a white powder (0.31 g); melting point 163-165 ° C; for C2iH2 Analytical calculation value for 5N505: C ,: 59.01; Hf, 5.90; N, 16.38. Found: C, 59.05; H, 5.93; N, 16.31. Example 93. Hexahydro? Phenyl 1 methyl} Benzylmethanamine Substituted 1- (2-pyridyl) hexahydroepigenol for 1- (2-aminophenylchloropyronyl) according to the procedure described in Example 91B. Well 'provided the title compound as an off-white residue. 1H NMR (300 MHz, CDC13) 5 2.40 (s, 3H), 2.75 (m5 4H), 3.60 (m, 4H), 4.40 (d, 2H, J = 6 Hz ), 6.58 (br s, 1H), 6.65 (m, 2H), 7.32 (d, 2H, J = 6 Hz), 7.40-7.55 (m, 2H), 7.55 (s5 1H), 8.2 (m, 1H); MS (DCI / NH3) m / e 311 (M + H) +; maleic acid salt: off-white solid; melting point 141-143 ° C; analysis of (: 2211261 \ [405 Calculated: C, 61.96; H, 6.15; N, 13.14. Found: C, 61.78; H, 6.08 85228 -212- 200404539; N, 13.09. Example 94 3-methyl-N-Ι-4- Phenyl-1-hexahydropyridyl) methyl-1 benzamidine Follow the procedure described in Example 91B to replace 1- (2-cyanophenyl) hexahydropyridine with 1-phenylhexahydropyridine Till, provide the title compound as a colorless oil. iHNMR (300 MHz, CDC13) 5 2.40 (s, 3H), 2.82 (m, 4H), 3.21 (m5 4H), 4.44 (d, 2H, J = 6 Hz), 6.60 (br s, 1H), 6.82-6.95 (m, 3H), 7.20 (m, 2H), 7.35 (d, 2H, J = 6 Hz), 7.58 (m, 1H) 7.63 (s, 1H); MS (DCI / NH3) m / e310 (M + H) +; Maleic acid: Obtained as an off-white powder; Melting point 145-147 ° C; Analytical calculated value for C23H27N305: C, 64.93; Rhenium, 6.40; N, 9.88. Measured value: C, 6 Tun 83; H, 6.38; N, 9.89 · Example 95 Μ _-_ {[4- (2 • methoxyphenylhydrazone-hexahydropyridyl 1methyl 丨 -3-methylbenzidine Example 95A "(3-Chlorobenzylidene) amine 1 methyl ester Follow the procedure described in Example 91A to replace N- (3-chlorobenzylidene) glycine with N- (3- Methylbenzyl) glycinate to provide the title compound. Modified Example 95B M-{"4- (2-methylbenzyl VI-hexahydroepentyl 1methyl 丨 3-methylbenzoate amine Following the procedure described in Example 91B, the product from Example 95A was replaced with the product from Example 91A and the 1- (2-cyanophenyl) was replaced with 1- (2-methoxyphenyl) hexahydropyrine. ) Hydroxypyrine, providing the title compound (1 .95 g). IHNMR (300 MHz, CDC13) 5 2.90 (m, 4H), 3.15 (m, 4H), 3.85 (s, 3H), 4.45 (d, 2H, J = 6 Hz), 6.55 ( bi · s, 1H), 6.84 (d, 1H, J = 7.5 Hz), 6.9-7.15 (m, 3H), 7.40 (t, 1H, J = 7.5 Hz), 7.5 (m, 1H), 7.68 (m , 1H) 7.8 (t, 1H, J = 3 Hz); MS (DCI / NH3) m / e 85228 -213- 200404539 360 (M + H) +; maleic acid salt: brown powder; melting point i39_i42 ° C; Analytical calculated value for C2 3 H26C1N306: C, 57.61; Η, 5.55; ν, 8.76. Found: C, 57.26; Η, 5.65; Ν, 8.69. Example 96 Ν-{[4 -(2-cyanophenyl) -1-hexahydroρ ratio ρ Wellyl 1methyl 丨 _2-methyl_ ^ benzoic acid amine

實例96A 醋酸Γ(2-甲基苯甲醯基）胺某1甲酿^ 按照實例91Α中所述之程序，以Ν-(2-甲基苯甲醯基）甘胺酸 取代N-(3-甲基苯甲酸基）甘胺酸，提供標題化合物。Example 96A Γ (2-methylbenzylidene) amine acetate 1 methyl ^ Following the procedure described in Example 91A, N- (2-methylbenzylidene) glycine was substituted for N- (3 -Methylbenzoate) glycine, to provide the title compound.

實例96B N-{「4-(2-氯基笨基）-1-穴氫？比p井基1甲基丨-2-甲基笨甲醯胺 按照實例91B中所述之程序，以得自實例96A之產物取代 得自實例91A之產物，提供標題化合物，為灰白色粉末。 1H NMR (300 MHz，CDC13) 5 2.50 (s，3H)，2.90 (t，4H，J=6 Ηζ)，3·25 (t，4H， J=6 Hz)，4.45 (d，2H，J=6 Hz)，6·18 (br s，1H)，7.0 (m，2H)，7·20_7·60 (m，6H); MS (DCI/NH3) m/e 335 (M+H)+ ;順丁晞二酸鹽：黃色粉末；熔點 62-64°C ;對 C24H26N405 ·0·20Η2Ο 之分析計算值·· C，63.48; h，5.86 ;Ν，12·34·實測值：C，63·19 ; H，5.77 ; N，11.97. 405145 f 例 97 !SMI~4-(2-氰基苯基H_六氫吡畊基1甲基丨_4-甲某苯甲醯胺Example 96B N-{"4- (2-Chlorobenzyl) -1-hole hydrogen? Than p-Ilmethyl 1-methyl-2-methylbenzidine, according to the procedure described in Example 91B, to obtain The product from Example 96A replaced the product from Example 91A to provide the title compound as an off-white powder. 1H NMR (300 MHz, CDC13) 5 2.50 (s, 3H), 2.90 (t, 4H, J = 6 Ηζ), 3 · 25 (t, 4H, J = 6 Hz), 4.45 (d, 2H, J = 6 Hz), 6.18 (br s, 1H), 7.0 (m, 2H), 7.20_7 · 60 (m, 6H); MS (DCI / NH3) m / e 335 (M + H) +; maleic acid: yellow powder; melting point 62-64 ° C; calculated for C24H26N405 · 0 · 20Η2〇 · C , 63.48; h, 5.86; N, 12.34. Found: C, 63 · 19; H, 5.77; N, 11.97. 405145 f Example 97! SMI ~ 4- (2-cyanophenyl H_hexahydro Pyridyl 1methyl 丨 _4-methylbenzidine

實例97A 醋酸ΙΪ4-甲基苯甲醯基）胺基1甲酯 按照實例91A中所述之程序，以N-(4-甲基苯甲醯基）甘胺酸 取代N-(3-甲基苯甲醯基）甘胺酸，提供標題化合物。 85228 -214- 200404539 實例97B - N-{「4_r2_f ·甚苯某vi-六氫吡畊基1甲某}冰甲基笨甲醯胺 按照實例91B中所述之程序，以得自實例97A之產物取代 得自實例91A之產物，提供標題化合物，為無色油。iHNMR (300 MHz, CDC13) δ 2.45 (s，3Η)，2.9 (t，4Η，J=6 Ηζ)，3·25 (t，4Η，J=6 Ηζ)， 4.45 (d，2H，J=6 Hz)，6.60 (br s，1H)，7.0 (m，2H)，7·25 (m，2H)，7.45-7.60 (m， 2H)，7.7 (d，2H，J=9 Hz) ; MS (DCI/NH3) m/e 335 (M+H)+ ;順丁 烯二酸 鹽：褐色粉末；對C24H26N4〇5之分析計算值：c，63.99; H，5.82 φ ;Ν，12.44.實測值：C，63.71 ; Η，5·78; Ν，12.18. 實例98 Ν_{「4_(3-氰某-2-吡啶基Η-六氫吡畊基1甲基卜3-甲基笨甲醯脖 按照實例91Β中所述之程序，以1-(2-氰基吡啶基）六氫吡畊 取代1-(2-氰基苯基）六氫吡畊，提供標題化合物，為褐色油。 1H NMR (300 MHz, CHC13) 5 2.40 (s? 3H)? 2.80 (t5 4H? J=6 Hz)? 3.75 (t5 4H? J=6 Hz)，4.40 (d，2H，J=6 Hz)，6.55 (br s，1H)，6_75 (dd，1H，J=12, 6 Hz)，7.32 (d，2H，J=6 Hz)，7.52-7.65 (m，2H)，7.75 (dd，1H，J=7.5, 3 Hz)，8.33 (dd，1H，# 6, 3 Hz) ; MS (DCI/NH3) m/e 336 (M+H)+ ;順丁晞二酸鹽：淡黃色 粉末；熔點128_130°C ;對C23H25N505之分析計算值：c，61.19 ;Η，5·58 ; N，15.51.實測值：C，61.46 ; H，5.57 ; N，15.57. 實例99 N-{f4-(3-氰基笨基Μ-六氫吡畊某1甲基卜3-甲基笨甲醯胺 按照實例91B中所述之程序，以1-(3-氰基苯基）六氫吡畊取 代1-(2-氰基苯基）六氫吡畊，提供標題化合物，為玻璃態固體 。iHNMRpOOMHACDC^) 5 2.40(s，3H)，2.80(t，4H，J=6Hz)，3.25(t， 85228 -215- 200404539 4H，J=6 Hz)，4.40 (d，2H，J=6 Hz)，6·50 (br s，1H)，7_1 (m，3H)，7·35 (m，3H)， 7.55-7.70 (m，2H) ; MS (DCI/NH3) m/e 335 (M+H)+ ;順丁晞二酸鹽： 灰白色粉末。溶點59-61°C ;對C24H26N405之分析計算值：c，63.99 ;H，5_82 ; N，12.44.實測值：C，63.76 ; Η，5·75 ; N，12.17. 實例100 Ν-{「4-(3-氰基苯基）小六氫吡畊基）甲基丨-2-甲基苯甲醯胺 按照實例91Β中所述之程序，以得自實例96Α之產物取代 得自實例91Α之產物，並以1-(3-氰基苯基）六氫吡畊取代1-(2-氰基苯基）六氫吡畊，提供標題化合物。iHNMRpOO MHz，CDC13) 5 2.48 (s，3H)，2·85 (t，4H，J=6 Hz)，3.25 (t，4H，J=6 Ηζ)，4·4 (d，2H，J=6 Hz)， 6.18 (br s，1H)，7.10 (m，3H)，7.22 (m5 2H)，7.30-7.45 (m，3H); MS (DCI/NH3) m/e 335 (M+H)+ ;順丁晞二酸鹽：灰白色粉末；熔點156-159°C ;對 C24H26N405 之分析計算值：C，63.99 ; H，5_82 ; N，12.44.實 測值：C，63.79 ; Η，5·67 ; Ν，12·29· 實例101 N-{[4-G-教某-2-吡啶基Η-六氫吡畊某1甲某丨苯甲醯胺 實例101Α 酸（笨甲醯胺某）甲酯 按照實例91A中所述之程序，以N-(苯甲醯基）甘胺酸取代N-(3-甲基苯甲醯基）甘胺酸，提供標題化合物。Example 97A N- (4-methylbenzyl) glycinate was replaced with N- (4-methylbenzyl) glycinate according to the procedure described in Example 91A. Benzamidine) glycine, to provide the title compound. 85228 -214- 200404539 Example 97B-N-{"4_r2_f · Benzene vi-Hydroxypyryl 1methyl} Ice methyl benzamidine Follow the procedure described in Example 91B to obtain from Example 97A The product replaced the product obtained from Example 91A to provide the title compound as a colorless oil. IHNMR (300 MHz, CDC13) δ 2.45 (s, 3Η), 2.9 (t, 4Η, J = 6 Ηζ), 3.25 (t, 4Η, J = 6 Ηζ), 4.45 (d, 2H, J = 6 Hz), 6.60 (br s, 1H), 7.0 (m, 2H), 7.25 (m, 2H), 7.45-7.60 (m, 2H), 7.7 (d, 2H, J = 9 Hz); MS (DCI / NH3) m / e 335 (M + H) +; maleic acid salt: brown powder; analytically calculated value for C24H26N405 : C, 63.99; H, 5.82 φ; N, 12.44. Found: C, 63.71; Η, 5.78; Ν, 12.18. Example 98 Ν _ {"4_ (3-cyano-2-pyridinylfluorene-hexa Hydroxypyridyl 1methyl 3-methylbenzyl chloroform was substituted for 1- (2-cyanophenyl) with 1- (2-cyanopyryl) hexahydropyridine according to the procedure described in Example 91B. ) Hexahydropyridine, providing the title compound as a brown oil. 1H NMR (300 MHz, CHC13) 5 2.40 (s? 3H)? 2.80 (t5 4H? J = 6 Hz)? 3.75 (t5 4H? J = 6 Hz ), 4.40 (d, 2H, J = 6 H z), 6.55 (br s, 1H), 6_75 (dd, 1H, J = 12, 6 Hz), 7.32 (d, 2H, J = 6 Hz), 7.52-7.65 (m, 2H), 7.75 (dd, 1H, J = 7.5, 3 Hz), 8.33 (dd, 1H, # 6, 3 Hz); MS (DCI / NH3) m / e 336 (M + H) +; maleic acid: light yellow powder ; Melting point 128_130 ° C; Analytical calculated value for C23H25N505: c, 61.19; Η, 5.58; N, 15.51. Found: C, 61.46; H, 5.57; N, 15.57. Example 99 N- {f4- ( 3-Cyanobenzyl M-Hydroxypyramine 1 Methyl 3-methylbenzylmethoxamine was replaced with 1- (3-cyanophenyl) hexylpyridine according to the procedure described in Example 91B. 1- (2-cyanophenyl) hexahydropyridine to provide the title compound as a glassy solid. IHNMRpOOMHACDC ^) 5 2.40 (s, 3H), 2.80 (t, 4H, J = 6Hz), 3.25 (t, 85228 -215- 200404539 4H, J = 6 Hz), 4.40 (d, 2H, J = 6 Hz), 6.50 (br s, 1H), 7_1 (m, 3H), 7.35 (m, 3H) , 7.55-7.70 (m, 2H); MS (DCI / NH3) m / e 335 (M + H) +; maleic acid: off-white powder. Melting point: 59-61 ° C; Analytical calculated value for C24H26N405: c, 63.99; H, 5-82; N, 12.44. Found: C, 63.76; Η, 5.75; N, 12.17. Example 100 Ν- {" 4- (3-Cyanophenyl) pyralinyl) methyl-2-methylbenzamide Following the procedure described in Example 91B, substituting the product from Example 96A for Example 91A Product and substituted 1- (2-cyanophenyl) hexahydropyrine with 1- (3-cyanophenyl) hexahydropyridine to provide the title compound. IHNMRpOO MHz, CDC13) 5 2.48 (s, 3H ), 2.85 (t, 4H, J = 6 Hz), 3.25 (t, 4H, J = 6 Ηζ), 4. · 4 (d, 2H, J = 6 Hz), 6.18 (br s, 1H), 7.10 (m, 3H), 7.22 (m5 2H), 7.30-7.45 (m, 3H); MS (DCI / NH3) m / e 335 (M + H) +; maleic acid salt: off-white powder; melting point 156-159 ° C; Analytical calculated value for C24H26N405: C, 63.99; H, 5_82; N, 12.44. Found: C, 63.79; Η, 5.67; Ν, 12.29. Example 101 N-{[[ 4-G-Pyridyl-2-pyridylpyrene-hexahydropyroxypyridine 1methyl 丨 Example of benzamidine 101A Acid (benzylamine) methyl ester Follow the procedure described in Example 91A, using N- (Benzylidene) glycine Acid substituted N- (3- benzoyl-yl-methyl) glycine to give the title compound.

實例101B N-{「4-(3-氨基-2^比咬基VI-六氫p比畊基1甲某}苯甲醯胺· 按照實例91B中所述之程序，以得自實例l〇lA之產物取代 得自實例91A之產物，並以氰基吡啶基）六氫吡畊取代卜(2- 85228 -216- 200404539 氰基苯基）六氫批p井，提供標題化合物，為無色油。1H NMR (300 MHz，CDC13) 5 2·80 (t，4H，J=6 Ηζ)，3·75 (t，4H，J=6 Ηζ)，4·40 (d，2H， 6 Hz)，6.55 (br s，1H)，6.75 (dd，1H，J=12, 6Hz)，7.40-7.60 (m，3H)，7.72-7.85 (m，3H)，8.35 (dd，1H，6, 3 Hz) ; MS (DCI/NH3) m/e 322 (M+H)+ · 順丁烯二酸鹽：白色固體；熔點133-136°C ;對C22H23N505之 分析計算值：C，60·40 ; Η，5·30 ; N，16.01.實測值：C，60.97 ; H，5.26 ；Ν, 16.31. 實例102 N_{f4_(3-氰基-2·ρ比症基Η-六氫ρ比呼基甲基卜4-甲基笨甲酸胺 按照實例91Β中所述之程序，以得自實例97Α之產物取代 得自實例91Α之產物，並以1-(2-氰基吡啶基）六氫吡畊取代1-(2-氰基苯基）六氫吡畊，提供標題化合物，為白色固體。1HNMR (300MHz，CDC13) 5 2.40 (s，3H)，2.85 (m，4H)，3.75 (m，4H)，4.43 (m，2H)， 6.75 (m，1H)，7.22 (m，2H)，7.70 (d，2H，J=9 Hz)，7.78 (dd, 1H，J=9, 3 Hz) 8.32 (dd，1H，J=6, 3 Hz) ; MS (DCI/NH3) m/e 336 (M+H)+ ;順丁烯二酸鹽 :白色固體；熔點134-136°C ;對C23H25N505之分析計算值： C，61.19 ; Η，5·58 ; N，15.51.實測值：C，60.91 ; Η，5·60 ; N，15.60 實例103 Ν-{「4-(3-氰基-2-峨淀基VI-六氫外井基1甲基丨-2-甲基苯甲酿胺 按照實例91Β中所述之程序，以得自實例96Α之產物取代 得自實例91Α之產物，並以1-(2-氰基吡啶基）六氫吡畊取代1-(2-氰基苯基）六氫吡啡，提供標題化合物，為玻璃態固體。 1H NMR (300 MHz，CDC13) 5 2.48 (s，3H)，2.8 (t，4H，J=6 Hz)，3.75 (t，4H， J=6 Hz)，4.4 (d，2H，J=6 Hz)，6.14 (br s，1H)，6.75 (dd，1H，J=12, 6 Hz)，7.18- 85228 -217- 200404539 7.41 (m，4H)，7.78 (dd，1H，J=9, 3 Hz)，8.35 (dd，1H，6, 3 Hz); MS (DCI/NH3) m/e 336 (M+H)+ ;順丁烯二酸鹽：灰白色粉末；熔點124_127°C ;對0：2 3 112 5^〇5之分析計算值：c，61_19; Η，5·58; Ν，15·51·實 測值：C，61.43 ; Η，5.39 ; Ν，15·81· 實例104 Ν-彳「4-Γ2-毗啶基Μ-六氪吡畊基1甲基}笨甲醯胺 按照實例91B中所述之程序，以得自實例101A之產物取代 得自實例91A之產物，並以1-(2-吡啶基）六氫吡畊取代1_(2_氰 基苯基）六氫外1： _，提供標題化合物，為白色膠黏性殘留物 。iHNMRpOOMHz’CDCld δ 2.75(t，4H，J=6Hz)，3.55(t，4H，J=6Hz)， 4.4 (d，2H，J=6 Hz)，6.50 (br s，1H)，6.65 (m，2H)，7.40-7.55 (m，4H)，7.75 (m， 2H)，8.20 (m，1H) ; MS (DCI/NH3 ) m/e 297 (M+H)+ ;順丁烯二酸鹽： 白色固體；熔點125-127°C ;對C21H24N405之分析計算值：C，61.15 ;Η，5·87 ; N，13.58.實測值：C，60·86 ; H，5.89 ; Ν，13·52. 實例105Example 101B N-{"4- (3-Amino-2 ^ pyridyl VI-hexahydrop-pyridyl 1methyl} benzamidine" Follow the procedure described in Example 91B to obtain from Example 10. The product of 1A was substituted with the product obtained from Example 91A and replaced with (2- 85228 -216- 200404539 cyanophenyl) hexahydropyridine in well P to provide the title compound as a colorless oil. 1H NMR (300 MHz, CDC13) 5 2 · 80 (t, 4H, J = 6 Ηζ), 3.75 (t, 4H, J = 6 Ηζ), 4 · 40 (d, 2H, 6 Hz), 6.55 (br s, 1H), 6.75 (dd, 1H, J = 12, 6Hz), 7.40-7.60 (m, 3H), 7.72-7.85 (m, 3H), 8.35 (dd, 1H, 6, 3 Hz) ; MS (DCI / NH3) m / e 322 (M + H) + · Maleic acid salt: white solid; melting point 133-136 ° C; Analytical calculated value for C22H23N505: C, 60 · 40; Η, 5.30; N, 16.01. Measured values: C, 60.97; H, 5.26; N, 16.31. Example 102 N_ {f4_ (3-cyano-2 · ρ-pyridyl-hexahydrop-pyridylmethyl) B. 4-Methylbenzyl carboxylic acid amine Following the procedure described in Example 91B, the product from Example 97A was replaced with the product from Example 91A and 1- (2-cyanopyridyl) hexahydropyridine was substituted for 1 -(2-cyano Hexahydropyridine to provide the title compound as a white solid. 1HNMR (300MHz, CDC13) 5 2.40 (s, 3H), 2.85 (m, 4H), 3.75 (m, 4H), 4.43 (m, 2H), 6.75 (m, 1H), 7.22 (m, 2H), 7.70 (d, 2H, J = 9 Hz), 7.78 (dd, 1H, J = 9, 3 Hz) 8.32 (dd, 1H, J = 6, 3 Hz); MS (DCI / NH3) m / e 336 (M + H) +; maleic acid salt: white solid; melting point 134-136 ° C; analytical calculated value for C23H25N505: C, 61.19; Η, 5.58; N, 15.51. Measured value: C, 60.91; Rhenium, 5.60; N, 15.60 Example 103 Ν-{"4- (3-cyano-2-erodolide VI-hexahydro outer well base 1 Methyl-2-methylbenzylamine Follow the procedure described in Example 91B, substituting the product from Example 96A with the product from Example 91A, and replace it with 1- (2-cyanopyridyl) Hydropyrine replaces 1- (2-cyanophenyl) hexahydropyridine to provide the title compound as a glassy solid. 1H NMR (300 MHz, CDC13) 5 2.48 (s, 3H), 2.8 (t, 4H, J = 6 Hz), 3.75 (t, 4H, J = 6 Hz), 4.4 (d, 2H, J = 6 Hz ), 6.14 (br s, 1H), 6.75 (dd, 1H, J = 12, 6 Hz), 7.18- 85228 -217- 200404539 7.41 (m, 4H), 7.78 (dd, 1H, J = 9, 3 Hz ), 8.35 (dd, 1H, 6, 3 Hz); MS (DCI / NH3) m / e 336 (M + H) +; maleic acid salt: off-white powder; melting point 124_127 ° C; to 0: 2 Analytical calculated value for 3 112 5 ^ 〇5: c, 61_19; Η, 5.58; Ν, 15.51. Found: C, 61.43; Η, 5.39; Ν, 15.81. Example 104 Ν-Ν " 4-Γ2-pyridinyl M-hexapyridinyl 1methyl} benzylamidine Following the procedure described in Example 91B, the product from Example 101A was replaced with the product from Example 91A, and (2-pyridyl) hexahydropyridine replaces 1_ (2_cyanophenyl) hexahydroxide 1 :: to provide the title compound as a white tacky residue. IHNMRpOOMHz'CDCld δ 2.75 (t, 4H, J = 6Hz), 3.55 (t, 4H, J = 6Hz), 4.4 (d, 2H, J = 6 Hz), 6.50 (br s, 1H), 6.65 (m, 2H), 7.40-7.55 (m, 4H) , 7.75 (m, 2H), 8.20 (m, 1H); MS (DCI / NH3) m / e 297 (M + H) +; Butenedioate: White solid; Melting point 125-127 ° C; Analytical calculated value for C21H24N405: C, 61.15; H, 5.87; N, 13.58. Found: C, 60 · 86; H, 5.89; Ν, 13.52. Example 105

氯苯基上]-六氫吡畊基1甲基}笨甲醯胺 按照實例91B中所述之程序，以得自實例101A之產物取代 得自實例91A之產物，並以1-(2-氯苯基）六氫吡畊取代1-(2-氰 基苯基）六氫吡畊，提供標題化合物，為無色油。iHNMR (300 MHz，CDC13) δ 2·86 (m，4Η)，3· 1 (m，4Η)，4·45 (d，2Η，J=6 Ηζ)，6·70 (br s，1Η)，7·1 (m，3Η)，7·00 (m，2Η)，7.25 (m，2Η)，7.4-7.26 (m，2Η) ； MS (DCI/NH3)m/e 330 (M+H)+ ;順丁烯二酸鹽：黃褐色固體；熔點 145-147°C ;對 C22H24C1N305之分析計算值·· C，59·26; Η，5_43; Ν，9_42· 實測值：C，58.98 ; Η，5·34 ; Ν，9.15· 85228 -218- 200404539 實例106 3- 氰-Ν-{「4-Γ2-氨基苯基）-1-六氫吡畊某1甲基}苯甲醯胺 按照實例91B中所述之程序，以得自實例95A之產物取代 得自實例91A之產物’提供標題化合物，為無色油。 1H NMR (300 MHz，CDC13) 5 2.92 (m，4H)，3.25 (m，4H)，4.45 (d，2H，J= 6 Hz)，6.75 (br s，1H)，7.00 (t，2H，J=6 Hz)，7_35-7·70 (m，5H)，7.82 (m，1H)； MS (DCI/NH3)m/e 355 (M+H)+ ;順丁烯二酸鹽：白色固體；熔點 143_146°(：;對€：231123(^405之分析計算值：〇：，58.66;11，4.92; N，11.90·實測值：C，58.30 ; H，5.01; Ν，11.67· 實例107 4- 1 -Ν-ίΓ4-ί2-甲氧苯基）-1-六氫吡畊墓1甲基}笨甲醯胺[Chlorophenyl] -hexahydropyridyl 1methyl} benzylamidine Following the procedure described in Example 91B, the product from Example 101A was replaced with the product from Example 91A and Chlorophenyl) hexahydropyrine replaces 1- (2-cyanophenyl) hexahydropyrine to provide the title compound as a colorless oil. iHNMR (300 MHz, CDC13) δ 2.86 (m, 4Η), 3.1 (m, 4Η), 4.45 (d, 2Η, J = 6 Ηζ), 6.70 (br s, 1Η), 7.1 (m, 3Η), 7:00 (m, 2Η), 7.25 (m, 2Η), 7.4-7.26 (m, 2Η); MS (DCI / NH3) m / e 330 (M + H) + ; Maleic acid salt: yellow-brown solid; melting point 145-147 ° C; analytical calculated value for C22H24C1N305 ·· C, 59 · 26; Η, 5_43; Ν, 9_42 · found: C, 58.98; Η, 5 · 34; Ν, 9.15 · 85228 -218- 200404539 Example 106 3-Cyano-N-{"4-Γ2-aminophenyl) -1-hexahydropyridine 1methyl} benzamide according to Example 91B The procedure described in above, replacing the product from Example 91A with the product from Example 95A 'provided the title compound as a colorless oil. 1H NMR (300 MHz, CDC13) 5 2.92 (m, 4H), 3.25 (m, 4H ), 4.45 (d, 2H, J = 6 Hz), 6.75 (br s, 1H), 7.00 (t, 2H, J = 6 Hz), 7_35-7 · 70 (m, 5H), 7.82 (m, 1H ); MS (DCI / NH3) m / e 355 (M + H) +; maleic acid salt: white solid; melting point 143_146 ° (:; analytical calculation for €: 231123 (^ 405: 0: ,, 58.66; 11, 4.92; N, 11.90 · Measured value: C, 58.30; H, 5 .01; Ν, 11.67 · Example 107 4- 1 -Ν-ίΓ4-ί2-methoxyphenyl) -1-hexahydropyridine 1methyl} benzidine

實例107A 醋酸氯」基苯甲醯基）胺基1甲酯 按照實例91A中所述之程序，以N-(4-氯基苯甲醯基）甘胺酸 取代N-(3-甲基苯甲醯基）甘胺酸，提供標題化合物。Example 107A N- (3-methylbenzyl) glycolic acid was substituted with N- (4-chlorobenzyl) glycine according to the procedure described in Example 91A. Formamyl) glycine to provide the title compound.

實例107BExample 107B

4_氣-N-丨[4-(2-甲乳+基）-1-六氮峨喷基1甲基}笨甲酿胺 按照實例91B中所述之程序，以得自實例107A之產物取代 得自實例91A之產物，並以1-(2•甲氧苯基）六氫吡畊取代1-(2-氰基苯基）六氫吡畊，提供標題化合物，為無色油。1H NMR (300 MHz，CDC13) 6 2.92 (m，4H)，3·15 (m，4H)，3.85 (s，3H)，4_45 (d，2H， J=6 Hz)，6_7 (br s，1H)，6.82-7.05 (m，4H)，7·44 (m，2H)，7.75 (m，2H) ; MS (DCI/NH3) m/e 360 (M+H)+ ;順丁烯二酸鹽：白色固體；熔點 145-147 °C ;對 C23H26C1N306 之分析計算值：C，58.04; Η，5·51; Ν，8·83· 85228 -219- 200404539 實測值：C，58.24 ; Η，5·18 ; Ν，8·83· 實例1084_Ga-N- 丨 [4- (2-methyl milk + yl) -1-hexaazaepentyl 1methyl} benzylamine was prepared according to the procedure described in Example 91B to obtain the product from Example 107A Substitution of the product obtained from Example 91A and replacement of 1- (2-cyanophenyl) hexahydropyridine with 1- (2 • methoxyphenyl) hexahydropyridine provided the title compound as a colorless oil. 1H NMR (300 MHz, CDC13) 6 2.92 (m, 4H), 3.15 (m, 4H), 3.85 (s, 3H), 4_45 (d, 2H, J = 6 Hz), 6_7 (br s, 1H ), 6.82-7.05 (m, 4H), 7.44 (m, 2H), 7.75 (m, 2H); MS (DCI / NH3) m / e 360 (M + H) +; maleate : White solid; melting point 145-147 ° C; analytical calculated value for C23H26C1N306: C, 58.04;., 5.51; Ν, 8.83 · 85228 -219- 200404539 found: C, 58.24; Η, 5 · 18; Ν, 8.33 Example 108

2-氯-Ν]「4-(3_氰基全毗啶基）小六氫吡畊基&quot;I甲某}笨甲醯I2-Chloro-N] "4- (3-Cyanoperpyridinyl) Hexahydropyrimyl &quot; I 甲某} 笨 甲 醯 I

實例108A 醋酸卫2-氯基笨甲醯基）胺某1甲酯 按照實例91A中所述之程序，以N-(2-氯基苯甲醯基）甘胺酸 取代N-(3-甲基苯甲醯基）甘胺酸，提供標題化合物。Example 108A Ethyl 2-chlorobenzylmethylfluorenyl) amine 1 methyl ester Following the procedure described in Example 91A, N- (2-chlorobenzylidene) glycine was substituted for N- (3-methyl Benzamidine) glycine, to provide the title compound.

實例108B 2-氯-N-丨「4-(3-氰基少吡啶基H-六氫吡畊某1甲某}装甲醯胺 按照實例91B中所述之程序，以得自實例108A之產物取代 得自實例91A之產物，並以1-(2-氰基吡啶基）六氫吡畊取代卜(2_ 氰基苯基）六氫吡畊，提供標題化合物，為黃色油。iHNMR (300 MHz，CDC13) (5 2.75 (t，4H，J=6 Hz)，3.55 (t，4H，J=6 Ηζ)，4·4 (d，2H，J= 6 Hz)，6.50 (br s，1H)，6.65 (m，2H)，7.40-7.55 (m，4H)，7.75 (m，2H); 8·20 (m， 1H) ; MS(DCI/NH3)m/e356 (M+H)+ ;順丁 烯二酸鹽：白色固體 ;熔點 137-139°(：;對〇221122(：1&gt;15〇5之分析計算值：〇,55.99;11，4.70 ;Ν，14·84.實測值：C，55_76 ; Η，4·74 ; N，14.60. 實例109 Ν-{「4-(3-氨某-2-吡啶基Η_六氫吡？井基1甲某丨_2-(三氟甲某） 苯甲驢胺 實例109Α 醋酸丨「2-(三氳甲基）笨甲醯基1胺某}甲酯 按照實例91中所述之程序，以Ν-[2-(三氟甲基）苯甲醯基]甘 胺酸取代Ν-(3-甲基苯甲醯基）甘胺酸，提供標題化合物。 85228 -220- 200404539Example 108B 2-Chloro-N- "4- (3-cyano-oligopyridylH-hexahydropyridine, 1methyl, 1} armored amidin Follow the procedure described in Example 91B to obtain the product from Example 108A Substitution of the product from Example 91A and substitution of (2-cyanophenyl) hexahydropyridine with 1- (2-cyanopyryl) hexahydropyridine provided the title compound as a yellow oil. IHNMR (300 MHz , CDC13) (5 2.75 (t, 4H, J = 6 Hz), 3.55 (t, 4H, J = 6 Ηζ), 4 · 4 (d, 2H, J = 6 Hz), 6.50 (br s, 1H) , 6.65 (m, 2H), 7.40-7.55 (m, 4H), 7.75 (m, 2H); 8.20 (m, 1H); MS (DCI / NH3) m / e356 (M + H) +; Butenedioate: white solid; melting point 137-139 ° (:; analytical calculation for 〇221122 (: 1> 150.5): 〇, 55.99; 11,4.70; N, 14.84. Found: C , 55_76; Hf, 4.74; N, 14.60. Example 109 N- {"4- (3-Ammonia-2-pyridylfluorene_hexahydropyridine? Well-based 1A and a _2_2- (trifluoromethyl A) Example of benzamidine 109A Acetic acid 丨 "2- (Tris (methyl) benzylidene 1amine"} methyl ester Follow the procedure described in Example 91, using N- [2- (trifluoromethyl) Benzamyl] glycine to replace N- (3-methylbenzyl Glycine to provide the title compound. 85228-220- 200 404 539

實例109BExample 109B

N-{「4-G-舉篡-2-吡啶基Η-六氫吡畊基1甲基丨-2-(三氣甲基J 笨甲醯胺 按照實例91B中所述之程序，以得自實例109A之產物取代 得自實例91A之產物，並以1-(2-氰基吡啶基）六氫吡畊取代1-(2-氰基苯基）六氫吡畊，提供標題化合物，為無色油。iHNMR (300 MHz，CDC13) 5 2.90 (m，4H)，3.80 (m，4H)，4.45 (d5 2H，J=6 Hz)，6.80 (dd，1H，J=12,6 Hz)，7.55-7.80 (m，5H)，8.35 (dd，1H，J=6, 3 Hz)，11.00 (br s5 1H) ; MS (DCI/NH3)m/e 390 (M+H)+·順丁烯二酸鹽：吸濕性白色 固體。 實例110 N-{|~4-(2-氰基苯基Η•六氫吡畊基1甲墓丨苯甲醯胺 按照實例91Β中所述之程序，以得自實例ΐ〇ΐΑ之產物取代 得自實例91Α之產物，提供標題化合物，為黃色油。1 η NMR (300 MHz，DMSO-d6) (5 2.71 (m，4Η)，3.15 (m，4Η)，4·22 (d，2Η，J=6.1 Ηζ)， 7.08 (dd，1H，J=7.8, 7.8 Hz)，7·15 (d，1H，J=8.5 Hz)，7.55 (m，4H)，7.68 (dd，1H， J=7.4, 1.3 Hz)，7.90 (m，2H)，8·95 (t，1H，J=6.1 Hz) ; MS (DCI/NH3) m/e 321 (M+H)+ ;順丁烯二酸鹽：黃褐色固體，熔點i48-15〇〇c ;對 C19H2〇N40.1.〇C4H404之分析計算值：C, 63.29 ; Η，5·54; N，12.84. 實測值：C，63_03 ; Η，5.47 ; Ν，12.79. 實例111 Μ[4-(2-甲氧苯某）-1-六氫吡啶基1甲某丨各甲某苽甲醯胺 將4-(2-甲氧苯基）六氫吡啶（286毫克，1.5毫莫耳）、得自實 例91A之產物（310毫克，1毫莫耳）及三乙胺（〇·42毫升，3毫莫 85228 -221- 200404539 耳）在乙腈（8毫升）中合併，並於室溫下攪拌18小時。使反應 混合物在減壓下濃縮，並使殘留物於矽膠上藉急驟式層析 純化（以二氯甲烷：甲醇9.5 : 0.5溶離），提供標題化合物（285 耄克，56.2% 產率）。1H NMR (300 MHz，DMSO-d6) 3 1.65 (m, 4H)，2.31 (m，2H)，2·37 (s，3H)，2.79 (m，1H)，2.93 (m，2H)，3.75 (s，3H)，4.15 (d，2H，J= 6 Hz)，6.90 (m，2H)，7.15 (m，2H)，7.36 (m，2H)，7.68 (m，2H)，8.69 (t，1H，J= 6 Hz) ; MS (DCI/NH3) m/e 339 (M+H)+ ;對 C2 ! H2 6 N2 02 · 0· 15 H2 O 之 分析計算值：C，73.94 ; H，7.77 ; Ν，8·21·實測值：c，73.56，H，7.72，鲁 Ν，8_15· 實例112 3-甲基-Ν-{「4-(2-ρ比淀基）-1-六氮ρ比症基1甲基}笨甲酿胺 按照實例111中所述之程序，以得自實例36C之產物取代4-(2-甲氧苯基）六氫吡啶，提供標題化合物（480毫克，64%產率） 。1 H NMR (300 MHz, DMSO-d6 ) 5 1.75 (m，4Η)，2.31 (m，2Η), 2_36 (s，3Η)， 2.59 (m，1Η)，2·95 (m，2H)，4.17 (d，2H，J=6 Hz)，7.18 (m，1H)，7·25 (d，1H，J= 6 Hz)，7.35 (m，2H)，7.69 (m，3H)，8.48 (m，1H)，8.71 (m，1H); MS (DCI/NH3) φ m/e310(M+H)+jiC19H23N3C^0.25H2O之分析計算值·· C，72.70 ;H，7.50; N，13.39·實測值：C，72.60，h7.50，N13.21· 實例113 3-甲基-N-「(4-笔# -3,6-二氫比途基）甲基1笨甲醯胺 按照實例111中所述之程序’以4-苯基-1，2,3,6-四氫p比淀取代 4-(2-甲氧苯基）六氫11比症，提供標題化合物（196毫克，64%產 率）。1H NMR (300 MHz，DMSO-d6) δ 2·35 (s，3H)，2·76 (t，2H，J=6 Hz)， 3·24 (d，2H)，4.25 (d, 4H，1=9 Hz)，6.16 (m，1H)，7.22 (t，1H，J=6 Hz)，7.32 (m， 85228 -222- 200404539 4H)，7.40 (m，2H)，7.66 (m，2H)，8.75 (t，1H，J=6 Hz) ； MS (DCI/NH3)m/e 307 (M+H)+.對 C2〇H22N20 · 0·10Η20 之分析計算值：C，77.94 ; H，7·26 ; N，9.09.實測值：C，77.64, H，7·34, N，8.86_ 實例114 化(3’，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基V3-甲基笨甲醯胺 按照實例111中所述之程序，以l’，2’,3’，6f-四氫_2,4’_聯吡啶鹽酸 鹽取代4-(2-甲氧苯基）六氫吡啶，提供標題化合物（310毫克， 81.5% 產率）。iHNMRpOOMHADMSO-c^) 5 2.35(s，3H)，2.58(m，2H)， 2.76 (t，2H，J=6 Hz)，3.29 (m，2H)，4·27 (d，2H，J=6 Hz)，6·70 (m，1H)，7.22 (m， 1H)，7·35 (d，2H，J=6 Hz)，7.51 (d，1H，J=9 Hz)，7.70 (m，3H)，8·51 (m，1H)， 8.76 (m，1H) ; MS (DCI/NH3) m/e 308 (M+H)+ _ 實例115 N-(3’，6’-二氫_2A-聯吡啶-Γ(2Ή)-基甲基V3-甲氣基笨甲醯胺 將3-甲氧基苯甲醯胺（1·13克，7·5毫莫耳）、K2C03(345毫克 ，2.5毫莫耳）、聚甲醛（0.5克，16毫莫耳）及rjJA-四氫-2,4’_ 聯吡啶鹽酸鹽（393毫克，2毫莫耳）在乙醇（25毫升）中合併， 並回流18小時。使反應混合物冷卻至室溫，及在減壓下濃 縮。使殘留物於醋酸乙醋（80毫升）與水（80毫升）之間作分液 處理。將有機層以鹽水（2 X 50毫升）洗濂，以MgS04脫水乾燥 ，過濾，並使濾液在減壓下濃縮。使殘留物於矽膠上藉急 騾式層析純化（以醋酸乙酯：乙醇溶離，9.0 : 1·0)，提供標 題化合物（180 毫克，49% 產率）。iHNMRpOOMHzjMSO-dd^ 2·58 (m，2H)，2.76 (t，2H，J=6 Hz)，3.29 (m，2H)，3.80 (s，3H)，4.27 (d，2H，J= 6 Hz)，6.70 (m，1H)，7·09 (m，1H)，7.22 (m，1H)，7.42 (m, 4H)，7.72 (m，1H)， 85228 -223- 200404539 8.51 (m，1Η)，8.83 (t，1H，J=6 Hz) ; MS (DCI/NH3) m/e 324 (M+H)+ · · 對0191121^02 ·0·60Η2Ο之分析計算值：C，68_28; Η，6·70; N，12.57· 實測值：C，68.19, Η，6.84, Ν，11·77· 實例116 N-n^-二氣聯吡啶-1Υ2Ή)-基甲基V3-氟基笨甲醯胺 按照實例115中所述之程序，以3-氟基苯甲醯胺取代3_甲氧 基苯甲醯胺，提供標題化合物（260毫克，42.6%產率）。^NMR (300 MHz，DMSO-d6) δ 2·58 (m，2Η)，2.76 (t，2Η，J=6 Ηζ)，3·29 (m，2Η)， φ 4·27 (d，J=6 Ηζ，2Η)，6.70 (m，1Η)，7·21 (m，1Η)，7.39 (m，1Η)，7·51 (m，2Η)， 7.72 (m，3H)，8.51 (m，1H)，8.93 (t，1H，J=6 Hz) ； MS (DCI/NH3) m/e 312 (M+H)+. 實例117 N-G’A-二f m葬吡啶-Γ(2Ή)_基甲基）-3,5-二氟笨甲醯胺 按照實例115中所述之程序，以3,5-二氟苯甲醯胺取代3-甲 氧基苯甲醯胺，提供標題化合物（140毫克，21%產率）。WNMR (300 MHz，DMSO-d6 ) δ 2·58 (m，2Η)，2·76 (t，2Η，J=6 Ηζ)，3·29 (m，2Η)， φ 4·27 (d，2Η，J=6 Ηζ)，6·70 (m，1Η)，7.21 (m，1Η)，7·51 (m，2Η)，7.60 (m，2Η)， 7.75 (m，1Η)，8·51 (m，1Η)，9·01 (t，1Η，J=6 Hz) ； MS (DCI/NH3) m/e 330 (M+H)+.對 q 8 7N3 OF2 · 0·70 H2 O 之兮析計算值：C，63.22 ; H，5.42 ;N，12.29.實測值：C，62.76, H，5.02, N，12.09· 實例118 244-(3-氰基-2-吡啶基VI-六氫吡畊基l-N-3-吡啶基乙醯胺 按照實例8中所述之程序，以2-氯-N-3-吡啶基乙醯胺 (Abdel Rahman，Α·Ε·等人；J· Ind. Chem. Soc· 1981，58, 171-173)取代 N- 85228 -224- 200404539 氯基乙聽基-3-硝基苯胺，提供標題化合物，13%產率。將自 由態驗以順丁烯二酸處理，提供順丁缔二酸鹽，為黃色固 體。1 H NMR (300 MHz，MeOH-d4 ) 5 8.43 (dd，1H，J=4.7，1.7 Hz)，8.33 (br d 1H，J=4.1 Hz)，8.17 (ddd，1H，J=8.5, 2.4, 1.4 Hz)，8.00 (dd，1H，J=7.8, 2.0 Hz)， 7.47 (dd，1H，J=8.5, 5.1 Hz)，7_00 (dd，1H，J=7.8, 5_1 Hz)，6·27 (s，2H)，3.88 (m， 6H)，3.28(m，4H); MS(DCI/NH3)m/e323 (M+H)+ ;對（：17!118^0· 1.2 C4H4O4 · 0·40 H20 之分析計算值：c，55.85 ; H，5.07 ; N, 17.92 ;實測值：C，55.66 ; H，5·14 ; N，17.91. 實例119N-{"4-G-enzyme-2-pyridylfluorene-hexahydropyridyl 1methyl-1--2- (trifluoromethyl J benzamidine) Follow the procedure described in Example 91B to obtain Substitution of the product from Example 109A with the product from Example 91A and replacement of 1- (2-cyanophenyl) hexahydropyridine with 1- (2-cyanopyryl) hexahydropyridine provided the title compound as Colorless oil. IHNMR (300 MHz, CDC13) 5 2.90 (m, 4H), 3.80 (m, 4H), 4.45 (d5 2H, J = 6 Hz), 6.80 (dd, 1H, J = 12, 6 Hz), 7.55-7.80 (m, 5H), 8.35 (dd, 1H, J = 6, 3 Hz), 11.00 (br s5 1H); MS (DCI / NH3) m / e 390 (M + H) + · cis-butene Diacid salt: hygroscopic white solid. Example 110 N- {| ~ 4- (2-Cyanophenylpyrene • Hydroxypyrimyl 1 Tomb 丨 Benzamidine Following the procedure described in Example 91B, The product from Example 91A was replaced with the product from Example 90A to provide the title compound as a yellow oil. 1 η NMR (300 MHz, DMSO-d6) (5 2.71 (m, 4Η), 3.15 (m, 4Η) ), 4.22 (d, 2Η, J = 6.1 Ηζ), 7.08 (dd, 1H, J = 7.8, 7.8 Hz), 7.15 (d, 1H, J = 8.5 Hz), 7.55 (m, 4H) , 7.68 (dd, 1H, J = 7.4, 1.3 Hz), 7.90 (m, 2 H), 8.95 (t, 1H, J = 6.1 Hz); MS (DCI / NH3) m / e 321 (M + H) +; maleate: yellow-brown solid, melting point i48-15. 〇c; Calculated value for C19H2ON40.1.〇C4H404: C, 63.29; Η, 5.54; N, 12.84. Found: C, 63_03; Η, 5.47; Ν, 12.79. Example 111 M [ 4- (2-Methoxybenzene) -1-hexahydropyridyl, 1methyl, 丨 each methylamidine, methylformamide, 4- (2-methoxyphenyl) hexahydropyridine (286 mg, 1.5 mmol) ), The product from Example 91A (310 mg, 1 mmol) and triethylamine (0.42 ml, 3 mmol 85228 -221- 200404539 ears) were combined in acetonitrile (8 ml), and room temperature The reaction mixture was stirred for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica gel (dichloromethane: methanol 9.5: 0.5) to provide the title compound (285 g, 56.2%). Yield). 1H NMR (300 MHz, DMSO-d6) 3 1.65 (m, 4H), 2.31 (m, 2H), 2.37 (s, 3H), 2.79 (m, 1H), 2.93 (m, 2H ), 3.75 (s, 3H), 4.15 (d, 2H, J = 6 Hz), 6.90 (m, 2H), 7.15 (m, 2H), 7.36 (m, 2H), 7.68 (m, 2H), 8 .69 (t, 1H, J = 6 Hz); MS (DCI / NH3) m / e 339 (M + H) +; Analytical calculation for C2! H2 6 N2 02 · 0 · 15 H2 O: C, 73.94; H, 7.77; N, 8.21. Found: c, 73.56, H, 7.72, LuN, 8_15. Example 112 3-methyl-N-{"4- (2-ρ 比基基)- 1-Hexaazepine 1methyl} benzylmethanamine Following the procedure described in Example 111, substituting 4- (2-methoxyphenyl) hexahydropyridine with the product from Example 36C to provide the title compound (480 mg, 64% yield). 1 H NMR (300 MHz, DMSO-d6) 5 1.75 (m, 4Η), 2.31 (m, 2Η), 2_36 (s, 3Η), 2.59 (m, 1Η), 2.95 (m, 2H), 4.17 (d, 2H, J = 6 Hz), 7.18 (m, 1H), 7.25 (d, 1H, J = 6 Hz), 7.35 (m, 2H), 7.69 (m, 3H), 8.48 (m, 1H), 8.71 (m, 1H); MS (DCI / NH3) φ m / e310 (M + H) + jiC19H23N3C ^ 0.25H2O Analytical calculated value ·· C, 72.70; H, 7.50; N, 13.39 : C, 72.60, h7.50, N13.21 · Example 113 3-methyl-N-"(4-pen # -3,6-dihydrobityl) methyl 1 benzamidine according to Example 111 The described procedure 'replaces 4- (2-methoxyphenyl) hexahydro 11 with 4-phenyl-1,2,3,6-tetrahydrop ratio to provide the title compound (196 mg, 64% Yield). 1H NMR (300 MHz, DMSO-d6) δ 2.35 (s, 3H), 2.76 (t, 2H, J = 6 Hz), 3.24 (d, 2H), 4.25 (d , 4H, 1 = 9 Hz), 6.16 (m, 1H), 7.22 (t, 1H, J = 6 Hz), 7.32 (m, 85228 -222- 200404539 4H), 7.40 (m, 2H), 7.66 (m , 2H), 8.75 (t, 1H, J = 6 Hz); MS (DCI / NH3) m / e 307 (M + H) +. Analytical calculated value for C20H22N20 · 0 · 10Η20: C, 77.94; H, 7.26; N, 9.09. Real Value: C, 77.64, H, 7.34, N, 8.86_ Example 114 (3 ', 6'_dihydro-2,4'-bipyridine-Γ (2Ή) -ylmethyl V3-methylbenzyl Formamidine was replaced with l ', 2', 3 ', 6f-tetrahydro_2,4'_bipyridine hydrochloride by the procedure described in Example 111. Pyridine, provided the title compound (310 mg, 81.5% yield). IHNMRpOOMHADMSO-c ^) 5 2.35 (s, 3H), 2.58 (m, 2H), 2.76 (t, 2H, J = 6 Hz), 3.29 (m , 2H), 4.27 (d, 2H, J = 6 Hz), 6.70 (m, 1H), 7.22 (m, 1H), 7.35 (d, 2H, J = 6 Hz), 7.51 ( d, 1H, J = 9 Hz), 7.70 (m, 3H), 8.51 (m, 1H), 8.76 (m, 1H); MS (DCI / NH3) m / e 308 (M + H) + _ Example 115 N- (3 ', 6'-dihydro_2A-bipyridine-Γ (2Ή) -ylmethyl V3-methylaminobenzylbenzylamine 3-methoxybenzidine (1.13 Grams, 7.5 millimoles), K2C03 (345 milligrams, 2.5 millimoles), polyoxymethylene (0.5 grams, 16 millimoles), and rjJA-tetrahydro-2,4'_bipyridine hydrochloride (393 (Mg, 2 mmol) in ethanol (25 ml) and refluxed for 18 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (80 ml) and water (80 ml). The organic layer was washed with brine (2 X 50 ml), dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (isolated with ethyl acetate: ethanol, 9.0: 1.0) to provide the title compound (180 mg, 49% yield). iHNMRpOOMHzjMSO-dd ^ 2.58 (m, 2H), 2.76 (t, 2H, J = 6 Hz), 3.29 (m, 2H), 3.80 (s, 3H), 4.27 (d, 2H, J = 6 Hz) , 6.70 (m, 1H), 7.09 (m, 1H), 7.22 (m, 1H), 7.42 (m, 4H), 7.72 (m, 1H), 85228 -223- 200404539 8.51 (m, 1Η), 8.83 (t, 1H, J = 6 Hz); MS (DCI / NH3) m / e 324 (M + H) + · · · Analytical calculation value for 0191121 ^ 02 · 0 · 60Η20: C, 68_28; Η, 6 · 70; N ， 12.57 · Measured value: C, 68.19, hydrazone, 6.84, Ν, 11.77 · Example 116 Nn ^ -Digas dipyridine-1Υ2Ή) -methylmethyl V3-fluorobenzylamine according to the example The procedure described in 115, replacing 3-methoxybenzamide with 3-fluorobenzamide to provide the title compound (260 mg, 42.6% yield). ^ NMR (300 MHz, DMSO-d6) δ 2.58 (m, 2Η), 2.76 (t, 2Η, J = 6 Ηζ), 3.29 (m, 2Η), φ 4 · 27 (d, J = 6 Ηζ, 2Η), 6.70 (m, 1Η), 7.21 (m, 1Η), 7.39 (m, 1Η), 7.51 (m, 2Η), 7.72 (m, 3H), 8.51 (m, 1H) ), 8.93 (t, 1H, J = 6 Hz); MS (DCI / NH3) m / e 312 (M + H) +. Example 117 N-G'A-di-fm-pyridine-Γ (2Ή) _ group (Methyl) -3,5-difluorobenzamide is replaced with 3,5-difluorobenzamide in accordance with the procedure described in Example 115 to provide the title compound (140 Mg, 21% yield). WNMR (300 MHz, DMSO-d6) δ 2.58 (m, 2Η), 2.76 (t, 2Η, J = 6 Ηζ), 3.29 (m, 2Η), φ 4 · 27 (d, 2Η , J = 6 Ηζ), 6.70 (m, 1Η), 7.21 (m, 1Η), 7.51 (m, 2Η), 7.60 (m, 2Η), 7.75 (m, 1Η), 8.51 ( m, 1Η), 9 · 01 (t, 1Η, J = 6 Hz); MS (DCI / NH3) m / e 330 (M + H) +. Analysis of q 8 7N3 OF2 · 0 · 70 H2 O Calculated: C, 63.22; H, 5.42; N, 12.29. Found: C, 62.76, H, 5.02, N, 12.09. Example 118 244- (3-cyano-2-pyridyl VI-hexahydropyridine 1N-3-pyridylacetamidamine Follow the procedure described in Example 8 using 2-chloro-N-3-pyridylacetamidamine (Abdel Rahman, A.E. et al .; J. Ind. Chem. Soc. 1981, 58, 171-173) substituted N- 85228 -224- 200404539 chloroethynyl-3-nitroaniline to provide the title compound in 13% yield. The free state was treated with maleic acid Provides maleic acid as a yellow solid. 1 H NMR (300 MHz, MeOH-d4) 5 8.43 (dd, 1H, J = 4.7, 1.7 Hz), 8.33 (br d 1H, J = 4.1 Hz) , 8.17 (ddd, 1H, J = 8.5, 2.4, 1.4 Hz), 8.00 (dd, 1H, J = 7.8, 2.0 Hz), 7.47 (dd 1H, J = 8.5, 5.1 Hz), 7_00 (dd, 1H, J = 7.8, 5_1 Hz), 6.27 (s, 2H), 3.88 (m, 6H), 3.28 (m, 4H); MS (DCI / NH3) m / e323 (M + H) +; Analytical calculated value for (: 17! 118 ^ 0 · 1.2 C4H4O4 · 0 · 40 H20: c, 55.85; H, 5.07; N, 17.92; measured value: C , 55.66; H, 5.14; N, 17.91. Example 119

甲基笨基）胺基1_2_酮基乙基丨六i.吡啶冰某錄 N-氣化物 實例119A L六氫吡啶-4-某吡錠N-氫化物鹽酸鹽 使2-[1-(第三-丁氧羰基）六氫吡啶_4_基风錠N-氧化物（1.24克 ’ 4.15愛莫耳）在二氯甲烷（3〇毫升）中冷卻至〇它，並以間-氯 過苯甲酸77% (1·4克，8.3毫莫耳）處理。在〇。〇下攪拌30分鐘 後’使混合物溫熱至室溫，且再攪拌2小時。將混合物以二 氯甲燒（50毫升）稀釋，以飽和NaHC〇3、鹽水洗滌，以MgS〇4 脫水乾燥，過濾，並使濾液在減壓下濃縮，提供白色固體 。使白色固體溶於醋酸乙酯（50毫升）中，並冷卻至-78。(：。使 HC1氣體起泡經過反應混合物，歷經15分鐘，並使混合物溫 熱至室溫。過濾混合物，並將濾餅以醋酸乙酯洗滌，然後 在南真空下乾燥，提供標題化合物（0.85克，96%產率）。 1HNMR(300MHz5DMSO-d6) 5 1.82 (m5 2H)? 2.10 (m5 2H), 3.06 (m? 2H)? 85228 - 225 - 200404539 3.36 (m，2H)，3.58 (m，1H)，7.45 (m，3H)，8.39 (d，J=9 Hz，1H)，9.04 (bs，1H); MS (DCI/NH3) m/z 179 (M+H)+.Methylbenzyl) amino 1_2_ketoethyl 丨 hexai. Example of pyridine ice N-gasification 119A L hexahydropyridine-4-some pyridinium N-hydride hydrochloride make 2- [1- (Third-butoxycarbonyl) hexahydropyridine_4_yl wind ingot N-oxide (1.24 g '4.15 Emole) was cooled in methylene chloride (30 ml) to 0, and then m-chloro Perbenzoic acid was treated with 77% (1.4 g, 8.3 mmol). At 〇. After stirring for 30 minutes at 0 ° ', the mixture was allowed to warm to room temperature and stirred for another 2 hours. The mixture was diluted with dichloromethane (50 ml), washed with saturated NaHC03, brine, dried over MgS04, filtered, and the filtrate was concentrated under reduced pressure to provide a white solid. The white solid was dissolved in ethyl acetate (50 ml) and cooled to -78. (:. HC1 gas was bubbled through the reaction mixture over 15 minutes and the mixture was allowed to warm to room temperature. The mixture was filtered and the filter cake was washed with ethyl acetate and then dried under a vacuum to provide the title compound (0.85 G, 96% yield) 1HNMR (300MHz5DMSO-d6) 5 1.82 (m5 2H)? 2.10 (m5 2H), 3.06 (m? 2H)? 85228-225-200404539 3.36 (m, 2H), 3.58 (m, 1H), 7.45 (m, 3H), 8.39 (d, J = 9 Hz, 1H), 9.04 (bs, 1H); MS (DCI / NH3) m / z 179 (M + H) +.

實例119B 2-(M2_「(3-甲基笨基）胺基1-2-酮基乙基}六氫吡啶-4-基）吡錄 N-氣化物 按照實例36D中所述之程序，以得自實例119A之產物取代 得自實例36C之產物，提供標題化合物（159毫克，48.8%產率） 。1H NMR (300 MHz，DMSO-d6) 51.89 (m，2H)，1·91 (m，2H)，2.30 (m，5H)， 2·99 (m，2H)，3·14 (s，2H)，3·25 (m，1H)，6.88 (d，J=7.5 Hz，1H)，7·19 (t，J=7.5 Hz，1H)，7.31 (m，2H)，7.45 (m，2H)，8.24 (m，1H)，9.6 (bs，1H); MS (DCI-NH3) m/z 310 (M+H)+. 將自由態鹼（156.7毫克）在乙醇（20毫升）中，以順丁烯二酸 (55.93毫克）處理，並將此溶液攪拌10分鐘，於減壓下濃縮， 提供順丁晞二酸鹽，為灰白色固體（212.6毫克）。iHNMR (300 MHz，DMSO-d6) 5 1.91 (m，2H)，2.15 (m，2H)，2.29 (s，3H)，3.30 (m，4H)， 3.50 (m，2H)，4.02 (m，1H)，6.04 (s，2H)，6·95 (d，J=7.5 Hz，1H)，7.23 (t，J=7.5 Hz，1H)，7.39 (m，5H)，8.29 (m，1H)，10.36 (bs，1H) ; MS (DCI-NH3) m/z 310 (M+H)+ ;對 0.25H2O.C23H27N3O6之分析計算值：C，61.94; H，6.22 ;N，9.42;實測值：C，61.56, H, 6.21，N，8.99. 實例121 N-2-金銦烷某-244-(3-氰基_2-吡啶基Η-六氫吡畊某1乙醯胺Example 119B 2- (M2 _ "(3-methylbenzyl) amino1-2-ketoethyl} hexahydropyridin-4-yl) pyrrolide N-gaside Following the procedure described in Example 36D, The product from Example 119A replaced the product from Example 36C to provide the title compound (159 mg, 48.8% yield). 1H NMR (300 MHz, DMSO-d6) 51.89 (m, 2H), 1.91 (m, 2H), 2.30 (m, 5H), 2.99 (m, 2H), 3.14 (s, 2H), 3.25 (m, 1H), 6.88 (d, J = 7.5 Hz, 1H), 7 · 19 (t, J = 7.5 Hz, 1H), 7.31 (m, 2H), 7.45 (m, 2H), 8.24 (m, 1H), 9.6 (bs, 1H); MS (DCI-NH3) m / z 310 (M + H) +. Treat the free base (156.7 mg) in ethanol (20 ml) with maleic acid (55.93 mg), stir the solution for 10 minutes, and concentrate under reduced pressure. Provide maleic acid as an off-white solid (212.6 mg). IHNMR (300 MHz, DMSO-d6) 5 1.91 (m, 2H), 2.15 (m, 2H), 2.29 (s, 3H), 3.30 (m , 4H), 3.50 (m, 2H), 4.02 (m, 1H), 6.04 (s, 2H), 6.95 (d, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H) , 7.39 (m, 5H), 8.29 (m, 1H), 10.36 (bs, 1H); MS (DCI-NH3) m / z 310 (M + H) +; Analytical calculated value for 0.25H2O.C23H27N3O6: C, 61.94; H, 6.22; N, 9.42; Found: C, 61.56, H, 6.21, N , 8.99. Example 121 N-2-A gold indium, -244- (3-cyano_2-pyridylfluorene-hexahydropyramine, 1 ethylamine

實例121A N-2-金鋼烷基-2_溴乙醯胺 按照實例1A中所述之程序，以2-金剛烷胺鹽酸鹽取代3-甲 85228 -226- 200404539Example 121A N-2-adamantyl-2-bromoacetamide Following the procedure described in Example 1A, 3-formamantamine hydrochloride was substituted for 3-methyl 85228 -226- 200404539

基苯胺，提供標題化合物（68%產率），為白色固體。1h NMR (300 MHz，DMSO-d6) (5 1.51 (d，2H，J=12.9 Hz)，1.78 (m，10H)，1.95 (d，2H， J=12.5 Hz)，3.82 (br d，1H，J=7.5 Hz)，3.92 (s，2H)，8.11 (br d，1H，J=7.1 Hz); MS (DCI/NH3) m/e 272 (M+H)+ ； 290(M+NH4)+.Aniline provided the title compound (68% yield) as a white solid. 1h NMR (300 MHz, DMSO-d6) (5 1.51 (d, 2H, J = 12.9 Hz), 1.78 (m, 10H), 1.95 (d, 2H, J = 12.5 Hz), 3.82 (br d, 1H, J = 7.5 Hz), 3.92 (s, 2H), 8.11 (br d, 1H, J = 7.1 Hz); MS (DCI / NH3) m / e 272 (M + H) +; 290 (M + NH4) + .

實例121B N-2-金鋼基-2-「4-(3-氰基-2-p比淀基）-1-六氫P比咕基乙酉義月条 將1_(2-氰基峨啶基）六氫被畊（680毫克，3.61毫莫耳）與n，N-二異丙基胺（2毫升）在甲苯（30毫升）中，以得自實例12ia之 產物（800毫克，2.94毫莫耳）處理，並加熱至6〇°c，歷經18小 時。使混合物冷卻至室溫，轉移至分液漏斗，並以飽和碳 酸氫鈉水溶液洗務。使有機相脫水乾燥（硫酸鋼），過濾， 並使滤液在減壓下濃縮。使殘留物於碎膠上藉急驟式管柱 層析純化（以20%醋酸乙酯：己垸溶離），提供917毫克（82% 產率）標題化合物，為白色固體。1HNMR(300MHz，DMSO-d6) 5 1.57 (d，2H，J=12.5 Hz)，1.79 (m，12H)，2.63 (m，4H)，3.04 (s，2H)，3.62 (m， 4H)，3.88 (br d，1H，J=7.8 Hz)，6.94 (dd，1H，J=7.5, 4.7 Hz)，7.69 (br d，1H， J=7.8 Hz)，8.08 (dd，1H，J=7.8, 2.0 Hz)，8.41 (dd，1H，J=4_8, 1.7 Hz) ； MS (DCI/NH3) m/e 380 (M+H)+ ;對 C2 2 H2 9N5 O 之分析計算值：c，69.63 ;H，7.70 ; N，18·45·實測值：C，69.45 ; H，7.90 ; N，18.07. 實例122 U4-(3-氰基-2-峨淀基）-1-六氫外1：喷某i-N-環己某乙醯胺Example 121B N-2-Gold-based 2- "4- (3-cyano-2-p ratio ytyl) -1-hexahydro P pyridyl acetazolium bar 1- (2-cyanorimidinyl) Hexahydrogen was cultivated (680 mg, 3.61 mmol) with n, N-diisopropylamine (2 ml) in toluene (30 ml) to obtain the product from Example 12ia (800 mg, 2.94 mmol) ), And heated to 60 ° C. for 18 hours. The mixture was cooled to room temperature, transferred to a separatory funnel, and washed with a saturated aqueous sodium bicarbonate solution. The organic phase was dehydrated and dried (sulphate steel), filtered, The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on gel (dissolved in 20% ethyl acetate: hexane) to provide 917 mg (82% yield) of the title compound as White solid. 1HNMR (300MHz, DMSO-d6) 5 1.57 (d, 2H, J = 12.5 Hz), 1.79 (m, 12H), 2.63 (m, 4H), 3.04 (s, 2H), 3.62 (m, 4H ), 3.88 (br d, 1H, J = 7.8 Hz), 6.94 (dd, 1H, J = 7.5, 4.7 Hz), 7.69 (br d, 1H, J = 7.8 Hz), 8.08 (dd, 1H, J = 7.8, 2.0 Hz), 8.41 (dd, 1H, J = 4_8, 1.7 Hz); MS (DCI / NH3) m / e 380 (M + H) +; for C2 2 Calculated values for H2 9N5 O: c, 69.63; H, 7.70; N, 18.45. Found: C, 69.45; H, 7.90; N, 18.07. Example 122 U4- (3-cyano-2- Edianji) -1-Hexane outside 1: spray iN-cyclohexylacetamide

實例122A 2-溴-N_環己基乙醯脍 於氯化溴乙醯（5.50毫升，66.9毫莫耳）在四氫吱喃（12〇毫升） 85228 -227- 200404539 中之溶液内，於0°C下，添加4-二甲基胺批淀（2.80克，22.9毫 莫耳）與環己胺（5.00毫升，43.7毫莫耳）在四氫味喃（6〇毫升） 中之混合物。使混合物溫熱至室溫’且再擾摔18小時。以 水使反應淬滅，並以二氯甲烷萃取。使有機相脫水乾燥（硫 鋼）’過滤’並使遽液在減壓下濃縮。使殘留物於珍膠上 藉急驟式管柱層析純化（以10%酷酸乙酯：己燒溶離），提供 標題化合物（25%產率），為白色固體。iHNMRpOOMHADMSadd 5 1.18 (m，5H)，1.64 (m，5H)，3·52 (m，1H)，3·99 (s，2H)，8.04 (bf d，1H，J=7.1Example 122A A solution of 2-bromo-N-cyclohexylacetamidine in ethidium bromide chloride (5.50 ml, 66.9 mmol) in tetrahydrofuran (120 ml) 85228 -227- 200404539, at 0 At ° C, a mixture of 4-dimethylamine batch (2.80 g, 22.9 mmol) and cyclohexylamine (5.00 ml, 43.7 mmol) in tetrahydrofuran (60 ml) was added. The mixture was allowed to warm to room temperature 'and was stirred for another 18 hours. The reaction was quenched with water and extracted with dichloromethane. The organic phase was dehydrated and dried (sulfur steel) 'filtered' and the mash was concentrated under reduced pressure. The residue was purified by gel column chromatography (dissolved in 10% ethyl acetate: hexane) to provide the title compound (25% yield) as a white solid. iHNMRpOOMHADMSadd 5 1.18 (m, 5H), 1.64 (m, 5H), 3.52 (m, 1H), 3.99 (s, 2H), 8.04 (bf d, 1H, J = 7.1

Hz) ； MS (DCI/NH3) m/e 237/239 (M+NH4)+.Hz); MS (DCI / NH3) m / e 237/239 (M + NH4) +.

實例122B 2-「4-(3-氰基-2-p比淀基）-1-六氫外(：吨基1-N-環己基乙醯胺 按照實例121B中所述之程序，以得自實例122A之產物取代 得自實例121之產物，提供標題化合物（46%產率），為白色 固體。1H NMR (300 MHz，DMSO-d6) 5 1.22 (m，3H)，1.38 (m，2H)，1.67 (m， 3H)，1.89 (m，2H)，2·68 (m，4H)，3.05 (s，2H)，3.75 (m，4H)，3.83 (m，1H)，6.79 (dd，1H，J=7.5, 4.8 Hz)，7.02 (br s，1H)，7.78 (dd，1H，J=7.6, 1.9 Hz)，8.35 (dd， 1H，J=4.8, 2.0 Hz) ; MS (DCI/NH3) m/e 328 (M+H)+ ;對 q 8 H2 5 N5 0 之 分析計算值：C，66.03 ; H，7.70 ; N，21.39.實測值：C，65.88 ; H，7.70 ；N, 21.28. 實例123Example 122B 2- "4- (3-Cyano-2-p than ydoyl) -1-hexahydroexo (: t-based 1-N-cyclohexylacetamidinyl) Follow the procedure described in Example 121B to obtain The product from Example 122A replaced the product from Example 121 to provide the title compound (46% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) 5 1.22 (m, 3H), 1.38 (m, 2H ), 1.67 (m, 3H), 1.89 (m, 2H), 2.68 (m, 4H), 3.05 (s, 2H), 3.75 (m, 4H), 3.83 (m, 1H), 6.79 (dd, 1H, J = 7.5, 4.8 Hz), 7.02 (br s, 1H), 7.78 (dd, 1H, J = 7.6, 1.9 Hz), 8.35 (dd, 1H, J = 4.8, 2.0 Hz); MS (DCI / NH3) m / e 328 (M + H) +; Analytical calculated value for q 8 H2 5 N50 0: C, 66.03; H, 7.70; N, 21.39. Found: C, 65.88; H, 7.70; N, 21.28. Example 123

2-「4_(3-氰基_2_吡啶某VI-六氫吡畊基l-N-5,6,7,8-四氫小苯基ZjMM2-``4_ (3-cyano_2_pyridine

實例123A 2-溴-N-5,6,7,8-四氫小茬基乙醯胺 按照實例1A中所述之程序，以5,6,7,8-四氫小莕胺取代3_甲 85228 -228- 200404539 基苯胺，提供標題化合物（14%產率），為白色固體。ijj NMR . (300 MHz，DMSO-d6) 5 1.70 (m，4H)，2.58 (m，2H)，2.73 (m，2H)，4·07 (s，2H)， 6.93 (d，1H，J=7.5 Hz)，7.07 (dd，1H，J=7.8, 7_8 Hz)，7.17 (d，1H，J=6.8 Hz)， 9.55 (br s，1H) ; MS (DCI/NH3) m/e 268/270 (M+H)+ ; 285/287 (M+NH4)+ ·Example 123A 2-Bromo-N-5,6,7,8-tetrahydropyridylacetamide Follow the procedure described in Example 1A to replace 3_ with 5,6,7,8-tetrahydropyridamine Methyl 85228 -228- 200404539 aniline, which provided the title compound (14% yield) as a white solid. ijj NMR. (300 MHz, DMSO-d6) 5 1.70 (m, 4H), 2.58 (m, 2H), 2.73 (m, 2H), 4.07 (s, 2H), 6.93 (d, 1H, J = 7.5 Hz), 7.07 (dd, 1H, J = 7.8, 7_8 Hz), 7.17 (d, 1H, J = 6.8 Hz), 9.55 (br s, 1H); MS (DCI / NH3) m / e 268/270 (M + H) +; 285/287 (M + NH4) + ·

實例123B 2-[~4-(3-氰基-2-外1：淀基）-1-六氫吡畊基1-N-5,6,7,8-四氫_1-蓋某乙醯胺 按照實例121B中所述之程序，以得自實例123A之產物取代 得自實例121A之產物，提供標題化合物（75%產率），為白色 _ 固體。WNMRPOOMHaDMSO-c^) (5 1.74(m，4H)，2.62(m，2H)，2.72 (m，6H)，3·20 (s，2H)，3·69 (m，4H)，6.88 (d，1H，J=7.5 Hz), 6·94 (dd，1H，J=7.8， 4.7 Hz)，7.07 (dd，1H，J=7.8 Hz)，7.59 (d，1H，J=7.8 Hz)，8.08 (dd，1H，J=7.5, 1· 7 Hz)，8.42 (dd，1H，J=4.8, 1.7 Hz)，9.33 (br s，1H) ; MS (DCI/NH3) m/e 376 (M+H)+ ;對 C22H25N5O*0.3H2O之分析計算值：C，69.38; H，6.77 ;N，18.39·實測值：C，69.40 ; H，6·63 ; N，18.13. 實例124 2_(3’,6’·二氫-2,聯吡啶基VN-(4-氟基-2-甲某苯基）乙醯胺 ·Example 123B 2- [~ 4- (3-Cyano-2-exo 1: Yodo) -1-hexahydropyridyl 1-N-5,6,7,8-tetrahydro_1-Gai The amidine was replaced with the product from Example 123A by the procedure described in Example 121B to provide the title compound (75% yield) as a white solid. WNMRPOOMHaDMSO-c ^) (5 1.74 (m, 4H), 2.62 (m, 2H), 2.72 (m, 6H), 3.20 (s, 2H), 3.69 (m, 4H), 6.88 (d, 1H, J = 7.5 Hz), 6.94 (dd, 1H, J = 7.8, 4.7 Hz), 7.07 (dd, 1H, J = 7.8 Hz), 7.59 (d, 1H, J = 7.8 Hz), 8.08 ( dd, 1H, J = 7.5, 1.7 Hz), 8.42 (dd, 1H, J = 4.8, 1.7 Hz), 9.33 (br s, 1H); MS (DCI / NH3) m / e 376 (M + H ) +; Analysis and calculation of C22H25N5O * 0.3H2O: C, 69.38; H, 6.77; N, 18.39. Found: C, 69.40; H, 6.63; N, 18.13. Example 124 2_ (3 ', 6 '· Dihydro-2, bipyridyl VN- (4-fluoro-2-methylphenyl) acetamidamine ·

實例124A 2-1 -N-(4-氟基-2-甲基笨基）乙醯胺 按照實例22A中所述之程序，以4-氟基-2-甲基苯基胺取代 3,4,5-三甲氧基苯胺，提供標題化合物（51%產率），為白色固 體。1H NMR (300 MHz, DMSO-d6) 5 2.19 (s，3H)，4.29 (s，2H)，7.01 (ddd， 1H，J=8.5, 8.5, 3.1 Hz)，7.10 (dd，1H，J=9.8, 3·1 Hz)，7·35 (dd，1H，J=8.8, 5·8 Hz), 9.67 (br s? 1H) ； MS (DCI/NH3) m/e 202 (M+H)+ ； 219 (M+NH4)+.Example 124A 2-1 -N- (4-Fluoro-2-methylbenzyl) acetamidine Following the procedure described in Example 22A, 3,4 was replaced with 4-fluoro-2-methylphenylamine , 5-trimethoxyaniline to provide the title compound (51% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) 5 2.19 (s, 3H), 4.29 (s, 2H), 7.01 (ddd, 1H, J = 8.5, 8.5, 3.1 Hz), 7.10 (dd, 1H, J = 9.8 , 3.1 Hz), 7.35 (dd, 1H, J = 8.8, 5.8 Hz), 9.67 (br s? 1H); MS (DCI / NH3) m / e 202 (M + H) +; 219 (M + NH4) +.

實例124B 85228 -229- 200404539Example 124B 85228 -229- 200404539

2-Γ3’·6’-二氫-2,聯吡啶-l’(2’HV基VN-(4-氣基_2_甲甚y基）乙醯胺 使1’,2’，3’，6’-四氫_[2,4’]聯吡啶鹽酸鹽（30毫克，〇·15毫莫耳，Saari， W.S.等人；J· Med_ Chem. 1984, 2入 1182)、得自實例 124A 之產物（40 毫克，0.20毫莫耳）及碳酸鈉（70毫克）在N，N-二甲基甲醯胺/ 水（2 : 1，2毫升）中之混合物，於室溫下振盪18小時。使所 形成之混合物在減壓下濃縮。使殘留物藉預備之HPLC純化 ’提供46毫克（70 %)所要之產物’為二氣醋酸鹽。NMR (300MHz，DMSOd6)5 2.20(s，3H)，2.96(brs，2H)，3.43-3.63 (m，2H)，4.03-4.20 (m，2H)，4_39 (s，2H)，6·72 (br s，1H)，7·10 (m，2H)，7·38 (m5 1H)，7.43 (m， 1H)，7.64 (d，J=7 Hz，1H)，7.84 (m，1H)，8.60 (m，1H)，10.00 (m，1H)，10.40 (br s5 1H) ； MS (ESI/APCI+) m/e 326 (M+H)+. 實例125 N-{『4-(2·^比淀基）-1-六氫p比淀基1甲基丨-3-(三氟甲基）笨甲酸胺 將得自實例36C之產物（20毫克，0_10毫莫耳）、聚甲醛（3〇 毫克，1毫莫耳）、3-三氟甲基苯甲醯胺（95毫克，0.5毫莫耳 ，Lancaster)及42毫克碳酸鉀（0.3毫莫耳）在2·5毫升無水乙醇中 之混合物，於氮氣下，加熱至回流過夜。使混合物冷卻至 室溫，過濾，並移除溶劑。使殘留物於矽膠上藉急驟式管 柱層析純化（10%甲醇：醋酸乙酯），而得11.2毫克（34% )純化 合物。1H NMR (500 MHz，DMSO-d6) 5 1 _72 (m，2Η)，1.82 (m，2Η)，2.34 (m5 2H)，2·60 (m，1H)，2.96 (m，2H)，4.20 (d，J=6.2 Hz，2H)，7.18 (ddd, J=7.5, 4.8， 1.1 Hz5 1H)? 7.25 (m5 1H)? 7.69 (td? J=7.6? 1.9 Hz? 1H)? 7.74 (t? J=7.8 Hz? 1H)? 7.92 (d，J=7.8 Hz，1H)，8.20 (d，J=7.8 Hz，1H)，8.24 (s，1H)，8.47 (ddd，J=5.0， 1.9, 0·9 Hz，1H)，9.02 (t，J=6.1 Hz，1H) ; MS (ESI/APCI-) m/e 362 (M-H)+ ·2-Γ3 '· 6'-dihydro-2, bipyridine-1' (2'HV group VN- (4-air group_2_methyl very yyl) acetamide to make 1 ', 2', 3 ' , 6'-tetrahydro_ [2,4 '] bipyridine hydrochloride (30 mg, 0.15 mmol, Saari, WS et al .; J. Med_Chem. 1984, 2 into 1182), obtained from the examples A mixture of the product of 124A (40 mg, 0.20 mmol) and sodium carbonate (70 mg) in N, N-dimethylformamide / water (2: 1,2 ml), shaken at room temperature for 18 Hours. The resulting mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to 'provide 46 mg (70%) of the desired product' as digas acetate. NMR (300 MHz, DMSOd6) 5 2.20 (s, 3H), 2.96 (brs, 2H), 3.43-3.63 (m, 2H), 4.03-4.20 (m, 2H), 4_39 (s, 2H), 6.72 (br s, 1H), 7.10 (m , 2H), 7.38 (m5 1H), 7.43 (m, 1H), 7.64 (d, J = 7 Hz, 1H), 7.84 (m, 1H), 8.60 (m, 1H), 10.00 (m, 1H ), 10.40 (br s5 1H); MS (ESI / APCI +) m / e 326 (M + H) +. Example 125 N- {"4- (2 · ^ 比 淀 基) -1-Hexane p-Hide The 1-methyl-1- (trifluoromethyl) benzyl carboxylate will be obtained from the product of Example 36C (2 0 mg, 0-10 mmol), polyoxymethylene (30 mg, 1 mmol), 3-trifluoromethylbenzamide (95 mg, 0.5 mmol, Lancaster) and 42 mg potassium carbonate (0.3 Mol) in 2.5 ml of absolute ethanol, heated to reflux under nitrogen overnight. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed. The residue was borrowed on a silica gel flash column (10% methanol: ethyl acetate) to obtain 11.2 mg (34%) of pure compound. 1H NMR (500 MHz, DMSO-d6) 5 1 _72 (m, 2Η), 1.82 (m, 2Η), 2.34 (m5 2H), 2.60 (m, 1H), 2.96 (m, 2H), 4.20 (d, J = 6.2 Hz, 2H), 7.18 (ddd, J = 7.5, 4.8, 1.1 Hz5 1H)? 7.25 ( m5 1H)? 7.69 (td? J = 7.6? 1.9 Hz? 1H)? 7.74 (t? J = 7.8 Hz? 1H)? 7.92 (d, J = 7.8 Hz, 1H), 8.20 (d, J = 7.8 Hz , 1H), 8.24 (s, 1H), 8.47 (ddd, J = 5.0, 1.9, 0.9 Hz, 1H), 9.02 (t, J = 6.1 Hz, 1H); MS (ESI / APCI-) m / e 362 (MH) + ·

JO 85228 -230- 200404539 實例126 一甲氧基比遠基）-1-六氫外1：淀基1甲某}苯甲驢胺 將得自實例36C之產物（20毫克，0.10毫莫耳）、聚甲醛（30 毫克，1毫莫耳）、3,5-二甲氧基苯甲醯胺（91毫克，0.5毫莫 耳’ Aldrich)及42毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水乙醇 中之混合物，於氮氣下，加熱至回流過夜。使混合物冷卻 至室溫，過濾，並移除溶劑。使殘留物於矽膠上藉急驟式 管柱層析純化（10%甲醇：醋酸乙酯），獲得118毫克（34% )純 化合物。1 H NMR (500 MHz，DMSO-d6) 51.73 (m，2Η)，1.82 (m，2Η)，2.36 (m，2H)，2.61 (m，1H)，2·96 (m，2H)，3·79 (s，6H)，4.18 (d，J=6.0 Hz，2H)，6.65 (s，1H)，7.05 (s，2H)，7.18 (t，J=5 Hz，1H)，7.25 (d，J=7 Hz，1H)，7.69 (t，J=7 Hz， 1H)，8.47 (d，J=4 Hz，1H)，8·75 (t，J=6 Hz，1H) ； MS (ESI/APCI-) m/e 354 (M-H)+. 實例127 N-IK-O外1：咬基）-1-六氫外i：途基i甲基}環己燒巍gf胺 將得自實例36C之產物（20毫克，〇.1〇毫莫耳）、聚甲醛（30 毫克，1毫莫耳）、環己烷羧酸醯胺（63毫克，0·5毫莫耳，Aldrich) 及42毫克碳酸鉀（0.3毫莫耳）在2.5毫升無水乙醇中之混合物 ，於氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過 濾，並移除溶劑。使殘留物於矽膠上藉急騾式管柱層析純 化（10%甲醇：醋酸乙酯），而得16毫克（56% )純化合物。 1H NMR (500 MHz, DMS0-d6) δ 1.38 (m5 2Η)? 1.19 (m? 4Η)? 1.73 (m? 2Η)? 1.68 (m，4Η)，1·80 (m，2Η)，2.18 (m，3Η)，2.58 (m，1Η)，2·92 (m，2Η)，3.92 (d， J=5 Hz? 2H)? 7.18 (t5 J=5 Hz, 1H)? 7.26 (d? J=7 Hz5 1H)5 7.69 (t? J=7 Hz5 1H)? 85228 -231- 200404539 7.95 (t，J=5 Hz，1Η)，8·55 (d, J=4 Hz，1H) ; MS (ESI/APCI+) m/e 302 (M+H)+ · 實例128 3,4-二氟吡啶基）-1-六氫吡啶基1甲某}苯甲醯胺 將得自實例36C之產物（20毫克，0.10毫莫耳）、聚甲醛（3〇 毫克，1毫莫耳）、3,4-二氟苯甲醯胺（79毫克，0.5毫莫耳， Lancaster)及42毫克碳酸钾（0.3毫莫耳）在2.5毫升無水乙醇中之 混合物，於氮氣下，加熱至回流過夜。使混合物冷卻至室 溫，過濾，並移除溶劑。使殘留物於矽膠上藉急騾式管柱 層析純化（10%甲醇：醋酸乙酯），獲得16毫克（56% )純化合 物。1 H NMR (500 MHz，DMSO-d6) 5 1.73 (m，2H)，1.82 (m，2H)，2.33 (m， 2H)5 2.60 (m? 1H), 2.95 (m? 2H)? 4.18 (d, J=5 Hz5 2H)? 7.18 (t? J=5 Hz? 1H)? 7.25 (d，J=7 Hz，1H)，7.58 (t，J=7 Hz，1H)，7.70 (t，J=7 Hz，1H)，7.80 (m，1H)， 7.95 (t，J=7 Hz，1H)，8.45 (d，J=4 Hz，1H)，8.95 (t，J=5 Hz，1H); MS (ESI/APCI-) m/e 330 (M-H)+. 實例129JO 85228 -230- 200404539 Example 126 Monomethoxy than faryl) 1-Hexahydro-1: Yodoyl 1A} Benzodonamine will be obtained from the product of Example 36C (20 mg, 0.10 mmol) , Polyoxymethylene (30 mg, 1 mmol), 3,5-dimethoxybenzamide (91 mg, 0.5 mmol 'Aldrich), and 42 mg potassium carbonate (0.3 mmol) The mixture in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 118 mg (34%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) 51.73 (m, 2Η), 1.82 (m, 2Η), 2.36 (m, 2H), 2.61 (m, 1H), 2.96 (m, 2H), 3 · 79 (s, 6H), 4.18 (d, J = 6.0 Hz, 2H), 6.65 (s, 1H), 7.05 (s, 2H), 7.18 (t, J = 5 Hz, 1H), 7.25 (d, J = 7 Hz, 1H), 7.69 (t, J = 7 Hz, 1H), 8.47 (d, J = 4 Hz, 1H), 8.75 (t, J = 6 Hz, 1H); MS (ESI / APCI -) m / e 354 (MH) +. Example 127 N-IK-O outer 1: bithenyl) -1-hexahydro outer i: tryl i methyl} cyclohexylpyridine gf amine will be obtained from Example 36C Product (20 mg, 0.10 mmol), polyoxymethylene (30 mg, 1 mmol), cyclohexylcarboxylate (63 mg, 0.5 mmol, Aldrich) and 42 mg of carbonic acid A mixture of potassium (0.3 mmol) in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed. The residue was purified on silica gel by flash column chromatography (10% methanol: ethyl acetate) to obtain 16 mg (56%) of the pure compound. 1H NMR (500 MHz, DMS0-d6) δ 1.38 (m5 2Η)? 1.19 (m? 4Η)? 1.73 (m? 2Η)? 1.68 (m, 4Η), 1.80 (m, 2Η), 2.18 (m , 3Η), 2.58 (m, 1Η), 2.92 (m, 2Η), 3.92 (d, J = 5 Hz? 2H)? 7.18 (t5 J = 5 Hz, 1H)? 7.26 (d? J = 7 Hz5 1H) 5 7.69 (t? J = 7 Hz5 1H)? 85228 -231- 200404539 7.95 (t, J = 5 Hz, 1Η), 8.55 (d, J = 4 Hz, 1H); MS (ESI / APCI +) m / e 302 (M + H) + · Example 128 3,4-difluoropyridyl) -1-hexahydropyridyl 1methyl} benzamidine will be obtained from the product of Example 36C (20 mg, 0.10 mmoles), polyformaldehyde (30 mg, 1 mmoles), 3,4-difluorobenzamide (79 mg, 0.5 mmoles, Lancaster) and 42 mg potassium carbonate (0.3 mmoles ) A mixture in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was cooled to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 16 mg (56%) of the purified compound. 1 H NMR (500 MHz, DMSO-d6) 5 1.73 (m, 2H), 1.82 (m, 2H), 2.33 (m, 2H) 5 2.60 (m? 1H), 2.95 (m? 2H)? 4.18 (d , J = 5 Hz5 2H)? 7.18 (t? J = 5 Hz? 1H)? 7.25 (d, J = 7 Hz, 1H), 7.58 (t, J = 7 Hz, 1H), 7.70 (t, J = 7 Hz, 1H), 7.80 (m, 1H), 7.95 (t, J = 7 Hz, 1H), 8.45 (d, J = 4 Hz, 1H), 8.95 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 330 (MH) +. Example 129

氨吡啶基）-1-六氤吡啶基1甲基}苯甲醯胺 將得自實例36C之產物（20毫克，〇·1〇毫莫耳）、聚甲醛（3〇 毫克’ 1¾莫耳）、3-氯苯甲酿胺（165毫克，0.5毫莫耳，Lancaster) 及42毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水乙醇中之混合物 ’於氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過 濾’並移除溶劑。使殘留物於矽膠上藉急驟式管柱層析純 化（10%甲醇··醋酸乙酯），而得U毫克（36% )純化合物。 iHNMRGOOMHADMSO-cy 5 1.73(m，2H)，1.82(m，2H)，2.33(m，2H)， 2·60 (m，1H)，2.95 (m，2H)，4·18 (d，J=5 Hz，2H)，7.18 (t，J=6 Hz，1H)，7·25 (d， 85228 -232- 200404539 J=7 Hz，1Η)，7·56 (t，J=7 Hz，1Η)，7·62 (d，J=6 Hz，1H)，7.72 (t，J=7 Hz，1H)， 7.85 (d，J=6 Hz，1H)，7.95 (s，1H)，8.48 (d5 J=6 Hz，1H)，8·95 (t，J=5 Hz，1H); MS (ESI/APCI-) m/e 328 (M-H)+. 實例130 2,3-二甲基-N-{「4-(2-峨淀基）-1-六氫峨p井基1甲基}笨甲酸胺 將1-吡啶-2-基六氫吡畊（16毫克，0.1毫莫耳，Aldrich)、聚甲 醛（30毫克，1毫莫耳）、2,3-二甲基苯甲醯胺（75毫克，0.5毫 莫耳，Lancaster)及42毫克碳酸鉀（0.3毫莫耳）在2毫升無水乙 醇中之混合物，於氮氣下，加熱至回流過夜。使混合物冷 卻至室溫，過濾，並移除溶劑。使殘留物於矽膠上藉急驟 式管柱層析純化（10%甲醇：醋酸乙酯），獲得29毫克（88% ) 純化合物。iHNMR (500.MHz，DMSO-d6 )5 2.20 (s，3H)，2.24 (s，3H)， 2.61 (t，J=4 Hz，4H)，3.48 (t，J=4 Hz，4H)，4.15 (d，J=5 Hz，1H)，6·62 (t，J=5 Hz， 1H)，6.81 (d，J=6 Hz，1H)，7.03 (m，2H)，7.21 (t，J=5 Hz，1H)，7.51 (t，J=6 Hz， 1H)，8.12 (d，J=5 Hz，1H)，8.52 (t，J=5 Hz，1H) ； MS (ESI/APCI-) m/e 323 實例131 _2,4’_聯吡啶-!’(2Ή)-基甲基V3-〔三崖^甲基）笨甲脖 將1，2,3’，6f-四氫-[2,4]聯p比淀鹽酸鹽（20毫克，毫莫耳， Saari，W.S.等人；J· Med· Chem. 1984, 27, 1182)、聚甲醛(3〇 毫克，i Φ莫耳）、3-三氟甲基苯甲酸胺（95毫克，〇·5毫莫耳）及42毫 克碳酸鉀（0.3毫莫耳）在2.5毫升無水乙醇中之混合物，於氮 氣下，加熱至回流過夜。使混合物冷卻至室溫，過淚，並 移除溶劑。使殘留物於矽膠上藉急騾式管柱層析純化（1〇% 85228 -233 - 200404539 甲醇·錯酸乙醋）’而得15毫克（41% )純化合物。1H NMR (500 MHz，DMSO-d6) δ 2.58 (m，2H)，2.80 (t，J=4 Hz，2H)，3·28 (m，2H)， 4.32 (d，J=5 Hz，2H)，6.71 (m，1H)，7.22 (m，1H)，7.52 (d，J=6 Hz，1H)，7.72 (m， 2H)? 7.95 (d5 J=6 Hz? 1H)? 8.22 (m? 2H)? 8.52 (m3 1H)? 9.08 (t? J-5 Hz? 1H)； MS (ESI/APCI-) m/e 360 (M-H)+. 實例132 3-氯二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）笨甲醯胺 將Γ，2’，3’，6’-四氫-[2,4’]聯吡啶鹽酸鹽（20毫克，0.10毫莫耳， Saari，W.S.等人；J_ Med· Chem· 1984, 27, 1182)、聚甲酸（30 毫克，1 毫莫耳）、3-氯苯甲驗胺（78毫克，0.5毫莫耳，Lancaster)及42 毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水乙醇中之混合物，於 氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過漉， 並移除溶劑。使殘留物於矽膠上藉急驟式管柱層析純化（1〇 %甲醇：醋酸乙酯），獲得20毫克（61% )純化合物。1HNMR (500 MHz，DMSO_d6 ) δ 62.58 (m，2Η)，2·79 (t，J=4 Ηζ，2Η)，3·30 (m，2Η)， 4·30 (d，J=5 Hz，2H)，6.71 (m，1H)，7.22 (m，1H)，7·52 (m，2H)，7_62 (d，J=6 Hz， 1H)，7.73 (t，J=6 Hz，1H)，7.85 (d，J=6 Hz，1H)，7.92 (s，1H)，8.52 (m，1H)，9.08 (t，J=5 Hz，1H) ; MS (ESI/APCI-) m/e 326 (M-H)+ · 實例133 N_(3\6f-二氫-2,4f-聯吡啶-l’(2’HV基甲基）環己烷#醯胺 將Γ，2’，3’，6’-四氫-[2,4T]聯吡啶鹽酸鹽（20毫克，〇.1〇毫莫耳， Saari，W.S·等人·’ J. Med. Chem· 1984, 27, 1182)、聚甲駿（30 毫克，1 毫莫耳）、環己说叛酸醒胺（64毫克，0.5毫莫耳，Aldrich)及42 毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水乙醇中之混合物，於 85228 -234- 200404539 氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過濾， 並移除溶劑。使殘留物於碎膠上藉急驟式管柱層析純化（10 %甲醇：醋酸乙酯），而得19毫克（64% )純化合物。1HNMR (500 MHz，DMSO-d6) 5 1·19 (m，4H)，1.26 (m，2H)，1·61 (m，1H)，1.68 (m， 3H)，2.18 (m，1H)，2.55 (m5 2H)，2.68 (m，2H)，3.18 (m，2H)，4_02 (d，J=5 Hz， 2H)，6.68 (m，1H)，7.22 (m，1H)，7.52 (d，J=6 Hz，1H)，7.73 (t5 J=6 Hz, 1H)， 8.02 (t，J=5 Hz，1H)，8.52 (m，1H) ; MS (ESI/APCI-) m/e 298 (M-H)+. 實例134 N-(3’,6’-二氫-2,4’-聯吡啶-m’HV某甲基V3,4-二氟笨甲醯胺 將Γ，2’，3’，6’-四氫-[2,4]聯吡啶鹽酸鹽（20毫克，0.10毫莫耳， Saari，W.S·等人；J. Med_ Chem· 1984, 27, 1182)、聚甲醛(30 毫克，1 毫莫耳）、3,4-二氟苯甲驢胺（79毫克，0.5毫莫耳，Lancaster) 及42毫克碳酸鉀（0·3毫莫耳）在2_5毫升無水乙醇中之混合物 ，於氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過 滤，並移除溶劑。使殘留物於矽膠上藉急驟式管柱層析純 化（10%甲醇：醋酸乙酯），獲得18毫克（55% )純化合物。 1H NMR (500 MHz，DMSO-d6) 5 2.58 (m，2Η)，2·79 (t，J=4 Ηζ，2Η)，3.32 (m， 2H)，4·28 (d，J=5 Hz，2H)，6.71 (m，1H)，7_22 (m，1H)，7_55 (m，2H)，7·83 (m， 2H)，7·95 (t，J=6 Hz，1H)，8.52 (m，1H) 8.95 (t，JN5 Hz，1H) ; MS (ESI/APCI-) m/e 328 (M-H)+. 實例135 N-(3f,6f-二氫-2,4’-聯吡啶-Γ(2Ήν基甲墓V3,5-二甲氫基笨甲醯胺 將1’，2’，3’，6’-四氫-[2,4’]聯吡啶鹽酸鹽（20毫克，〇.1〇毫莫耳， Saari，W.S.等人；J. Med· Chem· 1984, 27, 1182)、聚甲醛（30 毫克，1 85228 -235 - 200404539 毫莫耳）、3,5-二甲氧基苯甲醯胺（91毫克，〇·5毫莫耳，Aldrich) 及42毫克碳酸鉀（0.3毫莫耳）在2_5毫升無水乙醇中之混合物 ，於氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過 濾，並移除溶劑。使殘留物於矽膠上藉急驟式管柱層析純 化（10%甲醇：醋酸乙酯），而得19毫克（55% )純化合物。 1H NMR (500 MHz，DMSO-d6) 6 2.59 (m，2H)，2.79 (t，J=4 Hz，2H)，3_30 (m， 2H)，3.79 (s，3H)，3.80 (s，3H)，4·25 (d，J=5 Hz，2H)，6.65 (s，1H)，6.71 (m，1H)， 7.02 (s，2H)，7.22 (m，1H)，7.52 (d，J=6 Hz，1H)，7.75 (t，J=6 Hz，1H)，8.52 (m， 1H) 8.88 (t，J=5 Hz，1H) ; MS (ESI/APCI-) m/e 352 (M-H)+ · 實例136 N-(3-甲基苯基）-2-(4-苯基-1-六氫比咬基）乙酿胺 按照實例35中所述之程序，以4-苯基六氫吡啶取代4-(2-甲 氧苯基）六氫吡啶，提供標題化合物（99%產率）。iHNMR (300 MHz，DMSO-d6) 5 1.76 (m，4H)，2.28 (m，5H)，2.51 (m，1H)，2·98 (m， 2H)，3.12 (s，2H)，6_88 (d，J=6 Hz，1H)，7.19 (m，2H)，7.29 (m，4H)，7.46 (d，2H)， 9.61 (br s，1H); MS (DCI/NH3 ) m/e 310 (M+H)+ ;對 C2 〇 H2 4 N2 O · 0.2 H2 O 之分析計算值·· C，76.99 ; H，7·88 ; N, 8.98.實測值：C，76.88, H，7.85， N，8.81 實例137 2-(3f，6’-二氮-2,4’-聯π比淀-lf(2’H)·基）-N-(3-硝基笨基）乙酸胺 所要之物質係根據實例124B之程序，經由以2-氯-N-(3-硝基 苯基）乙醯胺（Lancaster)取代得自實例124A之產物而製成。產 量 48 毫克（97%)。111丽11(300^1112,0^^0-(16)(5 2.96〇^8,211)，3.45-3.75 (m，2H)，4.05-4.20 (m，2H)，4.38 (s，2H)，6.75 (br s，1H)，7.38 (m，1H)， 85228 -236- 200404539 7.66 (m，2H)，7.89 (m，2H)，8.00 (d，J=6 Hz，1Η)，8·60 (m，1H)，8.63 (br s，1H)， 10.45 (br s，1H)，11.08 (br s，1H) ; MS (ESI/APCI+) m/e 339 (M+H)+. 實例138 N-l_金鋼燒基-2-「4-(3•氰基-2-p比淀基）-1-六氫p比呼基乙酸胺Aminopyridyl) -1-hexamethylpyridyl 1methyl} benzylamine will be obtained from the product of Example 36C (20 mg, 0.10 mol), polyoxymethylene (30 mg '1¾ mol) A mixture of 3-chlorobenzamide (165 mg, 0.5 mmol, Lancaster) and 42 mg of potassium carbonate (0.3 mmol) in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered 'and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol · ethyl acetate) to obtain U mg (36%) of the pure compound. iHNMRGOOMHADMSO-cy 5 1.73 (m, 2H), 1.82 (m, 2H), 2.33 (m, 2H), 2.60 (m, 1H), 2.95 (m, 2H), 4.18 (d, J = 5 Hz, 2H), 7.18 (t, J = 6 Hz, 1H), 7.25 (d, 85228 -232- 200404539 J = 7 Hz, 1Η), 7.56 (t, J = 7 Hz, 1Η), 7.62 (d, J = 6 Hz, 1H), 7.72 (t, J = 7 Hz, 1H), 7.85 (d, J = 6 Hz, 1H), 7.95 (s, 1H), 8.48 (d5 J = 6 Hz, 1H), 8.95 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 328 (MH) +. Example 130 2,3-dimethyl-N- {" 4- (2-Edianyl) -1-hexahydroepisopropyl 1methyl} ammonium benzylcarboxylate 1-pyridin-2-ylhexahydropyridine (16 mg, 0.1 mmol, Aldrich), poly Formaldehyde (30 mg, 1 mmol), 2,3-dimethylbenzamide (75 mg, 0.5 mmol, Lancaster) and 42 mg potassium carbonate (0.3 mmol) in 2 ml of absolute ethanol The mixture was heated to reflux overnight under nitrogen. The mixture was cooled to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate), Obtained 29 mg (88%) of pure compound. IHNMR (500.MHz, DMSO-d6) 5 2.20 (s 3H), 2.24 (s, 3H), 2.61 (t, J = 4 Hz, 4H), 3.48 (t, J = 4 Hz, 4H), 4.15 (d, J = 5 Hz, 1H), 6.62 ( t, J = 5 Hz, 1H), 6.81 (d, J = 6 Hz, 1H), 7.03 (m, 2H), 7.21 (t, J = 5 Hz, 1H), 7.51 (t, J = 6 Hz, 1H), 8.12 (d, J = 5 Hz, 1H), 8.52 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 323 Example 131 _2,4'_bipyridine-! ' (2Ή) -Methylmethyl V3- [Sanya ^ methyl] benzyl 1,2,3 ', 6f-tetrahydro- [2,4] bi-p-pyridine hydrochloride (20 mg, mmol Ear, Saari, WS et al .; J. Med. Chem. 1984, 27, 1182), polyoxymethylene (30 mg, i Φmol), 3-trifluoromethylbenzoate (95 mg, 0.5 A mixture of 42 millimoles) and 42 mg of potassium carbonate (0.3 millimoles) in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, teared, and the solvent was removed. The residue was purified on silica gel by flash column chromatography (10% 85228 -233-200404539 methanol · ethyl acetate) to obtain 15 mg (41%) of the pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.58 (m, 2H), 2.80 (t, J = 4 Hz, 2H), 3.28 (m, 2H), 4.32 (d, J = 5 Hz, 2H) , 6.71 (m, 1H), 7.22 (m, 1H), 7.52 (d, J = 6 Hz, 1H), 7.72 (m, 2H)? 7.95 (d5 J = 6 Hz? 1H)? 8.22 (m? 2H )? 8.52 (m3 1H)? 9.08 (t? J-5 Hz? 1H); MS (ESI / APCI-) m / e 360 (MH) +. Example 132 3-chlorodihydro-2,4'-linked Pyridine-1 '(2Ή) -ylmethyl) benzylamidine will be Γ, 2', 3 ', 6'-tetrahydro- [2,4'] bipyridine hydrochloride (20 mg, 0.10 mmol) , Saari, WS et al .; J_ Med · Chem · 1984, 27, 1182), polyformic acid (30 mg, 1 mmol), 3-chlorobenzamide (78 mg, 0.5 mmol, Lancaster) and A mixture of 42 mg of potassium carbonate (0.3 mmol) in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 20 mg (61%) of the pure compound. 1HNMR (500 MHz, DMSO_d6) δ 62.58 (m, 2Η), 2.79 (t, J = 4 Ηζ, 2Η), 3 · 30 (m, 2Η), 4 · 30 (d, J = 5 Hz, 2H ), 6.71 (m, 1H), 7.22 (m, 1H), 7.52 (m, 2H), 7_62 (d, J = 6 Hz, 1H), 7.73 (t, J = 6 Hz, 1H), 7.85 (d, J = 6 Hz, 1H), 7.92 (s, 1H), 8.52 (m, 1H), 9.08 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 326 (MH ) + · Example 133 N_ (3 \ 6f-dihydro-2,4f-bipyridine-l '(2'HV-methyl) cyclohexane # fluorene amine, 2', 3 ', 6'-tetra Hydrogen- [2,4T] bipyridine hydrochloride (20 mg, 0.10 mmol, Saari, WS · et al. 'J. Med. Chem. 1984, 27, 1182), Polycarbamate (30 Milligram, 1 millimolar), cyclohexanone (64 milligrams, 0.5 millimoles, Aldrich), and 42 milligrams of potassium carbonate (0.3 millimoles) in 2.5 milliliters of absolute ethanol, 85228 -234- 200404539 Under nitrogen, heat to reflux overnight. Allow the mixture to cool to room temperature, filter, and remove the solvent. Purify the residue on a gel by flash column chromatography (10% methanol: ethyl acetate) To obtain 19 mg (64%) of pure compound. 1HNM R (500 MHz, DMSO-d6) 5 1.19 (m, 4H), 1.26 (m, 2H), 1.61 (m, 1H), 1.68 (m, 3H), 2.18 (m, 1H), 2.55 (m5 2H), 2.68 (m, 2H), 3.18 (m, 2H), 4_02 (d, J = 5 Hz, 2H), 6.68 (m, 1H), 7.22 (m, 1H), 7.52 (d, J = 6 Hz, 1H), 7.73 (t5 J = 6 Hz, 1H), 8.02 (t, J = 5 Hz, 1H), 8.52 (m, 1H); MS (ESI / APCI-) m / e 298 (MH ) +. Example 134 N- (3 ', 6'-dihydro-2,4'-bipyridine-m'HV a methyl V3,4-difluorobenzidine amine will be Γ, 2', 3 ', 6'-tetrahydro- [2,4] bipyridine hydrochloride (20 mg, 0.10 mmol, Saari, WS · et al .; J. Med_Chem · 1984, 27, 1182), polyformaldehyde (30 mg, 1 millimolar), 3,4-difluorobenzamide (79 mg, 0.5 millimolar, Lancaster) and 42 mg of potassium carbonate (0.3 millimolar) in 2-5 ml of absolute ethanol. Heat to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 18 mg (55%) of the pure compound. 1H NMR (500 MHz, DMSO-d6) 5 2.58 (m, 2Η), 2.79 (t, J = 4 Ηζ, 2Η), 3.32 (m, 2H), 4.28 (d, J = 5 Hz, 2H), 6.71 (m, 1H), 7_22 (m, 1H), 7_55 (m, 2H), 7.83 (m, 2H), 7.95 (t, J = 6 Hz, 1H), 8.52 (m , 1H) 8.95 (t, JN5 Hz, 1H); MS (ESI / APCI-) m / e 328 (MH) +. Example 135 N- (3f, 6f-dihydro-2,4'-bipyridine-Γ (2Ήν dimethyl cemetery V3,5-Dimethylhydrobenzidine, 1 ', 2', 3 ', 6'-tetrahydro- [2,4'] bipyridine hydrochloride (20 mg, 0.1 10 millimoles, Saari, WS et al .; J. Med · Chem · 1984, 27, 1182), polyoxymethylene (30 mg, 1 85228 -235-200404539 millimoles), 3,5-dimethoxy A mixture of benzamidine (91 mg, 0.5 mmol, Aldrich) and 42 mg of potassium carbonate (0.3 mmol) in 2-5 ml of absolute ethanol, heated to reflux overnight under nitrogen. The mixture was cooled to Filter at room temperature and remove the solvent. Purify the residue on silica gel by flash column chromatography (10% methanol: ethyl acetate) to obtain 19 mg (55%) of pure compound. 1H NMR (500 MHz , DMSO-d6) 6 2.59 (m, 2H ), 2.79 (t, J = 4 Hz, 2H), 3_30 (m, 2H), 3.79 (s, 3H), 3.80 (s, 3H), 4.25 (d, J = 5 Hz, 2H), 6.65 (s, 1H), 6.71 (m, 1H), 7.02 (s, 2H), 7.22 (m, 1H), 7.52 (d, J = 6 Hz, 1H), 7.75 (t, J = 6 Hz, 1H) , 8.52 (m, 1H) 8.88 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 352 (MH) + · Example 136 N- (3-methylphenyl) -2- (4-Phenyl-1-hexahydropyridyl) Ethylamine Follow the procedure described in Example 35 to replace 4- (2-methoxyphenyl) hexahydropyridine with 4-phenylhexahydropyridine to provide Title compound (99% yield). IHNMR (300 MHz, DMSO-d6) 5 1.76 (m, 4H), 2.28 (m, 5H), 2.51 (m, 1H), 2.98 (m, 2H), 3.12 (s, 2H), 6_88 (d, J = 6 Hz, 1H), 7.19 (m, 2H), 7.29 (m, 4H), 7.46 (d, 2H), 9.61 (br s, 1H); MS (DCI / NH3) m / e 310 (M + H) +; Analytical calculated value for C2 0H2 4 N2 O · 0.2 H2 O · C, 76.99; H, 7.88; N, 8.98. Found: C, 76.88, H, 7.85, N, 8.81 Example 137 2- (3f, 6'-diaza-2,4'-bi-pi ratio-lf (2'H) · yl) -N- (3-nitrobenzyl The desired substance is based on Example 124B. Program, via 2-chloro -N- (3- nitrophenyl) acetyl amine (Lancaster) substituted product from Example 124A made of. Yield 48 mg (97%). 111 Li 11 (300 ^ 1112, 0 ^^ 0- (16) (5 2.96〇 ^ 8,211), 3.45-3.75 (m, 2H), 4.05-4.20 (m, 2H), 4.38 (s, 2H), 6.75 (br s, 1H), 7.38 (m, 1H), 85228 -236- 200404539 7.66 (m, 2H), 7.89 (m, 2H), 8.00 (d, J = 6 Hz, 1Η), 8.60 (m , 1H), 8.63 (br s, 1H), 10.45 (br s, 1H), 11.08 (br s, 1H); MS (ESI / APCI +) m / e 339 (M + H) +. Example 138 N-l _Jingang Burning Group-2- "4- (3 • cyano-2-p ratio ytyl) -1-hexahydro p-pyridyl amine acetate

實例138A N-1-金鋼烷某-2-溴乙醯胺 按照實例1A中所述之程序，以1-金剛烷胺取代3·甲基苯胺 ，提供標題化合物（77%產率），為白色固體。iHNMRpOO MHz， DMSO-d6) 6 1.61 (m，6H)，1·91 (m，6H), 2.01 (m，3H)，3·76 (s，2H)，7.74 (br s， 1H) ； MS (DCI/NH3) m/e 272/274 (M+H)+ ； 289/291 (M+NH4 )+.Example 138A N-1-adamantane-2-bromoacetamidine Following the procedure described in Example 1A, substituting 3-methylaniline with 1-adamantanamine provided the title compound (77% yield) as White solid. iHNMRpOO MHz, DMSO-d6) 6 1.61 (m, 6H), 1.91 (m, 6H), 2.01 (m, 3H), 3.76 (s, 2H), 7.74 (br s, 1H); MS ( DCI / NH3) m / e 272/274 (M + H) +; 289/291 (M + NH4) +.

實例138B N-l-金鋼fe基-2-「4_(3-氰基-2-p比遠基）-1-六氫p比喷基1乙酸胺 按照實例121B中所述之程序，以得自實例138A之產物取代 得自實例121A之產物，提供標題化合物（50%產率），為無色 油。1 H NMR (300 MHz，DMSO-d6) 6 1.63 (m，6H)，1.95 (m，6H)，2.01 (m， 3H)5 2.59 (m? 4H)? 3.32 (s5 2H)5 3.62 (m? 4H)? 6.93 (dd? 1H5 J=7.8? 5.1 Hz)5 7.11 (br s，1H)，8.06 (dd，1H，J=7.5, 1.7 Hz)，8·41 (dd，1H，J=4.8, 1.7 Hz) ; MS (DCI/NH3) m/e 380 (M+H)+. 順丁烯二酸鹽：白色固體；對(^22^129^(^0.9(：4114〇4争0.3〇4118〇2 之分析計算值：C，63.07; H，6.91; N，13.72·實測值：c，63.41; H，6.72 ；N5 13.45. 實例139 k甲基-N-丨「2-甲基-4-(2-吡啶某VI-六氫吡畊基1甲基}茉甲醯胺Example 138B Nl-Gold steel feyl-2- "4- (3-cyano-2-p to faryl) -1-hexahydro p-pyridyl 1 amine Acetic acid was obtained according to the procedure described in Example 121B to obtain from The product of Example 138A replaced the product from Example 121A to provide the title compound (50% yield) as a colorless oil. 1 H NMR (300 MHz, DMSO-d6) 6 1.63 (m, 6H), 1.95 (m, 6H ), 2.01 (m, 3H) 5 2.59 (m? 4H)? 3.32 (s5 2H) 5 3.62 (m? 4H)? 6.93 (dd? 1H5 J = 7.8? 5.1 Hz) 5 7.11 (br s, 1H), 8.06 (dd, 1H, J = 7.5, 1.7 Hz), 8.41 (dd, 1H, J = 4.8, 1.7 Hz); MS (DCI / NH3) m / e 380 (M + H) +. Diacid salt: white solid; Calculated value for analysis of (^ 22 ^ 129 ^ (^ 0.9 (: 4114〇4 and 0.3〇4118〇2: C, 63.07; H, 6.91; N, 13.72. Found: c, 63.41; H, 6.72; N5 13.45. Example 139 k methyl-N- 丨 2-methyl-4- (2-pyridine VI-hexahydropyridyl 1methyl} momethamine

實例139A 85228 -237- 200404539 3_甲基-1-(2-?比嗓基）六—良叶卜井氧逸齡_ 將2-甲基六氫吡畊（1.0克，0.01莫耳，外消旋混合物）與孓 溴基吡啶（10毫升，0.1莫耳）之溶液加熱至120°C，歷經16小 時。使反應混合物冷卻至室溫，並於醋酸乙酯與水之間作 分液處理。分離液層，並使水層在減壓下濃縮。將殘留物 以醋酸乙酯、二氯甲烷及甲醇研製，而得460毫克（26%產率） 外消旋3-甲基-l-p比違-2-基-7T氳外b”井氫溴酸鹽，為灰白色固體 。WNMRpOOMHz’DMSO-cU 5 1.27(d，J=6.6HZ，3H)，2.90(dd，J=l〇.5, 14.1 Hz，1H)，3·10 (m，2H)，3·40 (m，2H)，4.32 (m，2H)，6·77 (dd，J=4.8, 6·9 Hz， 1H)，6.98 (d，J=8.1 Hz，1H)，7.64 (m，1H)，8.15 (m，1H)，8.63 (br s，1H)，8·92 (br s，1H) ; MS (APCI) m/e 178 (M+H)+ ·Example 139A 85228 -237- 200404539 3-methyl-1- (2-? Specific base) six-Liang Yebujing oxygen escape age_ 2-methylhexahydropyridine (1.0 g, 0.01 mole, outside A solution of the racemic mixture) and stilbenepyridine (10 ml, 0.1 mole) was heated to 120 ° C for 16 hours. The reaction mixture was allowed to cool to room temperature and was partitioned between ethyl acetate and water. The liquid layers were separated, and the aqueous layer was concentrated under reduced pressure. The residue was triturated with ethyl acetate, dichloromethane, and methanol to obtain 460 mg (26% yield) of racemic 3-methyl-lp than 2--2-yl-7T. Exo b "well hydrobromic acid Salt as an off-white solid. WNMRpOOMHz'DMSO-cU 5 1.27 (d, J = 6.6HZ, 3H), 2.90 (dd, J = 10.5, 14.1 Hz, 1H), 3.10 (m, 2H), 3.40 (m, 2H), 4.32 (m, 2H), 6.77 (dd, J = 4.8, 6.9 Hz, 1H), 6.98 (d, J = 8.1 Hz, 1H), 7.64 (m, 1H), 8.15 (m, 1H), 8.63 (br s, 1H), 8.92 (br s, 1H); MS (APCI) m / e 178 (M + H) + ·

實例139B 3-甲基-N-{〖2-甲基-4-(2-外1：淀基M-六氡外1： p井基1甲基}笨甲驢脸 將得自實例139A之產物（250毫克，0.97毫莫耳）、得自實例 91A之產物（201毫克，0.97毫莫耳）及三乙胺（342毫克，3.39毫 莫耳）在乙腈（10毫升）中之溶液，於室溫下攪拌72小時。將 反應混合物倒入水中，並以醋酸乙酯萃取。然後以另外之 飽和碳酸氫鈉水溶液及鹽水洗滌醋酸乙酯溶液，接著以硫 酸鈉脫水乾燥，過濾，及在減壓下濃縮。使殘留物於矽膠 上藉急騾式管柱層析純化（2-5%乙醇：醋酸乙酯），而得216 毫克（69% 產率）標題化合物。iHNMR(300 MHz，DMSO-d6) 3 1.21 (d，J=5.4 Hz，3H)，2.34 (s5 3H)，2·50 (m，3H)，2·85 (m，2H)，4·06 (br d，J=10.5 Hz，2H)，4.29 (dd，J=13.5, 6.0 Hz，1H)，4.43 (dd，J=13.5, 6.0 Hz，1H)，6.58 (m， 1H)5 6.82 (d5 J=8.7 Hz? 1H), 7.34 (m? 2H)? 7.48 (m51H)? 7.63 (m9 2H)? 8.07 (m9 85228 -238 - 200404539 1H)，8.54 (dd，J=6.0, 6·0 Hz，1H) ; MS (ESI) m/e 325 (M+H)+. 實例140 社(β-甲基苯基V2-「2_甲基斗(2-吡啶基M-六氫吡畊某1乙醯胺 將得自實例139A之產物（250毫克，0.97毫莫耳）、得自實例 1A之產物（221毫克，〇_97毫莫耳）、n，N-二異丙基乙胺（313毫 克’ 2_42 φ莫耳）及甲苯（8毫升）之溶液，於下加熱16小 時’然後冷卻至室溫。使反應混合物在減壓下濃縮，並使 殘留物於矽膠上藉急騾式管柱層析純化（醋酸乙酯），而得256 毫克（81% 產率）標題化合物。iHNMR(300MHz，DMSO-d6) δ 1·06 (d，J=6.3 Ηζ，3Η)，2.27 (s，3Η)，2·58 (m，2Η)，2·80 (dd，J=12.3, 9·0 Ηζ，1Η)， 2_84 (m，1H)，3.10 (d，J=16.5 Hz，1H)，3.11 (m，1Η)，3·38 (d，J=16.5 Hz，1H)， 4.00 (m，2H)，6.63 (dd，J=8.1，6.3 Hz，1H)，6.84 (d，J=11.1 Hz，1H)，6.89 (m， 1H)，7.18 (m，1H)，7.44 (m，2H)，7·52 (m，1H)，8_10 (m，1H)，9.63 (br s，1H); MS (ESI) m/e 325 (M+H)+. 實例141 Μ·二甲基-N-{[4-(2-峨淀基）-1-六氫p比淀基i甲某}苯甲酸胺 將得自實例36C之產物（20毫克，〇.1〇毫莫耳）、聚甲醛（3〇 毫克，1毫莫耳）、3,5-二甲基苯曱醯胺（75毫克，0.5毫莫耳） 及42毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水乙醇中之混合物 ’於氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過 濾’並移除溶劑。使殘留物於矽膠上藉急騾式管柱層析純 化（10%甲醇：醋酸乙酯），獲得23毫克（72% )純化合物。 1H NMR (500 MHz，DMSO-d6) δ 1.73 (m，2H)，1.82 (m，2H)，2.29 (m，2H)， 2.32 (s，6H)，2·60 (m，1H)，2.95 (m，2H)，4.18 (d，J=5 Hz, 2H)，7.18 (m，2H)， 85228 -239- 200404539 7.25 (d，J=6 Hz，1Η)，7·50 (s，2H)，7.68 (t，J=6 Hz，1Η)，8·48 (d，J=6 Hz，1H)， 8.62 (t? J=5 Hz5 1H) ； MS (ESI/APCI-) m/e 322 (M-H)+. 實例142 N-(3T,6f-二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）-3,5-二甲基笨甲醯胺 將r，2f，3’，6’-四氫-[2,4’]聯吡啶鹽酸鹽（20毫克，0.10毫莫耳， Saari，W.S·等人；J· Med. Chem· 1984, 27, 1182)、聚甲醛（30 毫克，1 毫莫耳）、3,5-二甲基苯甲醯胺（75毫克，0.5毫莫耳）及42毫克 碳酸鉀（〇_3毫莫耳）在2.5毫升無水乙醇中之混合物，於氮氣 下，加熱至回流過夜。使混合物冷卻至室溫，過濾，並移 除溶劑。使殘留物於矽膠上藉急騾式管柱層析純化（10%甲 醇··醋酸乙酯），而得18毫克（56%)純化合物。1HNMR (500 MHz， DMSO-d6) 5 2.33 (s，6H)，2.56 (m，2H)，2·78 (t，J=4 Hz，2H)，3.28 (m，2H)， 4.18 (d，J=5 Hz，2H)，6.71 (m，1H)，7.18 (s，1H)，7.22 (m，1H)，7.50 (m，3H)， 7.75 (t，J=6 Hz，1H)，8.52 (d，J=5 Hz，1H)，8.62 (t，J=5 Hz，1H); MS (ESI/APCI-) m/e 320 (M-H)+. 實例143 3-甲基_N-「(3:f.基-3丄6’-二新.-2·4，-聯吡啶-1，(2，HV其甲基1笨甲醯胺Example 139B 3-methyl-N-{[2-methyl-4- (2-exo-1: Yodo M-hexanexo 1: p-Isoyl 1 methyl} stupid donkey face will be obtained from Example 139A The product (250 mg, 0.97 mmol), the product from Example 91A (201 mg, 0.97 mmol) and a solution of triethylamine (342 mg, 3.39 mmol) in acetonitrile (10 ml) were Stir at room temperature for 72 hours. Pour the reaction mixture into water and extract with ethyl acetate. Then wash the ethyl acetate solution with another saturated aqueous sodium bicarbonate solution and brine, then dehydrate and dry over sodium sulfate, filter, and reduce the The residue was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (2-5% ethanol: ethyl acetate) to obtain 216 mg (69% yield) of the title compound. IHNMR (300 MHz, DMSO -d6) 3 1.21 (d, J = 5.4 Hz, 3H), 2.34 (s5 3H), 2.50 (m, 3H), 2.85 (m, 2H), 4.06 (br d, J = 10.5 Hz, 2H), 4.29 (dd, J = 13.5, 6.0 Hz, 1H), 4.43 (dd, J = 13.5, 6.0 Hz, 1H), 6.58 (m, 1H) 5 6.82 (d5 J = 8.7 Hz? 1H) , 7.34 (m? 2H)? 7.48 (m51H)? 7.63 (m9 2H)? 8.07 (m9 85228 -238-200404539 1H), 8.5 4 (dd, J = 6.0, 6.0 Hz, 1H); MS (ESI) m / e 325 (M + H) +. Example 140 (β-methylphenyl V2- "2-methyl bucket ( 2-pyridyl M-hexahydropyramine 1 acetamide will be obtained from the product of Example 139A (250 mg, 0.97 mmol), the product from Example 1A (221 mg, 0-97 mmol), A solution of n, N-diisopropylethylamine (313 mg '2-42 mol) and toluene (8 ml) was heated underneath for 16 hours' and then cooled to room temperature. The reaction mixture was concentrated under reduced pressure, and The residue was purified by flash column chromatography (ethyl acetate) on silica gel to obtain 256 mg (81% yield) of the title compound. IHNMR (300 MHz, DMSO-d6) δ 1.06 (d, J = 6.3 Ηζ, 3Η), 2.27 (s, 3Η), 2.58 (m, 2Η), 2.80 (dd, J = 12.3, 9 · 0 Ηζ, 1Η), 2_84 (m, 1H), 3.10 ( d, J = 16.5 Hz, 1H), 3.11 (m, 1Η), 3.38 (d, J = 16.5 Hz, 1H), 4.00 (m, 2H), 6.63 (dd, J = 8.1, 6.3 Hz, 1H ), 6.84 (d, J = 11.1 Hz, 1H), 6.89 (m, 1H), 7.18 (m, 1H), 7.44 (m, 2H), 7.52 (m, 1H), 8_10 (m, 1H) , 9.63 (br s, 1H); MS (ESI) m / e 325 (M + H) +. Example 141 M. dimethyl-N-{[4- (2-eodoyl) -1-hexahydro p ratio yodoyl i methyl} benzoic acid amine will be obtained from the product of Example 36C (20 mg, 0.1. 10 millimoles), polyoxymethylene (30 mg, 1 millimoles), 3,5-dimethylbenzidine (75 mg, 0.5 millimoles), and 42 mg potassium carbonate (0.3 millimoles Mol) in 2.5 ml of absolute ethanol 'under nitrogen, heated to reflux overnight. The mixture was allowed to cool to room temperature, filtered 'and the solvent was removed. The residue was purified on silica gel by flash column chromatography (10% methanol: ethyl acetate) to obtain 23 mg (72%) of the pure compound. 1H NMR (500 MHz, DMSO-d6) δ 1.73 (m, 2H), 1.82 (m, 2H), 2.29 (m, 2H), 2.32 (s, 6H), 2.60 (m, 1H), 2.95 ( m, 2H), 4.18 (d, J = 5 Hz, 2H), 7.18 (m, 2H), 85228 -239- 200404539 7.25 (d, J = 6 Hz, 1Η), 7.50 (s, 2H), 7.68 (t, J = 6 Hz, 1Η), 8.48 (d, J = 6 Hz, 1H), 8.62 (t? J = 5 Hz5 1H); MS (ESI / APCI-) m / e 322 (MH ) +. Example 142 N- (3T, 6f-Dihydro-2,4'-bipyridine-1 '(2Ή) -ylmethyl) -3,5-dimethylbenzidine, r, 2f, 3 ', 6'-tetrahydro- [2,4'] bipyridine hydrochloride (20 mg, 0.10 mmol, Saari, WS · et al .; J. Med. Chem. 1984, 27, 1182), poly Formaldehyde (30 mg, 1 mmol), 3,5-dimethylbenzamide (75 mg, 0.5 mmol) and 42 mg potassium carbonate (0-3 mmol) in 2.5 ml of absolute ethanol The mixture was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed. The residue was purified on silica gel by flash column chromatography (10% methanol · ethyl acetate) to obtain 18 mg (56%) of the pure compound. 1HNMR (500 MHz, DMSO-d6) 5 2.33 (s, 6H), 2.56 (m, 2H), 2.78 (t, J = 4 Hz, 2H), 3.28 (m, 2H), 4.18 (d, J = 5 Hz, 2H), 6.71 (m, 1H), 7.18 (s, 1H), 7.22 (m, 1H), 7.50 (m, 3H), 7.75 (t, J = 6 Hz, 1H), 8.52 (d , J = 5 Hz, 1H), 8.62 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 320 (MH) +. Example 143 3-methyl_N- "(3: f. radical-3'6'-dioxin.-2.4, -bipyridine-1, (2, HV its methyl 1 benzamidine

實例143A 3-甲基i，6f-二氫_2·4，_聯毗啶-1，(2，HV#酸第三-丁醋 將4-三氟甲烷磺醯氧基j，6-二氫-2H-吡啶-1-羧酸第三-丁酯 (8.10 克，24.8 晕莫耳；Bursavich，M.G 等人；〇rg. Lett. 2001，3,2317) 在四氫吱喃（50晕升）中之溶液，以溴化3_甲基_2_吡啶基鋅 (0.5M ’在四氫味喃中，65.0毫升，Aldrich)、肆（三苯膦）_鈀（0X280 愛克，0.24毫莫耳）處理，並將混合物加熱至，歷經2小 85228 -240- 200404539 時。使混合物冷卻至室溫，在減壓下濃縮，使殘留物溶於 二氯甲烷中，並以1N氫氧化鈉洗滌。使有機相脫水乾燥（硫 酸鎂），過濾，及在減壓下濃縮。使殘留物於矽膠上藉急騾 式管柱層析純化（以50%醋酸乙|旨：己燒溶離），提供5·5〇克（82 %產率）標題化合物，為淡黃色油。1HNMR(300MHz，DMSO-d6) 5 1.44 (s，9H)，2.32 (s，3H)，2.44 (m，2H)，3.54 (m，2H)，3·99 (m，2H)，5.88 (br s，1H)，7·17 (dd，1H，J=7.8, 4_8 Hz)，7.62 (br d，1H，J=7.5 Hz)，8.36 (dd，1H，J= 4.8, 1.7 Hz) ； MS (DCI/NH3) m/e 275 (M+H)+ ； 292 (M+NH4)+. 實例143B 3-甲基_1’二3’·6’-四氤_2,4’_聯吡啶 使得自實例143A之產物（1.00克，3.64毫莫耳）在醋酸乙酯（25 毫升）中冷卻至-78°C，並以氯化氫氣流處理10分鐘。使反應 混合物溫熱至室溫，並攪拌。於減壓下移除溶劑，並將殘 留物以醋酸乙酿研製，過濾，及在真空下乾燥過夜，提供 標題化合物，為白色固體（HC1鹽）。iHNMRpOOMHiDMSO-c^) 5 2.43 (s，3H)，2.71 (m，2H)，3.31 (m，2H)，3·79 (m，2H)，6.08 (to s，1H)，7.66 (dd，1H，J=6.8, 5.8 Hz)，8.18 (br d，1H，J=6.6 Hz)，8·58 (d，1H，J=5.1 Hz) ; MS (DCI/NH3) m/e 175 (M+H)+.Example 143A 3-methyl i, 6f-dihydro_2,4, _bipyridine-1, (2, HV # acid tert-butyric acid 4-trifluoromethanesulfonyloxy j, 6-di Hydrogen-2H-pyridine-1-carboxylic acid tert-butyl ester (8.10 g, 24.8 hamol; Bursavich, MG et al .; rg. Lett. 2001, 3, 2317) in tetrahydrocran (50 ha ) Solution with 3_methyl_2_pyridyl zinc bromide (0.5M 'in tetrahydrofuran, 65.0 ml, Aldrich), (triphenylphosphine) _palladium (0X280 Aike, 0.24 milligrams) Mol), and the mixture was heated to 2852 85228-240-200404539. The mixture was cooled to room temperature, concentrated under reduced pressure, the residue was dissolved in dichloromethane, and 1N sodium hydroxide was used. Washing. Dehydrating the organic phase (magnesium sulfate), filtering, and concentrating under reduced pressure. Purifying the residue on silica gel by flash column chromatography (50% ethyl acetate | Purpose: Dissolved by burning), Provided 5.50 g (82% yield) of the title compound as a pale yellow oil. 1HNMR (300 MHz, DMSO-d6) 5 1.44 (s, 9H), 2.32 (s, 3H), 2.44 (m, 2H), 3.54 (m, 2H), 3.99 (m, 2H), 5.88 (br s, 1H), 7.17 (dd, 1H, J = 7.8, 4_8 Hz), 7.62 (br d, 1H, J = 7.5 Hz), 8.36 (dd, 1H, J = 4.8, 1.7 Hz); MS (DCI / NH3) m / e 275 (M + H) +; 292 (M + NH4) +. Example 143B 3-methyl_1'di 3 '· 6'-tetrapyrene_2,4'_bipyridine was obtained from the product of Example 143A (1.00 g, 3.64 mmol) ) Cooled to -78 ° C in ethyl acetate (25 ml) and treated with a stream of hydrogen chloride for 10 minutes. The reaction mixture was allowed to warm to room temperature and stirred. The solvent was removed under reduced pressure, and the residue was dried under reduced pressure. Triethyl acetate was developed, filtered, and dried under vacuum overnight to provide the title compound as a white solid (HC1 salt). IHNMRpOOMHiDMSO-c ^) 5 2.43 (s, 3H), 2.71 (m, 2H), 3.31 (m, 2H), 3.79 (m, 2H), 6.08 (to s, 1H), 7.66 (dd, 1H, J = 6.8, 5.8 Hz), 8.18 (br d, 1H, J = 6.6 Hz), 8.58 (d, 1H, J = 5.1 Hz); MS (DCI / NH3) m / e 175 (M + H) +.

實例143C 3-甲基-N4(3甲基-3’，6’·二氫-2,4’-聯吡啶基）甲基1笨甲醯胺 將得自實例143B之產物（三氟醋酸鹽；29毫克，0·1毫莫耳） 、聚甲醛（30毫克，1毫莫耳）、3-甲基苯甲醯胺（68毫克，0.5 毫莫耳，Aldrich)及42毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 85228 -241- 200404539 冷卻至室溫，過濾，並移除溶劑。使殘留物於矽膠上藉急 驟式管柱層析純化（10%甲醇：醋酸乙酯），而得12.5毫克（39 % )純化合物。1 H NMR (500 MHz，DMSO-d6) 6 2.30 (s，3H)，2.38 (s，3H)， 2·48 (m，2H)，2.78 (m，2H)，3.25 (m，2H)，4.28 (d，J=6 Hz，2H)，5.82 (m，1H)， 7·18 (t，J=6 Hz，1H)，7.38 (m，2H)，7.60 (t，J二6 Hz，1H)，7.71 (m，2H)，8·38 (d， J=6 Hz，1H)，8.79 (t，J=6 Hz，1H) ; MS (ESI/APCI-) m/e 320 (M-H)+ · 實例144 M(3_氰基二氫-2,-聯吡啶-1ϊ2Ήν基）甲基1·3_甲基苯甲醯胺 實例144Α !_·氰基-3\6’-二· -2,4’-聯吡啶-r(2，HV勒酸第三-丁酯 將4_三氟甲烷磺醯氧基_3,6_二氫-2H-吡啶·1_羧酸第三-丁酯 (0.90 克，2.7 毫莫耳；Bursavich，M.G等人；〇rg.Lett.2001，3,2317) 、氯化鐘（0.9克’ 20毫莫耳）、六甲基二錫（ι·〇毫克，3.05毫 莫耳）及肆（三苯膦）免（0χ0·38克，〇·32毫莫耳）在二氧陸圜⑼ 笔升）中之混合物，於Ν2及100。(：下加熱過夜。使混合物冷卻 至室溫，及濃縮。將殘留物以醋酸乙酯（1〇〇毫升）稀釋，經 過Celite®過滤，以碳酸氫鈉溶液（3〇毫升）及鹽水⑼毫升）洗 滌濾液。使有機相以硫酸鎂脫水乾燥，濃縮，獲得L3克粗 產物，使用之而無需純化。將上文粗製固體2_氯基各氰基吡 啶（U當量）、氯化鋰(0.9克，20毫莫耳）及肆（三苯膦）鈀(〇χ〇·34 克，〇·3毫莫耳）在Ν，Ν-二甲基甲醯胺（35毫升）中之混合物， 於Ν2及12(TC下加熱過夜。使混合物冷卻至室溫，及濃縮。 將殘留物以醋酸乙酯（100毫升）稀釋，以水（2χ3〇毫升）洗滌 ，以硯酸鎂脫水乾燥，及濃縮。使殘留物於矽膠上藉急騾 -242- 85228 200404539 式管柱層析純化，而得0.39克產物。1HNMR(300MHz，DMSO-d6) 5 1.40 (s，9H)，2.60 (m，2H)，3.55 (m，2H)，4.05 (m，2H)，6.50 (br s，1H)，7.50 (m，1H)，8.35 (m，1H)，8.90 (m，1H).Example 143C 3-methyl-N4 (3methyl-3 ', 6' · dihydro-2,4'-bipyridyl) methyl 1 benzamidine will be obtained from the product of Example 143B (trifluoroacetate 29 mg, 0.1 millimolar), polyoxymethylene (30 mg, 1 millimolar), 3-methylbenzamide (68 mg, 0.5 millimolar, Aldrich), and 42 mg potassium carbonate ( 3 mmol) in 2.5 ml of absolute ethanol and heated to reflux overnight under nitrogen. The mixture 85228 -241- 200404539 was cooled to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 12.5 mg (39%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) 6 2.30 (s, 3H), 2.38 (s, 3H), 2.48 (m, 2H), 2.78 (m, 2H), 3.25 (m, 2H), 4.28 (d, J = 6 Hz, 2H), 5.82 (m, 1H), 7.18 (t, J = 6 Hz, 1H), 7.38 (m, 2H), 7.60 (t, J = 6 Hz, 1H) , 7.71 (m, 2H), 8.38 (d, J = 6 Hz, 1H), 8.79 (t, J = 6 Hz, 1H); MS (ESI / APCI-) m / e 320 (MH) + · Example 144 M (3-Cyanodihydro-2, -bipyridine-1ϊ2Ήνyl) methyl 1 · 3-methylbenzylamine Example 144A!-· Cyano-3 \ 6'-di · -2, 4'-bipyridine-r (2, HV tert-butyl tert-butyl ester) 4-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine · 1-carboxylic acid tert-butyl ester ( 0.90 g, 2.7 mmol; Bursavich, MG et al .; Org. Lett. 2001, 3, 2317), Bell Chloride (0.9 g '20 mmol), hexamethylditin (ι · 0 mg, 3.05 mmol) and tris (triphenylphosphine) free (0x0.38 g, 0.32 mmol) in dioxolane (1 litre), at N2 and 100. (: Overnight heating. The mixture was cooled to room temperature, and concentrated. The residue was diluted with ethyl acetate (100 ml), filtered through Celite®, sodium bicarbonate solution (30 ml) and brine ⑼ml ) Wash the filtrate. The organic phase was dried over magnesium sulfate and concentrated to obtain L3 g of a crude product which was used without purification. The above crude solid 2-chloro cyanopyridine (U equivalent), lithium chloride (0.9 g, 20 mmol) and tris (triphenylphosphine) palladium (0 × 0.34 g, 0.3 mmol) A mixture of mol) in N, N-dimethylformamide (35 ml) was heated at N2 and 12 (TC overnight. The mixture was cooled to room temperature, and concentrated. The residue was ethyl acetate ( (100 ml) diluted, washed with water (2 x 30 ml), dried over magnesium acetate, and concentrated. The residue was purified by silica gel column chromatography on a silica gel-242- 85228 200404539 to obtain 0.39 g of product 1HNMR (300MHz, DMSO-d6) 5 1.40 (s, 9H), 2.60 (m, 2H), 3.55 (m, 2H), 4.05 (m, 2H), 6.50 (br s, 1H), 7.50 (m, 1H), 8.35 (m, 1H), 8.90 (m, 1H).

實例144B 1，2\3\6f-四氨_2,4f-聯口比淀-3·甲月膏 於得自實例144A之產物中，在室溫下，添加三氟醋酸/二 氯甲烷（1 : 1，10毫升）。將混合物攪拌5小時。移除溶劑， 獲得 0.55 克產物。1 H NMR (300 MHz，DMSO-d6) 5 2.80 (m，2H)，3.40 (m， 2H)，3.95 (m，2H)，6·55 (br s，1H)，7·60 (m，1H)，8.40 (m5 1H)，8·90 (m，1H)， 9.00 (m? 2H) ； MS (ESI/APCI+) m/e 186 (M+H)+.Example 144B 1,2 \ 3 \ 6f-tetraammonia-2,4f-Lianbibitan-3 · Yueyue paste In the product obtained from Example 144A, trifluoroacetic acid / dichloromethane was added at room temperature ( 1: 1, 10 ml). The mixture was stirred for 5 hours. Removal of the solvent gave 0.55 g of product. 1 H NMR (300 MHz, DMSO-d6) 5 2.80 (m, 2H), 3.40 (m, 2H), 3.95 (m, 2H), 6.55 (br s, 1H), 7.60 (m, 1H ), 8.40 (m5 1H), 8.90 (m, 1H), 9.00 (m? 2H); MS (ESI / APCI +) m / e 186 (M + H) +.

實例144C N-『(3-氰基-3\6’-二氲-2,4’-聯吡啶基）甲基1-3-甲基苯甲醯胺 將得自實例144Β之產物（30毫克，0.1毫莫耳）、聚甲醛（30 毫克，1毫莫耳）、3-甲基苯甲醯胺（70毫克，0.5毫莫耳）及42 毫克碳酸鉀（0.3毫莫耳）在2.5毫升無水乙醇中之混合物，於 氮氣下，加熱至回流過夜。使混合物冷卻至室溫，過濾， 及在減壓下移除溶劑。使殘留物於矽膠上藉急騾式管柱層 析純化（10%甲醇：醋酸乙酯），而得10毫克（32% )純化合物Example 144C N-"(3-Cyano-3 \ 6'-difluorene-2,4'-bipyridyl) methyl1-3-methylbenzidine. The product obtained from Example 144B (30 mg , 0.1 millimolar), polyoxymethylene (30 mg, 1 millimolar), 3-methylbenzamide (70 mg, 0.5 millimolar), and 42 mg potassium carbonate (0.3 millimolar) in 2.5 ml The mixture in absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (10% methanol: ethyl acetate) to obtain 10 mg (32%) of pure compound.

。1H NMR (500 MHz, DMSO-d6) δ 2·36 (s，3Η)，2.62 (m，2Η)，2.79 (m，2Η)， 3.32 (m? 2H)5 4.24 (d, J=5 Hz5 2H)? 4.66 (d? J=5 Hz? 1H)5 6.50 (m? 1H)5 7.35 (m? 2H)，7.49 (m，1H)，7.72 (m，2H)，8.29 (d，J=6 Hz，1H)，8.78 (m，1H) ； MS (ESI/APCI-) m/e 331 (M-H)+. 實例145 N-(2,6-二甲基笨基）-2-(3-甲基二氪-2,4’-聯吡啶·1’(2Ήν基） 85228 -243 - 200404539 乙醯胺 - 使得自實例143B之產物（三氟醋酸鹽；23毫克，0·08毫莫耳） 、2-鼠·Ν-(2,6-一甲基苯基）乙酿胺（20毫克，0.1毫莫耳，Aldrich) 及碳酸鈉（50毫克）在二甲基甲醯胺/水p : 1，i毫升）中之混 合物，於室溫下振盪18小時。使所形成之混合物在減壓下 濃縮。使殘留物藉預備之HPLC純化，提供10毫克（28% )標題 化合物，為三氟醋酸鹽。iH NMR (300 MHz，DMSO-d6) 5 2.20 (s，6H)， 2.40 (s，3H)，2_80 (m，2H)，3.50-3.70 (m，2H)，4.00-4.15 (m，2H)，4.39 (s，2H)， φ 5.92 (br s，1H)，7.10 (m，3H)，7·33 (m，1H)，7·78 (m，1H)，8.43 (m，1H)，10.00 (br s，1H)，10.42 (m，1H) ; MS (ESI/APCI+) m/e 336 (M+H)+. 實例146 K4-氟苯基）-2-(3-甲基_3’，6’_二氫-2，#_聯吡啶-Γ(2Ή)-基）乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-N-(4-氟苯 基）乙醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而製 成。產量 9 毫克（26% )。1H NMR (300 MHz，DMSO-d6) 5 2.40 (s，3H)， 2.80 (m，2H)，3_50-3·70 (m，2H)，4·00-4_15 (m，2H)，4.36 (s，2H)，5.92 (br s，1H)，# 7·20 (m，2H)，7.35 (m，1H)，7.63 (m，2H)，7.80 (m，1H)，8.43 (m，1H)，10.45 (m， 1H)5 10.62 (br s? 1H) ； MS (ESI/APCI+) m/e 326 (M+H)+. 實例147 N-(2,4-二氟苯基V2-(3-甲基_3’，6’_二氫-2,4’-聯吡啶基）乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-N-(2,4-二氟 苯基）乙醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而 製成。產量 12 毫克（33% )。1H NMR (300 MHz，DMSO-d6) 5 2_40 (s， 3H)，2.80 (m，2H)，3.50-3.70 (m，2H)，4.00-4.15 (m，2H)，4_38 (s，2H)，5·90 (br s， 85228 -244- 200404539 1H)，7.12 (m，1H)，7.35 (m，1H)，7.40 (m，1Η)，7·78 (m，1Η)，7·82 (m，1Η)，8·42 - (m，1H)，10.40 (m，1H)，10.45 (br s，1H) ; MS (ESI/APCI+) m/e 344 (M+H)+ · 實例148 2-(3-甲基-3f,6^二氫-2,4’-聯吡啶基甲基笨基）乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-N-鄰-甲苯 基乙醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而製成 。產量 12 毫克（34% )。iHNMRpOOMHz.DMSO-ds) 5 2.22(s，3H)， 2.40 (s，3H)，2_80 (m，2H)，3.50-3.70 (m，2H)，4.00-4.15 (m，2H)，4.38 (s，2H)， φ 5.92 (br s，1H)，7·19 (m，1H)，7.22 (m，1Η)，7·26 (m，1H)，7.36 (m，1H)，7.42 (m， 1H)，7.80 (m，1H)，8.44 (m，1H)，10.00 (br s，1H)，10.42 (m，1H); MS (ESI/APCI+) m/e 322 (M+H)+. 實例149 2-Π-甲基-3\6’-二氫_2,4’_聯吡啶-Γ(2Ή)-基VN-「3-(三氟甲基）苯基1 乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-N-(3-三氟 甲基笨基）乙酸胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醢 春 胺而製成。產量 9 毫克（23% )。iHNMRpOOMH^DMSO-c^) 5 2·40 (s，3Η)，2.80 (m，2Η)，3.50-3.70 (m，2Η)，4.00-4.15 (m，2Η)，4.37 (s，2Η)，5·92 (br s，1H)，7.37 (m，1H)，7.52 (m，1H)，7.62 (m，1H)，7·79 (m，2H)，8.10 (m，1H)， 8.44 (m，1H)，10.42 (m，1H)，11.00 (br s，1H) ； MS (ESI/APCI+) m/e 376 (M+H)+· 實例150 N-(3_氮基 _4-氟苯基）-2-(3-甲基-3’,6’-二氫-2,4f-聯吡啶-r(2’HV基） 乙醯胺 85228 -245 - 200404539 所要之物質係根據實例145之程序，經由以2-氯-N-(3-氯基-4- · 氟苯基）乙醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺 而製成。產量 9 毫克（24% )。iHNMRpOOMHzjMSO-d6) 6 2.40 (s，3H)，2.80 (m，2H)，3.50-3.70 (m，2H)，4.00-4.15 (m，2H)，4.33 (s，2H)，5·95 (br s，1H)，7.36 (m，1H)，7.44 (m，2H)，7.78 (m，1H)，7·92 (m，1H)，8.44 (m，1H)， 10.42 (m，1H)，10.82 (br s，1H) ; MS (ESI/APCI+) m/e 360 (M+H)+. 實例151 2-(3-甲基-3’,6’-二氫-2,4’-聯吡啶基）-N-「4_(三氟甲氣基）笨基1 · 乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-N-(4-三氟 甲氧苯基）乙醯胺（Maybridge)取代2_氯-N-(2,6-二甲基苯基）乙醯 胺而製成。產量 9 毫克（22% )。iHNMRpOOMHz.DMSO-A) 5 2.40 (s，3H)，2.80 (m，2H)，3.50-3.70 (m，2H)，4.00-4.15 (m，2H)，4.30 (s，2H)，5.92 (br s，1H)，7·36 (m，1H)，7.40 (m，2H)，7.77 (m，2H)，7.82 (m，1H)，8.42 (m，1Η)， 10.42 (m? 1H)? 10.80 (br s5 1H) ； MS (ESI/APCI+) m/e 392 (M+H)+. 實例152 · 2-(3-甲基-3W-二氫-2,4’-聯吡啶-Γ(2Ήν基VN-「2-(三氟甲基）笨基1 乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-N-(2-三氟 甲基苯基）乙醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯 胺而製成。產量 10 毫克（26% )。iHNMROOOMHADMSO-A) 5 2·40 (s，3H)，2.80 (m，2H)，3.50-3.70 (m，2H)，4.00-4·15 (m，2H)，4.35 (s，2H)， 5.92 (br s，1H)，7.36 (m，1H)，7.60 (m，2H)，7.80 (m，3H)，8.42 (m，1H)，10.40 (br s，1H)，10.42 (m，1H) ; MS (ESI/APCI+) m/e 376 (M+H)+. 85228 -246- 200404539 實例153 · N-(2,3-二氯苯某V2-〔3-甲基-3’,6L二氫-2,4’-聯吡啶-1’(2Ή)-基）乙醯胺 所要之物質係根據實例145之程序，經由以2-氯-Ν-(3,4-二氯 苯基）乙醯胺（Maybridge)取代2-氯-Ν-(2,6-二甲基苯基）乙醯胺而 製成。產量 10 毫克（26% )。1H NMR (300 MHz，DMSO-d6) 5 2.40 (s， 3H)，2·80 (m，2H)，3_50·3·70 (m，2H)，4.00-4.15 (m，2H)，4.40 (s，2H)，5.92 (br s， 1H)，7.37 (m，1H)，7·42 (m，1H)，7.58 (m，1H)，7.77 (m5 1H)，7.81 (m，1H)，8.42 (m，1H)，10·42 (br s，1H)，10.45 (m，1H) ; MS (ESI/APCI+) m/e 377 (M+H)+ · φ 實例154 2-(3_甲基_3’，6’-二氫_2,聯吡啶_Γ(2Ή)_基VN-「4-(三氟甲基）笨基1 乙醯胺 所要之物質係根據實例145之程序，經由以2_氯-N-(4-三氟 甲基苯基）乙醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯 胺而製成。產量 11 毫克（28% )。iHNMRpOOMHADMSOO 5 2.40 (s5 3H)5 2.80 (m5 2H)5 3.50-3.70 (m5 2H)5 4.00-4.15 (m5 2H)5 4.37 (s, 2H)? 5.92 (br s，1H)，7.36 (m，1H)，7.78 (m，3H)，7.82 (m，2H)，8.42 (m，1H)，10.42 · (m，1H)，10.98 (br s，1H) ; MS (ESI/APCI+) m/e 376 (M+H)+ · 實例155 之-『4-(3-氰基-2^塞吩基）-3,6-二氫-1(2印-峨淀基&quot;|-&gt;1-(3-甲基苯基）. 1H NMR (500 MHz, DMSO-d6) δ 2.36 (s, 3Η), 2.62 (m, 2Η), 2.79 (m, 2Η), 3.32 (m? 2H) 5 4.24 (d, J = 5 Hz5 2H )? 4.66 (d? J = 5 Hz? 1H) 5 6.50 (m? 1H) 5 7.35 (m? 2H), 7.49 (m, 1H), 7.72 (m, 2H), 8.29 (d, J = 6 Hz , 1H), 8.78 (m, 1H); MS (ESI / APCI-) m / e 331 (MH) +. Example 145 N- (2,6-dimethylbenzyl) -2- (3-methyl Difluorene-2,4'-bipyridine · 1 '(2Ήν group) 85228 -243-200404539 Ethylamine-the product from Example 143B (trifluoroacetate; 23 mg, 0.08 mmol), 2 -Rat · N- (2,6-monomethylphenyl) ethylamine (20 mg, 0.1 mmol, Aldrich) and sodium carbonate (50 mg) in dimethylformamide / water p: 1, imL) and shake at room temperature for 18 hours. The resulting mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 10 mg (28%) of the title compound as trifluoroacetate. iH NMR (300 MHz, DMSO-d6) 5 2.20 (s, 6H), 2.40 (s, 3H), 2_80 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4.15 (m, 2H), 4.39 (s, 2H), φ 5.92 (br s, 1H), 7.10 (m, 3H), 7.33 (m, 1H), 7.78 (m, 1H), 8.43 (m, 1H), 10.00 ( br s, 1H), 10.42 (m, 1H); MS (ESI / APCI +) m / e 336 (M + H) +. Example 146 K4-fluorophenyl) -2- (3-methyl-3 ', 6'_Dihydro-2, # _ bipyridine-Γ (2Ή) -yl) acetamidin The desired substance was obtained according to the procedure of Example 145 via 2-chloro-N- (4-fluorophenyl) acetamidine. Maybridge is produced by replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 9 mg (26%). 1H NMR (300 MHz, DMSO-d6) 5 2.40 (s, 3H), 2.80 (m, 2H), 3_50-3 · 70 (m, 2H), 4.00-4_15 (m, 2H), 4.36 (s , 2H), 5.92 (br s, 1H), # 7.20 (m, 2H), 7.35 (m, 1H), 7.63 (m, 2H), 7.80 (m, 1H), 8.43 (m, 1H), 10.45 (m, 1H) 5 10.62 (br s? 1H); MS (ESI / APCI +) m / e 326 (M + H) +. Example 147 N- (2,4-difluorophenyl V2- (3- Methyl_3 ', 6'_dihydro-2,4'-bipyridyl) acetamidin The desired material was obtained according to the procedure of Example 145 via 2-chloro-N- (2,4-difluorobenzene Maybridge was substituted by 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 12 mg (33%). 1H NMR (300 MHz, DMSO-d6 ) 5 2_40 (s, 3H), 2.80 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4.15 (m, 2H), 4_38 (s, 2H), 5.90 (br s, 85228- 244- 200404539 1H), 7.12 (m, 1H), 7.35 (m, 1H), 7.40 (m, 1Η), 7.78 (m, 1Η), 7.82 (m, 1Η), 8.42-( m, 1H), 10.40 (m, 1H), 10.45 (br s, 1H); MS (ESI / APCI +) m / e 344 (M + H) + · Example 148 2- (3-methyl-3f, 6 ^ Dihydro-2,4'-bipyridylmethylbenzyl) The substance was prepared according to the procedure of Example 145 by replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide with 2-chloro-N-o-tolylacetamide (Maybridge). Yield 12 mg (34%). IHNMRpOOMHz.DMSO-ds) 5 2.22 (s, 3H), 2.40 (s, 3H), 2_80 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4.15 ( m, 2H), 4.38 (s, 2H), φ 5.92 (br s, 1H), 7.19 (m, 1H), 7.22 (m, 1Η), 7.26 (m, 1H), 7.36 (m, 1H), 7.42 (m, 1H), 7.80 (m, 1H), 8.44 (m, 1H), 10.00 (br s, 1H), 10.42 (m, 1H); MS (ESI / APCI +) m / e 322 ( M + H) +. Example 149 2-Π-methyl-3 \ 6'-dihydro_2,4'_bipyridine-Γ (2Ή) -yl VN- "3- (trifluoromethyl) phenyl 1 The desired substance for acetamide was according to the procedure of Example 145, by substituting 2-chloro-N- (3-trifluoromethylbenzyl) acetamide (Maybridge) with 2-chloro-N- (2,6-di Methylphenyl) ethinolamine. Yield 9 mg (23%). iHNMRpOOMH ^ DMSO-c ^) 5 2.40 (s, 3Η), 2.80 (m, 2Η), 3.50-3.70 (m, 2Η), 4.00-4.15 (m, 2Η), 4.37 (s, 2Η), 5 · 92 (br s, 1H), 7.37 (m, 1H), 7.52 (m, 1H), 7.62 (m, 1H), 7.79 (m, 2H), 8.10 (m, 1H), 8.44 (m, 1H), 10.42 (m, 1H), 11.00 (br s, 1H); MS (ESI / APCI +) m / e 376 (M + H) + · Example 150 N- (3_Amino_4-fluorophenyl ) -2- (3-methyl-3 ', 6'-dihydro-2,4f-bipyridine-r (2'HV group) acetamide 85228 -245-200404539 The desired substance is based on the procedure of Example 145 By replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide with 2-chloro-N- (3-chloro-4-fluorophenyl) acetamide (Maybridge) Made. Yield 9 mg (24%). IHNMRpOOMHzjMSO-d6) 6 2.40 (s, 3H), 2.80 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4.15 (m, 2H), 4.33 ( s, 2H), 5.95 (br s, 1H), 7.36 (m, 1H), 7.44 (m, 2H), 7.78 (m, 1H), 7.92 (m, 1H), 8.44 (m, 1H) ), 10.42 (m, 1H), 10.82 (br s, 1H); MS (ESI / APCI +) m / e 360 (M + H) +. Example 151 2- (3-methyl-3 ', 6'- Dihydro-2,4'-bipyridyl) -N- "4_ (trifluoromethane ) Benzyl 1 · Acetylamine was obtained according to the procedure of Example 145, by replacing 2-chloro-N- (with 2-chloro-N- (4-trifluoromethoxyphenyl) acetamide (Maybridge) 2,6-dimethylphenyl) acetamide. Yield 9 mg (22%). IHNMRpOOMHz.DMSO-A) 5 2.40 (s, 3H), 2.80 (m, 2H), 3.50-3.70 ( m, 2H), 4.00-4.15 (m, 2H), 4.30 (s, 2H), 5.92 (br s, 1H), 7.36 (m, 1H), 7.40 (m, 2H), 7.77 (m, 2H) ), 7.82 (m, 1H), 8.42 (m, 1Η), 10.42 (m? 1H)? 10.80 (br s5 1H); MS (ESI / APCI +) m / e 392 (M + H) +. Example 152 · 2- (3-Methyl-3W-dihydro-2,4'-bipyridine-Γ (2Ήν group VN- "2- (trifluoromethyl) benzyl 1 acetamido The desired substance is based on Example 145 Procedure by replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide with 2-chloro-N- (2-trifluoromethylphenyl) acetamide (Maybridge) . Yield 10 mg (26%). iHNMROOOMHADMSO-A) 5 2 · 40 (s, 3H), 2.80 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4 · 15 (m, 2H), 4.35 (s, 2H), 5.92 ( br s, 1H), 7.36 (m, 1H), 7.60 (m, 2H), 7.80 (m, 3H), 8.42 (m, 1H), 10.40 (br s, 1H), 10.42 (m, 1H); MS (ESI / APCI +) m / e 376 (M + H) +. 85228 -246- 200404539 Example 153N- (2,3-dichlorobenzene V2- [3-methyl-3 ', 6L dihydro- The desired material for 2,4'-bipyridine-1 '(2Ή) -yl) acetamide was obtained according to the procedure of Example 145 via 2-chloro-N- (3,4-dichlorophenyl) acetamide. (Maybridge) substituted 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 10 mg (26%). 1H NMR (300 MHz, DMSO-d6) 5 2.40 (s, 3H), 2.80 (m, 2H), 3_50 · 3 · 70 (m, 2H), 4.00-4.15 (m, 2H), 4.40 (s , 2H), 5.92 (br s, 1H), 7.37 (m, 1H), 7.42 (m, 1H), 7.58 (m, 1H), 7.77 (m5 1H), 7.81 (m, 1H), 8.42 ( m, 1H), 10 · 42 (br s, 1H), 10.45 (m, 1H); MS (ESI / APCI +) m / e 377 (M + H) + · φ Example 154 2- (3_methyl_ 3 ', 6'-dihydro_2, bipyridine_Γ (2Ή) _yl VN- "4- (trifluoromethyl) benzyl 1 Acetylamine The desired substance was obtained according to the procedure of Example 145, followed by 2 _Chloro-N- (4-trifluoromethylphenyl) acetamide (Maybridge) is substituted for 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 11 mg ( 28%). IHNMRpOOMHADMSOO 5 2.40 (s5 3H) 5 2.80 (m5 2H) 5 3.50-3.70 (m5 2H) 5 4.00-4.15 (m5 2H) 5 4.37 (s, 2H)? 5.92 (br s, 1H), 7.36 (m, 1H), 7.78 (m, 3H), 7.82 (m, 2H), 8.42 (m, 1H), 10.42 · (m, 1H), 10.98 (br s, 1H); MS (ESI / APCI +) m / e 376 (M + H) +-Example 155 of "4- (3-Cyano-2 ^ sedenyl) -3,6-dihydro-1 (2-Indyl-Edianyl &quot; |-&gt; 1- (3-methylphenyl)

乙醯胺 實例155 A 2-(1，2,3,6-四氳-4-口比症基）-3-口塞吩甲月青三氟酷酸鹽 所要之物質係根據實例144A與144B之程序，經由以碟吩-3-甲腈取代2_溴基各甲基^比啶而製成。1H NMR (300 MHz，DMSO-d6 )Acetylamine Example 155 A 2- (1,2,3,6-tetramidine-4-orthobenzyl) -3-orcephine methocyanine trifluoroacrylic acid The required substance is according to Examples 144A and 144B The procedure was prepared by substituting 2-bromo-methyl-pyridine with stilbene-3-carbonitrile. 1H NMR (300 MHz, DMSO-d6)

85228 -247- 200404539 (5 2.80 (m，2H)，3.40 (m，2H), 3.90 (m，2H)，6.45 (br s，1H)，7.45 (m，1H)，7.75 · (m，1H)，8·95 (m，2H) ; MS (ESI/APCI+) m/e 191 (M+H)+ ·85228 -247- 200404539 (5 2.80 (m, 2H), 3.40 (m, 2H), 3.90 (m, 2H), 6.45 (br s, 1H), 7.45 (m, 1H), 7.75 · (m, 1H) , 8.95 (m, 2H); MS (ESI / APCI +) m / e 191 (M + H) + ·

實例155B 2-「4-(3-氰基-2-嘧吩基V3,6-二氫-U2HV吡啶基甲基笨基） 乙醯胺 所要之物質係根據實例145之程序，經由以得自實例155A 之產物取代得自實例143B之產物，並以得自實例33A之產物 取代2-氯·Ν-(2,6-二甲基苯基）乙醯胺而製成。產量13毫克（36% ) 癱 。1H NMR (300 MHz，DMSO_d6 ) δ 2.30 (s，3Η)，2·90 (m，2Η)，3.50-4.20 (m， 4Η)，4.30 (s，2Η)，6·43 (br s，1Η)，6·98 (m，1ΗΧ 7·24 (m，1Η)，7·42 (m，2Η)， 7.50 (m，1H)，7.78 (m，1H)，10.42 (m，1H)，10.44 (br s，1H) ; MS (ESI/APCI+) m/e 338 (M+H)+. A iH 156 K3-氰基-3’，6’-二氫-2,4f-聯吡啶 基 VN-(2,6-二甲基苯基） ;醯胺 所要之物質係根據實例145之程序，經由以得自實例144B # 之產物取代實例143B之產物而製成。產量1〇毫克（27% )。 1H NMR (300 MHz，DMSO-d6) (5 2.20 (s，6H)，2.90 (m，2H)，3.50-3.70 (m， 2H)，4.00-4.15 (m，2H)，4·37 (s，2H)，6.55 (br s，1H)，7·20 (m，3H)，7.55 (m，1H)， 8.40 (m，1H)，8·80 (m，1H)，10.00 (br s，1H)，10.45 (m，1H) ; MS (ESI/APCI+) m/e 347(M+H)+. A 例 157 M3-氰基-3’,6f-二氫-2,4f-撒峨啶-ΐ’(2Ή)-基VN-(4-氟笨基）乙醯胺Example 155B 2- "4- (3-Cyano-2-pyridinyl V3,6-dihydro-U2HV pyridylmethylbenzyl) Acetylamine The desired material was obtained according to the procedure of Example 145 and was obtained from The product of Example 155A was prepared by substituting the product from Example 143B and the product from Example 33A was substituted for 2-chloro · N- (2,6-dimethylphenyl) acetamide. Yield 13 mg (36 %) Paralysis. 1H NMR (300 MHz, DMSO_d6) δ 2.30 (s, 3Η), 2.90 (m, 2Η), 3.50-4.20 (m, 4Η), 4.30 (s, 2Η), 6.43 (br s, 1Η), 6.98 (m, 1Ηχ 7.24 (m, 1Η), 7.42 (m, 2Η), 7.50 (m, 1H), 7.78 (m, 1H), 10.42 (m, 1H) , 10.44 (br s, 1H); MS (ESI / APCI +) m / e 338 (M + H) +. A iH 156 K3-cyano-3 ', 6'-dihydro-2,4f-bipyridyl VN- (2,6-dimethylphenyl); The desired material was obtained according to the procedure of Example 145 by replacing the product of Example 143B with the product from Example 144B #. Yield 10 mg (27 %). 1H NMR (300 MHz, DMSO-d6) (5 2.20 (s, 6H), 2.90 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4.15 (m, 2H), 4.37 (s, 2H), 6.55 (br s, 1H), 7.20 (m, 3H) , 7.55 (m, 1H), 8.40 (m, 1H), 8.80 (m, 1H), 10.00 (br s, 1H), 10.45 (m, 1H); MS (ESI / APCI +) m / e 347 ( M + H) +. A Example 157 M3-cyano-3 ', 6f-dihydro-2,4f-thameridine-fluorene' (2fluorene) -yl VN- (4-fluorobenzyl) acetamide

所要之物質係根據實例M5之程序，經由以得自實例144B 85228 -248- 200404539 之產物取代實例143B之產物，並以2-氯-N-(4-氟苯基）乙醯胺 · (Maybridge)取代2-氯-N-(2,6_二甲基苯基）乙醯胺而製成。產量11 毫克（31% )。1H NMR (300 MHz，DMSO-d6) 5 2.95 (m，2H)，3.50-3.70 (m， 2H)，4.00-4.15 (m，2H)，4.37 (s，2H)，6.55 (br s，1H)，7.20 (m，2H)，7·65 (m，3H)， 8_40 (m，1H)，8.85 (m，1H)，10.50 (m，1H)，10.70 (br s，1H) ; MS (ESI/APCI+) m/e 337 (M+H)+. 實例158 2-(3-氰基-3’，6’-二氫-2,4’-聯吡啶_1’(2邗-基）-化(2,4-二氯苯基）乙_脸 · 所要之物質係根據實例145之程序，經由以得自實例i44B 之產物取代實例143B之產物，並以2-氯-N-(2,4-二氟苯基）乙酸 胺(Maybridge)取代2-氯_N-(2,6-二甲基苯基）乙醯胺而製成。產量 11 毫克（29% )。1H NMR (300 MHz，DMSO-d6) 5 2·95 (m，2H)，3.50-3.70 (m，2Η)，4.00-4.15 (m，2Η)，4·35 (s，2H)，6·55 (br s，1Η)，7·20 (m，1Η)，7·40 (m， 1H)，7.60 (m，1H)，7·85 (m，1H)，8_40 (m，1H)，8.85 (m，1H)，10.50 (m，iH)， 10.55 (br s，1H) ; MS (ESI/APCI+) m/e 355 (M+H)+ · 實例159 · 2-(3-氰基-3T，6L二氫-2,4f-聯外I：淀-Γ(2Ή)-基）-N-(2-甲基笨某）乙醯胺 所要之物質係根據實例145之程序，經由以得自實例ι44Β 之產物取代實例143B之產物，並以2-氯-N-鄰-甲苯基乙醯胺 (Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙驗胺而製成。產量11 毫克（31% )。1H NMR (300 MHz，DMSO-d6) δ 2.20 (s，3H)，2.95 (m，2H)， 3.50-3.70 (m，2ΗΧ 4·00-4·15 (m，2Η)，4.35 (s，2Η)，6.60 (br s，1Η)，7·20 (m，3Η), 7.45 (m，1H)，7.60 (m，1H)，8.40 (m，1H)，8·80 (m，1H)，10.00 (br s，ih)，10.55 (m，1H) ; MS (ESI/APCI+) m/e 333 (M+H)+ · 85228 -249- 200404539 實例160 · 2-(3-氰基-3f，6’-二氫-2,4f•聯吡啶·1’(2Ήν基VN43-(三氟甲某）茉某1 乙醯胺 所要之物質係根據實例145之程序，經由以得自實例144B 之產物取代實例143B之產物，並以2-氯-N-(3_三氟甲基苯基）乙 醯胺（Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而製成。產 量 11 毫克（28%)。111厕11(30〇]^1^，0%80-(16)(5 2.90(111，211)，3.50- 3.70 (m，2H)，4·00_4·15 (m，2H)，4.30 (s，2H)，6.55 (br s，1H)，7.60 (m，3H)， φ 7.75 (m，1H)，8·10 (m5 1H)，8.40 (m，lHX 8.80 (m，1H)，10.50 (m，1H)，10.95 (br s，1H) ; MS (ESI/APCI+) m/e 387 (M+H)+ · 實例161 2-(3-氰基-3’,6’-二氫-2,4’-聯吡啶-1’(2阳-基）-仏「4-(三氟甲氧基）笨基1 乙醯胺 所要之物質係根據實例145之程序，經由以得自實例144B 之產物取代實例143B之產物，並以2-氯-N-(4-三氟甲氧苯基）乙 醯胺(Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而製成。產 _ 量 11 毫克（27%)。1«[丽11(30〇]^1^，01^0-(16)(5 2.90(111，211)，3.50- 3.70 (m，2H)，4.00-4.15 (m，2H)，4.35 (s，2H)，6.55 (br s，1H)，7.40 (m，2H)， 7.60 (m，1HX 7·75 (m，2H)，8.40 (m，1H)，8.80 (m，1H)，10.50 (m，1Η)，10·80 (br s? 1H) ； MS (ESI/APCI+) m/e 403 (M+H)+. 實例162 K3-氰基_3’，6’_二氤-2.4’-聯吡啶-Γ(2Ή)-基三氟甲基）苯基1 乙醯胺The desired material was according to the procedure of Example M5, by replacing the product of Example 143B with the product obtained from Example 144B 85228 -248- 200404539 and replacing it with 2-chloro-N- (4-fluorophenyl) acetamidamine (Maybridge ) Instead of 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 11 mg (31%). 1H NMR (300 MHz, DMSO-d6) 5 2.95 (m, 2H), 3.50-3.70 (m, 2H), 4.00-4.15 (m, 2H), 4.37 (s, 2H), 6.55 (br s, 1H) , 7.20 (m, 2H), 7.65 (m, 3H), 8_40 (m, 1H), 8.85 (m, 1H), 10.50 (m, 1H), 10.70 (br s, 1H); MS (ESI / APCI +) m / e 337 (M + H) +. Example 158 2- (3-cyano-3 ', 6'-dihydro-2,4'-bipyridine_1' (2 邗 -yl)- (2,4-Dichlorophenyl) ethane. The desired substance was obtained by substituting the product from Example i44B with the product from Example 143B and replacing it with 2-chloro-N- (2,4 -Difluorophenyl) amine acetate (Maybridge) substituted 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 11 mg (29%). 1H NMR (300 MHz, DMSO-d6) 5 2.95 (m, 2H), 3.50-3.70 (m, 2Η), 4.00-4.15 (m, 2Η), 4.35 (s, 2H), 6.55 (br s, 1Η) , 7.20 (m, 1Η), 7.40 (m, 1H), 7.60 (m, 1H), 7.85 (m, 1H), 8_40 (m, 1H), 8.85 (m, 1H), 10.50 (m, iH), 10.55 (br s, 1H); MS (ESI / APCI +) m / e 355 (M + H) + · Example 159 · 2- (3-cyano-3T, 6L dihydro-2, 4f-Exo I: Yodo-Γ (2Ή) -based) -N- (2-methyl (A) The desired substance for acetamide was according to the procedure of Example 145, by replacing the product of Example 143B with the product obtained from Example 44B, and replacing 2- with 2-chloro-N-o-tolylacetamide (Maybridge). Chloro-N- (2,6-dimethylphenyl) ethylamine was produced. Yield 11 mg (31%). 1H NMR (300 MHz, DMSO-d6) δ 2.20 (s, 3H), 2.95 ( m, 2H), 3.50-3.70 (m, 2Ηχ 4.00-4 · 15 (m, 2Η), 4.35 (s, 2Η), 6.60 (br s, 1Η), 7.20 (m, 3Η), 7.45 (m, 1H), 7.60 (m, 1H), 8.40 (m, 1H), 8.80 (m, 1H), 10.00 (br s, ih), 10.55 (m, 1H); MS (ESI / APCI +) m / e 333 (M + H) + · 85228 -249- 200404539 Example 160 · 2- (3-cyano-3f, 6'-dihydro-2,4f · bipyridine · 1 '(2Ήν group VN43- ( Trifluoromethane) Moss 1 Acetylamine was obtained according to the procedure of Example 145 by replacing the product of Example 143B with the product obtained from Example 144B and replacing it with 2-chloro-N- (3-trifluoromethyl Phenyl) acetamide (Maybridge) is produced by replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 11 mg (28%). 111 toilet 11 (30〇) ^ 1 ^, 0% 80- (16) (5 2.90 (111,211), 3.50-3.70 (m, 2H), 4.00_4 · 15 (m, 2H), 4.30 (s , 2H), 6.55 (br s, 1H), 7.60 (m, 3H), φ 7.75 (m, 1H), 8.10 (m5 1H), 8.40 (m, lHX 8.80 (m, 1H), 10.50 (m , 1H), 10.95 (br s, 1H); MS (ESI / APCI +) m / e 387 (M + H) + · Example 161 2- (3-cyano-3 ', 6'-dihydro-2, 4'-Bipyridine-1 '(2 cation-yl) -fluorene "4- (trifluoromethoxy) benzyl 1 acetamidine The desired substance was obtained according to the procedure of Example 145 through the product obtained from Example 144B. Substitute the product of Example 143B and replace 2-chloro-N- (2,6-dimethylphenyl) acetamidine with 2-chloro-N- (4-trifluoromethoxyphenyl) acetamide (Maybridge) Made from amines. Yield 11 mg (27%). 1 «[Li 11 (30〇] ^ 1 ^, 01 ^ 0- (16) (5 2.90 (111,211), 3.50-3.70 (m, 2H), 4.00-4.15 (m, 2H), 4.35 (s, 2H), 6.55 (br s, 1H), 7.40 (m, 2H), 7.60 (m, 1HX 7.75 (m, 2H), 8.40 ( m, 1H), 8.80 (m, 1H), 10.50 (m, 1Η), 10.80 (br s? 1H); MS (ESI / APCI +) m / e 403 (M + H) +. Example 162 K3- Cyano_3 ', 6'_difluorene-2.4'-bipyridine-Γ (2Ή)- Trifluoromethyl) phenyl 1 acetamide

所要之物質係根據實例145之程序，經由以得自實例144B 85228 -250- 200404539 之產物取代實例143B之產物，並以2-氯-N-(2-三氟甲基苯基）乙 · 醯胺(Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而製成。產 量 11 ΐ*(28%)°1ΗΝΜΓΙ(300ΜΗΖ，ΟΜ30-(16)(5 2·90(ηι，2Η)，3·50- 3.70 (m，2Η)，4.00-4.15 (m，2Η)，4.35 (s，2Η)，6.55 (br s，1Η)，7.55 (m，3Η)，The desired material was obtained according to the procedure of Example 145 by replacing the product of Example 143B with the product obtained from Example 144B 85228 -250- 200404539 and replacing it with 2-chloro-N- (2-trifluoromethylphenyl) ethane. Maybridge is produced by replacing 2-chloro-N- (2,6-dimethylphenyl) acetamide. Yield 11 ΐ * (28%) ° 1ΗNΜΓΙ (300MΗZ, OM30- (16) (5 2.90 (ηι, 2Η), 3.50-3.70 (m, 2Η), 4.00-4.15 (m, 2Η), 4.35 (s, 2Η), 6.55 (br s, 1Η), 7.55 (m, 3Η),

7.80 (m，2H)，8.40 (m，1H)，8·80 (m，1H)，10.40 (br s，1H)，10.50 (in，1H); MS (ESI/APCI+) m/e 387 (M+H)+. 實例1637.80 (m, 2H), 8.40 (m, 1H), 8.80 (m, 1H), 10.40 (br s, 1H), 10.50 (in, 1H); MS (ESI / APCI +) m / e 387 (M + H) +. Example 163

2- (3-氰基-3’，6’-二氫-2,4f-聯吡啶基VN-(2,3_二蠹.苯基）乙醯胺 · 所要之物質係根據實例145之程序，經由以得自實例144B 之產物取代實例143B之產物，並以2-氯-N-(2,3-二氯苯基）乙醯 胺(Maybridge)取代2-氯-N-(2,6-二甲基苯基）乙醯胺而製成。產量 12 毫克（30% )。1H NMR (300 MHz, DMSO-d6 ) 5 2.90 (m5 2H), 3.50-3.70 (m，2H)，4.00-4.15 (m，2H)，4·35 (s，2H)，6.55 (br s，1H)，7·40 (m，2H)，7.60 (m， 2H)，8.40 (m，1H)，8.80 (m，1H)，10.50 (m，2H) ； MS (ESI/APCI+) m/e 388 (M+H)' 實例164 · 3- 甲基_N-丨「4-(6-酮基-1(6HV嗒畊基VI-六氤吡啶基~l甲基j苯甲醯胺 按照實例111中所述之程序，以得自實例40B之產物取代4-(2- 甲氧苯基）六氫吡啶，提供標題化合物（99%產率）。iHNMR (300 MHz，DMSO-d6) 5 1·74 (m，2H)，1.88 (m，2H)，2.37 (s，3H)，2.39 (m，2H)， 2.99 (m，2H)，4.19 (m，2H)，4·71 (s，1H)，6.91 (dd，J=9,1.5 Hz，1H)，7·38 (m， 3H)，7.69 (m，2H)，7.96 (dd，J=9.0, 3·0 Hz，1H)，8.75 (br s，1H); MS (DCI/NH3) m/e 327 (M+H)' 順丁晞二酸鹽：對C18H22N402，1.25C4H404，1_5H20之分析計 85228 -251 - 200404539 算值：C，55.42 ; Η，6·07 ; N，11.24.實測值：C，55·25 ; H，5·88 ; Ν，13·03_ 實例165 Ν-(3’,6’-二氤-2.4’-聯吡啶基甲基）小金剛烷羧醯胺 以如實例115之相同方式，以1-金剛烷羧醯胺（Aldrich)取代3-甲氧基苯甲醯胺而製成（43毫克，6%產率）。iHNMR (300 MHz， DMSO-d6 ) 5 1 ·66 (m，6H)，1.80 (m，6H)，1.95 (m，3H)，2.30 (m，2H)，2.66 (t， J=4.5 Hz? 2H), 3.15 (m? 2H)? 4.06 (d? J=6 Hz, 2H), 6.68 (m? 1H)5 7.21 (m3 1H)5 7.51 (d，J=6 Hz，1H)，7_72 (m，2H)，8·51 (m，1H) ; MS (DCI/NH3) m/e 352 (M+H)+_ 實例166 3-甲基-N-丨「4-(l，3-遠也-2-基）-3,6-二氫-1(2H)^比咬基1甲基}苯甲酸胺2- (3-cyano-3 ', 6'-dihydro-2,4f-bipyridyl VN- (2,3_difluorenyl.phenyl) acetamidamine · The desired substance was prepared according to the procedure of Example 145 By replacing the product of Example 143B with the product from Example 144B and replacing 2-chloro-N- (2,6 with 2-chloro-N- (2,3-dichlorophenyl) acetamide (Maybridge) -Dimethylphenyl) acetamide. Yield 12 mg (30%). 1H NMR (300 MHz, DMSO-d6) 5 2.90 (m5 2H), 3.50-3.70 (m, 2H), 4.00- 4.15 (m, 2H), 4.35 (s, 2H), 6.55 (br s, 1H), 7.40 (m, 2H), 7.60 (m, 2H), 8.40 (m, 1H), 8.80 (m , 1H), 10.50 (m, 2H); MS (ESI / APCI +) m / e 388 (M + H) 'Example 164 · 3-methyl_N- 丨 "4- (6-keto-1 (6HV Dalkenyl VI-hexapyridyl ~ lmethylj benzamidine Following the procedure described in Example 111, substituting 4- (2-methoxyphenyl) hexahydropyridine with the product from Example 40B, provided Title compound (99% yield). IHNMR (300 MHz, DMSO-d6) 5 1.74 (m, 2H), 1.88 (m, 2H), 2.37 (s, 3H), 2.39 (m, 2H), 2.99 (m, 2H), 4.19 (m, 2H), 4.71 (s, 1H), 6.91 (dd, J = 9, 1.5 Hz, 1H), 7.38 (m, 3H) 7.69 (m, 2H), 7.96 (dd, J = 9.0, 3.0 Hz, 1H), 8.75 (br s, 1H); MS (DCI / NH3) m / e 327 (M + H) ' Diacid salt: Analytical meter for C18H22N402, 1.25C4H404, 1_5H20 85228 -251-200404539 Calculated value: C, 55.42; Η, 6.07; N, 11.24. Found: C, 55 · 25; H, 5.88 Ν, 13 · 03_ Example 165 N- (3 ', 6'-Difluorene-2.4'-bipyridylmethyl) pyrimantanecarboxamide In the same manner as in Example 115, 1-adamantylcarboxamidine Amine (Aldrich) substituted with 3-methoxybenzidine (43 mg, 6% yield). IHNMR (300 MHz, DMSO-d6) 5 1 · 66 (m, 6H), 1.80 (m, 6H), 1.95 (m, 3H), 2.30 (m, 2H), 2.66 (t, J = 4.5 Hz? 2H), 3.15 (m? 2H)? 4.06 (d? J = 6 Hz, 2H), 6.68 ( m? 1H) 5 7.21 (m3 1H) 5 7.51 (d, J = 6 Hz, 1H), 7_72 (m, 2H), 8.51 (m, 1H); MS (DCI / NH3) m / e 352 ( M + H) + _ Example 166 3-methyl-N- 丨 4- (l, 3-distal-2-yl) -3,6-dihydro-1 (2H) ^ } Benzoate

實例166 A 4-(1,3-嘧唑冬基V3,6-二氤-U2HV吡啶羧酸第三-丁酯 按照實例143A中所述之程序，以2-嘧唑基溴化鋅取代3-甲 基-2-吡啶基溴化鋅，提供標題化合物（56%產率）。1H NMR (300 MHz5 CDC13) δ 1.5 (s5 9Η)5 2.7 (m5 2Η)? 3.33 (t5 2Η, J=6 Hz)? 4.10 (q? 2H5 J= 3 Hz)，6.60 (m，1H)，7·21 (d，1H，J=3 Hz)，7.78 (d，1H，J=3 Hz); MS (DCI/NH3) m/e 267 (M+H)+.Example 166 A 4- (1,3-pyrazolidyl V3,6-diamidino-U2HV pyridinecarboxylic acid tertiary-butyl ester. Substitute 3 with 2-pyrazolyl zinc bromide according to the procedure described in Example 143A. -Methyl-2-pyridylzinc bromide to provide the title compound (56% yield). 1H NMR (300 MHz5 CDC13) δ 1.5 (s5 9Η) 5 2.7 (m5 2Η)? 3.33 (t5 2Η, J = 6 Hz)? 4.10 (q? 2H5 J = 3 Hz), 6.60 (m, 1H), 7.21 (d, 1H, J = 3 Hz), 7.78 (d, 1H, J = 3 Hz); MS (DCI / NH3) m / e 267 (M + H) +.

實例166BExample 166B

4-(1，3-者吐_2_基）-1，2,3,6-四氫？比读 將得自實例166A之產物（3.62克，13·6毫莫耳）在25%三氟醋 酸/二氯甲烷（30毫升）中之溶液，於室溫下揽拌2小時。使 反應物在減壓下濃縮，而得褐色油（1.69克，74% )。1H NMR (300 MHz，CDC13) 5 2.55 (m，2Η)，3.12 (t，2Η，J=6 Ηζ)，3·59 (m，2Η)，6.63 (m， 85228 -252- 200404539 1H)，7.20 (d，1H，J=3 Hz)，7.75 (d，1H，J=3 Hz) ； MS (DCI/NH3)m/e 167 (M+H)+.4- (1,3-Those_2_2yl) -1,2,3,6-tetrahydro? Comparison Reading A solution of the product from Example 166A (3.62 g, 13.6 mmol) in 25% trifluoroacetic acid / dichloromethane (30 ml) was stirred at room temperature for 2 hours. The reaction was concentrated under reduced pressure to give a brown oil (1.69 g, 74%). 1H NMR (300 MHz, CDC13) 5 2.55 (m, 2Η), 3.12 (t, 2Η, J = 6 Ηζ), 3.59 (m, 2Η), 6.63 (m, 85228 -252- 200404539 1H), 7.20 (d, 1H, J = 3 Hz), 7.75 (d, 1H, J = 3 Hz); MS (DCI / NH3) m / e 167 (M + H) +.

實例166C 3-甲基-N{「H3-破唑-2-基&gt;3,6-二氫-1(2HV吡啶基1甲基}苯甲醯胺 按照實例200中所述之程序，以得自實例166B之產物取代 得自實例119A之產物，提供標題化合物，為黃色膠黏性殘 留物 680 毫克（36% )。1H NMR (300 MHz，CDC13)占 2.4 (s，3H)，2.8 (m， 2H)，2·95 (t，2H，4.5 Hz)，3.42 (m，2H)，4·5 (d，2H，J=6 Hz), 6.6 (m，1H)，7·2 (d， 1H，J=3 Hz)，7.35 (dd，2H，J=4.5 Hz，1.5 Hz)，7·49 (m，1H)，7_52 (s，1H)，7.78 (d， lH，J=3Hz) ; MS(DCI/NH3)m/e314(M+H)+.順丁 烯二酸鹽：對 C17H19N3OS.1.0C4H4O4 ·0·5Η2Ο 之分析計算值：c，57.52; H，5_52 ;Ν，9·58·實測值：C，57.48 ; Η，5·33 ; Ν，9·52· 實例167 2-『4-(3-氣基-2-ρ比淀基）-1-7Τ氮峨ρ井基1-Ν-1，2,3,4-四氣-1-蕃基乙g盡胺Example 166C 3-methyl-N {"H3-oxazol-2-yl &gt; 3,6-dihydro-1 (2HV pyridyl 1methyl} benzamide) Following the procedure described in Example 200, The product from Example 166B replaced the product from Example 119A to provide the title compound as a yellow sticky residue 680 mg (36%). 1H NMR (300 MHz, CDC13) accounted for 2.4 (s, 3H), 2.8 ( m, 2H), 2.95 (t, 2H, 4.5 Hz), 3.42 (m, 2H), 4.5 (d, 2H, J = 6 Hz), 6.6 (m, 1H), 7.2 (d , 1H, J = 3 Hz), 7.35 (dd, 2H, J = 4.5 Hz, 1.5 Hz), 7.49 (m, 1H), 7_52 (s, 1H), 7.78 (d, lH, J = 3Hz) ; MS (DCI / NH3) m / e314 (M + H) +. Maleic acid salt: Analytical calculated value for C17H19N3OS.1.0C4H4O4 · 0 · 5Η2Ο: c, 57.52; H, 5_52; N, 9 · 58. Measured value: C, 57.48; Hf, 5.33; N, 9.52. Example 167 2- "4- (3-Gasyl-2-ρ ratio lake base) -1-7T Nitrogen well foundation 1-N-1,2,3,4-Tetraki-1-fanylethylg

實例167 A 2-溴_N_1，2,3,4-四氫小签基乙醯胺 按照實例1A中所述之程序，以（± )-1，2,3,4-四氫小萘胺鹽酸 鹽取代3-甲基苯胺，提供標題化合物（22%產率），為白色固 體。1 H NMR (300 MHz，DMSO-d6) 5 1.75 (m，4H)，2.73 (m，2H)，3.87 (ABq， 2H，JAB =10.5 Hz，△ vAB =8.5 Hz)，4.91 (m，1H)，7.15 (m，4H)，8.65 (br d，1H， J=8.5 Hz); MS (DCI/NH3)m/e 268/270 (M+H)+ ; 285/287 (M+NH4)+.Example 167 A 2-Bromo_N_1,2,3,4-tetrahydropyridylacetamidinide Follow the procedure described in Example 1A with (±) -1,2,3,4-tetrahydropethamidamine The hydrochloride substituted 3-methylaniline to provide the title compound (22% yield) as a white solid. 1 H NMR (300 MHz, DMSO-d6) 5 1.75 (m, 4H), 2.73 (m, 2H), 3.87 (ABq, 2H, JAB = 10.5 Hz, △ vAB = 8.5 Hz), 4.91 (m, 1H) , 7.15 (m, 4H), 8.65 (br d, 1H, J = 8.5 Hz); MS (DCI / NH3) m / e 268/270 (M + H) +; 285/287 (M + NH4) +.

實例167B 2-「4-(3-氰基-2-p比淀基）-1·六氫I?比咕基i_N-1,2,3,4-四惫t -1-審基乙縫胳 按照實例121B中所述之程序，以得自實例167A之產物取代 85228 -253 - 200404539 得自實例121A之產物，提供標題化合物（87%產率），為白色 -固體。1H NMR (300 MHz, DMSO-d6) 5 1.81 (m，4H)，2·63 (m，4H)，2.74 (m， 2H)，3.08 (ABq，2H，JAB=15.3 Hz，△]； ΑΒ=8·δ Hz)，3·62 (m，4H)，5·02 (m， 1H)，6_92 (dd，1H，J=7.5, 4.8 Hz)，7.13 (m，4H)，8.06 (dd，1H，J=7.8, 2.0 Hz)， 8.06 (m 重疊，1H)，8·40 (dd，1H，J=4_8, 2.0 Hz) ; MS (DCI/NH3) m/e 376 (M+H)+ ;對 C22H25N50 之分析計算值：C，70.38 ; H，6.71 ; N，18.65. 實測值：C，69.99 ; H，6.85 ; N，18.59· 實例168 · 2-「4-(3-氰基-2-吡啶基Vl_六氫吡畊基1-1^「(18)-1，2,3,4-四氤小萁某1Example 167B 2- "4- (3-Cyano-2-p-pyridyl) -1 · hexahydro I? Pyroxy i_N-1,2,3,4-tetratyl t-1-yl Follow the procedure described in Example 121B to replace 85228-253-200404539 with the product from Example 167A. The product from Example 121A provided the title compound (87% yield) as a white-solid. 1H NMR (300 MHz , DMSO-d6) 5 1.81 (m, 4H), 2.63 (m, 4H), 2.74 (m, 2H), 3.08 (ABq, 2H, JAB = 15.3 Hz, △]; ΑB = 8 · δ Hz) , 3.62 (m, 4H), 5.02 (m, 1H), 6_92 (dd, 1H, J = 7.5, 4.8 Hz), 7.13 (m, 4H), 8.06 (dd, 1H, J = 7.8, 2.0 Hz), 8.06 (m overlap, 1H), 8.40 (dd, 1H, J = 4_8, 2.0 Hz); MS (DCI / NH3) m / e 376 (M + H) +; analysis and calculation of C22H25N50 Values: C, 70.38; H, 6.71; N, 18.65. Found: C, 69.99; H, 6.85; N, 18.59. Example 168. 2- "4- (3-cyano-2-pyridyl) Vl_hexa Hydropyridyl 1-1 ^ ((18) -1,2,3,4-tetrahydropyrazine 1

乙醯胺 實例168A 2-溴-1^「(18)-1，2,3,4_四氤小荃基~1乙醯胺 按照實例1A中所述之程序，以（S)_l，2,3,4-四氫小荅胺（Lancaster) 取代3_甲基苯胺，提供標題化合物（87%產率），為白色固體 。1H NMR (300 MHz，DMSO-d6 ) 5 1.79 (m，4H)，2.73 (m，2H)，3.87 (ABq， 2H，JAB =10.9 Hz，Hz)，4.93 (m，1H)，7.15 (m，4H)，8.65 (br d，1H， · J=8.5Hz)； MS (DCI/NH3)m/e 268/270 (M+H)+ ； 285/287 (M+NH4 )+.Acetylamine Example 168A 2-Bromo-1 ^ ((18) -1,2,3,4_Tetramethylpyridyl ~ 1 Acetylamine Follow the procedure described in Example 1A with (S) -1, 2 , 3,4-Tetrahydroberberamine (Lancaster) substituted 3-methylaniline to provide the title compound (87% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) 5 1.79 (m, 4H ), 2.73 (m, 2H), 3.87 (ABq, 2H, JAB = 10.9 Hz, Hz), 4.93 (m, 1H), 7.15 (m, 4H), 8.65 (br d, 1H, J = 8.5Hz) ; MS (DCI / NH3) m / e 268/270 (M + H) +; 285/287 (M + NH4) +.

實例168B 244-(3-氰基-2-毗啶某Vl_六氫吡畊基1-化「(18)_1，2,3,4_四i. -l_:j:基1 乙醯胺 按照實例121B中所述之程序，以得自實例168A之產物取代 得自實例121A之產物，提供標題化合物（67%產率），為白色 固體。[a]23D-39.37o(c0.315，CHCl3); iHNMRpOOMHADMSOcU (51.81 (m，4H)，2.62 (m，4H)，2.74 (m，2H)，3.08 (ABq，2H，Jab=14.9 Hz， 85228 -254- 200404539 △〉αβ=8·8 Hz)，3.61 (m，4H)，5.00 (m，1H)，6.92 (dd，1H，J=7.8, 4.8 Ηζ)，7·12 . (m，4H)，8.06 (dd，1H，J=7.8, 2.0 Hz)，8·06 (m 重疊，1H)，8.40 (dd，1H，J=4.8， 2.0 Hz); MS(DCI/NH3)m/e376(M+H)+ ;對 C22H25N50 之分析計算 值：C，70.38 ; H，6·71 ; N，18.65.實測值：C，70.00 ; H，6.90 ; N，18.26. 實例169 2-『4-(3-氰基-2-外|：淀基）-1-六氫外(：呼基&quot;|-&gt;1-((1幻-1，2,3,4-四氫-1-签基1 乙醯胺 實例169A ❿ 2-溴-N-「(1RH，2,3,4-四氫-1-篇:某1乙醯脖 按照實例1A中所述之程序，以（R)-l，2,3,4-四氫小蓁胺（Lancaster) 取代3-甲基苯胺，提供標題化合物（52%產率），為白色固體 。iHNMRpOOMHiDMSO-c^) 5 l/78(m，4H)，2.73(m，2H)，3.87(ABq， 2H5 Jab=10.9 Hz5 Δι^αβ=8.6 Hz), 4.93 (m? 1H)? 7.15 (m5 4H), 8.65 (brd? 1H5 J=8.5 Hz) ； MS (DCI/NH3) m/e 268/270 (M+H)+ ； 285/287 (M+NH4)+.Example 168B 244- (3-Cyano-2-pyridine 1-Hydroxypyridyl 1-Hydroxy ((18) _1,2,3,4_tetrai. -L_: j: yl 1 acetamide Following the procedure described in Example 121B, replacing the product from Example 121A with the product from Example 168A provided the title compound (67% yield) as a white solid. [A] 23D-39.37o (c0.315, CHCl3); iHNMRpOOMHADMSOcU (51.81 (m, 4H), 2.62 (m, 4H), 2.74 (m, 2H), 3.08 (ABq, 2H, Jab = 14.9 Hz, 85228 -254- 200404539 △> αβ = 8 · 8 Hz ), 3.61 (m, 4H), 5.00 (m, 1H), 6.92 (dd, 1H, J = 7.8, 4.8 Ηζ), 7.12. (M, 4H), 8.06 (dd, 1H, J = 7.8, 2.0 Hz), 8.06 (m overlap, 1H), 8.40 (dd, 1H, J = 4.8, 2.0 Hz); MS (DCI / NH3) m / e376 (M + H) +; Analytical calculated value for C22H25N50 : C, 70.38; H, 6.71; N, 18.65. Found: C, 70.00; H, 6.90; N, 18.26. Example 169 2- 『4- (3-cyano-2-exo |: Yodo ) -1-Hexahydro (: Hexyl &quot; |-&gt; 1-((1 Magic-1,2,3,4-tetrahydro-1-hydoxy 1 acetamidine example 169A ❿ 2-bromo- N-"(1RH, 2,3,4-tetrahydro-1-part: A certain acetonitrile following the procedure described in Example 1A, using (R) -1,2,3,4- Tetrahydroberberamine (Lancaster) substituted 3-methylaniline to provide the title compound (52% yield) as a white solid. IHNMRpOOMHiDMSO-c ^) 5 l / 78 (m, 4H), 2.73 (m, 2H) , 3.87 (ABq, 2H5 Jab = 10.9 Hz5 Δι ^ αβ = 8.6 Hz), 4.93 (m? 1H)? 7.15 (m5 4H), 8.65 (brd? 1H5 J = 8.5 Hz); MS (DCI / NH3) m / e 268/270 (M + H) +; 285/287 (M + NH4) +.

實例169B 244-(3-氰基-2-吨淀基M-六氫峨畊基~1_N_[Y1RV1，2,3,4-四氫_1_签基1 · 乙醯胺 按照實例121B中所述之程序，以得自實例169A之產物取代 得自實例121A之產物，提供標題化合物（69%產率），為白色 固體。[a]23D+41.97o(c0.305，CHCl3); WNMRPOOMHaDMSO^) δ 1.79 (m，4H)，2.63 (m，4H)，2.74 (m，2H)，3.08 (ABq，2H，Jab=15.3 Hz， △ νΑΒ=8·8 Hz)，3.61 (m，4H)，5.01 (m，1H)，6.92 (dd，1H，J=7.8, 4.8 Hz)，7.12 (m，4H)，8.06 (dd，1H，J=7.8, 2.0 Hz)，8.06 (m 重疊，1H)，8.40 (dd，1H，J=4.8， 2.0 Hz) ; MS (DCI/NH3) m/e 376 (M+H)+ ;對 C2 2 H2 5 N5 O · 0.2 H2 O 之 85228 - 255 - 200404539 分析計算值：C，69.71 ; Η，6·75 ; N，18.47·實測值：c，69.63 ; H，6.75 ;N，18.49. 實例170 N二(g_，6-二乙基苯基峨啶某）_i_六氫p比淀基1乙醯脍 於2,6-二乙基苯胺（59毫克，〇·394毫莫耳）與二氯甲烷〇·5毫 升）之23°C溶液中，添加吡啶（52毫克，〇·656毫莫耳）與氯化氯 乙醯（37耄克’ 0.328毫莫耳），並將反應混合物激烈振盪3小 時。於此反應混合物中’添加得自實例36C之產物（鹽酸鹽 ，50毫克，0_253毫莫耳）、碳酸鈉⑴5毫克，108毫莫耳）、Ν,Ν_ 二甲基甲酸胺（2·2毫升）及水（ι·ι毫升）之懸浮液，並使所形成 之混合物振盪過夜16小時。於減壓下移除溶劑，並使殘留 物懸浮於二甲亞颯（1.5毫升）與甲醇（1.5毫升）之溶液中。將此 懸浮液經過Celite®墊過濾，並使濾液於12分鐘（15分鐘操作時 間）内，在流率70毫升/分鐘下，於WatersNova-PakHRC18管 柱上經由預備之HPLC純化（40毫米X 1〇〇毫米，6微米粒子大 小），使用梯度液10%至100%乙腈：醋酸銨水溶液（1〇 mM)， 提供標題化合物（產量：22.7毫克，0.065毫莫耳，26% )。 ΧΗΝΜΚ(300 MHz, DMSO-d6) δ 1.12 (t, J=7.5 Hz, 6H)? 1.90 (m5 4H)5 2.32 (m5 2H)5 2.50 (q5 J=7.5 Hz5 4H)5 2.70 (m5 1H)5 3.05 (m? 2H)5 3.14 (s5 2H)5 7.09 (m，2H)，7.19 (m，2H)，7.32 (d，J=8.1 Hz，1H)，7.72 (ddd，J=2.1，7.5, 7·5 Hz，1H)， 8.49 (m，1H)，9.23 (br s，1H) ; MS (ESI) m/e 352 (M+H)+ ;對 C2 2 H2 9N3 O • 0.25 C2H402 · 0·25 H20 之分析計算值·· C，72.84 ; H，8.29 ; N，11.33. 實測值：C，72.71 ; H，8.04 ; N，11.59· 實例171 85228 -256- 200404539 2-「4-(2·吡啶某VI-六氤吡啶基1-Ν-(2,4,6-三氟笨基）乙醯胺 標題化合物係根據實例170之方法，以2,4,6-三氟苯胺取代 2.6- 二乙基苯胺而製成（產量：35.3毫克，0.101毫莫耳，40% ) 。1H NMR (300 MHz，DMSO-d6) 51.86 (m，4H)，2.27 (m，2H)，2.67 (m，1H)， 3.01 (br d，J=10.5 Hz，2H)，3·18 (s，2H)，7.24 (m，4H)，7·73 (ddd，J= 2.1，7.5， 7.5 Hz，1H)，8.49 (m，1H)，9_44 (br s，1H) ; MS (ESI) m/e 350 (M+H)+ ;對 0181118?3化0*〇.1€211402 *0.11120之分析計算值：（：，61.20; H，5·25 ; N，11.77.實測值：C，61·22 ; H，5·18 ; N，11.78. 實例172 N-(4-氯基-2,6-二甲基笨基V2-「4-(2-吡啶基VI•六氫吡啶基1乙醯胺 標題化合物係根據實例170之方法，以4_氯基-2,6-二甲苯胺 鹽酸鹽取代2,6-二乙基苯胺，並添加另一當量之各吡啶與碳 酸鈉而製成。（產量：22.9毫克，0.064毫莫耳，25%)。iHNMR (300 MHz，DMSO-d6) 5 1.90 (m，4H)，2·05 (s，3H)，2·14 (s，6H)，2·30 (m，2H)， 2·67 (m，1Η)，3·04 (m，2Η)，3.16 (s，2Η)，4·67 (br s，1Η)，6·83 (s，2Η，較小旋 轉），7.16 (s，2H，主要旋轉），7.20 (m，1H)，7·29 (br d，J=7.5 Hz，1H)，7·72 (ddd，J=2.1，7·5, 7·5 Hz，1H)，8.48 (m，1H)，9·27 (br s，1H); MS (ESI) m/e 358 (M+H)+ ;對 C2〇H24C1N30 · 0.35 C2H402 · 0.15 H20 之分析計算值 :C，65.15 ; H，6_79; N，11.01.實測值：C，65.19 ; Η，6·76; Ν，11·02· 實例173 2-『4-(2_吡啶某VI-六氤吡啶基l-N-(2,4,6-三氣笨基）乙醯胺 標題化合物係根據實例170之方法，以2,4,6_三氯苯胺取代 2.6- 二乙基苯胺而製成（產量：21_2毫克，0_053毫莫耳，21% ) 。1H NMR (300 MHz，DMSO-d6) δ 1.84 (m，4H)，2_48 (m，2H)，2·67 (m，1H)， 85228 -257- 200404539 3.10 (brd，J=10.5 Hz，2H)，3·17 (s，2H)，7.21 (m，1H)，7·30 (d，J=7.8 Hz，1H)， 7.72 (ddd，J=2.1，7.5, 7·5 Hz，1H)，7.77 (s，2H)，8_48 (m，1H) ; MS (ESI) m/e 400(M+H)+ ;對(3181118€13化0*0.1(^411404 .0.551120之分析計算 值：C，50.36 ; H，4·44 ; N，8.01.實測值：C，50.32 ; H，4_17 ; N，7.74. 實例174 N-(2,6_二乙基苯基二氫·2,4，_聯吡啶-l’(2，HV基）乙醯胺 標題化合物係根據實例170之方法，以1，，2，，3，，6，-四氫_[2,4’]聯 吡啶鹽酸鹽（Saari，W.S.等人；J. Med. Chem. 1984, 27, 1182)取代得 自實例36C之產物而製成。純化作用亦採用ai%三氟醋酸水 溶液取代醋酸銨水溶液（10 mM)。（產量：45毫克，0.067毫莫 耳，26% )。1H NMR (300 MHz，DMSO-d6) 5 U4 (t，J=7.5, 7·5 Hz，6H)， 2.50 (q，J=7.5 Hz，4H)，2.92 (m，2H)，3.46 (m，1H)，3.50 (m，1H)，4.02 (m，1H)， 4.17 (m，1H)，4.39 (s，2H)，6.74 (br s，1H)，7.16 (m，2H)，7.24 (dd，J=6_0, 8.4 Hz， 1H)，7.34 (m，1H)，7_66 (m，1H)，7.85 (ddd，J=2_l，7.5, 7·5 Hz，1H)，8.60 (m，1H ),9·93 (s，1H) ; MS (ESI) m/e 350 (M+H)+ ;對 C2 2 H2 7 N3 O · 2.8 C2 HF3 02 之分析計算值：C，49.57 ; H，4·49 ; N，6.28.實測值：C，49.48 ; H，4.50 ;N，6_33· 實例175 2-迅6’-二氫_2，纽吡啶-ΐ’(2Ή)_基VN-(2A6-三氟芄签R _賒 標題化合物係根據實例170之方法，以2,4,6-三氟苯胺取代 2,6-二乙基苯胺，並以1’，2’，3’，6’-四氫-[2,4，]聯吡啶鹽酸鹽（saari，W.S. 等人；J· Med. Chem. 1984, 27,1182)取代得自實例36C之產物而製 成。純化作用亦採用〇·1 %三氟醋酸水溶液取代醋酸铵水溶 液（10 mM)。（產量：59 毫克，0.084 毫莫耳，33% )。1H NMR (300 MHz， 85228 -258 - 200404539 DMSO-d6) (5 2·92 (m，2H)，3·45 (m，1H)，3.68 (m，1H)，4·03 (m，1Η)，4·12 (m， 1H)，4.42 (s，2H)，6.71 (br s，1H)，7.37 (m，3H)，7.66 (d，J=8.4 Hz，1H)，7.85 (ddd，J= 2.1，7.5, 7·5 Hz，1H)，8.58 (m，1H)，10.44 (s，1H) ; MS (ESI) m/e 348 (M+H)+ ;對 C18H16F3N30.3.1C2HF302 之分析計算值·· C，41_48; H，2.75 ; N，6.00·實測值：C，41.54 ; H，2·57 ; N，5.99· 實例176 处:(4-氯基-2,6-二甲基笨基V2-(3’,6，·二氤·2.4，·聯吡啶-1，(2，HV基） 乙醯胺Example 169B 244- (3-Cyano-2-Tontoyl M-Hexahydroehenyl ~ 1_N_ [Y1RV1,2,3,4-tetrahydro_1_signature 1 · Acetylamine as described in Example 121B The procedure described replaces the product from Example 121A with the product from Example 169A to provide the title compound (69% yield) as a white solid. [A] 23D + 41.97o (c0.305, CHCl3); WNMRPOOMHaDMSO ^ ) δ 1.79 (m, 4H), 2.63 (m, 4H), 2.74 (m, 2H), 3.08 (ABq, 2H, Jab = 15.3 Hz, ΔνΑΒ = 8.8 Hz), 3.61 (m, 4H), 5.01 (m, 1H), 6.92 (dd, 1H, J = 7.8, 4.8 Hz), 7.12 (m, 4H), 8.06 (dd, 1H, J = 7.8, 2.0 Hz), 8.06 (m overlap, 1H), 8.40 (dd, 1H, J = 4.8, 2.0 Hz); MS (DCI / NH3) m / e 376 (M + H) +; Analysis and calculation of C28 2-H2 5 N5 O · 0.2 H2 O 85228-255-200404539 Value: C, 69.71; Thallium, 6.75; N, 18.47. Found: c, 69.63; H, 6.75; N, 18.49. Example 170 Nbis (g_, 6-diethylphenyleridine) _i _Hydrogen p-pyridyl 1 acetamidine in a 23 ° C solution of 2,6-diethylaniline (59 mg, 0.394 mmol) and methylene chloride 0.5 ml), and pyridine ( 52 mg, 0.665 mmol ) And chloro acetyl chloride (37 g Mao '0.328 mmol), and the reaction mixture was vigorously shaken for 3 hours. To this reaction mixture was added the product obtained from Example 36C (hydrochloride, 50 mg, 0-253 millimoles), sodium carbonate ⑴5 mg, 108 millimoles, and N, N-dimethylformamide (2.2 Ml) and water (mL) and the resulting mixture was shaken overnight for 16 hours. The solvent was removed under reduced pressure, and the residue was suspended in a solution of dimethylarsine (1.5 ml) and methanol (1.5 ml). This suspension was filtered through a Celite® pad, and the filtrate was purified by preparative HPLC (40 mm X 1) on a WatersNova-PakHRC18 column at a flow rate of 70 ml / min within 12 minutes (15 minutes of operation time). (00 mm, 6 micron particle size) using a gradient solution of 10% to 100% acetonitrile: ammonium acetate in water (10 mM) to provide the title compound (yield: 22.7 mg, 0.065 mmol, 26%). ΧΗΝΜΚ (300 MHz, DMSO-d6) δ 1.12 (t, J = 7.5 Hz, 6H)? 1.90 (m5 4H) 5 2.32 (m5 2H) 5 2.50 (q5 J = 7.5 Hz5 4H) 5 2.70 (m5 1H) 5 3.05 (m? 2H) 5 3.14 (s5 2H) 5 7.09 (m, 2H), 7.19 (m, 2H), 7.32 (d, J = 8.1 Hz, 1H), 7.72 (ddd, J = 2.1, 7.5, 7 5 Hz, 1H), 8.49 (m, 1H), 9.23 (br s, 1H); MS (ESI) m / e 352 (M + H) +; for C2 2 H2 9N3 O • 0.25 C2H402 · 0 · 25 Analytical calculation of H20 ·· C, 72.84; H, 8.29; N, 11.33. Found: C, 72.71; H, 8.04; N, 11.59. Example 171 85228 -256- 200404539 2- "4- (2 · Pyridine The title compound of a VI-hexapyridyl 1-N- (2,4,6-trifluorobenzyl) acetamidinide was substituted with 2,4,6-trifluoroaniline in accordance with the method of Example 170 to replace 2.6-diethyl Based on aniline (yield: 35.3 mg, 0.101 mmol, 40%). 1H NMR (300 MHz, DMSO-d6) 51.86 (m, 4H), 2.27 (m, 2H), 2.67 (m, 1H) , 3.01 (br d, J = 10.5 Hz, 2H), 3.18 (s, 2H), 7.24 (m, 4H), 7.73 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.49 ( m, 1H), 9_44 (br s, 1H); MS (ESI) m / e 350 (M + H) +; for 0181118? 3 0 * 〇.1 € 211402 * 0.11120 Analytical calculation value: (:, 61.20; H, 5.25; N, 11.77. Found: C, 61 · 22; H, 5.18; N, 11.78. Example 172 N- (4-chloro group -2,6-Dimethylbenzyl V2- "4- (2-pyridyl VI • hexahydropyridyl 1 acetamidine The title compound was prepared according to the method of Example 170 using 4-chloro-2,6-di Toluidine hydrochloride was substituted for 2,6-diethylaniline, and added another equivalent of each pyridine and sodium carbonate. (Yield: 22.9 mg, 0.064 mmol, 25%). IHNMR (300 MHz, DMSO-d6) 5 1.90 (m, 4H), 2.05 (s, 3H), 2.14 (s, 6H), 2.30 (m, 2H), 2.67 (m, 1Η), 3. · 04 (m, 2Η), 3.16 (s, 2Η), 4.67 (br s, 1Η), 6.83 (s, 2Η, small rotation), 7.16 (s, 2H, main rotation), 7.20 (m , 1H), 7 · 29 (br d, J = 7.5 Hz, 1H), 7 · 72 (ddd, J = 2.1, 7 · 5, 7 · 5 Hz, 1H), 8.48 (m, 1H), 9 · 27 (br s, 1H); MS (ESI) m / e 358 (M + H) +; Analytical calculated value for C20H24C1N30 · 0.35 C2H402 · 0.15 H20: C, 65.15; H, 6_79; N, 11.01. Found: C, 65.19; Hf, 6.76; N, 11.02. Example 173 2- "4- (2_pyridine VI-hexafluorene" Pyridyl 1N- (2,4,6-trifluorobenzyl) acetamidinide The title compound was prepared according to the method in Example 170, substituting 2,4,6-trichloroaniline for 2.6-diethylaniline (yield) : 21_2 mg, 0_053 millimoles, 21%). 1H NMR (300 MHz, DMSO-d6) δ 1.84 (m, 4H), 2_48 (m, 2H), 2.67 (m, 1H), 85228 -257- 200404539 3.10 (brd, J = 10.5 Hz, 2H) , 3.17 (s, 2H), 7.21 (m, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.72 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 7.77 (s, 2H), 8_48 (m, 1H); MS (ESI) m / e 400 (M + H) +; Analytical calculation for (3181118 € 13130 * 0.1 (^ 411404.0.551120): C, 50.36 H, 4.44; N, 8.01. Found: C, 50.32; H, 4-17; N, 7.74. Example 174 N- (2,6-diethylphenyldihydro-2,4, _bipyridine -l '(2, HV group) acetamidine The title compound was prepared according to the method of Example 170 as 1,1,2,3,6, -tetrahydro- [2,4'] bipyridine hydrochloride (Saari , WS et al .; J. Med. Chem. 1984, 27, 1182) instead of the product obtained from Example 36C. Purification was also replaced by an ai% trifluoroacetic acid aqueous solution instead of an ammonium acetate aqueous solution (10 mM). (Yield: 45 mg, 0.067 mmol, 26%). 1H NMR (300 MHz, DMSO-d6) 5 U4 (t, J = 7.5, 7.5 Hz, 6H), 2.50 (q, J = 7.5 Hz, 4H) , 2.92 (m, 2H), 3.46 (m, 1H), 3.50 (m, 1H), 4.02 (m, 1H) ), 4.17 (m, 1H), 4.39 (s, 2H), 6.74 (br s, 1H), 7.16 (m, 2H), 7.24 (dd, J = 6_0, 8.4 Hz, 1H), 7.34 (m, 1H ), 7_66 (m, 1H), 7.85 (ddd, J = 2_1, 7.5, 7.5 Hz, 1H), 8.60 (m, 1H), 9.93 (s, 1H); MS (ESI) m / e 350 (M + H) +; Analytical calculation for C2 2 H2 7 N3 O · 2.8 C2 HF3 02: C, 49.57; H, 4.49; N, 6.28. Found: C, 49.48; H, 4.50; N, 6_33 · Example 175 2-Xun 6'-dihydro_2, neopyridine-fluorene '(2Ή) _yl VN- (2A6-trifluorofluorene, R_credit) The title compound was prepared according to the method of Example 170 with 2 , 4,6-trifluoroaniline substituted 2,6-diethylaniline, and 1 ', 2', 3 ', 6'-tetrahydro- [2,4,] bipyridine hydrochloride (saari, WS Et al .; J. Med. Chem. 1984, 27, 1182) were prepared in place of the product obtained from Example 36C. For purification, a 0.1% trifluoroacetic acid aqueous solution was used instead of the ammonium acetate aqueous solution (10 mM). (Yield: 59 mg, 0.084 mmol, 33%). 1H NMR (300 MHz, 85228 -258-200404539 DMSO-d6) (5 2.92 (m, 2H), 3.45 (m, 1H), 3.68 (m, 1H), 4.03 (m, 1Η) , 4 · 12 (m, 1H), 4.42 (s, 2H), 6.71 (br s, 1H), 7.37 (m, 3H), 7.66 (d, J = 8.4 Hz, 1H), 7.85 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.58 (m, 1H), 10.44 (s, 1H); MS (ESI) m / e 348 (M + H) +; Analysis and calculation of C18H16F3N30.3.1C2HF302 C, 41_48; H, 2.75; N, 6.00. Found: C, 41.54; H, 2.57; N, 5.99. Example 176: (4-chloro-2,6-dimethylbenzyl V2- (3 ', 6, · Difluorene · 2.4, · Bipyridine-1, (2, HV group) Ethylamine

標題化合物係根據實例170之方法，以4-氣基-2,6-二甲苯胺 鹽酸鹽取代2,6-二乙基苯胺；以1，，2，，3，，6，-四氫-[2,4，]聯吡啶鹽酸 鹽（Saari，W.S_ 等人；J_ Med, Chem. 1984, 27, 1182)取代得自實例 36C 之產物；並添加另一當量之各吡啶與碳酸鈉而製成。純化 作用亦採用0.1%三氟醋酸水溶液取代醋酸銨水溶液（1〇 mM) 。（產量：53 毫克，0.075 毫莫耳，29% )。iHNMRpOOMHz， DMSO-d6) 5 2·18 (s，6H)，2.92 (m，2H)，3.46 (m，1H)，3.68 (m5 1H)，4·03 (m， 1H)，4.14 (m，1H)，4.38 (s，2H)，6_73 (br s，1H)，7.23 (s，m)，7.34 (m，1H)，7.66 (br d，J=8.4 Hz，1H)，7.85 (ddd，J=2.1，7.5, 7.5 Hz, 1H), 8.59 (m，1H)，10.0 (s， 1H) ; MS (ESI) m/e 356 (M+H)+ ;對 C2 〇H2 2 C1N3 0 · 3.1 C2HF3 02 之分 析計算值：C，44.36 ; H，3.57 ; Ν，5·92·實測值：C，44.31 ; H，3.60 ;Ν，5·91. 實例177 氫-2,4’-聯吡啶-1Y2’HV某）-N-(2A6-三氢茇某）乙醯胺 標題化合物係根據實例170之方法，以2,4,6-三氯苯胺取代 2,6_二乙基苯胺，並以Γ，2'，3’，6’-四氫_[2,4，]聯吡啶鹽酸鹽（Saari，W.S· 85228 •259- 200404539 等人；J· Med· Chem· 1984, 27, 1182)取代得自實例36C之產物而製 成。純化作用亦採用0.1%三氟醋酸水溶液取代醋酸銨水溶 液（10mM)。（38毫克；0.050 毫莫耳，20%)。βΝΜίφΟΟΜΗζ， DMSO-d6) 5 2.92 (m，2Η)，3·46 (m，1Η)，3.68 (m，1Η)，4.02 (m，1Η)，4_14 (m， 1H)，4.42 (s，2H)，6.72 (br s，1H)，7.35 (m，1H)，7.66 (br d，J=8_4 Hz，1H)，7·84 (m，3H)，8·58 (m5 1H)，10.73 (br s，1H) ; MS (ESI) m/e 398 (M+H)+ ；對 C18H16C13N3CU3.15C2HF302 之分析計算值：C，38.61; H，2.55; N，5·56·實測值：C，38.65 ; H，2.45 ; N，5.61. 實例178 N_{[4-(2-吡啶基M-六氪吡畊基1甲基丨_3-〔三氟甲基）苯甲醯胺 將1&quot;^比矣-2-基六氫外(16毫克，0.1毫莫耳，Aldrich)、聚甲 醛（30毫克，1毫莫耳）、3-三氟甲基苯甲醯胺（95毫克，0.5毫 莫耳）及42毫克碳酸鉀（0.3毫莫耳）在2毫升無水乙醇中之混 合物，於氮氣下，加熱至回流過夜。使混合物冷卻至室溫 ，過濾，及在減壓下移除溶劑。使殘留物於矽膠上藉急騾 式管柱層析純化（10%甲醇：醋酸乙酯），獲得30毫克（55% ) 純化合物。1 H NMR (500 MHz，DMSO-d6) (5 2.60 (t，J=4 Hz，4H)，3.52 (t， J=4 Hz，4H)，4.22 (d，J=5 Hz，1H)，6.62 (t，J=5 Hz，1H)，6.81 (d，J=6 Hz，1H)， 7.51 (t，J=6 Hz，1H)，7.75 (d，J=6 Hz，1H)，7.92 (d，J=6 Hz，1H)，8.12 (d，J=5 Hz， 1H)，8.10 (m，2H)，9.05 (t，J=5 Hz，1H) ; MS (ESI/APCI·) m/e 363 (M-H)+ · 實例179 3,5-二甲氧基-N-丨「4-(2-吡啶基）-1-六氫外1：畊基1甲某}笨甲醯胺 將1-峨淀-2-基六氫外I： p井（16愛克，0.1晕莫耳，Aldrich)、聚甲 醛（30毫克，1毫莫耳）、3,5-二甲氧基苯甲醯胺（91毫克，〇.5 85228 -260- 200404539 毫莫耳，Lancaster)及42毫克碳酸鉀（〇·3毫莫耳）在2毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫’過濾’及在減壓下移除溶劑。使殘留物於碎 膠上藉急驟式管柱層析純化（10%甲醇··醋酸乙酯），而得38.5 毫克（72% )純化合物。1 H NMR (500 MHz, DMSO-d6 ) 6 2.59 (t，J=4 Hz， 4H)，3_48 (t，J=4 Hz，4H)，3.78 (s，6H)，4·20 (d，J=5 Hz, 1H)，6.62 (m，2H)，6·81 (d，J=6 Hz，1H)，7.03 (s，2H)，7·50 (t，J=6 Hz，1H)，8·10 (d，J=5 Hz, 1H)，8.78 (t， J=5 Hz，1H) ; MS (ESI/APCI-) m/e 355 (M-H)+ · 實例180 N-{[4-(2^比淀基）-1-六氫T?比喷基1甲基丨環己燒教硫胺 將1-吡啶-2-基六氫吡畊（16毫克，〇·1毫莫耳，Aidrich)、聚甲 醛（30毫克，1毫莫耳）、環己烷羧酸醯胺（64毫克，〇.5毫莫耳 ，Aldrich)及42毫克碳酸鉀（〇·3毫莫耳）在2毫升無水乙醇中之 混合物，於氮氣下，加熱至回流過夜。使混合物冷卻至室 溫，過濾，及在減壓下移除溶劑。使殘留物於矽膠上藉急 驟式管柱層析純化（10%甲醇：醋酸乙酯），獲得30毫克（66% ) 純化合物。1 H NMR (500 MHz，DMSO-d6) 5 1·05-1·40 (m，5H)，1_59-1·68 (m，5Η)，2.15 (m5 1Η)，2·48 (m，4Η)，3.45 (t，J=4 Ηζ，4Η)，3.95 (d，J=5 Ηζ，1Η), 6.62 (t，J=6 Hz，1H)，6.81 (d，J=6 Hz，1H)，7.53 (t，J=6 Hz，1H)，8.01 (t，J=5 Hz， 1H)，8.10 (d，J=5 Hz，1H) ; MS (ESI/APCI-) m/e 301 (M-H)+ · 實例181 N-(2,6-二甲基笨基V244-(2-吡啶基VI-六氫吡畊基1乙醯胺 使Ι-p比淀-2-基氫u比p井（24毫克，0.15毫莫耳，Aldrich)、N-(2,6_ 二甲基苯基）-2-氯乙醯胺（39毫克，0.20毫莫耳，Aldrich)及碳 85228 -261- 200404539 酸鈉（50毫克）在N，N-二甲基甲醯胺/水(2 : 1，2毫升）中之混 合物’於室溫下振盛18小時。將所形成之混合物傾析，在 減壓下濃縮，並使殘留物藉預備之HPLC純化，提供43.7毫克 (90.9% )所要之產物。iHNMRpoOMHz.DMSOd 6 2.08(s，6H)， 2.65 (t，J=4 Hz，4H)，3.18 (s，2H)，3.58 (t，J=4 Hz，4H)，6·63 (t，J=5 Hz，1H)， 6.83 (d，J=5 Hz，1H)，7_08 (s，3H)，7.52 (t，J=5 Hz，1H)，8.10 (d，J=5 Hz，1H)， 9.23 (s, 1H) ； MS (ESI/APCI+) m/e 325 (M+H)+. 實例182 M-(4_氟苯基V2-[4-(2-吡啶某VI-六氤吡畊基1乙醯胺 使1-吡啶-2-基六氫吡畊（24毫克，0.15毫莫耳，Aldrich)、N-(4-氟苯基）_2_氯乙酸胺（38毫克，0.20毫莫耳，Maybridge)及碳酸 鈉（50毫克）在N，N-二甲基甲醯胺/水（2 : 1，2毫升）中之混合 物，於室溫下振盪18小時。將所形成之混合物傾析，在減 壓下濃縮，並使殘留物藉預備之HPLC純化，提供45毫克（95 % )所要之產物。1H NMR (500 MHz，DMSO-d6 ) 5 2·60 (m，4H)，3.18 (s， 2Η)，3.58 (m，4Η)，6.63 (m，1Η)，6·83 (d，J=5 Ηζ，1Η)，7·14 (dd，J=8.7, 8·7 Ηζ， 2H)，7.55 (m，1H)，7·66 (m，2H)，8.18 (d，J=5 Hz，1H), 9.80 (s，1H); MS (ESI/APCI+) m/e 315 (M+H)+. 實例183 一乱本基峨症基V1-7T氮峨？井基1乙硫脸 使l-ρ比咬-2-基六氫π比呼（24毫克，0.15毫莫耳，Aldrich)、N_(2,4-二氟苯基）-2-氯乙醯胺（41毫克，0.20毫莫耳，Maybridge)及礙 酸鈉（50毫克）在N，N-二甲基甲醯胺/水(2 : 1，2毫升）中之混 合物，於室溫下振盪18小時。將所形成之混合物賴析，在 85228 -262- 200404539 減壓下濃縮，並使殘留物藉預備之HPLC純化，提供37.3毫克 (74.8% )所要之產物。1H NMR (500 MHz，DMSO-d6 ) 6 2.52 (t，J=4 Hz， 4H)，3.23 (s，2H)，3.58 (t，J=4 Hz，4H)，6.63 (t，J=5 Hz，1H)，6.83 (d，J=6 Hz， 1H)5 7.08 (t? J=6 Hz? 1HX 7.38 (t5 J=6 Hz5 1H)5 7.53 (t? J=6 Hz5 1H)5 7.92 (m5 1H)，8.12 (d，J=5 Hz，1H)，9.60 (s，1H) ; MS (ESI/APCI+) m/e 333 (M+H)+ · 實例184 N-(2-甲基苯基）-2-「4-(2-p比淀基）-1-六氫p比呼基i乙酸胺 使1-吡啶_2-基六氫吡畊（24毫克，〇·15毫莫耳，Aldrich)、N-(2-甲基苯基）-2-氯乙醯胺（37毫克，〇·2〇毫莫耳，Maybridge)及碳 酸鈉（50毫克）在N，N-二甲基甲醯胺/水(2 : 1，2毫升）中之混 合物，於室溫下振盪18小時。將所形成之混合物傾析，在 減壓下濃縮，並使殘留物藉預備之HPLC純化，提供29.3毫克 (63% )所要之產物。1H NMR (500 MHz，DMSO-d6) 5 2.23 (s，3H)，2.62 (t，J=4 Hz，4H)，3.20 (s5 2H)，3.58 (t，J=4 Hz，4H)，6·63 (t，J=5 Hz，1H)，6.83 (d， J=6 Hz，1H)，7·〇5 (t，J=6 Hz，1H)，7.10 (m，2H)，7別（t，J=5 Hz，1H)，7.78 (d， J=6 Hz，1H)，8· 12 (d，J=5 Hz，1H)，9.40 (s，1H) ; MS (ESI/APCI+) m/e 311 (M+H)+. 實例185 m_(24b啶基）_l_六氤吡畊某三氟甲某）笨某]匕醯眩 使1-吡啶-2_基六氫吡畊（24毫克，〇_15毫莫耳，Aldrich)、N-(3-三氟苯基）-2-氯乙醯胺（48毫克，0.20毫莫耳，Maybridge)及碳 酸鈉（50毫克）在N，N-二甲基甲醯胺/水（2 : 1，2毫升）中之混 合物，於室溫下振盪18小時。將所形成之混合物傾析，在 減壓下濃縮，並使殘留物藉預備之HPLC純化，提供27毫克（47 85228 -263 - 200404539 % )所要之產物。1H NMR (500 MHz，DMSO-d6 ) 5 2.62 (t，J=4 Hz, 4H)， 3.22 (s，2H)，3.58 (t，J=4 Hz, 4H)，6.63 (t，J=5 Hz，1H)，6.83 (d，J=6 Hz，1H)， 7Λ1 (d，J=6 Hz，1H)，7.58 (m，2H)，7.92 (d，J=6 Hz，1H)，8·12 (d，J=5 Hz，1H)， 8.18 (s，1H)，10.06 (s，1H) ; MS (ESI/APCI+) m/e 365 (M+H)+ · 實例186 N-(3-鼠笨基比淀基）-1-六氮峨p井基1乙縫胺 使1-吡啶_2-基六氫吡畊（24毫克，0.15毫莫耳，Aldrich)、N-(3-氯苯基）-2-氯乙酸胺（41毫克，0·20毫莫耳，Maybridge)及碳酸 鈉（50毫克）在N，N-二甲基甲醯胺/水（2 : 1，2毫升）中之混合 物，於室溫下振盪18小時。將所形成之混合物傾析，在減 壓下濃縮，並使殘留物藉預備之HPLC純化，提供16毫克（32 % )所要之產物。1H NMR (500 MHz，DMSO-d6) 5 2.60 (t，J=4 Hz，4H)， 3.20 (s，2H)，3.58 (t，J=4 Hz，4H)，6·63 (t，J=5 Hz，1H)，6.83 (d，J=6 Hz，1H)， 7.13 (d? J=6 Hz? 1H)3 7.38 (t? J=6 Hz? 1H)5 7.58 (m, 2H)5 7.95 (s5 1H)5 8.12 (d5 J=5 Hz，1H)，9.95 (s，1H) ; MS (ESI/APCI+) m/e 331 (M+H)+ · 實例187 K罕基-2-『4-(2·^比咬基）-1-六氫外1：呼基1乙酼胺 使1-吡啶冬基六氫吡畊（24毫克，0·15毫莫耳，Aldrich)、N-苄基-2-氯乙醯胺（37毫克，0.20毫莫耳，Maybridge)及碳酸鈉（50 毫克）在N，N-二甲基甲酸胺/水（2 : 1，2毫升）中之混合物， 於室溫下振盪18小時。將所形成之混合物傾析，在減壓下 濃縮，並使殘留物藉預備之HPLC純化，提供16毫克（32% )所 要之產物。1 H NMR (500 MHz，DMSO-d6) 5 2.58 (m，4H)，3.05 (s，2H)， 3.52 (m，4H)，4.35 (d，J=5 Hz，2H)，6.63 (t，J=5 Hz，1H)，6.82 (d，J=6 Hz，1H)， 85228 -264- 200404539 7·28 (m，5H)，7·55 (t，J=6 Hz，1H)，8·12 (t，J=5 Hz，1H)，8.35 (s，1H); MS (ESI/APCI+) m/e 311 (M+H)+. 實例188 吡啶基）-1-六氫吡畊基三氟甲氣基）笨基i乙醯胺 使1-吡啶-2_基六氫吡畊（24毫克，0.15毫莫耳，Aldrich)、N_(4-二氟甲氧苯基）-2-氯乙酿胺（51毫克，0.20毫莫耳，Maybridge) 及碳酸鈉（50毫克）在N，N-二甲基甲醯胺/水（2: 1，2毫升）中 之混合物，於室溫下振盪18小時。將所形成之混合物傾析 ，，在減壓下濃縮，使殘留物藉預備之HPLC純化，提供16 毫克（32% )所要之產物。1H NMR (500 MHz，DMSO-d6 ) 5 2.60 (t，J= 4 Hz，4H)，3.21 (s，2H)，3.58 (t，J=4 Hz，4H)，6.63 (t，J=5 Hz，1H)，6·83 (d，J= 6 Hz，1H)，7.35 (d，J=6 Hz，2H)，7.55 (t，J=6 Hz，1H)，7.76 (m，2H)，8.12 (d，J= 5 Hz，1H)，9_98 (s，1H) ; MS (ESI/APCI+) m/e 381 (M+H)+ · 實例189 g-[4-(2-吡啶基）-1-六氫吡畊基VN-「2-(三氟甲基）笨基1乙醯胺 使1-外1：淀-2-基六氫峨呼（24毫克，0.15毫莫耳，Aldrich)、Ν-(2· 三氟甲基苯基）-2-氯乙醯胺（48毫克，0.20毫莫耳，Maybridge) 及碳酸鈉（50毫克）在N，N-二甲基甲醯胺/水（2: 1，2毫升）中 之混合物，於室溫下振盪18小時。將所形成之混合物傾析 ，在減壓下濃縮，並使殘留物藉預備之HPLC純化，提供41 毫克（75% )所要之產物。iHNMRpOOMI^DMSOO 5 2.65 (t? J=4 Hz? 4H)5 3.23 (s5 2H)5 3.58 (t, J=4 Hz, 4H)5 6.65 (t5 J=5 Hz? 1H)5 6.85 (d, J=6 Hz, 1H)5 7.38 (t? J=6 Hz? 1H)? 7.55 (t? J=6 Hz, 1H)? 7.73 (m? 2H)? 8.15 (d? J=5 Hz，1H)，8.22 (d5 J=6 Hz，1H)，9.95 (s，1H) ； MS (ESI/APCI+) m/e 365 85228 -265 - 200404539 (M+H)' 實例190 这&quot;(l氯苯某V2-「4-(2-吡啶某M-六氫吡畊基1乙_脍 使1_吡啶_2_基六氫吡畊（24毫克，0.15毫莫耳，Aldrich)、Ν·(4· 氟冬基）-2-氯乙酸胺（41毫克，〇·2〇毫莫耳，Maybridge)及碳酸 鋼（50毫克）在N，N-二甲基甲醯胺/水（2 : 1，2毫升）中之混合 物’於室溫下振i 18小時。將所形成之混合物傾析，在減 壓下濃縮，並使殘留物藉預備之HPLC純化，提供42毫克（85 % )所要之產物。1H NMR (500 MHz，DMSO_d6) 5 2.60 (t，J=4 Hz，4H)， 3.21 (s，2H)，3.58 (t，J=4 Hz，4H)，6.63 (t，J=5 Hz，1H)，6.83 (d，J=6 Hz，1H)， 7.38 (d5 J=6 Hz? 2H)5 7.54 (t5 J-6 Hz? 1H)? 7.70 (d5 J=6 Hz, 2H)? 8.12 (d5 J=5 Hz5 1H)，9.90 (s，1H) ; MS (ESI/APCI+) m/e 331 (M+H)+ · 實例191 座(2,3-二氯苯某V2-f4-(2-吡晗某M-六氫吡畊基1乙醯脖 使1-峨咬-2-基六氫外匕p井（24毫克，0·15毫莫耳，Aldrich)、N-(2,3-一鼠冬基）-2•氯乙酸胺（48毫克，0.20毫莫耳，Maybridge)及碳 酸鈉（50毫克）在N，N-二甲基甲醯胺/水(2 : 1，2毫升）中之混 合物，於室溫下振盪18小時。將所形成之混合物傾析，在 減壓下濃縮，使殘留物純化藉預備之HPLC，提供9毫克（16% ) 所要之產物，為三氟醋酸鹽。1：«^]\111(500]\«^，〇]\48〇-(16)(5 2.62 (t，J=4 Hz，4H)，3.23 (s，2H)，3.58 (t，J=4 Hz，4H)，6.63 (t，J=5 Hz, 1H)，6.83 (d， J=6 Hz，1H)，7.55 (t，J=6 Hz，1H)，7.68 (m，2H)，7.88 (m，2H)，8·12 (d，J=5 Hz， 1H)，10.12 (s，1H) ; MS (ESI/APCI+) m/e 365 (M+H)+ · 實例192 85228 •266- 200404539 止(3,4-二氯笨基V2-RK2-吡啶某Μ-六氫吡畊基1乙醯脸 使1-吡啶-2-基六氫吡畊（24毫克，0.15毫莫耳，Aldrich)、Ν-(3,4-二氯苯基）-2-氯乙醯胺（48毫克，0.20毫莫耳，Maybridge)及碳 酸鈉（50毫克）在N，N-二甲基甲醯胺/水(2 : 1，2毫升）中之混 合物，於室溫下振盪18小時。將所形成之混合物傾析，在 減壓下濃縮，並使殘留物藉預備之HPLC純化，提供58毫克（41 % )所要之產物。1H NMR (500 MHz，DMSO-d6 ) 5 2.65 (t，J=4 Hz，4H)， 3.23 (s5 2H)? 3.58 (t? J=4 Hz5 4H)5 6.65 (t, J=5 Hz? 1H)5 6.85 (d, J=6 Hz? 1H)5 7·41 (m，2H)，7.55 (t，J=6 Hz，1H)，8.12 (d，J=5 Hz，1H)，8.25 (d，J=6 Hz，1H)， 10.08 (s5 1H) ； MS (ESI/APCI+) m/e 365 (M+H)+. 實例193 M4-(2-吡啶基）小六氫吡畊某三氟甲某）苯基1乙醯賒 使1-吡啶-2-基六氫吡畊（24毫克，0.15毫莫耳，Aldrich)、N-(4-三氟甲基苯基）-2-氯乙醯胺（48毫克，0.20毫莫耳，Maybridge) 及碳酸鈉（50毫克）在N，N-二甲基甲酸胺/水（2: 1，2毫升）中 之混合物，於室溫下振盪18小時。將所形成之混合物傾析 ，在減壓下濃縮，並使殘留物藉預備之HPLC純化，提供20 毫克（37% )所要之產物。1H NMR (500 MHz，DMSO-d6) 5 2.60 (t， 4 Hz，4H)，3·21 (s，2H)，3.58 (t，J=4 Hz，4H)，6.63 (t，J=5 Hz，1H)，6·83 (d，J=6 Hz，1H)，7.30 (m，1H)，7.55 (m，2H)，7.80 (m，2H)，8.12 (d，J=5 Hz，1H)，10.08 (s? 1H) ； MS (ESI/APCI+) m/e 365 (M+H)+. 實例194 3-氯-N-{「4-(2-吡啶基VI-六氫吡畊某i甲基}笨甲醯胺 將Ι-p比淀-2-基穴氣峨_ (16當克，0.1毫莫耳，Aldrich)、聚甲The title compound was substituted for 2,6-diethylaniline with 4-amino-2,6-xylylamine hydrochloride according to the method of Example 170; and with 1, 2, 2, 3, 6, 6-tetrahydro -[2,4,] bipyridine hydrochloride (Saari, W.S. et al .; J_ Med, Chem. 1984, 27, 1182) in place of the product obtained from Example 36C; and another equivalent of each pyridine and carbonic acid was added Made of sodium. For purification, a 0.1% trifluoroacetic acid aqueous solution was used instead of an ammonium acetate aqueous solution (10 mM). (Yield: 53 mg, 0.075 mmol, 29%). iHNMRpOOMHz, DMSO-d6) 5 2 · 18 (s, 6H), 2.92 (m, 2H), 3.46 (m, 1H), 3.68 (m5 1H), 4.03 (m, 1H), 4.14 (m, 1H ), 4.38 (s, 2H), 6_73 (br s, 1H), 7.23 (s, m), 7.34 (m, 1H), 7.66 (br d, J = 8.4 Hz, 1H), 7.85 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.59 (m, 1H), 10.0 (s, 1H); MS (ESI) m / e 356 (M + H) +; for C2 〇H2 2 C1N3 0 · 3.1 C2HF3 02 Analytical calculated values: C, 44.36; H, 3.57; N, 5.92. Found: C, 44.31; H, 3.60; N, 5.91. Example 177 Hydrogen-2,4'-bipyridine-1Y2 ' HV) -N- (2A6-trihydroamidine) acetamidine The title compound was obtained by substituting 2,4,6-trichloroaniline for 2,6-diethylaniline according to the method of Example 170, and using Γ, 2 ', 3', 6'-tetrahydro_ [2,4,] bipyridine hydrochloride (Saari, WS 85228 • 259-200404539 et al .; J. Med. Chem. 1984, 27, 1182) Prepared from the product of Example 36C. For purification, a 0.1% trifluoroacetic acid aqueous solution was used instead of the ammonium acetate aqueous solution (10mM). (38 mg; 0.050 millimoles, 20%). βΝΜίφΟΟΜΗζ, DMSO-d6) 5 2.92 (m, 2Η), 3.46 (m, 1Η), 3.68 (m, 1Η), 4.02 (m, 1Η), 4_14 (m, 1H), 4.42 (s, 2H) , 6.72 (br s, 1H), 7.35 (m, 1H), 7.66 (br d, J = 8_4 Hz, 1H), 7.84 (m, 3H), 8.58 (m5 1H), 10.73 (br s , 1H); MS (ESI) m / e 398 (M + H) +; Analysis and calculation of C18H16C13N3CU3.15C2HF302: C, 38.61; H, 2.55; N, 5.56. Found: C, 38.65; H , 2.45; N, 5.61. Example 178 N _ {[4- (2-pyridyl M-hexapyridinyl 1methyl 丨 _3- [trifluoromethyl) benzylamine will be 1 &quot; ^ 比 矣- 2-ylhexahydro (16 mg, 0.1 mmol, Aldrich), polyoxymethylene (30 mg, 1 mmol), 3-trifluoromethylbenzamide (95 mg, 0.5 mmol) and A mixture of 42 mg of potassium carbonate (0.3 mmol) in 2 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography (10% methanol: ethyl acetate) on silica gel to obtain 30 mg (55%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) (5 2.60 (t, J = 4 Hz, 4H), 3.52 (t, J = 4 Hz, 4H), 4.22 (d, J = 5 Hz, 1H), 6.62 (t, J = 5 Hz, 1H), 6.81 (d, J = 6 Hz, 1H), 7.51 (t, J = 6 Hz, 1H), 7.75 (d, J = 6 Hz, 1H), 7.92 (d , J = 6 Hz, 1H), 8.12 (d, J = 5 Hz, 1H), 8.10 (m, 2H), 9.05 (t, J = 5 Hz, 1H); MS (ESI / APCI ·) m / e 363 (MH) + · Example 179 3,5-Dimethoxy-N- 丨 "4- (2-pyridyl) -1-Hexahydro-1: Phenyl 1methyl} Bentamidine will be 1- Edo-2-ylhexahydrogen I: p-well (16 gram, 0.1 halo, Aldrich), polyoxymethylene (30 mg, 1 mmol), 3,5-dimethoxybenzamide (91 mg, 0.585228-260-200404539 mmol, Lancaster) and 42 mg of potassium carbonate (0.3 mmol) in 2 ml of absolute ethanol, heated to reflux overnight under nitrogen. The mixture was cooled to room temperature and 'filtered' and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography (10% methanol · · ethyl acetate) on crushed gel to give 38.5 mg (72% ) Pure compound. 1 H NMR (500 MHz, DMSO-d6) 6 2.59 (t, J = 4 Hz, 4H), 3_48 (t, J = 4 Hz, 4H), 3.78 (s, 6H), 4.20 (d, J = 5 Hz, 1H), 6.62 (m, 2H), 6.81 (d , J = 6 Hz, 1H), 7.03 (s, 2H), 7.50 (t, J = 6 Hz, 1H), 8.10 (d, J = 5 Hz, 1H), 8.78 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 355 (MH) + · Example 180 N-{[4- (2 ^ 比比 基) -1-Hexane T? Pyridyl 1 methyl丨 Cyclohexylamine thiamine 1-pyridin-2-ylhexahydropyridine (16 mg, 0.1 mmol, Aidrich), polyformaldehyde (30 mg, 1 mmol), cyclohexanecarboxylic acid A mixture of amidine (64 mg, 0.5 mmol, Aldrich) and 42 mg of potassium carbonate (0.3 mmol) in 2 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was cooled to At room temperature, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 30 mg (66%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) 5 1.05-1 · 40 (m, 5H), 1_59-1 · 68 (m, 5Η), 2.15 (m5 1Η), 2.48 (m, 4Η) , 3.45 (t, J = 4 Ηζ, 4Η), 3.95 (d, J = 5 Ηζ, 1Η), 6.62 (t, J = 6 Hz, 1H), 6.81 (d, J = 6 Hz, 1H), 7.53 (t, J = 6 Hz, 1H), 8.01 (t, J = 5 Hz, 1H), 8.10 (d, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 301 (MH) + Example 181 N- (2,6-Dimethylbenzyl V244- (2-pyridyl VI-hexahydropyridyl 1 acetamidine) to make 1-p ratio lake 2-yl hydrogen u ratio p well (24 Mg, 0.15 mmol, Aldrich), N- (2,6-dimethylphenyl) -2-chloroacetamide (39 mg, 0.20 mmol, Aldrich), and sodium carbon 85228-261-200404539 ( 50 mg) of a mixture in N, N-dimethylformamide / water (2: 1,2 ml) was shaken at room temperature for 18 hours. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 43.7 mg (90.9%) of the desired product. IHNMRpoOMHz.DMSOd 6 2.08 (s, 6H), 2.65 (t, J = 4 Hz, 4H), 3.18 (s, 2H ), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H), 6.83 (d, J = 5 Hz, 1H), 7_08 (s 3H), 7.52 (t, J = 5 Hz, 1H), 8.10 (d, J = 5 Hz, 1H), 9.23 (s, 1H); MS (ESI / APCI +) m / e 325 (M + H) + Example 182 M- (4-fluorophenyl V2- [4- (2-pyridine VI-hexapyridinyl 1 acetamidamine 1-pyridin-2-ylhexahydropyridine (24 mg, 0.15 mmol Mol, Aldrich), N- (4-fluorophenyl) -2-chloroacetamide (38 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / The mixture in water (2: 1, 2 ml) was shaken at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 45 mg (95 %) Desired product. 1H NMR (500 MHz, DMSO-d6) 5 2.60 (m, 4H), 3.18 (s, 2Η), 3.58 (m, 4Η), 6.63 (m, 1Η), 6.83 (d, J = 5 Ηζ, 1Η), 7 · 14 (dd, J = 8.7, 8 · 7 Ηζ, 2H), 7.55 (m, 1H), 7.66 (m, 2H), 8.18 (d, J = 5 Hz, 1H), 9.80 (s, 1H); MS (ESI / APCI +) m / e 315 (M + H) +. Jingji 1 ethyl thiosulfate makes l-ρ ratio bite-2-ylhexahydropi pi specific (24 mg, 0.15 mmol, Aldrich), N_ (2,4-difluorophenyl) -2-chloroacetamidine A mixture of amine (41 mg, 0.20 mmol, Maybridge) and sodium obstructer (50 mg) in N, N-dimethylformamide / water (2: 1,2 ml), shaken at room temperature 18 hours. The resulting mixture was lysed, concentrated under reduced pressure of 85228-262-200404539, and the residue was purified by preparative HPLC to provide 37.3 mg (74.8%) of the desired product. 1H NMR (500 MHz, DMSO-d6) 6 2.52 (t, J = 4 Hz, 4H), 3.23 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz , 1H), 6.83 (d, J = 6 Hz, 1H) 5 7.08 (t? J = 6 Hz? 1HX 7.38 (t5 J = 6 Hz5 1H) 5 7.53 (t? J = 6 Hz5 1H) 5 7.92 (m5 1H), 8.12 (d, J = 5 Hz, 1H), 9.60 (s, 1H); MS (ESI / APCI +) m / e 333 (M + H) + · Example 184 N- (2-methylphenyl ) -2- "4- (2-p than yodoyl) -1-hexahydrop-pyridyl i-aminoacetic acid to make 1-pyridin-2-ylhexahydropyridine (24 mg, 0.15 mmol, Aldrich), N- (2-methylphenyl) -2-chloroacetamidamine (37 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide The mixture in amidine / water (2: 1,2 ml) was shaken at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 29.3 Mg (63%) of the desired product. 1H NMR (500 MHz, DMSO-d6) 5 2.23 (s, 3H), 2.62 (t, J = 4 Hz, 4H), 3.20 (s5 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H), 6.83 (d, J = 6 Hz, 1H), 7.05 (t, J = 6 Hz, 1H), 7.10 ( m ， 2 H), 7 types (t, J = 5 Hz, 1H), 7.78 (d, J = 6 Hz, 1H), 8.12 (d, J = 5 Hz, 1H), 9.40 (s, 1H); MS (ESI / APCI +) m / e 311 (M + H) +. Example 185 m_ (24b pyridyl) _l_hexamethylpyridine trifluoromethyl) stupid] dazzle makes 1-pyridine-2_yl Hexahydropyrine (24 mg, 0-15 mmol, Aldrich), N- (3-trifluorophenyl) -2-chloroacetamide (48 mg, 0.20 mmol, Maybridge), and sodium carbonate ( 50 mg) of a mixture in N, N-dimethylformamide / water (2: 1, 2 ml) was shaken at room temperature for 18 hours. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 27 mg (47 85228 -263-200404539%) of the desired product. 1H NMR (500 MHz, DMSO-d6) 5 2.62 (t, J = 4 Hz, 4H), 3.22 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H), 6.83 (d, J = 6 Hz, 1H), 7Λ1 (d, J = 6 Hz , 1H), 7.58 (m, 2H), 7.92 (d, J = 6 Hz, 1H), 8.12 (d, J = 5 Hz, 1H), 8.18 (s, 1H), 10.06 (s, 1H) ; MS (ESI / APCI +) m / e 365 (M + H) + · Example 186 N- (3-Merbenzylpyridyl) -1-Hexazine p-based 1 Ethylamine makes 1-pyridine_2-ylhexahydropyridine (24 mg, 0.15 mmol, Aldrich), N- (3-chlorophenyl) -2-chloroacetamine (41 mg, 0.20 mmol) Moore, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1,2 ml) were shaken at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 16 mg (32%) of the desired product. 1H NMR (500 MHz, DMSO-d6) 5 2.60 (t, J = 4 Hz, 4H), 3.20 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H), 6.83 (d, J = 6 Hz, 1H), 7.13 (d? J = 6 Hz? 1H) 3 7.38 (t? J = 6 Hz? 1H) 5 7.58 (m, 2H) 5 7.95 (s5 1H) 5 8.12 (d5 J = 5 Hz, 1H), 9.95 (s, 1H); MS (ESI / APCI +) m / e 331 (M + H) + · Example 187 K 汉 基 -2- 『4 -(2 · ^ Specific group) -1-Hexahydro 1: Hexyl-1acetamidine makes 1-pyridoyl hexahydropyridine (24 mg, 0.15 mmol, Aldrich), N-benzyl A mixture of 2-methyl-2-chloroacetamide (37 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1, 2 ml), Shake at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 16 mg (32%) of the desired product. 1 H NMR (500 MHz, DMSO-d6) 5 2.58 (m, 4H), 3.05 (s, 2H), 3.52 (m, 4H), 4.35 (d, J = 5 Hz, 2H), 6.63 (t, J = 5 Hz, 1H), 6.82 (d, J = 6 Hz, 1H), 85228 -264- 200404539 7 · 28 (m, 5H), 7.55 (t, J = 6 Hz, 1H), 8.12 (t, J = 5 Hz, 1H), 8.35 (s, 1H); MS (ESI / APCI +) m / e 311 (M + H) +. Example 188 pyridyl) -1-hexahydropyridyl trifluoro (Methylamino) benzyl acetamidine makes 1-pyridine-2_ylhexahydropyridine (24 mg, 0.15 mmol, Aldrich), N_ (4-difluoromethoxyphenyl) -2-chloroethyl Mixture of fermented amine (51 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1, 2 ml), shake at room temperature 18 hours. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 16 mg (32%) of the desired product. 1H NMR (500 MHz, DMSO-d6) 5 2.60 (t, J = 4 Hz, 4H), 3.21 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz , 1H), 6.83 (d, J = 6 Hz, 1H), 7.35 (d, J = 6 Hz, 2H), 7.55 (t, J = 6 Hz, 1H), 7.76 (m, 2H), 8.12 (d, J = 5 Hz, 1H), 9_98 (s, 1H); MS (ESI / APCI +) m / e 381 (M + H) + · Example 189 g- [4- (2-pyridyl) -1 -Hydroxypyridyl VN- "2- (trifluoromethyl) benzyl 1acetamidamine 1-out 1: yodo-2-yl hexahydroehu (24 mg, 0.15 mmol, Aldrich), Ν- (2 · trifluoromethylphenyl) -2-chloroacetamide (48 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1, 2 ml) and shake at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 41 mg (75%) ) Desired product. IHNMRpOOMI ^ DMSOO 5 2.65 (t? J = 4 Hz? 4H) 5 3.23 (s5 2H) 5 3.58 (t, J = 4 Hz, 4H) 5 6.65 (t5 J = 5 Hz? 1H) 5 6.85 (d, J = 6 Hz, 1H) 5 7.38 (t? J = 6 Hz? 1H)? 7.55 (t? J = 6 Hz, 1H)? 7.73 (m? 2H)? 8.15 (d? J = 5 Hz, 1H) 8.22 (d5 J = 6 Hz, 1H), 9.95 (s, 1H); MS (ESI / APCI +) m / e 365 85228 -265-200404539 (M + H) 'Example 190 This &quot; (lchlorobenzene a certain V2 -"4- (2-pyridine, M-hexahydropyridyl, 1-ethylpyridine, 1-pyridin-2-yl hexahydropyridine (24 mg, 0.15 mmol, Aldrich), N · (4 · fluoro Winter based) amine-2-chloroacetate (41 mg, 0.20 mmol, Maybridge) and carbonic acid steel (50 mg) in N, N-dimethylformamide / water (2: 1, 2 ml The mixture in ') was shaken at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 42 mg (85%) of the desired product. 1H NMR (500 MHz, DMSO_d6) 5 2.60 (t, J = 4 Hz, 4H), 3.21 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H) , 6.83 (d, J = 6 Hz, 1H), 7.38 (d5 J = 6 Hz? 2H) 5 7.54 (t5 J-6 Hz? 1H)? 7.70 (d5 J = 6 Hz, 2H)? 8.12 (d5 J = 5 Hz5 1H), 9.90 (s, 1H); MS (ESI / APCI +) m / e 331 (M + H) + · Example 191 (2,3-dichlorobenzene V2-f4- (2-pyridine)晗 A M-hexahydropyridyl 1 acetone neck 1-E bite-2-yl hexahydroxide outer well (24 mg, 0 · 15 Moore, Aldrich), N- (2,3-monoratyl) -2 • chloroacetamide (48 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethyl A mixture of formamidine / water (2: 1,2 ml) was shaken at room temperature for 18 hours. The resulting mixture was decanted and concentrated under reduced pressure to purify the residue by preparative HPLC to provide 9 mg (16%) of the desired product as trifluoroacetate. 1: «^] \ 111 (500) \« ^, 〇] \ 48〇- (16) (5 2.62 (t, J = 4 Hz, 4H), 3.23 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H), 6.83 (d, J = 6 Hz, 1H), 7.55 (t, J = 6 Hz, 1H), 7.68 (m, 2H), 7.88 (m, 2H), 8 · 12 (d, J = 5 Hz, 1H), 10.12 (s, 1H); MS (ESI / APCI +) m / e 365 (M + H) + · Example 192 85228 • 266- 200404539 only (3,4-dichlorobenzyl V2-RK2-pyridine, M-hexahydropyridyl 1 acetamidine, 1-pyridin-2-yl hexahydropyridine (24 mg, 0.15 mmol, Aldrich ), N- (3,4-dichlorophenyl) -2-chloroacetamide (48 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / Water (2: 1,2 ml), shake at room temperature for 18 hours. The resulting mixture was decanted, concentrated under reduced pressure, and the residue was purified by preparative HPLC to provide 58 mg ( 41%) desired product. 1H NMR (500 MHz, DMSO-d6) 5 2.65 (t, J = 4 Hz, 4H), 3.23 (s5 2H)? 3.58 (t? J = 4 Hz5 4H) 5 6.65 (t , J = 5 Hz? 1H) 5 6.85 (d, J = 6 Hz? 1H) 5 7 · 41 (m, 2H), 7.55 (t, J = 6 Hz, 1H), 8.12 (d, J = 5 Hz , 1H) , 8.25 (d, J = 6 Hz, 1H), 10.08 (s5 1H); MS (ESI / APCI +) m / e 365 (M + H) +. Example 193 M4- (2-pyridyl) small hexahydropyridine Phenol trifluoromethyl) Phenyl 1 acetamidine 1-pyridin-2-ylhexahydropyridine (24 mg, 0.15 mmol, Aldrich), N- (4-trifluoromethylphenyl)- Mixture of 2-chloroacetamidamine (48 mg, 0.20 mmol, Maybridge) and sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1, 2 ml) in the chamber Shake at room temperature for 18 hours. Decant the resulting mixture, concentrate under reduced pressure, and purify the residue by preparative HPLC to provide 20 mg (37%) of the desired product. 1H NMR (500 MHz, DMSO-d6 ) 5 2.60 (t, 4 Hz, 4H), 3.21 (s, 2H), 3.58 (t, J = 4 Hz, 4H), 6.63 (t, J = 5 Hz, 1H), 6.83 (d , J = 6 Hz, 1H), 7.30 (m, 1H), 7.55 (m, 2H), 7.80 (m, 2H), 8.12 (d, J = 5 Hz, 1H), 10.08 (s? 1H); MS (ESI / APCI +) m / e 365 (M + H) +. Example 194 3-Chloro-N-{"4- (2-pyridyl VI-hexahydropyridine) methyl benzamidine -p 比 淀 -2- 基 穴 气 埃 _ (16 dg, 0.1 mmol, Aldrich), poly

85228 -267- 200404539 酸（3〇愛克，1毫莫耳）、3_氯苯甲醯胺（78毫克，〇·5毫莫耳， Maybridge)及42毫克碳酸鉀（〇·3毫莫耳）在2毫升無水乙醇中之 混合物，於氮氣下，加熱至回流過夜。使混合物冷卻至室 溫’過滤，及在減壓下移除溶劑。使殘留物於矽膠上藉急 驟式管柱層析純化（10%甲醇：醋酸乙酯），獲得26毫克（52% ) 純化合物。1 H NMR (500 MHz，DMSO-d6 ) 5 2.58 (t，J=4 Hz，4H)，3.50 (t， J=4 Hz，4H)，4.19 (d，J=5 Hz，1H)，6_62 (t，J=5 Hz，1H)，6·81 (d，J=6 Hz，1H), 7.51 (m，2H)，7.61 (m，1H)，7.82 (d，J=6 Hz，1H)，7.92 (s，1H)，8.12 (d，J=5 Hz， 1H)，8.93 (t，J=5 Hz，1H) ; MS (ESI/APCI-) m/e 329 (M-H)+ · 實例195 基_3-甲基吡啶某VI-六氫吡畊某1甲基}茉甲醯脉 將1-外1：咬-2-基六氫p比p井（16毫克，〇·1毫莫耳，Aldricli)、聚甲 酸（30毫克，1毫莫耳）、4-氟基-3-甲基苯甲醯胺（77毫克，0.5 毫莫耳，Oakwood)及42毫克碳酸鉀（〇·3毫莫耳）在2毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫’過滤，及在減壓下移除溶劑。使殘留物於碎 膠上藉急騾式管柱層析純化（10%甲醇··醋酸乙酯），而得25 毫克（51 % )純化合物。1 H NMR (500 MHz，DMSO_d6) δ 2.25 (s，3Η)， 2.58 (t? J=4 Hz? 4H)5 3.52 (t? J=4 Hz5 4H)5 4.18 (d5 J=5 Hz5 1H)5 6.61 (t? J=5 Hz, 1H)，6·81 (d，J=6 Hz，1H)，7.21 (t，J=6 Hz，1H)，7.51 (t，J=5 Hz，1H)，7.75 (t，J= 5 Hz，1H)，7.82 (d，J=6 Hz，1H)，8·12 (d，J=5 Hz, 1H)，8.76 (t，J=5 Hz，1H); MS (ESI/APCI-) m/e 327 (M-H)+. 實例196 N-(3’，6’-二氫-2,4’-聯吡啶-r(2’HV基甲基V4-氟基-3-甲基苯甲醯脍 85228 -268- 200404539 將Γ，2’，3’，6’-四氫-[2,4’]聯p比淀鹽酸鹽（20毫克，〇·ι〇毫莫耳，85228 -267- 200404539 acid (30 gram, 1 mmol), 3-chlorobenzamide (78 mg, 0.5 mmol, Maybridge) and 42 mg potassium carbonate (0.3 mmol) ) The mixture in 2 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was cooled to room temperature 'and filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography (10% methanol: ethyl acetate) on silica gel to obtain 26 mg (52%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) 5 2.58 (t, J = 4 Hz, 4H), 3.50 (t, J = 4 Hz, 4H), 4.19 (d, J = 5 Hz, 1H), 6_62 ( t, J = 5 Hz, 1H), 6.81 (d, J = 6 Hz, 1H), 7.51 (m, 2H), 7.61 (m, 1H), 7.82 (d, J = 6 Hz, 1H), 7.92 (s, 1H), 8.12 (d, J = 5 Hz, 1H), 8.93 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 329 (MH) + · Example 195 base _3-methylpyridine VI-hexahydropyridine 1-methyl} jasmine veins 1-out 1: bite-2-yl hexahydro p ratio p well (16 mg, 0.1 millimolar, Aldricli), polyformic acid (30 mg, 1 mmol), 4-fluoro-3-methylbenzamide (77 mg, 0.5 mmol, Oakwood), and 42 mg potassium carbonate (0.3 mmol) Ear) in 2 ml of absolute ethanol, and heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature 'and filtered, and the solvent was removed under reduced pressure. The residue was purified on a gel by flash column chromatography (10% methanol · · ethyl acetate) to obtain 25 mg (51%) of the pure compound. 1 H NMR (500 MHz, DMSO_d6) δ 2.25 (s, 3Η), 2.58 (t? J = 4 Hz? 4H) 5 3.52 (t? J = 4 Hz5 4H) 5 4.18 (d5 J = 5 Hz5 1H) 5 6.61 (t? J = 5 Hz, 1H), 6.81 (d, J = 6 Hz, 1H), 7.21 (t, J = 6 Hz, 1H), 7.51 (t, J = 5 Hz, 1H), 7.75 (t, J = 5 Hz, 1H), 7.82 (d, J = 6 Hz, 1H), 8.12 (d, J = 5 Hz, 1H), 8.76 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 327 (MH) +. Example 196 N- (3 ', 6'-dihydro-2,4'-bipyridine-r (2'HV-based methyl V4-fluoro) -3-methylbenzidine 85228 -268- 200404539 will be Γ, 2 ', 3', 6'-tetrahydro- [2,4 '] bi p ratio lake hydrochloride (20 mg, 〇 · ι〇 No moles,

Saari，W.S.等人；J· Med· Chem. 1984, 27, 1182)、聚甲醛（3〇 毫克，1 毫莫耳）、4-氟基-3_甲基苯甲醯胺（77毫克，〇·5毫莫耳，〇akwood) 及42毫克碳酸鉀（0.3毫莫耳）在2.5毫升無水乙醇中之混合物 ’於氮氣下’加熱至回流過夜。使混合物冷卻至室溫，過 濾，及在減壓下移除溶劑。使殘留物於矽膠上藉急驟式管 柱層析純化（10%甲醇：醋酸乙酯），獲得9毫克（28% )純化合 物。1 H NMR (500 MHz，DMSO-d6) 5 2.28 (s，3H)，2.56 (m，2H)，2.76 (m， 2H)，3.30 (m，2H)，4.26 (d，J=5 Hz，2H)，6_70 (m，1H)，7.20 (m5 2H)，7.50 (d，J= 6 Hz，1H)，7.75 (m，2H)，7.85 (d，J=6 Hz，1H)，8.51 (m，1H) 8·77 (t，J=5 Hz，1H) ；MS(ESI/APCI-)m/e324(M-H)+. 實例197 1_-甲基-义{「4-(1，3-噚唑-2-基&gt;)-3,6-二氤_1(211)_吡啶篡1甲某}Saari, WS et al .; J. Med. Chem. 1984, 27, 1182), polyoxymethylene (30 mg, 1 mmol), 4-fluoro-3-methylbenzamide (77 mg, 0.7 mg. -A mixture of 5 mmol, Oakwood) and 42 mg of potassium carbonate (0.3 mmol) in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 9 mg (28%) of the purified compound. 1 H NMR (500 MHz, DMSO-d6) 5 2.28 (s, 3H), 2.56 (m, 2H), 2.76 (m, 2H), 3.30 (m, 2H), 4.26 (d, J = 5 Hz, 2H ), 6_70 (m, 1H), 7.20 (m5 2H), 7.50 (d, J = 6 Hz, 1H), 7.75 (m, 2H), 7.85 (d, J = 6 Hz, 1H), 8.51 (m, 1H) 8.77 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e324 (MH) +. Example 197 1_-methyl-sense {"4- (1,3-oxazole -2-yl &gt;)-3,6-difluorene_1 (211) _pyridine

苯甲酿胺 實例197 A 4-(l，3-崎嗤_2_基）_3,6_二氫比症幾酸第三-丁酉旨 將崎唑（1.00克，14.5毫莫耳）在無水四氫呋喃中，於-78°C下 ，以正-丁基鋰（2·5 Μ，6.4毫升，15,9毫莫耳）處理。持續攪 拌，並於30分鐘後，添加氯化鋅（1Μ溶液，43.0毫升，43.4毫 莫耳），且使反應溫熱至室溫，並攪拌1小時。於此溶液中 添加4-三氟甲烷磺醯氧基-3,6-二氫-2Η-吡啶-1-叛酸第三-丁酯 (Bursavich，M.G.等人；〇rg. Lett. 2001，3,2317，4.8 克，14.5 毫莫耳） ，並攪拌。個別製備鈀觸媒溶液，其方式是將氯化雙（三苯 膦）免(11)(5%莫耳）（526.4毫克，0.75毫莫耳）在四氫呋喃中，於 85228 -269- 200404539 1溫下’以正· 丁基鋰（2.5M溶液，ι·6毫升，L5毫莫耳）處理 · 。將免觸媒添加至含有三氟甲烷磺酸鹽之反應混合物中， 並回流過夜。使反應物冷卻至室溫，以醋酸乙酯稀釋，並 以水進行分液處理。分離有機相，以鹽水洗滌，以無水硫 酸鎂脫水乾燥，及在減壓下濃縮，而得濃稠黃色油（15克，41 % )，其係於靜置時固化。1H NMR (300 MHz，0)(¾) 6 1.50 9H)， 2.62 (m，2H)，3·60 (t，2H，J=6 Hz)，4.10 (m5 2H)，6.65 (m，1H)，7.10 (d，1H，J= 0.25 Hz)，7.60 (d，1H，J=0.25 Hz) ; MS (DCI/NH3) m/e 251 (M+H)+ · ·Example of benzylamine 197 A 4- (l, 3-crazy_2_yl) _3,6_dihydrobiorroxacin tertiary-butyrazine Purpose razol (1.00 g, 14.5 mmol) in anhydrous Tetrahydrofuran was treated with n-butyllithium (2.5 M, 6.4 ml, 15,9 mmol) at -78 ° C. Stirring was continued, and after 30 minutes, zinc chloride (1M solution, 43.0 ml, 43.4 mmol) was added, and the reaction was allowed to warm to room temperature and stirred for 1 hour. To this solution was added 4-trifluoromethanesulfonyloxy-3,6-dihydro-2pyridine-pyridine-1-tricarboxylic acid tert-butyl ester (Bursavich, MG et al .; rg. Lett. 2001, 3 , 2317, 4.8 g, 14.5 mmol) and stir. Individually prepare palladium catalyst solutions by dissolving bis (triphenylphosphine) chloride (11) (5% mole) (526.4 mg, 0.75 mmol) in tetrahydrofuran at 85228 -269- 200404539 1 Under 'Treatment with n-butyllithium (2.5M solution, 6ml, L5 mmol). Catalyst-free was added to the reaction mixture containing trifluoromethanesulfonate and refluxed overnight. The reaction was cooled to room temperature, diluted with ethyl acetate, and separated with water. The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a thick yellow oil (15 g, 41%), which solidified upon standing. 1H NMR (300 MHz, 0) (¾) 6 1.50 9H), 2.62 (m, 2H), 3.60 (t, 2H, J = 6 Hz), 4.10 (m5 2H), 6.65 (m, 1H), 7.10 (d, 1H, J = 0.25 Hz), 7.60 (d, 1H, J = 0.25 Hz); MS (DCI / NH3) m / e 251 (M + H) + · · ·

實例197B 4_(1，3』亏吐-2-基）-1,2·3,6_四氣外匕淀 按照實例166Β中所述之程序，以得自實例197Α之產物取代 得自實例166Α之產物，提供標題化合物，為褐色油（1.75克， 92% ) 。 iHNMRpOOMHACDCU) 5 2.90 (m，2H)，3.45 (m，2H)，3.95 (s，2H)，6.70 (m，1H)，7.28 (d，1H，J=0.25 Hz)，7·68 (d，1H，J=0.25 Hz) ; MS (DCI/NH3) m/e 151 (M+H)+. 實例197C · 3-甲某嘮唑-2_基V3.6•二氫-1(2HV吡啶基1甲基} 笨甲醯胺 按照實例200中所述之程序，以得自實例166B之產物取代 得自實例119A之產物’提供標題化合物’為褐色膠黏性殘 留物（280 毫克，15% )。1H NMR (300 MHz，CDC13) δ 62.40 (s，3H)，2.68 (m，2H)，2.87 (t，2H，J=6 Hz)，3.40 (q，2H，J=4.5 Ηζ)，4·45 (d，2H，J=6 Hz)， 6·70 (m，1H)，7.10 (d，1H，J=0.25 Hz)，7.31 (d，2H，J=6 Hz)，7.55 (m，2H)，7.61 (s5 1H) ； MS (DCI/NH3) m/e 298 (M+H)+. 85228 -270- 200404539 順丁埽二酸鹽：對C17H19N3O2*1.0C4H4O4之分析計算值： C，61_01; H，5.61; N，10.16;實測值：c，60.65 ; H，5.46; N，9.91. 實例198 U^N-[(3-甲基_3’，6匕二氫-2,4’-聯吡啶_1，(2，HV基）甲基1笨甲醯胺 將得自實例143B之產物（三氟醋酸鹽，29毫克，0.1毫莫耳） 、聚甲醛（30毫克，1毫莫耳）、2-甲基苯甲醯胺（68毫克，0.5 毫莫耳，Aldrich)及42毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫，過濾，及在減壓下移除溶劑。使殘留物於矽 膠上藉急騾式管柱層析純化（10%甲醇：醋酸乙酯），而得12.5 毫克（39% )純化合物。1 H NMR (500 MHz，DMSO-d6) 5 2.32 (s，3H)， 2·37 (s，3H)，2.48 (m，2H)，2_80 (m，2H)，3·27 (m，2H)，4.26 (d，J=5 Hz，2H)， 5.82 (m，1H)，7.15 (m，1H)，7·24 (m，2H)，7.35 (m，2H)，7·60 (d，J=6 Hz，1H)， 8.15 (m，1H)，8.35 (d，J=6 Hz，1H)，8.61 (t，J=5 Hz，1H) ; MS (ESI/APCI-) m/e 320 (M-H)+. 實例199 氰基-2-吡啶基&gt;1-六氫吡啶基1-n-(2,6-二甲基笨基）乙醯胺 使得自實例58D之產物（三氟醋酸鹽，30毫克，0.1毫莫耳） 、N-(2,6_一甲基冬基）-2·氣乙驗胺（23毫克，0.15毫莫耳，Aldrich) 及碳酸鈉（50毫克）在N，N_二甲基甲醯胺/水（2: 1，2毫升）中 ，於室溫下振盪18小時。將所形成之混合物傾析，在減壓 下濃縮。使殘留物藉預備之HPLC純化，提供7毫克（28% )所 要之產物。1 H NMR (500 MHz，DMSO-d6) 6 1.82 (m，2H)，2.05 (m，2H)， 2·12 (s，6H)，2·35 (m，2H)，3.05 (m，3H)，3.15 (s，2H)，7.05 (m，3H)，7.45 (dd， 85228 -271 - 200404539 J=6 Hz，1H)，8.25 (d，J=6 Hz，1H)，8.79 (dd，J=6 Hz，1Η)，9.21 (s, 1H) ; MS (ESI/APCI+) m/e 349 (M+H)+. 實例200Example 197B 4_ (1,3 "Deutero-2-yl) -1,2 · 3,6_Four gas outer dagger Follow the procedure described in Example 166B and replace the product from Example 197A with the product from Example 166A The product provided the title compound as a brown oil (1.75 g, 92%). iHNMRpOOMHACDCU) 5 2.90 (m, 2H), 3.45 (m, 2H), 3.95 (s, 2H), 6.70 (m, 1H), 7.28 (d, 1H, J = 0.25 Hz), 7.68 (d, 1H ， J = 0.25 Hz); MS (DCI / NH3) m / e 151 (M + H) +. Example 197C · 3-Methoxazole-2_yl V3.6 • Dihydro-1 (2HV pyridyl 1 Methyl} benzamidine Following the procedure described in Example 200, the product from Example 166B was substituted for the product from Example 119A 'Providing the title compound' as a brown tacky residue (280 mg, 15%). 1H NMR (300 MHz, CDC13) δ 62.40 (s, 3H), 2.68 (m, 2H), 2.87 (t, 2H, J = 6 Hz), 3.40 (q, 2H, J = 4.5 Ηζ), 4.45 (d, 2H, J = 6 Hz), 6.70 (m, 1H), 7.10 (d, 1H, J = 0.25 Hz), 7.31 (d, 2H, J = 6 Hz), 7.55 (m, 2H) , 7.61 (s5 1H); MS (DCI / NH3) m / e 298 (M + H) +. 85228 -270- 200404539: maleic acid: calculated for C17H19N3O2 * 1.0C4H4O4: C, 61_01; H, 5.61; N, 10.16; Found: c, 60.65; H, 5.46; N, 9.91. Example 198 U ^ N-[(3-methyl_3 ', 6-dihydro-2,4'-linked Pyridine-1, (2, HV group) methyl 1 benzamidine will be obtained from the product of Example 143B (trifluoro Acid salt, 29 mg, 0.1 millimolar), polyoxymethylene (30 mg, 1 millimolar), 2-methylbenzamide (68 mg, 0.5 millimolar, Aldrich), and 42 mg potassium carbonate ( · 3 mmol) in 2.5 ml of absolute ethanol, heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was borrowed on silica gel. Purified by column chromatography (10% methanol: ethyl acetate) to obtain 12.5 mg (39%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) 5 2.32 (s, 3H), 2.37 (s, 3H), 2.48 (m, 2H), 2_80 (m, 2H), 3.27 (m, 2H), 4.26 (d, J = 5 Hz, 2H), 5.82 (m, 1H), 7.15 ( m, 1H), 7.24 (m, 2H), 7.35 (m, 2H), 7.60 (d, J = 6 Hz, 1H), 8.15 (m, 1H), 8.35 (d, J = 6 Hz , 1H), 8.61 (t, J = 5 Hz, 1H); MS (ESI / APCI-) m / e 320 (MH) +. Example 199 Cyano-2-pyridyl &gt; 1-hexahydropyridyl 1 -n- (2,6-dimethylbenzyl) acetamidamine gives the product from Example 58D (trifluoroacetate, 30 mg, 0.1 mmol), N- (2,6-monomethyl winteryl ) -2 · Pyroethylamine (23 mmol) G, 0.15 mmol, Aldrich) and sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1,2 ml) and shake at room temperature for 18 hours. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 7 mg (28%) of the desired product. 1 H NMR (500 MHz, DMSO-d6) 6 1.82 (m, 2H), 2.05 (m, 2H), 2.12 (s, 6H), 2.35 (m, 2H), 3.05 (m, 3H) , 3.15 (s, 2H), 7.05 (m, 3H), 7.45 (dd, 85228 -271-200404539 J = 6 Hz, 1H), 8.25 (d, J = 6 Hz, 1H), 8.79 (dd, J = 6 Hz, 1Η), 9.21 (s, 1H); MS (ESI / APCI +) m / e 349 (M + H) +. Example 200

甲基本甲酿基）胺基1甲基丨·4_六氡p比淀基 &gt;比鍵]Sf-氧化物 將2-六氫吡啶_4_基吡錠N-氧化物鹽酸鹽（得自實例119Α)(4·16 克’ 16.4毫莫耳）在甲苯/二氧陸圜（6〇毫升/ 6毫升）中，於 室溫下，以粉末狀碳酸鉀（2.69克，19.37毫莫耳）處理，並攪 拌30分鐘。於此混合物中添加3-甲基苯甲醯胺（7.89克，58.4 毫莫耳）與37%甲醛水溶液（4·7毫升，58毫莫耳）。將反應混 合物於80°C下加熱3小時，冷卻至室溫，以另一份3-甲基苯 甲醯胺（2.63克，19.5毫莫耳）與37%甲醛（1.57毫升，19.5毫莫 耳）處理。將反應混合物在80°C下攪拌1小時，冷卻，及在減 壓下濃縮。使用甲苯以移除水（2 X 75毫升）。於此殘留物中 添加3%甲醇：二氯甲烷，並濾出無機鹽。使濾液在減壓下 濃縮。使殘留物藉急騾式管柱層析純化，使用10%甲醇：二 氯甲烷，接著是15%甲醇：二氯甲烷，提供標題化合物，為 固體。熔點 177-180°C ; iHNMRpOOMHz.DMSO-dJ 5 1.52(m，2H)， 1.89 (m，2H)，2.33 (m，2H)，2.38 (s，3H)，2.96 (m5 2H)，3.19 (m，1H)，4.17 (d， J=6 Hz，2H)，7·31 (m，5H)，7.69 (m，2H)，8.23 (m，1H)，8.71 (m，1H) ； MS (DCI/NH3)m/e310(M+H-16)+ ;對 C19H23N302 之分析計算值： C，70.13 ; H，7.12 ; N，12.91.實測值 C，69·94 ; H，7.19 ; N，12.96. 實例201 N-(3-甲基苯基）-2-「4-(3•甲基-2-p比淀基VI-六氫p比？井基1乙酸胺Methylbenzyl) amine 1 methyl 丨 4-hexamethylpyridine &gt; specific bond] Sf-oxide will be 2-hexahydropyridine 4-ylpyridine N-oxide hydrochloride ( Obtained from Example 119A) (4.16 g '16.4 mmol) in toluene / dioxolane (60 ml / 6 ml) at room temperature with powdered potassium carbonate (2.69 g, 19.37 mmol) Ear), and stir for 30 minutes. To this mixture was added 3-methylbenzamide (7.89 g, 58.4 mmol) and a 37% aqueous formaldehyde solution (4.7 ml, 58 mmol). The reaction mixture was heated at 80 ° C for 3 hours, cooled to room temperature, and another portion of 3-methylbenzamide (2.63 g, 19.5 mmol) with 37% formaldehyde (1.57 mL, 19.5 mmol) )deal with. The reaction mixture was stirred at 80 ° C for 1 hour, cooled, and concentrated under reduced pressure. Use toluene to remove water (2 X 75 ml). To this residue was added 3% methanol: dichloromethane, and the inorganic salt was filtered off. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography using 10% methanol: dichloromethane, followed by 15% methanol: dichloromethane to provide the title compound as a solid. 177-180 ° C; iHNMRpOOMHz.DMSO-dJ 5 1.52 (m, 2H), 1.89 (m, 2H), 2.33 (m, 2H), 2.38 (s, 3H), 2.96 (m5 2H), 3.19 (m , 1H), 4.17 (d, J = 6 Hz, 2H), 7.31 (m, 5H), 7.69 (m, 2H), 8.23 (m, 1H), 8.71 (m, 1H); MS (DCI / NH3) m / e310 (M + H-16) +; Analytical calculated values for C19H23N302: C, 70.13; H, 7.12; N, 12.91. Found C, 69 · 94; H, 7.19; N, 12.96. Examples 201 N- (3-methylphenyl) -2- "4- (3 • methyl-2-p ratio Yodo group VI-hexahydro p ratio? Jingji 1 amine acetate

實例201A 85228 -272- 200404539 1-(3-甲基-2-外1:淀基）六氫批 於2-溴基-3-甲基吡啶（3.30毫升，29.6毫莫耳）在正-丁醇中之 漿液内，添加六氫吡畊（25.0克，290毫莫耳），並反應物加熱 至回流，歷經3天。使混合物冷卻，及在減壓下移除溶劑。 使殘留物於水與醋酸乙酯之間作分液處理。使有機相脫水 乾燥（硫酸鈉），及濃縮。使殘留物於碎膠上藉急驟式管柱 層析純化（以15%甲醇：二氯甲烷溶離），提供標題化合物， 為黃色油。1HNMR(300MHz，CDCl3)(5 2·28(s，3H)，3·01(m，4H)，Example 201A 85228 -272- 200404539 1- (3-Methyl-2-exo-1: yl) hexahydrogen was batched with 2-bromo-3-methylpyridine (3.30 ml, 29.6 mmol) in n-butyl To the slurry in the alcohol, hexahydropyrine (25.0 g, 290 mmol) was added and the reaction was heated to reflux for 3 days. The mixture was allowed to cool and the solvent was removed under reduced pressure. The residue was separated between water and ethyl acetate. The organic phase was dried (sodium sulfate) and concentrated. The residue was purified on flash gel by flash column chromatography (dissolved in 15% methanol: dichloromethane) to provide the title compound as a yellow oil. 1HNMR (300MHz, CDCl3) (5 2 · 28 (s, 3H), 3.01 (m, 4H),

3.11 (m，4H)，6.84 (dd，1H，J=7.1，4·8 Hz)，7.39 (m，1H)，8.16 (m，1H) ； MS (DCI/NH3) m/e 178 (M+H)+.3.11 (m, 4H), 6.84 (dd, 1H, J = 7.1, 4.8 Hz), 7.39 (m, 1H), 8.16 (m, 1H); MS (DCI / NH3) m / e 178 (M + H) +.

實例201B N-(3-甲基笨基）-2-「4_(3_甲基-2-p比淀基六氳p比p井基&quot;[乙醯胺 按照實例33C中所述之程序，以得自實例2〇1Α之產物取代 得自實例33B之產物，提供標題化合物。iHNMRpOOMHz， DMSO-d6) 5 2.23 (s? 3H)? 2.28 (s5 3H)5 2.68 (m5 4H)? 3.13 (m5 4H)? 3.18 (s? 2H)，6_90 (m，2H)，7.18 (dd，1H，J=7.8, 7.8 Hz)，7.47 (m，3H)，8.10 (dd，1H，J= 4.7, 1.7 Hz)，9.65 (br s，1H) ; MS (DCI/NH3) m/e 325 (M+H)+ ; 對 C19H24N40之分析計算值：C，70.34 ; H，7.46; N, 17.27.實測值 :C，70.13 ; H，7_36 ; N，17.20. 實例202 2-「4-G-氰盡-2-吡啶基VI-六i.吡畊基VN44-(三氟甲基）茉某1 乙醯胺 將2-氯-N-(4-三氟甲基苯基）乙醯胺（820毫克，3.45毫莫耳， Maybridge)與N，N-二異丙基胺（2.5毫升）在甲苯(50毫升）中，以2- 85228 -273 - 200404539 六氫吡畊小基菸鹼腈（800毫克，4·25毫莫耳，Chess)處理，並 加熱至60 C ’歷經18小時。使混合物冷卻至室溫，轉移至分 液漏斗，並以飽和碳酸氫鈉水溶液洗滌。使有機相脫水乾 燥（硫酸鈉），過濾，並使濾液在減壓下濃縮。使殘留物於 矽膠上藉急驟式管柱層析純化（以20%至40%醋酸乙酯：己 烷梯度溶離），提供1.05克（78%產率）標題化合物，為白色固 體。1HNMR(300 MHz，DMSO-d6)52.69 (m，4H)，3.26 (s，2H)，3.68 (m， 4H)，6·93 (dd，1H，J=7.5, 4.7 Hz)，7·68 (AA，BB，，2H，J=8.8 Hz)，7·88 (AA，BB，， 2H，J=8.5 Hz)，8.07 (dd，1H，J=7.8, 2.0 Hz)，8.42 (dd，1H，J=4.7, 2·0 Hz)，10.14 (br s，1H) ; MS (DCI/NH3) m/e 390 (M+H)+ ;對 C! 9 Hi 8 F3 N5 O 之分析 計算值：C，58.61 ; H，4.66 ; N, 17.99.實測值：C，58.35 ; H，4.45 ; N，18.02. 實例203 N_(2-乙基-6-甲基笨基）-244-(2-吡啶基）小六氫吡啶基1乙醯胺 標題化合物係根據實例170之方法，以2-乙基-6-甲基苯胺取 代2,6-二乙基苯胺而製成（產量：48.5毫克，0.144毫莫耳，28 % )。1H NMR (300 MHz，DMSO-d6) 5 1.08 (t，J=7.5 Hz，3H)，1.90 (m，4H)， 2.14 (s，3H)，2.32 (m，2H)，2.50 (q5 J=7.5 Hz，2H)，2.68 (m，1H)，3.04 (br d，J= 11·4 Hz，2H)，3.15 (s，2H)，7.10 (m，3H)，7.21 (ddd，J=1.5, 4.5, 7·5 Hz，1H)， 7.30 (d，J=8.4 Hz，1H)，7.72 (ddd, J=2.1，7.5, 7·5 Hz，1H)，8.28 (m，1H)，9.22 (br s，1H) ; MS (ESI) m/e 338 (M+H)+ ;對 C2 丄 H2 7 N3 Ο · 0·3Η2 O 之分析 計算值：C，73.56 ; H，8.11; N，12.26.實測值·· C，73.46 ; Η，7·93; N，12.07. 實例204 85228 274- 200404539 N-(2-_先...¾....基-6-甲基表基）-2_「4-(2-p比淀基）_1_六氫u比咬基1乙_脸 標題化合物係根據實例170之方法，以2-異丙基-6-甲基苯胺 取代2,6-二乙基苯胺而製成（產量：45.3毫克，0.129毫莫耳， 25 % )。1H NMR (300 MHz，DMSO-d6) 1 · 13 (d，J=7.2 Hz，6H)，1.90 (m， 4H)，2.14 (s，3H)，2.32 (m，2H)，2.70 (m，1H)，3.05 (m，3H)，3.16 (s，2H)，7.06 (m，1H)，7.18 (m，3H)，7·29 (d，J=8.4 Hz，1H)，7.72 (ddd，J=2.1，7.5, 7·5 Hz，1H)， 8.48 (m，1H)，9·22 (br s，1H) ; MS (ESI) m/e 352 (M+H)+ ;對 C2 2 H2 9N3 O • 0.35 H20 之分析計算值：c，73.85 ; H，8·37 ; N，11.74·實測值·· C，74·04;H，8·41;N，11·58· 實例205 N-O氯基-6-甲基苯基）-244-(2^比邊基）-1-六氫IT比淀基1乙醯脖 標題化合物係根據實例170之方法，以2-氯基-6-甲基苯胺取 代2,6-二乙基苯胺而製成（產量·· 62·8毫克，0.183毫莫耳，36 %)。iHNMRpOOMHz’DMSOO^l.SSCmJHpjtHsdHUJOCm， 2H)，2.68 (m，1H)，3.12 (m，2H)，3.17 (s，2H)，7.21 (m，2H)，7.29 (d，J=8.4 Hz， 1H), 7.36 (m? 1H)? 7.73 (ddd, J=2.1? 7.5, 7.5 Hz, 1H)5 8.48 (m5 1H), 9.43 (br s? 1H); MS(ESI)m/e344(M+H)+ ;對(：191122(：11^3〇.0.1〇«2(：12之分析 計算值：C，65.11 ; Η,6·35 ; N，11.93.實測值：C，64.83 ; Η，6·04 ; N, 11.88. 實例206 N-(2-甲氧基-6-甲基笨基）-2-『4-(2-峨淀基）-1-六氫p比淀基1乙驢胺 標題化合物係根據實例170之方法，以2-甲氧基-6-甲基苯胺 取代2,6-二乙基苯胺而製成（產量：38.1毫克，0.112毫莫耳，22 % )。1H NMR (300 MHz，DMSOd6) 51.87 (m，4Η)，2· 14 (s5 3Η)，2.29 ㈣ 85228 -275- 200404539 2H)，2.69 (m，1H)，3.08 (m，4H)，3.72 (s，3H), 6·84 (m，2H)，7.13 (dd，J=8.4, 8·4 、Example 201B N- (3-methylbenzyl) -2- "4- (3_methyl-2-p ratio to ytyl hexapyridine p ratio p well group" &quot; [ethylammonium amine according to the procedure described in Example 33C Substituting the product from Example 201A with the product from Example 33B to provide the title compound. IHNMR pOOMHz, DMSO-d6) 5 2.23 (s? 3H)? 2.28 (s5 3H) 5 2.68 (m5 4H)? 3.13 ( m5 4H)? 3.18 (s? 2H), 6_90 (m, 2H), 7.18 (dd, 1H, J = 7.8, 7.8 Hz), 7.47 (m, 3H), 8.10 (dd, 1H, J = 4.7, 1.7 Hz), 9.65 (br s, 1H); MS (DCI / NH3) m / e 325 (M + H) +; Analytical calculated value for C19H24N40: C, 70.34; H, 7.46; N, 17.27. Measured value: C, 70.13; H, 7_36; N, 17.20. Example 202 2- "4-G-cyano-2-pyridyl VI-hexai. Pyridyl VN44- (trifluoromethyl) japan 1 acetamidine Combine 2-chloro-N- (4-trifluoromethylphenyl) acetamide (820 mg, 3.45 mmol, Maybridge) with N, N-diisopropylamine (2.5 ml) in toluene (50 ml) ), Treated with 2- 85228 -273-200404539 hexahydropyridine nicotinic nitrile (800 mg, 4.25 mmol, Chess), and heated to 60 C 'over 18 hours. Allow the mixture to cool to room temperature. Warm, transfer to The separatory funnel was washed with a saturated aqueous sodium bicarbonate solution. The organic phase was dried (sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (using 20% to 40% ethyl acetate: hexane gradient dissolution), providing 1.05 g (78% yield) of the title compound as a white solid. 1HNMR (300 MHz, DMSO-d6) 52.69 (m, 4H), 3.26 (s , 2H), 3.68 (m, 4H), 6.93 (dd, 1H, J = 7.5, 4.7 Hz), 7.68 (AA, BB ,, 2H, J = 8.8 Hz), 7.88 (AA, BB ,, 2H, J = 8.5 Hz), 8.07 (dd, 1H, J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 4.7, 2.0 Hz), 10.14 (br s, 1H); MS (DCI / NH3) m / e 390 (M + H) +; Analytical calculated value for C! 9 Hi 8 F3 N5 O: C, 58.61; H, 4.66; N, 17.99. Found: C, 58.35; H , 4.45; N, 18.02. Example 203 N_ (2-ethyl-6-methylbenzyl) -244- (2-pyridyl) hexahexapyridyl 1acetamidine The title compound was prepared according to the method of Example 170, It was prepared by replacing 2,6-diethylaniline with 2-ethyl-6-methylaniline (yield: 48.5 mg, 0.144 mmol, 28%). 1H NMR (300 MHz, DMSO-d6) 5 1.08 (t, J = 7.5 Hz, 3H), 1.90 (m, 4H), 2.14 (s, 3H), 2.32 (m, 2H), 2.50 (q5 J = 7.5 Hz, 2H), 2.68 (m, 1H), 3.04 (br d, J = 11.4 Hz, 2H), 3.15 (s, 2H), 7.10 (m, 3H), 7.21 (ddd, J = 1.5, 4.5 , 7.5 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.72 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.28 (m, 1H), 9.22 (br s , 1H); MS (ESI) m / e 338 (M + H) +; Analytical calculated value for C2 丄 H2 7 N3 〇 · 0 · 3Η2 O: C, 73.56; H, 8.11; N, 12.26. Measured value ··· C, 73.46; Η, 7.93; N, 12.07. Example 204 85228 274- 200404539 N- (2-_first ... ¾ .... yl-6-methylepoxy) -2_ "4 -(2-pbitoyl) _1_hexahydroubibityl1ethyl_face The title compound was substituted for 2,6-diethyl with 2-isopropyl-6-methylaniline according to the method of Example 170. Aniline (yield: 45.3 mg, 0.129 mmol, 25%). 1H NMR (300 MHz, DMSO-d6) 1 · 13 (d, J = 7.2 Hz, 6H), 1.90 (m, 4H), 2.14 (s, 3H), 2.32 (m, 2H), 2.70 (m, 1H), 3.05 (m, 3H), 3.16 (s, 2H), 7.06 (m, 1H), 7.18 (m, 3H), 7 · 29 (d, J = 8.4 Hz, 1H), 7.72 (ddd, J = 2.1, 7.5, 7 · 5 Hz, 1H), 8.48 (m, 1H), 9.22 (br s, 1H); MS (ESI) m / e 352 ( M + H) +; Analytical calculations for C2 2 H2 9N3 O • 0.35 H20: c, 73.85; H, 8.37; N, 11.74. Measured value. C, 74.04; H, 8.41; N, 11 · 58 · Example 205 NO Chloro-6-methylphenyl) -244- (2 ^ specific side group) -1-hexahydro IT ratio yodoyl 1 Acetyl title compound according to the method of Example 170 It was produced by substituting 2,6-diethylaniline with 2-chloro-6-methylaniline (yield: 62.8 mg, 0.183 mmol, 36%). iHNMRpOOMHz'DMSOO ^ l.SSCmJHpjtHsdHUJOCm, 2H), 2.68 (m, 1H), 3.12 (m, 2H), 3.17 (s, 2H), 7.21 (m, 2H), 7.29 (d, J = 8.4 Hz, 1H) , 7.36 (m? 1H)? 7.73 (ddd, J = 2.1? 7.5, 7.5 Hz, 1H) 5 8.48 (m5 1H), 9.43 (br s? 1H); MS (ESI) m / e344 (M + H) +; Pair (: 191122 (: 11 ^ 30.3.0.1) «2 (: Analytical calculated value of 12: C, 65.11; Η, 6.35; N, 11.93. Found: C, 64.83; Η, 6. · 04; N, 11.88. Example 206 N- (2-methoxy-6-methylbenzyl) -2- "4- (2-etherediyl) -1-hexahydrop-pyridyl 1ethyldonylamine The title compound was prepared according to the method of Example 170, substituting 2,6-diethylaniline with 2-methoxy-6-methylaniline (yield: 38.1 mg, 0.112 mmol, 22%). 1H NMR (300 MHz, DMSOd6) 51.87 (m, 4Η), 2.14 (s5 3Η), 2.29 ㈣ 85228 -275- 200404539 2H), 2.69 (m, 1H), 3.08 (m, 4H), 3.72 (s, 3H ), 6.84 (m, 2H), 7.13 (dd, J = 8.4, 8 · 4,

Hz，1H)，7·20 (dd(U=1.5, 4.5, 7.5 Hz，1H)，7·31 (d，J=8.4 Hz，1H)，7.72 (ddd， J=2.1，7.5, 7.5 Hz，1H)，8·48 (m，1H)，8.94 (br s，1H) ； MS (ESI) m/e 340 (M+H)+ ;對 C20H25N3CN0.4H2O之分析計算值·· C，69.30 ; H，7.50 ;N，12.12.實測值：C，69.45 ; H，7·48 ; N，11.82· 實例207 2-(3’，6f-二氫_2,4’_聯吡啶某VN-(2-乙基-6-甲基笨基）乙醯胺 標題化合物係根據實例170之方法，以2-乙基_6_甲基苯胺取 _ 代2,6-二乙基苯胺，並以1，，2’，3!，6’-四氫-[2,4’]聯吡啶鹽酸鹽取代 得自實例36C之產物而製成。（產量：50.2毫克，0.150毫莫耳 ，29%) 〇 iHNMRpOOMHsDMSO-c^) 51.09(t，J=7.5Hz，3H)，2.16(s， 3H)? 2.52 (m? 2H)? 2.68 (m, 2H)5 2.82 (t? J=5.7 Hz? 2H)? 3.28 (s? 2H), 3.36 (m? 2H)，6.73 (m，1H)，7.08 (m，3H)，7.23 (ddd，J=1.0, 5·1，7·5 Hz，1H)，7·57 (d，J= 7.5 Hz，1H)，7·75 (ddd，J=2.1，7.5, 7·5 Hz，1H)，8.54 (m，1H)，9.23 (br s，1H); MS (ESI) m/e 336 (M+H)+ ;對 C2 丨 H2 5 N3 O · 0.3 CH2 Cl2 之分析計算值 :C，70·88 ; H，7·15 ; N，11.64.實測值：C，70·92 ; H，7.06 ; N，11.78. # 實例208 2-_σ，心二氫-2,4’-聯毗啶某VN-(2-異丙某_6_甲基茉某） 乙醯胺 標題化合物係根據實例170之方法，以2-異丙基各甲基苯胺 取代2,6-二乙基苯胺，並以i’，2’，3’，6’-四氫-[2,4f]聯p比啶鹽酸鹽Hz, 1H), 7.20 (dd (U = 1.5, 4.5, 7.5 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.72 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.48 (m, 1H), 8.94 (br s, 1H); MS (ESI) m / e 340 (M + H) +; Analytical calculated value for C20H25N3CN0.4H2O ... C, 69.30; H , 7.50; N, 12.12. Found: C, 69.45; H, 7.48; N, 11.82. Example 207 2- (3 ', 6f-dihydro_2,4'_bipyridine, VN- (2- Ethyl-6-methylbenzyl) acetamidine The title compound was prepared according to the method of Example 170, substituting 2-ethyl-6-methylaniline for 2,6-diethylaniline, and 2 ', 3!, 6'-Tetrahydro- [2,4'] bipyridine hydrochloride was prepared by substituting the product obtained from Example 36C. (Yield: 50.2 mg, 0.150 mmol, 29%) 〇HNMRpOOMHsDMSO -c ^) 51.09 (t, J = 7.5Hz, 3H), 2.16 (s, 3H)? 2.52 (m? 2H)? 2.68 (m, 2H) 5 2.82 (t? J = 5.7 Hz? 2H)? 3.28 (s? 2H), 3.36 (m? 2H), 6.73 (m, 1H), 7.08 (m, 3H), 7.23 (ddd, J = 1.0, 5 · 1, 7 · 5 Hz, 1H), 7.57 (d, J = 7.5 Hz, 1H), 7.75 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.54 (m, 1H), 9.23 (br s, 1H); MS (ESI) m / e 336 (M + H) +; C2 丨 H2 5 N3 O · 0.3 CH2 Cl2 Analytical calculation value: C, 70 · 88; H, 7.15; N, 11.64. Found: C, 70 · 92; H, 7.06; N, 11.78. # Example 208 2-_σ, cardiodihydro-2,4'-bipyridine VN- (2-isopropyl_6_methylmozine) Acetylamine The title compound was prepared according to the method of Example 170 using 2-iso Propyl methylaniline replaces 2,6-diethylaniline and i ', 2', 3 ', 6'-tetrahydro- [2,4f] bipyridine hydrochloride

(Saari，W.S·等人；J. Med_ Chem. 1984, 27, 1182)取代得自實例 36C 之 產物而製成。（產量：37·4毫克，0.110毫莫耳，21%)。^NMR (300 MHz，DMSO-d6)占 U2 (d，J=6.9 Hz，6H)，2.15 (s，3H)，2.67 (m，2H)， 85228 -276- 200404539(Saari, W.S. et al .; J. Med_Chem. 1984, 27, 1182) was prepared in place of the product obtained from Example 36C. (Yield: 37.4 mg, 0.110 mmol, 21%). ^ NMR (300 MHz, DMSO-d6) accounts for U2 (d, J = 6.9 Hz, 6H), 2.15 (s, 3H), 2.67 (m, 2H), 85228 -276- 200404539

2.82 (t，J=5.7 Hz，2H)，3·07 (m，1Η)，3.27 (s，2H)，3.37 (m，2H)，6.73 (m，1H)， 7.06 (dd，J=3.0, 9·0 Hz，1H)，7.15 (m，2H)，7·23 (ddd，J=1.0, 5.1，7.5 Hz，1H)， 7.56 (d，J=8.4 Hz，1H)，7.76 (ddd，J=2.1，7.5, 7.5 Hz，1H)，8.53 (m，1H)，9.21 (br s，1H); MS (ESI) m/e 350 (M+H)+ ·對 C2 2 H2 7 N3 O · 0.3 C2 H4 02 0· 1 H2 O 之分析計算值：C，73.51; H，7.75 ; N，11.38.實測值：C, 73.42; H，7.67 ;N, 11.40. 實例209 N-(2-氯基-6-甲某笨某V2-(3T,6’·二氫-2,4’-聯吡啶-1’(2Ή)_基）乙醯胺 · 標題化合物係根據實例170之方法，以2-氯基-6-甲基苯胺取 代2,6-二乙基苯胺，並以1’，2’，3’，6’-四氫_[2,4，]聯吡啶鹽酸鹽 (8&amp;&amp;4，\¥.8.等人；11^(1〇^111.1984,27，1182)取代得自實例360：之 產物而製成。（產量：49.5毫克，0.145毫莫耳，28% )。1H NMR (300 MHz，DMSO-d6 ) δ 2.20 (s，3Η)，2·68 (m，2Η)，2.83 (t，J=5.7 Ηζ，2Η)， 3.29 (s5 2H), 3.38 (m? 2H)5 6.72 (m5 1H)5 7.22 (m5 3H)5 7.35 (dd5 J=2.15 7.5 Hz, 1H)5 7.57 (d5 J=8.4 Hz? 1H), 7.76 (ddd5 J=2.1? 7.5? 7.5 Hz5 1H), 8.53 (m5 1H)? 9.43 (br s，1H) ; MS (ESI) m/e 342 (M+H)+ ·對 q 9 H2 0 C1N3 O · 0.25C2 H4 02 φ 之分析計算值：C，65.63 ; Η, 5·93 ; N，11.78.實測值：C，65.44; H，5.72 ，N，11.88. 實例210 2·(3\6Τ-二i. -2,4’-聯吡啶-Γ(2Ήν墓VN_(2-甲氣某-6-甲基苯某） 乙醯胺 標題化合物係根據實例170之方法，以2-甲氧基各甲基苯胺 取代2,6-二乙基苯胺，並以1’，2’，3’，6’_四氫_[2,4’]聯卩比淀鹽酸鹽 (Saari，W.S.等人；J. Med· Chem. 1984, 27, 1182)取代得自實例 36C 之 85228 -277- 200404539 產物而製成。（產量·· 50.3毫克，0.149毫莫耳，29% )。iHNMR (300 MHz，DMSO-d6) δ 2·13 (s，3Η)，2·70 (m，2Η)，2·82 (t，J=5.7 Ηζ，2Η)， 3.24 (s，2Η)，3.35 (m，2Η)，3.74 (s，3Η)，6.74 (m，1Η)，6·86 (dd，J=8.4, 13·8, 1Η)， 7.14 (dd，J=7.5, 7.5 Hz，1H)，7.24 (ddd，J=1.0, 5.1，7.5 Hz，1H)，7.58 (d，J=8.4 Hz, 1H)5 7.78 (ddd? J=2.1? 7.5? 7.5 Hz, 1H), 8.54 (m5 1H)? 8.94 (br s? 1H) ； MS (ESI) m/e 338 (M+H)+ ·對 C2 〇 H2 3 N3 O · 0.05 CH2 Cl2 之分析計算值： C，70.48 ; H，6·81 ; N，12.30·實測值：C，70.40 ; H，6·67 ; N，12.38. 實例211 1二氯-N-IT3-甲基二氫-2，-聯吡啶-1丫2Ήν某）甲基1笨甲醯胺 將得自實例143Β之產物（三氟醋酸鹽，29毫克，0.1毫莫耳） 、聚甲酸（30毫克，1毫莫耳）、3-氯苯甲醯胺（78毫克，0.5毫 莫耳，Maybridge)及42毫克碳酸鉀（0.3毫莫耳）在2·5毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫，過濾，及在減壓下移除溶劑。使殘留物於矽 膠上藉急驟式管柱層析純化（10%甲醇：醋酸乙酯），而得8.6 毫克（25% )純化合物。1 H NMR (500 MHz，DMSO-d6) 5 2·28 (s，3Η)， 2·45 (m，2Η)，2.73 (m，2Η)，3.23 (m，2Η)，4.28 (d，J=6 Ηζ，2Η)，5.80 (m，1Η)， 7.15 (m，1H)，7.52 (t，J=6 Hz，1H)，7.61 (m，2H)，7.86 (d，J=6 Hz，1H)，7.94 (m， 1H)，8.34 (d，J=6 Hz，1H)，8.95 (t，J=6 Hz，1H) ; MS (ESI/APCI-) m/e 340 實例212 3-氟-N-「(3-甲基-3’,6’-二氫-2,4’-聯吡啶)甲基&quot;I笨甲醯胺 將得自實例143B之產物（三氟醋酸鹽，29毫克，0.1毫莫耳） 、聚甲醛（30毫克，1毫莫耳）、3-氟基苯甲醯胺（70毫克，〇.5 85228 -278 - 200404539 毫莫耳，Aldrich)及42毫克碳酸卸（〇·3毫莫耳）在2·5毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫，過濾，及在減壓下移除溶劑。使殘留物於矽 膠上藉急驟式管柱層析純化（10%甲醇··酷酸乙酯），獲得24 毫克（74% )純化合物。1 H NMR (500 MHz，DMSO-d6 ) 5 2.30 (s，3Η)， 2·47 (m，2H)，2.76 (m，2H)，3.25 (m，2H)，4.28 (d，J=6 Hz，2H)，5.80 (m，1H)， 7·14 (m，1H)，7.39 (t，J=6 Hz，1H)，7.55 (m，2H)，7.69 (d5 J=6 Hz，1H)，7.76 (d5 J=6 Hz，1H)，8·34 (d，J=6 Hz，1H)，8.91 (t，J=6 Hz，1H) ; MS (ESI APCI-) m/e 324 (M-H)+. 實例213 li.甲基-N__{[(2S)-2-甲基比症某Vl_六氫被啼基1甲基丨笨甲酼脖2.82 (t, J = 5.7 Hz, 2H), 3.07 (m, 1Η), 3.27 (s, 2H), 3.37 (m, 2H), 6.73 (m, 1H), 7.06 (dd, J = 3.0, 9 · 0 Hz, 1H), 7.15 (m, 2H), 7.23 (ddd, J = 1.0, 5.1, 7.5 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.76 (ddd, J = 2.1, 7.5, 7.5 Hz, 1H), 8.53 (m, 1H), 9.21 (br s, 1H); MS (ESI) m / e 350 (M + H) + · For C2 2 H2 7 N3 O · 0.3 Analytical calculated values for C2 H4 02 0 · 1 H2 O: C, 73.51; H, 7.75; N, 11.38. Found: C, 73.42; H, 7.67; N, 11.40. Example 209 N- (2-chloro- 6-Formamylbenzyl V2- (3T, 6 '· dihydro-2,4'-bipyridine-1' (2 基) _yl) acetamide · The title compound was prepared according to the method of Example 170 using 2-chloro -6-methylaniline substituted 2,6-diethylaniline and substituted with 1 ', 2', 3 ', 6'-tetrahydro_ [2,4,] bipyridine hydrochloride (8 &amp; &amp; 4, \ ¥ .8. And others; 11 ^ (1 ^^ 111.1984, 27, 1182) was prepared in place of the product obtained from Example 360: (yield: 49.5 mg, 0.145 mmol, 28%). 1H NMR (300 MHz, DMSO-d6) δ 2.20 (s, 3Η), 2.68 (m, 2Η), 2.83 (t, J = 5.7 Ηζ, 2Η), 3.29 (s5 2H), 3.38 (m? 2H) 5 6.72 (m5 1H) 5 7.22 (m5 3H) 5 7.35 (dd5 J = 2.15 7.5 Hz, 1H) 5 7.57 (d5 J = 8.4 Hz? 1H), 7.76 (ddd5 J = 2.1? 7.5? 7.5 Hz5 1H), 8.53 (m5 1H)? 9.43 (br s, 1H); MS (ESI) m / e 342 (M + H) + · Analytical calculated value for q 9 H2 0 C1N3 O · 0.25C2 H4 02 φ: C, 65.63 Η, 5.93; N, 11.78. Found: C, 65.44; H, 5.72, N, 11.88. Example 210 2 · (3 \ 6T-bisi. -2,4'-bipyridine-Γ (2Ήν Tomb VN_ (2-methylgas-6-methylbenzyl) The title compound of acetamidine was replaced with 2-methoxydimethylaniline according to the method of Example 170, and replaced with 2,6-diethylaniline. 1 ', 2', 3 ', 6'_tetrahydro_ [2,4'] bipyridine hydrochloride (Saari, WS et al .; J. Med · Chem. 1984, 27, 1182) substitutions are obtained from 8528-277-200404539 from Example 36C. (Yield ·· 50.3 mg, 0.149 mmol, 29%). iHNMR (300 MHz, DMSO-d6) δ 2.13 (s, 3Η), 2.70 (m, 2Η), 2.82 (t, J = 5.7 Ηζ, 2Η), 3.24 (s, 2Η), 3.35 (m, 2Η), 3.74 (s, 3Η), 6.74 (m, 1Η), 6.86 (dd, J = 8.4, 13.8, 1Η), 7.14 (dd, J = 7.5, 7.5 Hz, 1H) , 7.24 (ddd, J = 1.0, 5.1, 7.5 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H) 5 7.78 (ddd? J = 2.1? 7.5? 7.5 Hz, 1H), 8.54 (m5 1H) ? 8.94 (br s? 1H); MS (ESI) m / e 338 (M + H) + · Analytical calculated value for C2 0H2 3 N3 O · 0.05 CH2 Cl2: C, 70.48; H, 6.81; N, 12.30 · Measured value: C, 70.40; H, 6.67; N, 12.38. Example 211 1 Dichloro-N-IT3-methyldihydro-2, -bipyridine-1 y 2 Ή ν) Methyl 1 Benzimidamine will be obtained from the product of Example 143B (trifluoroacetate, 29 mg, 0.1 mmol), polyformic acid (30 mg, 1 mmol), 3-chlorobenzamide (78 mg, 0.5 A mixture of millimoles, Maybridge) and 42 mg of potassium carbonate (0.3 millimoles) in 2.5 ml of absolute ethanol was heated to reflux overnight under nitrogen. The mixture was allowed to cool to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel (10% methanol: ethyl acetate) to obtain 8.6 mg (25%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) 5 2 · 28 (s, 3Η), 2.45 (m, 2Η), 2.73 (m, 2Η), 3.23 (m, 2Η), 4.28 (d, J = 6 Ηζ, 2Η), 5.80 (m, 1Η), 7.15 (m, 1H), 7.52 (t, J = 6 Hz, 1H), 7.61 (m, 2H), 7.86 (d, J = 6 Hz, 1H) , 7.94 (m, 1H), 8.34 (d, J = 6 Hz, 1H), 8.95 (t, J = 6 Hz, 1H); MS (ESI / APCI-) m / e 340 Example 212 3-Fluoro-N -"(3-methyl-3 ', 6'-dihydro-2,4'-bipyridyl) methyl &quot; I benzamidine will be obtained from the product of Example 143B (trifluoroacetate, 29 mg, 0.1 millimolar), polyoxymethylene (30 mg, 1 millimolar), 3-fluorobenzamide (70 mg, 0.5 85228 -278-200404539 millimolar, Aldrich) and 42 mg carbonic acid ( (0.3 mmol) in 2.5 ml of absolute ethanol, heated to reflux under nitrogen overnight. The mixture was cooled to room temperature, filtered, and the solvent was removed under reduced pressure. The residue was subjected to silica gel. Purified by flash column chromatography (10% methanol · · ethyl acyl acetate) to obtain 24 mg (74%) of pure compound. 1 H NMR (500 MHz, DMSO-d6) 5 2.30 (s, 3Η), 2.47 (m, 2H), 2. 76 (m, 2H), 3.25 (m, 2H), 4.28 (d, J = 6 Hz, 2H), 5.80 (m, 1H), 7.14 (m, 1H), 7.39 (t, J = 6 Hz 1H), 7.55 (m, 2H), 7.69 (d5 J = 6 Hz, 1H), 7.76 (d5 J = 6 Hz, 1H), 8.34 (d, J = 6 Hz, 1H), 8.91 (t , J = 6 Hz, 1H); MS (ESI APCI-) m / e 324 (MH) +. Example 213 li. Methyl-N __ {[(2S) -2-methyl ratio disease Vl_Hexane Cryl 1 methyl

實例213A (3S)-3-甲基比淀基）六氫峨ρ井 將（S)-(+)-2-甲基六氫吡畊（〇·5〇 克，0.005 莫耳，CAS 74879-18-8 ，Aldrich39,717-2，99%)與2-溴基吡啶（5毫升，0.05莫耳）之溶 液加熱至120°C，歷經14小時。使反應混合物冷卻至23°C，並 _ 於醋酸乙酯與水之間作分液處理。分離液層，並將水層再 以醋酸乙酯萃取兩次。以飽和碳酸氫鈉溶液與固體碳酸鈉 將水相調整至pH〜11。添加氯化鈉，並將飽和水溶液以醋酸 乙酯（2x)與二氯甲燒（2χ)萃取。使合併之有機萃液以硫酸鈉 脫水乾燥，過濾，及在減壓下濃縮，而得〇·6克（67%產率）標 題化合物。1 H NMR (400 MHz，DMSO_d6) .02 (d，J=6.0 Ηζ，3Η)，2·27 (dd，J=12, 10 Hz，1H)，2·67 (m，3H)，2.92 (m，1H)，4.07 (m，2H)，6.58 (dd，J= 8, 6 Hz，1H)，6.77 (d，J=8 Hz，1H)，7.49 (m，1H)，8.08 (m，1H) ; MS (ESI) m/e 85228 -279- 200404539 178 (M+H)'Example 213A (3S) -3-Methylpyridyl) Hexahydro-Er. Well (S)-(+)-2-methylhexahydropyracine (0.50 g, 0.005 mole, CAS 74879- A solution of 18-8, Aldrich 39,717-2, 99%) and 2-bromopyridine (5 ml, 0.05 mole) was heated to 120 ° C for 14 hours. The reaction mixture was cooled to 23 ° C., and was separated between ethyl acetate and water. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The aqueous phase was adjusted to pH ~ 11 with a saturated sodium bicarbonate solution and solid sodium carbonate. Sodium chloride was added and the saturated aqueous solution was extracted with ethyl acetate (2x) and dichloromethane (2x). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 0.6 g (67% yield) of the title compound. 1 H NMR (400 MHz, DMSO_d6) .02 (d, J = 6.0 Ηζ, 3Η), 2.27 (dd, J = 12, 10 Hz, 1H), 2.67 (m, 3H), 2.92 (m , 1H), 4.07 (m, 2H), 6.58 (dd, J = 8, 6 Hz, 1H), 6.77 (d, J = 8 Hz, 1H), 7.49 (m, 1H), 8.08 (m, 1H) ; MS (ESI) m / e 85228 -279- 200404539 178 (M + H) '

實例213B 基-N-{〖(2SV2:甲基-4-(2-吡啶基M-六j.吡畊基1甲某}苽^^ 將得自實例213A之產物（250毫克，1.40毫莫耳）、得自實例 91A之產物（291毫克，ΐ·4〇毫莫耳）及三乙胺（354毫克，3.50毫 莫耳）在乙腈（10毫升）中之溶液，於23°C下攪拌72小時。將反 應混合物倒入水中，並以醋酸乙酯萃取。然後以另外之飽 和碳酸氫鈉水溶液及鹽水洗滌醋酸乙酯溶液。使有機相以 硫酸鈉脫水乾燥，過濾，及在減壓下濃縮。使殘留物於矽 膠上藉急驟式管柱層析純化（2-5%乙醇：醋酸乙酯），而得396 毫克（87% 產率）標題化合物。iHNMR(300MHz，DMSO_d6) 5 1.21 (d，J=5.4 Hz，3H)，2.34 (s，3H)，2.50 (m，3H)，2_85 (m，2H)，4·06 (br d5 J= 10.5 Hz，2H)，4.29 (dd，J=13.5, 6.0 Hz，1H)，4.43 (dd，J=13.5, 6.0 Hz，1H)，6.58 (m, 1H)，6.82 (d，J=8.7 Hz，1H)，7.34 (m，2H)，7.48 (m，1H)，7.63 (m，2H)，8.07 (m，1H)，8.54 (dd，J=6-0,6.0 Hz，1H) ; MS (ESI) m/e 325 (M+H)+ ; 對之分析計算值：c，70.34; Η，7·46; Ν，17·27·實測值 ·· C，70.07 ; Η，7·55 ; Ν，17·03. 實例214 βΐυ基苯卷j-2-『(2S)-2-甲基斗(2·吡啶某VI-六氪吡畊基1乙醯胺 將得自實例213Α之產物（100毫克，0.562毫莫耳）、得自實 例1Α之產物（128毫克，〇_562毫莫耳）及ν，Ν_二異丙基乙胺（109 毫克’ 0.843愛莫耳）在甲苯（5¾升）中之溶液，於6〇。〇下加熱16 小時’然後冷卻至23°C。使反應混合物在減壓下濃縮，並使 殘留物於矽膠上藉急騾式管柱層析純化（以醋酸乙酯溶離） 85228 -280- 200404539 ，而得125毫克（68%產率）標題化合物。iHNMRpOOMHz， DMSO-d6) (5 1.06 (d, J=6.3 Hz，3H)，2.27 (s，3H)，2.58 (m，2H)，2·80 (dd，J= 12.3, 9·0 Hz，1H)，2.84 (m，1H)，3.10 (d，J=16.5 Hz，1H)，3.11 (m，1H)，3·38 (d， J=16.5 Hz，1H)，4.00 (m，2H)，6.63 (dd，J=8.1，6·3 Hz，1H)，6.84 (d，J=ll.l Hz， 1H)? 6.89 (m? 1H), 7.18 (m? 1H)5 7.44 (m? 2H)5 7.52 (m? 1H)? 8.10 (m5 1H), 9.63 (brs，lH); MS(ESI)m/e325 (M+H)+;對(3191124]^40 之分析計算值 :C，70.34 ; H，7·46 ; N，17.27.實測值：C，70.25 ; H，7.62 ; N，17.29· 實例215 3-甲基-N-m2RV2-甲基·4-(2-吡啶基M_六氫吡畊基1甲基}笨甲醯胺Example 213B group -N-{[(2SV2: methyl-4- (2-pyridyl M-hexaj.pyracyl 1A)} ^^ The product obtained from Example 213A (250 mg, 1.40 mmol) Ear), the product from Example 91A (291 mg, 毫克 40 mmol) and triethylamine (354 mg, 3.50 mmol) in acetonitrile (10 ml), stirred at 23 ° C 72 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate solution was then washed with additional saturated aqueous sodium bicarbonate solution and brine. The organic phase was dried over sodium sulfate, filtered, and under reduced pressure. Concentrated. The residue was purified by flash column chromatography on silica gel (2-5% ethanol: ethyl acetate) to give 396 mg (87% yield) of the title compound. IHNMR (300 MHz, DMSO_d6) 5 1.21 ( d, J = 5.4 Hz, 3H), 2.34 (s, 3H), 2.50 (m, 3H), 2_85 (m, 2H), 4.06 (br d5 J = 10.5 Hz, 2H), 4.29 (dd, J = 13.5, 6.0 Hz, 1H), 4.43 (dd, J = 13.5, 6.0 Hz, 1H), 6.58 (m, 1H), 6.82 (d, J = 8.7 Hz, 1H), 7.34 (m, 2H), 7.48 (m, 1H), 7.63 (m, 2H), 8.07 (m, 1H), 8.54 (dd, J = 6-0, 6.0 Hz, 1H ); MS (ESI) m / e 325 (M + H) +; Analyze and calculate the value: c, 70.34; Η, 7.46; Ν, 17.27. Measured value. C, 70.07; Η, 7 · 55; Ν, 17.03. Example 214 βΐυphenylbenzene roll j-2-"(2S) -2-methylpyridine (2 · pyridine VI-hexamethylpyridyl 1 acetamidine will be obtained from Example 213A The product (100 mg, 0.562 millimoles), the product from Example 1A (128 mg, 0-562 millimoles), and ν, N-diisopropylethylamine (109 mg '0.843 emole) The solution in toluene (5¾ liters) was heated at 60 ° C for 16 hours and then cooled to 23 ° C. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to flash column chromatography on silica gel. Purified (dissolved with ethyl acetate) 85228 -280- 200404539 to give 125 mg (68% yield) of the title compound. IHNMRpOOMHz, DMSO-d6) (5 1.06 (d, J = 6.3 Hz, 3H), 2.27 (s , 3H), 2.58 (m, 2H), 2.80 (dd, J = 12.3, 9.0 Hz, 1H), 2.84 (m, 1H), 3.10 (d, J = 16.5 Hz, 1H), 3.11 ( m, 1H), 3.38 (d, J = 16.5 Hz, 1H), 4.00 (m, 2H), 6.63 (dd, J = 8.1, 6.3 Hz, 1H), 6.84 (d, J = ll. l Hz, 1H)? 6.89 (m? 1H), 7.18 (m? 1H) 5 7.44 (m? 2H) 5 7.52 (m? 1H)? 8.10 (m5 1H), 9.63 (brs, lH); MS (ESI) m / e325 (M + H) +; Analysis and calculation of (3191124) ^ 40: C, 70.34; H, 7.46; N, 17.27. Found: C, 70.25; H, 7.62; N, 17.29. Example 215 3-A -N-m2RV2-methyl4- (2-pyridylM_hexahydropyridyl 1methyl) benzidine

實例215A (3RV3-甲基-1-(2-吡啶基）六氫吡畊 將（R)-(-)-2_ 甲基六氫吡畊（0.50 克，0.005 莫耳，CAS 75336-86_6 ，Aldrich 39,716-4，99% )與2-溴基吡啶（5毫升，0.05莫耳）之溶 液加熱至120°C，歷經14小時。使反應混合物冷卻至23°C，並 於大量醋酸乙酯與水之間作分液處理。分離液層，然後將 另外之水添加至醋酸乙酯溶液中。將數滴1N鹽酸溶液添加 至水/醋酸乙酯混合物中，並激烈混合，直到所有產物均轉 移至水相為止。分離液層，並使合併之水相在減壓下濃縮 ，及與甲苯/甲醇共沸（5x)，而得1.29克（&gt;99%產率）3-(R)-甲 基-1_吡啶-2-基-六氫吡畊氫溴酸鹽。1 H NMR (300 MHz，DMSO-d6) (5 1·27 (d，J=6.6 Hz，3H)，2.90 (dd, J=10.5, 14·1 Hz，1H)，3.10 (m，2H)，3.40 (m， 2H)，4_32 (m，2H)，6.77 (dd，J=4.8, 6.9 Hz，1H)，6.98 (d，J=8.1 Hz，1H), 7.64 (m， 1H)，8.15 (m，1H)，8_63 (br s，1H)，8.92 (br s，1H) ; MS (ESI) m/e 178 (M+H)+.Example 215A (3RV3-Methyl-1- (2-pyridyl) hexahydropyridine (R)-(-)-2_methylhexahydropyridine (0.50 g, 0.005 moles, CAS 75336-86_6, Aldrich 39,716-4, 99%) and 2-bromopyridine (5 ml, 0.05 mole) was heated to 120 ° C over 14 hours. The reaction mixture was cooled to 23 ° C, and a large amount of ethyl acetate and water Separate the solution between layers. Separate the layers and add additional water to the ethyl acetate solution. Add a few drops of 1N hydrochloric acid solution to the water / ethyl acetate mixture and mix vigorously until all products are transferred to The aqueous phase was separated. The liquid layers were separated and the combined aqueous phases were concentrated under reduced pressure and azeotroped with toluene / methanol (5x) to give 1.29 g (&gt; 99% yield) of 3- (R) -formaldehyde. 1-pyridin-2-yl-hexahydropyrine hydrobromide. 1 H NMR (300 MHz, DMSO-d6) (5 1.27 (d, J = 6.6 Hz, 3H), 2.90 (dd, J = 10.5, 14 · 1 Hz, 1H), 3.10 (m, 2H), 3.40 (m, 2H), 4_32 (m, 2H), 6.77 (dd, J = 4.8, 6.9 Hz, 1H), 6.98 (d , J = 8.1 Hz, 1H), 7.64 (m, 1H), 8.15 (m, 1H), 8_63 (br s, 1H), 8.92 (br s, 1H); MS (ESI) m / e 178 (M + H) +.

實例215BExample 215B

85228 -281- 200404539 k甲基_4·(2·吡啶基）小六氫吡畊基[甲基}笨甲醯&amp; 將得自實例215A之產物（250毫克，0·97毫莫耳）、得自實例 91Α之產物（201毫克，〇·97毫莫耳）及三乙胺（342毫克，3 39毫 莫耳）在乙腈（10毫升）中之溶液，於23。〇下攪拌72小時。將反 應混合物倒入水中，並以醋酸乙酯萃取。然後，以另外之 飽和碳酸氫鈉水溶液及鹽水洗滌醋酸乙酯溶液。使有機相 以硫酸鈉脫水乾燥，過濾，及在減壓下濃縮。使殘留物於 砍膠上藉急騾式管柱層析純化（2_5%乙醇：醋酸乙酯），而得 245 毫克（78% 產率）標題化合物。1 η NMR (300 MHz，DMSO-d6) 5 1.21 (d，J=5.4 Hz，3H)，2.34 (s，3H)，2_50 (m，3H)，2·85 (m，2H)，4.06 (br d，J= 10.5 Hz, 2H), 4.29 (dd? J=13.5, 6.0 Hz? 1H)? 4.43 (dd? J=13.5, 6.0 Hz? 1H)? 6.58 (m，1H)，6.82 (d，J=8.7 Hz，1H)，7.34 (m，2H)，7.48 (m5 1H)，7.63 (m，2H)，8·07 (m，1H)，8·54 (dd，J=6.0, 6·0 Hz，1H) ; MS (ESI) m/e 325 (M+H)+ ; 對〇191124&gt;140 之分析計算值：c，70.34; Η，7·46; N，17.27·實測值 ·· C，70.61 ; Η，7·41 ; Ν，16·95· 實例216 · Ν-(3-甲基笨基）·24(2Ι〇-2-甲某·4_(2-吡啶基Η-六氫吡畊基1乙醯胺 將得自215Α之產物（250毫克，0.97毫莫耳）、得自實例1Α之 產物（221毫克，0.97毫莫耳）及Ν，Ν-二異丙基乙胺（313毫克，2.42 毫莫耳）在甲苯（8毫升）中之溶液，於60°C下加熱16小時，然 後冷卻至23°C。使反應混合物在減壓下濃縮，並使殘留物於 矽膠上藉急騾式管柱層析純化（以醋酸乙酯溶離），而得261 毫克（83% 產率）標題化合物。iHNMRGOO MHz，DMSO-d6) 5 1·〇6 (d，J=6.3 Ηζ，3Η)，2.27 (s，3Η)，2·58 (m，2Η)，2·80 (dd，J=12.3, 9·0 Ηζ，1Η)， 85228 -282- 200404539 2.84 (m，1H)，3.10 (d，J=16.5 Hz，1H)，3·11 (m，1H)，3.38 (d，J=16.5 Hz，1H)， 4.00 (m，2H)，6.63 (dd，J=8.1，6·3 Hz，1H)，6.84 (d，J=11·1 Hz，1H)，6.89 (m， 1H)，7.18 (m，1H)，7.44 (m，2H)，7.52 (m，1H)，8.10 (m，1H)，9.63 (br s，1H); MS(ESI)m/e325 (M+H)+ ; —C19H24N4O.0.3H2O 之分析計算值： C，69.19 ; H，7·52 ; N，16·99·實測值：C，69.09 ; H，7·42 ; N，16.92. 實例217 3-甲氧基甲基-3f，6f•二氫-2,4*-聯峨淀-1·(2Ή)-基）甲基1 苯甲醯胺 將得自實例143Β之產物（三氟醋酸鹽，29毫克，0.1毫莫耳） 、聚甲醛(30毫克，1毫莫耳）、3-甲氧基苯甲醯胺（76毫克，0.5 毫莫耳，Lancaster)及42毫克碳酸鉀（0.3毫莫耳）在2.5毫升無水 乙醇中之混合物，於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫’過滤’及在減壓下移除溶劑。使殘留物於硬 膠上藉急驟式管柱層析純化（10%甲醇：醋酸乙酯），獲得25 毫克（75% )純化合物。1 H NMR (500 MHz，DMSO-d6 ) (5 2.30 (s，3H)， 2.47 (m，2H)，2·76 (m，2H)，3.25 (m，2H)，3·79 (s，3H)，4.27 (d，J=6 Hz，2H)， 5.80 (m，1H)，7·11 (d，J=6 Hz，1H)，7.14 (t，J=6 Hz，1H)，7.38 (t，J=6 Hz，1H)， 7.45 (s，1H)，7.49 (d，J=6 Hz，1H)，7.59 (d，J=6 Hz，1H)，8.34 (d，J=6 Hz，1H)， 8.81 (t，J=6 Hz，1H) ; MS (ESI APCI·) m/e 336 (M-H)+ · 實例218 甲基-3’,6’-二氫_2,4’_聯吡啶-l’(2’HV某）甲基1笨甲醯胺 將得自實例143B之產物（三氟醋酸鹽，29毫克，0.1毫莫耳） 、聚甲醛（30毫克，1毫莫耳）、4-氟基苯甲醯胺（7〇毫克，〇.5 毫莫耳，Aldrich)及42毫克碳酸鉀（〇·3毫莫耳）在2.5毫升無水 85228 -283 - 200404539 乙醇中之混合物’於氮氣下，加熱至回流過夜。使混合物 冷卻至室溫，過濾，及在減壓下移除溶劑。使殘留物於矽 膠上藉急騾式管柱層析純化（10%甲醇··醋酸乙酯），而得3〇 毫克（94% )純化合物。1H NMR (500 MHz，DMSO-d6) 6 2.30 (s，3H)， 2.46 (m，2H)，2.77 (m，2H)，3.24 (m，2H)，4.28 (d，J=5 Hz，2H)，5.80 (m，1H)， 7.14 (t5 J=5 Hz? 1H)? 7.30 (t5 J=6 Hz? 2H)5 7.58 (d? J=5 Hz, 1H)5 7.98 (t5 J=6 Hz? 2H)，8.34 (d，J=5 Hz，1H)，8.85 (t，J=5 Hz，1H) ; MS (ESI APCI-) m/e 324 (M-H)+. 實例219 氯基 _3f,6f•二氫-2,4f-聯吡啶某 VN-(2,6-二甲基茉某)85228 -281- 200404539 k methyl_4 · (2 · pyridinyl) pyrrolidine [methyl] benzylmethoxine &amp; The product obtained from Example 215A (250 mg, 0.97 mmol) A solution of the product from Example 91A (201 mg, 0.97 mmol) and triethylamine (342 mg, 3 39 mmol) in acetonitrile (10 ml) at 23. Stir for 72 hours. The reaction mixture was poured into water and extracted with ethyl acetate. Then, the ethyl acetate solution was washed with another saturated aqueous sodium hydrogen carbonate solution and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified on a gel by flash column chromatography (2-5% ethanol: ethyl acetate) to obtain 245 mg (78% yield) of the title compound. 1 η NMR (300 MHz, DMSO-d6) 5 1.21 (d, J = 5.4 Hz, 3H), 2.34 (s, 3H), 2_50 (m, 3H), 2.85 (m, 2H), 4.06 (br d, J = 10.5 Hz, 2H), 4.29 (dd? J = 13.5, 6.0 Hz? 1H)? 4.43 (dd? J = 13.5, 6.0 Hz? 1H)? 6.58 (m, 1H), 6.82 (d, J = 8.7 Hz, 1H), 7.34 (m, 2H), 7.48 (m5 1H), 7.63 (m, 2H), 8.07 (m, 1H), 8.54 (dd, J = 6.0, 6.0 Hz ， 1H); MS (ESI) m / e 325 (M + H) +; Analytical calculated value for 〇191124 &gt; 140: c, 70.34; Η, 7.46; N, 17.27 · Measured value ·· C, 70.61 Η, 7.41; Ν, 16.95 · Example 216 · Ν- (3-methylbenzyl) · 24 (2Ι〇-2-methyl · 4_ (2-pyridylfluorene-hexahydropyridyl) 1 Acetylamine will be the product from 215A (250 mg, 0.97 mmol), the product from Example 1A (221 mg, 0.97 mmol) and N, N-diisopropylethylamine (313 mg, 2.42 mmol) in toluene (8 ml), heated at 60 ° C for 16 hours, and then cooled to 23 ° C. The reaction mixture was concentrated under reduced pressure and the residue was dried on silica gel. Purification by column chromatography (dissolved in ethyl acetate) to give 261 milligrams (83% yield) title compound. IHNMRGOO MHz, DMSO-d6) 5 1.06 (d, J = 6.3 Ηζ, 3Η), 2.27 (s, 3Η), 2.58 (m, 2Η), 2 · 80 (dd, J = 12.3, 9 · 0 Ηζ, 1Η), 85228 -282- 200404539 2.84 (m, 1H), 3.10 (d, J = 16.5 Hz, 1H), 3.11 (m, 1H), 3.38 (d, J = 16.5 Hz, 1H), 4.00 (m, 2H), 6.63 (dd, J = 8.1, 6.3 Hz, 1H), 6.84 (d, J = 11 · 1 Hz, 1H), 6.89 ( m, 1H), 7.18 (m, 1H), 7.44 (m, 2H), 7.52 (m, 1H), 8.10 (m, 1H), 9.63 (br s, 1H); MS (ESI) m / e325 (M + H) +; —C19H24N4O.0.3H2O Analytical calculation value: C, 69.19; H, 7.52; N, 16.99. Found: C, 69.09; H, 7.42; N, 16.92. Example 217 3-methoxymethyl-3f, 6f • dihydro-2,4 * -biyando-1 · (2Ή) -yl) methyl 1 benzamidine will be obtained from the product of Example 143B (trifluoroacetic acid Salt, 29 mg, 0.1 mmol, acetal (30 mg, 1 mmol), 3-methoxybenzamide (76 mg, 0.5 mmol, Lancaster) and 42 mg potassium carbonate (0.3 Millimoles) in 2.5 ml of absolute ethanol, heated under reflux under nitrogen . The mixture was allowed to cool to room temperature 'filtered' and the solvent was removed under reduced pressure. The residue was purified on a hard gel by flash column chromatography (10% methanol: ethyl acetate) to obtain 25 mg (75%) of the pure compound. 1 H NMR (500 MHz, DMSO-d6) (5 2.30 (s, 3H), 2.47 (m, 2H), 2.76 (m, 2H), 3.25 (m, 2H), 3.79 (s, 3H ), 4.27 (d, J = 6 Hz, 2H), 5.80 (m, 1H), 7.11 (d, J = 6 Hz, 1H), 7.14 (t, J = 6 Hz, 1H), 7.38 (t , J = 6 Hz, 1H), 7.45 (s, 1H), 7.49 (d, J = 6 Hz, 1H), 7.59 (d, J = 6 Hz, 1H), 8.34 (d, J = 6 Hz, 1H ), 8.81 (t, J = 6 Hz, 1H); MS (ESI APCI ·) m / e 336 (MH) + · Example 218 Methyl-3 ', 6'-dihydro_2,4'_bipyridine -l '(2'HV) methyl 1 benzamidine will be obtained from the product of Example 143B (trifluoroacetate, 29 mg, 0.1 mmol), polyformaldehyde (30 mg, 1 mmol), A mixture of 4-fluorobenzamide (70 mg, 0.5 mmol, Aldrich) and 42 mg of potassium carbonate (0.3 mmol) in 2.5 ml of anhydrous 85228 -283-200404539 ethanol. Heat to reflux overnight under nitrogen. Allow the mixture to cool to room temperature, filter, and remove the solvent under reduced pressure. Purify the residue on silica gel by flash column chromatography (10% methanol · · ethyl acetate ) To obtain 30 mg (94%) of the pure compound. 1H NMR (500 MHz, DMSO-d6) 6 2.30 (s, 3H), 2.46 (m, 2H), 2.77 (m, 2H), 3.24 (m, 2H), 4.28 (d, J = 5 Hz, 2H), 5.80 (m, 1H), 7.14 (t5 J = 5 Hz? 1H)? 7.30 (t5 J = 6 Hz? 2H) 5 7.58 (d? J = 5 Hz, 1H) 5 7.98 (t5 J = 6 Hz? 2H ), 8.34 (d, J = 5 Hz, 1H), 8.85 (t, J = 5 Hz, 1H); MS (ESI APCI-) m / e 324 (MH) +. Example 219 Chloro-3f, 6f • Dihydro-2,4f-bipyridine VN- (2,6-dimethyl jasmine)

乙醯胺 實例219A K3-氣基-2-ρ比淀基基-1-六·，比咬教酸第三-丁酿 於1，4_二氮雙環并[2.2.2]辛烷(DABCO，680毫克，6_06毫莫耳） 在乙醚（20毫升）中之溶液内，於-78°C下，添加正-丁基鋰（2.5M ’在己燒中，3.0毫升），並持續攪拌20分鐘。於此混合物中 ’以3_氯吡啶（7〇〇毫克，6.16毫莫耳）在乙醚（5毫升）中之溶 液添加。30分鐘後，將4-§同基-1-7T氯p比淀叛酸第三-丁 g旨（1 30 克，6.52毫莫耳）以在乙醚（1毫升）中之溶液添加。將反應混 合物於-78°C下攪拌2.5小時，然後溫熱至-50°C，並以水使反 應淬滅。使混合物溫熱至室溫過夜。分離液層，並使有機 相脫水乾燥’過濾’及在減壓下濃縮。使殘留物於碎膠上 藉急驟式管柱層析純化（以20%至99%醋酸乙酿··己燒梯度 溶離），提供標題化合物（110毫克，9%產率）。1 η Nmr (5⑻MHz， 85228 -284- 200404539 CDC13) 51.38 (b!· d，2H，J=13.7 Hz)，1.50 (s，9H)，2.73 (ddd，2H，J=13.1，13.1， 5.3 Hz)，3_31 (br m，2H), 4.09 (br m，2H)，7.25 (m，1H)，7.74 (dd，1H，J=7.8， 1.3 Hz)，8.46 (dd，1H，J=4_7, 1·6 Hz).Example of Acetylamine 219A K3-Gasyl-2-ρ is more than yridyl-1-hexa ·, Titanic acid tert-butyl is brewed in 1,4-diazabicyclo [2.2.2] octane , 680 mg, 6_06 mmoles) in a solution of ether (20 ml) at -78 ° C, add n-butyllithium (2.5M 'in hexane, 3.0 ml) and continue stirring for 20 minute. To this mixture was added a solution of 3-chloropyridine (700 mg, 6.16 mmol) in diethyl ether (5 ml). Thirty minutes later, 4-§isopropyl-1-7T chloropyridine tertiary-butanoic acid tert-butyl g (130 g, 6.52 mmol) was added as a solution in ether (1 ml). The reaction mixture was stirred at -78 ° C for 2.5 hours, then warmed to -50 ° C, and the reaction was quenched with water. The mixture was allowed to warm to room temperature overnight. The layers were separated and the organic phase was dried and 'filtered' and concentrated under reduced pressure. The residue was purified by flash column chromatography (dissolved in a 20% to 99% ethyl acetate · hexane burn gradient) to provide the title compound (110 mg, 9% yield). 1 η Nmr (5⑻MHz, 85228 -284- 200404539 CDC13) 51.38 (b! · D, 2H, J = 13.7 Hz), 1.50 (s, 9H), 2.73 (ddd, 2H, J = 13.1, 13.1, 5.3 Hz) , 3_31 (br m, 2H), 4.09 (br m, 2H), 7.25 (m, 1H), 7.74 (dd, 1H, J = 7.8, 1.3 Hz), 8.46 (dd, 1H, J = 4_7, 1 · 6 Hz).

實例219B 3m6L二氫-2,4’-聯吡啶_r(2’HV讀酸第三丁酯 按照實例237B中所述之程序，以得自實例219A之產物取代 得自實例237A之產物，提供標題化合物（42毫克，50% )。 1H NMR (500 MHz? DMSO-d6) (5 1.44 (s，9H)，2·47 (m，2H)，3.54 (m，2H)， 4.02 (m，2H)，6.14 (br s，1H)，7.33 (dd，1H，J=8.1，4.7 Hz)，7·93 (ddd，1H，J=8.1， 1.6 Hz)，8·51 (dd，1H，J=4.5, 1.4 Hz) ; MS (DCI/NH3) m/e 295 (M+H)+ ·Example 219B 3m6L dihydro-2,4'-bipyridine_r (2'HV tert. Title compound (42 mg, 50%). 1H NMR (500 MHz? DMSO-d6) (5 1.44 (s, 9H), 2.47 (m, 2H), 3.54 (m, 2H), 4.02 (m, 2H) ), 6.14 (br s, 1H), 7.33 (dd, 1H, J = 8.1, 4.7 Hz), 7.93 (ddd, 1H, J = 8.1, 1.6 Hz), 8.51 (dd, 1H, J = 4.5, 1.4 Hz); MS (DCI / NH3) m / e 295 (M + H) + ·

實例219C 3-氣基-Γ，2’,3’，6’-四氫-2,4’-聯吡凃 按照實例166B中所述之程序，以得自實例219B之產物取代 得自實例166A之產物，提供標題化合物。MS (DCI/NH3) m/e 195 (Μ+Η)+·Example 219C 3-Gasyl-Γ, 2 ', 3', 6'-tetrahydro-2,4'-bipyridine. Follow the procedure described in Example 166B, substituting the product from Example 219B for Example 166A. The product provides the title compound. MS (DCI / NH3) m / e 195 (Μ + Η) + ·

實例219D 拉-氯基-3’，6’_二氫-2,4’-聯吡啶-1|(2’11)-基）-义(2.6_二甲某苽某） 乙醯胺 使得自實例219C之產物（30毫克，0.1毫莫耳）、ν-(2,6-二甲 基笨基）-2-氯乙酸胺（23毫克，0.15毫莫耳，Aldrich)及碳酸鈉（50 毫克）在N，N-二甲基甲醯胺/水(2 : 1，2毫升）中之混合物， 於室溫下振盪18小時。將所形成之混合物傾析，在減壓下 濃縮。使殘留物藉預備之HPLC純化，提供20毫克（59% )所要 之產物。1 H NMR (500 MHz，DMSO-d6) δ 2.18 (s，6H)，2.49 (m，2H), 2.85 85228 -285 - 200404539 (m，2H)，4.38 (m，2H)，6.25 (s，1H)，7·09 (m，3H)，7_40 (dd，J=6 Hz，1H), 8.00 (d，J=6 Hz, 1H)，8.56 (dd，J=6 Hz，1H)，10.00 (s，1H) ; MS (ESI APCI+) m/e 356 (M+H)+. 實例220 Κ3·氯基-3\6’-二氫_2,4’_聯吡啶-Γ(2Ή)_基甲甚笨基）乙醯胺 使得自實例219C之產物（30毫克，0.1毫莫耳）、N-(2-甲基苯 基）-2-氯乙酿胺（21毫克，0.15毫莫耳，Maybridge)及碳酸鈉（50 毫克）在N，N-二甲基甲醯胺/水（2 : 1，2毫升）中之混合物， 於室溫下振盪18小時。將所形成之混合物傾析，在減蜃下 濃縮。使殘留物藉預備之HPLC純化，提供21毫克（64% )所要 之產物。1 H NMR (500 MHz，DMSO-d6) 5 2.24 (s，3H)，2.75-2.85 (m，2H)， 2·86 (m，2H)，3.05 (m，2H)，4.32 (m，2H)，6.25 (s，1H)，7.00-7.25 (m，3H)，7·45 (m，2H)，8.00 (d，J=6 Hz，1H)，8·55 (dd，J=6 Hz，1H)，10.00 (s，1H); MS (ESI APCI+) m/e 342 (M+H)+. 實例221 迎二氫夂4’_聯吡啶_m，HV基甲某V1_:甲醯胺 按照實例115中所述之程序，以莕小羧醯胺取代3-甲氧基 苯甲醯胺’提供標題化合物（28%產率）。將此化合物（164毫 克）在乙醇中以順丁晞二酸（55·5毫克）處理，攪拌1〇分鐘，然 後於減壓下濃縮’而得帶黃色黏性固體，使其溶於二氯甲 k中’並使用乙醚使化合物沉澱，過濾，接著以乙醚洗滌 ’脫水乾燥，而得順丁烯二酸鹽（144毫克）。iHNMR(3〇〇MHz， DMSO-d6) 5 2.86 (m，2H)，3·4 (m，2H)，3.91 (m，2H)，4·57 (m，2H)，6·12 (s， 2H)，6·76 (m，1H)，7.32 (m，1H)，7.61 (m，4H)，7_8G (m，2H)，8.G2 (m，1H)，8·10 85228 -286- 200404539 (d，J=9 Hz，1Η)，8·28 (m，1Η)，8·58 (m，1H)，9·55 (m，1H); MS (DCI/NH3) m/e 324如+11)+;對€：221121化0.1.20411404之分析計算值：（：，66.68 ;H，5·39 ; N，8·70_ 實測值；C66.38 ; H，5·43 ; N，8·75· 實例222 N-{『4-(3-氰基-2-吡啶基Vl_六氤毗畊基1甲基丨-3-氟基笨甲醯胺 按照實例200中所述之程序，以2-六氫吡畊小基菸鹼腈取代 實例119A中之產物，與以3-氟基苯甲醯胺取代3-甲基苯甲醯 胺，提供標題化合物（80%產率）。1H NMR (300 MHz，DMSO-d6) δ 2.66 (m，4Η)，3·59 (m，4Η)，4·22 (d，J=6.1 Ηζ，2Η)，6·91 (dd，J=7.6,4·9 Ηζ， 1Η)，7·39 (tdd，J=8.5, 8.5, 2.6, 1·0 Ηζ，1Η)，7.53 (td，J=8.0, 5·8 Ηζ，1Η)，7·68 (ddd5 J=10.0, 2.5, 1.4 Hz, 2Η)? 7.74 (dt? J=7.75 1.2 Hz, 1H)5 8.39 (dd5 J=4.9? 1.9 Hz, 1H)，8.91 (t，J=6.1 Hz，1H) ; MS (DCI/NH3) m/e 340 (M+H)+ ；對 C18H18N5OF之分析計算值：c，63.70; Η，5·35; Ν，20·60·實測值 ·· C，63.54 ; Η，5.22 ; Ν，20.47. 實例224 3-甲基-Ν-{[~4-(1，3-碟吐-2-基VI-六氫峨淀基1甲基}苯甲醯胺 使得自實例166C之產物（490毫克）於氫氣壓力（60psi)下，在 甲醇中，以10% Pd/C觸媒氫化42小時。將混合物過濾，及在 減壓下濃縮。使殘留物於矽膠上藉急騾式管柱層析純化（5% 乙醇：醋酸乙酯），提供標題化合物（1〇〇毫克，22% )。1H NMR (300 MHz，CDC13) 5 1 ·85 (dq，2H，J=12, 6 Ηζ)，2·20 (m，2H)，2.40 (s，3H)， 2.48 (m，2H)，3·10 (m，3H)，4.35 (d，2H，J=6 Hz)，6.50 (m，1H)，7_20 (d，1H，J= 3.3 Hz)，7.35 (m，2H)，7.60 (m，2H)，7.70 (d，1H，Hz) ; MS (DCI/NH3) m/e316(M+H)' 85228 -287- 200404539 順丁烯二酸鹽：對〇171121叫08*1.2(：411404之分析計算值： C，57.11 ; Η，5·85 ; Ν，9·48·實測值：C，57.48 ; H，5.33 ; Ν，9·52· 實例225 氟基-2-甲基笨基倫篡酮某乙基M-六氫吡啶某） 口比鍵Ν-氧化物 實例225Α 2-溴氟某-2·甲甚笨基）乙醯胺 按照實例1Α中所述之程序，以4-氟基-2-甲基苯基胺取代3-甲基苯胺，提供標題化合物，為粉紅色固體。！HNMR(300MHz， DMSO-d6) 5 2.20 (s5 3H)，4.06 (s，2H)，7·01 (ddd，1H，J=8.8, 8·8, 3.0 Hz)，7.10 (dd，1H，J=9.5, 3_0 Hz), 7.34 (dd，1H，J=8.8, 5_4 Hz)，9_74 (br s，1H) ; MS (DCI/NH3) m/e 246/248 (M+H)+ ； 263/265 (M+NH4)+.Example 219D R-Chloro-3 ', 6'_dihydro-2,4'-bipyridine-1 | (2'11) -yl) -sense (2.6_dimethylformamidine) Acetylamine makes Product of Example 219C (30 mg, 0.1 mmol), v- (2,6-dimethylbenzyl) -2-chloroacetamide (23 mg, 0.15 mmol, Aldrich) and sodium carbonate (50 mg ) A mixture in N, N-dimethylformamide / water (2: 1,2 ml) was shaken at room temperature for 18 hours. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 20 mg (59%) of the desired product. 1 H NMR (500 MHz, DMSO-d6) δ 2.18 (s, 6H), 2.49 (m, 2H), 2.85 85228 -285-200404539 (m, 2H), 4.38 (m, 2H), 6.25 (s, 1H ), 7.09 (m, 3H), 7_40 (dd, J = 6 Hz, 1H), 8.00 (d, J = 6 Hz, 1H), 8.56 (dd, J = 6 Hz, 1H), 10.00 (s , 1H); MS (ESI APCI +) m / e 356 (M + H) +. Example 220 Κ3 · chloro-3 \ 6'-dihydro_2,4'_bipyridine-Γ (2Ή) _ylmethyl Very benzyl) acetamidinated the product from Example 219C (30 mg, 0.1 mmol), N- (2-methylphenyl) -2-chloroethylamine (21 mg, 0.15 mmol), Maybridge ) And sodium carbonate (50 mg) in N, N-dimethylformamide / water (2: 1,2 ml), shake at room temperature for 18 hours. The resulting mixture was decanted and concentrated under reduced pressure. The residue was purified by preparative HPLC to provide 21 mg (64%) of the desired product. 1 H NMR (500 MHz, DMSO-d6) 5 2.24 (s, 3H), 2.75-2.85 (m, 2H), 2.86 (m, 2H), 3.05 (m, 2H), 4.32 (m, 2H) , 6.25 (s, 1H), 7.00-7.25 (m, 3H), 7.45 (m, 2H), 8.00 (d, J = 6 Hz, 1H), 8.55 (dd, J = 6 Hz, 1H ), 10.00 (s, 1H); MS (ESI APCI +) m / e 342 (M + H) +. Example 221 Welcome dihydropyridine 4'_bipyridine_m, HV methyl a certain V1_: formamidine according to the example The procedure described in 115, substituting 3-methoxybenzamide with ammonium carboxamide provides the title compound (28% yield). This compound (164 mg) was treated with maleic acid (55 · 5 mg) in ethanol, stirred for 10 minutes, and then concentrated under reduced pressure to obtain a yellow sticky solid, which was dissolved in dichloromethane. Compound A was precipitated with ether and filtered, followed by washing with ether to dehydrate and dry to give maleate (144 mg). iHNMR (300 MHz, DMSO-d6) 5 2.86 (m, 2H), 3.4 (m, 2H), 3.91 (m, 2H), 4.57 (m, 2H), 6.12 (s, 2H), 6.76 (m, 1H), 7.32 (m, 1H), 7.61 (m, 4H), 7_8G (m, 2H), 8.G2 (m, 1H), 8.10 85228 -286- 200404539 (d, J = 9 Hz, 1Η), 8.28 (m, 1Η), 8.58 (m, 1H), 9.55 (m, 1H); MS (DCI / NH3) m / e 324 as + 11) +; Analysis and calculation of €: 221121 to 0.1.20411404: (:, 66.68; H, 5.39; N, 8.70_ Found; C66.38; H, 5.43; N, 8 · 75 · Example 222 N- {"4- (3-cyano-2-pyridyl Vl_hexamethylpyridinyl 1methyl 丨 -3-fluorobenzylbenzylamine) Follow the procedure described in Example 200 to 2-Hexahydropyridine nicotinic nitrile substituted the product in Example 119A with 3-fluorobenzamide to replace 3-methylbenzamide to provide the title compound (80% yield). 1H NMR (300 MHz, DMSO-d6) δ 2.66 (m, 4Η), 3.59 (m, 4Η), 4.22 (d, J = 6.1 Ηζ, 2Η), 6.91 (dd, J = 7.6, 4 · 9 Ηζ, 1Η), 7.39 (tdd, J = 8.5, 8.5, 2.6, 1.0 Ηζ, 1Η), 7.53 (td, J = 8.0, 5 · 8 Ηζ, 1Η), 7.68 (ddd5 J = 10.0, 2.5, 1.4 Hz, 2Η) 7.74 (dt? J = 7.75 1.2 Hz, 1H) 5 8.39 (dd5 J = 4.9? 1.9 Hz, 1H), 8.91 (t, J = 6.1 Hz, 1H); MS (DCI / NH3) m / e 340 ( M + H) +; Analysis and calculation of C18H18N5OF: c, 63.70; 70, 5.35; Ν, 20 · 60 · Measured value ·, C, 63.54; Η, 5.22; Ν, 20.47. Example 224 3-A -N-{[~ 4- (1,3-Detto-2-yl VI-hexahydroeodoyl 1methyl} benzamide) allows the product from Example 166C (490 mg) to be hydrogen pressure (60 psi) ), In methanol, hydrogenated with 10% Pd / C catalyst for 42 hours. The mixture was filtered and concentrated under reduced pressure. The residue was purified on silica gel by flash column chromatography (5% ethanol: Ethyl acetate) to provide the title compound (100 mg, 22%). 1H NMR (300 MHz, CDC13) 5 1 · 85 (dq, 2H, J = 12, 6 Ηζ), 2 · 20 (m, 2H), 2.40 (s, 3H), 2.48 (m, 2H), 3 · 10 (m, 3H), 4.35 (d, 2H, J = 6 Hz), 6.50 (m, 1H), 7_20 (d, 1H, J = 3.3 Hz), 7.35 (m, 2H), 7.60 (m, 2H ), 7.70 (d, 1H, Hz); MS (DCI / NH3) m / e316 (M + H) '85228 -287- 200404539 Maleic acid salt: 08 * 1.2 for 0171121 (: Analysis of 411404 Calculated: C, 57.11; Hf, 5.85; N, 9.48. Found: C, 57.48; H, 5.33; N, 9.52. Example 225 Fluoro-2-methylbenzylidene ketone Some ethyl M-hexahydropyridine Some) N-oxide examples of specific bonds 225A 2-bromofluorosome-2 · methylbenzyl) acetamidamine Follow the procedure described in Example 1A, using 4-fluoro- 2-methylphenylamine substituted 3-methylaniline to provide the title compound as a pink solid. !! HNMR (300MHz, DMSO-d6) 5 2.20 (s5 3H), 4.06 (s, 2H), 7.01 (ddd, 1H, J = 8.8, 8 · 8, 3.0 Hz), 7.10 (dd, 1H, J = 9.5, 3_0 Hz), 7.34 (dd, 1H, J = 8.8, 5_4 Hz), 9_74 (br s, 1H); MS (DCI / NH3) m / e 246/248 (M + H) +; 263/265 (M + NH4) +.

實例225B 2:(1-{2_；：[(4-氧基-2-甲基笨基）胺基i_2_g同基乙基}_4_六氫p比淀基） 吡錠N-氫化物 將得自實例225A之產物（0.64克，2.6毫莫耳）、得自實例119A 之產物（0·63克，2.5毫莫耳）及k2C〇3(72〇毫克，5·2毫莫耳）在 N，N-二甲基甲醯胺（12毫升）中之混合物，於4〇t下加熱過夜 。使反應混合物冷卻，及在減壓下移除溶劑。使殘留物於 鹽水與醋酸乙酯之間作分液處理。將水層以醋酸乙酯（3 χ 2〇〇 毫升）萃取。使合併之有機物質以硫酸鎂脫水乾燥，及濃縮 。使殘留物於矽膠上藉急驟式管柱層析純化，使用4%甲醇 •二氯甲烷，而得所要之產物，為灰白色固體。（649毫克， 76%)。hNMRGOOMI^DMSO-cy (M.68(m，2H)，1.92(d，J=5.8Hz， 85228 -288 - 200404539 2H)，2.24 (s，3H)，2.36 (m，2H)，3.04 (d，J=11.5 Hz，2H)，3.17 (s，2H)，3.29 (m， 2H)，7_03 (m，1H)，7·11 (dd，J=9.7, 2·9 Hz，1H)，7.35 (m，2H)，7.67 (dd，J=8.8， 5.8 Hz，1H)，8.26 (m，1H)，9·40 (s，1H) ; MS (DCI/NH3) m/e 328 (M+H-16)+ ；344(M+H)+. 順丁烯二酸鹽（856 毫克）：對 q 9H22N302F · 1_0 C4H404 · 0.75 H20 之分析計算值：C，58.41 ; H，5.86 ; N，8.88.實測值：C58.02 ; H，5.83 ;N，8.67. 實例226 2-(l_(2-「(4-氟某-3-甲基苯基）胺基1-2-酮墓乙基丨_4-六氫吡啶基） 吡錠N-氣化物 按照實例225B中所述之程序，以得自實例27A之產物取代 得自實例225A之產物，提供標題化合物。（139毫克，57% )。 1H NMR (300 MHz，DMSO-d6) &lt;5 1.68 (m，2H)，1 _92 (d，J=5.8 Hz，2H)，2.22 (s5 3H)? 2.46 (m? 2H)? 3.04 (m5 2H)? 3.25 (s, 3H)? 7.03 (t5 J=6? 1H)5 7.35 (m? 2H)5 7.44 (dd，J=4.5, 1·5 Hz，1H)，7.48 (m，1H)，7.54 (dd，J=4.5, 1·5 Hz，1H)，8·26 (d， J=4.5, 1H)，9.79 (s，1H) ; MS (DCI/NH3) m/e 328 (M+H-16)+ ; 344 (M+H)+ · 順丁晞二酸鹽（171 毫克）··對(：191122%02?· 1.0C4H4O4之分析 計算值：C5 60.12; H，5.12; N，9.15·實測值：C，59·91; H，5.79; Ν，9·05· 實例227 氟苯基)胺基1-2-酮基乙基V4-六氪ρ比淀基V比鍵Ν-氣化物 按照實例225Β中所述之程序，以得自實例254Α之產物取代 得自實例225Α之產物，提供標題化合物。（157毫克，68% )。 ^NMRCSOOMHz.DMSO-^) δ 1.68 (m? 2Η)? 1.92 (d? J=5.8 Ηζ? 2Η)? 2.30 (m，2Η)，3·01 (m，2Η)，3·19 (s，2Η)，3.25 (m，1Η)，6·89 (m，1Η)，7·35 (m，3Η)， 85228 -289 - 200404539 7·42 (m，2H)，7.68 (m，1H)，8.26 (d，J=4.5, 1H)，9.91 (s，1H) ; MS (DCI/NH3) m/e 330 (M+H)+. 順丁晞二酸鹽（190毫克广對〇18112(^3〇2?*1.0(^114〇4*0.2112〇 之分析計算值：C，58_84 ; H，5_48 ; N，9.36.實測值：C，58.52 ; H，5.45 ;Ν，9·04· 674532 實例 228 丨(2-氟基-5-甲基笨基）胺某1-2-酮基乙基M-六氤吡晗篡、 吡錠Ν-氣化物 實例228Α L氯-Ν-(2-氟某-5-甲某笨基）乙醯胺 按照實例22Α中所述之程序，以2-氟基-5-甲基苯基胺取代 3,4,5-三甲氧基苯胺，提供標題化合物（83%產率），為白色固 體。1 H NMR (400 MHz，DMSO-d6) 5 2.28 (s，3Η)，4.34 (s，2Η)，6.98 (m，1Η)， 7.14 (dd，1H，8.6 Hz)，7.69 (d，1H，J=7.4 Hz)，9.99 (br s，1Η) ; MS (DCI/NH3)m/e202(M+H)+ ； 219(M+NH4)+.Example 225B 2: (1- {2_ ;: [(4-oxy-2-methylbenzyl) amino i_2_g isopropylethyl} _4_hexahydro p-pyridyl) Pyridinium N-hydride will give The product from Example 225A (0.64 g, 2.6 mmol), the product from Example 119A (0.63 g, 2.5 mmol) and k2CO3 (72 mg, 5.2 mmol) at N The mixture in N-dimethylformamide (12 ml) was heated at 40 t overnight. The reaction mixture was allowed to cool and the solvent was removed under reduced pressure. The residue was partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3 x 200 ml). The combined organic materials were dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel using 4% methanol • dichloromethane to give the desired product as an off-white solid. (649 mg, 76%). hNMRGOOMI ^ DMSO-cy (M.68 (m, 2H), 1.92 (d, J = 5.8Hz, 85228 -288-200404539 2H), 2.24 (s, 3H), 2.36 (m, 2H), 3.04 (d, J = 11.5 Hz, 2H), 3.17 (s, 2H), 3.29 (m, 2H), 7_03 (m, 1H), 7.11 (dd, J = 9.7, 2 · 9 Hz, 1H), 7.35 (m , 2H), 7.67 (dd, J = 8.8, 5.8 Hz, 1H), 8.26 (m, 1H), 9.40 (s, 1H); MS (DCI / NH3) m / e 328 (M + H-16 ) +; 344 (M + H) +. Maleic acid salt (856 mg): Analytical calculated value for q 9H22N302F · 1_0 C4H404 · 0.75 H20: C, 58.41; H, 5.86; N, 8.88. Measured value : C58.02; H, 5.83; N, 8.67. Example 226 2- (l_ (2-"(4-Fluoro-3-methylphenyl) amino 1- 2-one-ketoethyl 丨 _4- Hexahydropyridyl) Pyridinium N-gasate Following the procedure described in Example 225B, substituting the product from Example 27A with the product from Example 225A to provide the title compound. (139 mg, 57%). 1H NMR ( 300 MHz, DMSO-d6) &lt; 5 1.68 (m, 2H), 1 _92 (d, J = 5.8 Hz, 2H), 2.22 (s5 3H)? 2.46 (m? 2H)? 3.04 (m5 2H)? 3.25 (s, 3H)? 7.03 (t5 J = 6? 1H) 5 7.35 (m? 2H) 5 7.44 (dd, J = 4.5, 1.5 Hz, 1H), 7.48 (m, 1 H), 7.54 (dd, J = 4.5, 1.5 Hz, 1H), 8.26 (d, J = 4.5, 1H), 9.79 (s, 1H); MS (DCI / NH3) m / e 328 ( M + H-16) +; 344 (M + H) + · maleic acid dibasic acid salt (171 mg) ··· (: 191122% 02? · 1.0C4H4O4 Analytical calculation value: C5 60.12; H, 5.12; N, 9.15. Found: C, 59.91; H, 5.79; N, 9.05. Example 227 Fluorophenyl) amino 1--2-ketoethyl V4-Hexaphthaloyl V ratio bond N-Gas was replaced with the product from Example 254A by the procedure described in Example 225B to provide the title compound. (157 mg, 68%). ^ NMRCSOOMHz.DMSO- ^) δ 1.68 (m? 2Η)? 1.92 (d? J = 5.8 Ηζ? 2Η)? 2.30 (m, 2Η), 3.01 (m, 2Η), 3.19 (s, 2Η ), 3.25 (m, 1Η), 6.89 (m, 1Η), 7.35 (m, 3Η), 85228 -289-200404539 7.42 (m, 2H), 7.68 (m, 1H), 8.26 ( d, J = 4.5, 1H), 9.91 (s, 1H); MS (DCI / NH3) m / e 330 (M + H) +. 2? * 1.0 (^ 114〇4 * 0.2112〇 Analytical calculation value: C, 58_84; H, 5_48; N, 9.36. Found: C, 58.52; H, 5.45; N, 9.04. 674532 Example 228 丨(2-Fluoro-5-methylbenzyl) amine 1-2-ketoethyl M-hexamethylpyridine, pyridinium N-gaseous example 228A Lchloro-N- (2-fluorom- 5-Methylbenzyl) acetamidine Following the procedure described in Example 22A, substituting 3,4,5-trimethoxyaniline with 2-fluoro-5-methylphenylamine provided the title compound (83% Yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) 5 2.28 (s, 3Η), 4.34 (s, 2Η), 6.98 (m, 1Η), 7.14 (dd, 1H, 8.6 Hz) , 7.69 (d, 1H, J = 7.4 Hz), 9.99 (br s, 1Η); MS (DCI / NH3) m / e202 (M + H) +; 219 (M + NH4) +.

實例228B 2-(l-{2-『(2-氣基-5-甲基笨基）胺基1_2-嗣基乙基丨-4-六氮p比淀基） 吡錠N-氣化物 按照實例225B中所述之程序，以得自實例228A之產物取代 得自實例225A之產物，提供標題化合物。（88毫克，36.6% )。 WNMRPOOMHaDMSO-c^) (5 1.63(m，2H)，1.95(d，J=12Hz，2H)，2.27 (s，3H)，3·50 (m，2H)，3.01 (d，J=12 Hz，2H)，3·20 (s，2H)，3.30 (m，1H)，6_93 (m， 1H)，7.15 (dd，J=9, 3 Hz，1H)，7.31 (m，2H)，7.42 (m，1H)，7.84 (m，1H)，8.26 (m，1H)，9.59 (s，1H) ; MS (DCI/NH3) m/e 328 (M+H-16)+ ; 344 (M+H)+ · 85228 -290- 200404539 順丁晞二酸鹽（190 毫克）：對 Cl 9h22N3 02F · 1.0 C4H404 · 0.2 H20 之分析計算值·· C，58·84 ; H，5·48 ; N，9·36·實測值·· C，58.52 ; H，5.45 ;N，9.04. 實例229 MMl-甲基甲基笨基胺基1-2-酮基乙基丨-4-六氫吡啶某）Example 228B 2- (l- {2-"(2-Gas-5-methylbenzyl) amino 1_2-fluorenylethyl 丨 -4-hexazol p ratio yl) pyridinium N-gas The procedure described in Example 225B replaced the product from Example 228A with the product from Example 225A to provide the title compound. (88 mg, 36.6%). WNMRPOOMHaDMSO-c ^) (5 1.63 (m, 2H), 1.95 (d, J = 12Hz, 2H), 2.27 (s, 3H), 3.50 (m, 2H), 3.01 (d, J = 12 Hz, 2H), 3.20 (s, 2H), 3.30 (m, 1H), 6_93 (m, 1H), 7.15 (dd, J = 9, 3 Hz, 1H), 7.31 (m, 2H), 7.42 (m , 1H), 7.84 (m, 1H), 8.26 (m, 1H), 9.59 (s, 1H); MS (DCI / NH3) m / e 328 (M + H-16) +; 344 (M + H) + · 85228 -290- 200404539 Maleic acid salt (190 mg): Analytical calculation for Cl 9h22N3 02F · 1.0 C4H404 · 0.2 H20 ·· C, 58 · 84; H, 5.48; N, 9 · 36. Measured value. C, 58.52; H, 5.45; N, 9.04. Example 229 MMl-methylmethylbenzylamino 1-2-ketoethyl 丨 -4-hexahydropyridine)

吡錠N-氣化物 實例229A 2_溴-N-(3-甲某茉基）丙醯胺 按照實例1A中所述之程序，以氯化2-溴基丙醯取代氯化溴 乙醯，提供標題化合物（92%產率），為白色固體。iHNMR (300 MHz，DMSO-d6) (5 1.74 (d，3H，J=6.8 Ηζ)，2·28 (s5 3H)，4.69 (q，1H，J= 6.8 Hz)? 6.90 (d5 1H? J=7.5 Hz)5 7.20 (dd? 1H5 J=7.8, 7.8 Hz)5 7.37 (br d51H5 J= 8.5 Hz)，7.44 (br s，1H)，10.22 (br s，1H); MS (DCI/NH3) m/e 242/244 (M+H)+ ；259/261 (M+NH4)+.Example of pyridinium N-gases 229A 2-bromo-N- (3-methylamoyl) propanilamine Following the procedure described in Example 1A, 2-bromopropylammonium chloride was substituted for acetamidine chloride The title compound was provided (92% yield) as a white solid. iHNMR (300 MHz, DMSO-d6) (5 1.74 (d, 3H, J = 6.8 Ηζ), 2.28 (s5 3H), 4.69 (q, 1H, J = 6.8 Hz)? 6.90 (d5 1H? J = 7.5 Hz) 5 7.20 (dd? 1H5 J = 7.8, 7.8 Hz) 5 7.37 (br d51H5 J = 8.5 Hz), 7.44 (br s, 1H), 10.22 (br s, 1H); MS (DCI / NH3) m / e 242/244 (M + H) +; 259/261 (M + NH4) +.

實例229B 2-(1-{1-甲基-24(3-甲基苯基）胺基1-2-g同某乙基}-4-六氫吡啶基） 外匕錠N-氣化物 按照實例225B中所述之程序，以得自實例229A之產物取代 得自實例225A之產物，提供標題化合物。（153毫克，64.6% ) 。1H NMR (300 MHz，DMSO-d6) 5 1.20 (d，J=6 Hz，2H)，1.41 (d，J=6 Hz， 1H)，1.65 (m，2H)，1.91 (m，2H)，2.28 (s，3H)，2.29 (m，1H)，2.45 (m，1H)，3.30 (m，3H)，6·88 (d，J=7.5 Hz，1H)，7.19 (t，J=7.5 Hz，1H)，7.31 (m，2H)，7.45 (m， 3H)，8.24 (m，1H)，9·68 (s，1H)，9.94 (s，1H) ; MS (DCI/NH3) m/e 324 (M+H-16)+ ; 340(M+H)+· 85228 -291- 200404539 順丁烯二酸鹽（187 毫克）：對(：201125!^〇2 · l.〇C4H404 · 1·2Η20 之 分析計算值：C，60.42 ; Η，6·63; Ν，8.81.實測值：C，60.41 ; Η，6.38 ;Ν，8·01. 實例230 之-(1_{24(4-氟茉某）脖某1-2-酮基乙基Μ-六氫峨淀基 &gt;比錠Ν-氣化物 按照實例225Β中所述之程序，以Ν_氯基乙醯基-4-氟苯胺 (Avacado)取代得自實例225Α之產物，提供標題化合物（45%產 率）。1H NMR (300 MHz，DMSO-d6) 5 1.68 (m，2H)，1 ·92 (d5 J=5.8 Hz， 2H)，2_30 (m，2H)，3.01 (m，2H)，3.19 (s，2H)，3.25 (m，1H)，6.89 (m，1H)，7.35 (m，3H)，7.42 (m，2H)，7.68 (m，1H)，8.26 (d，J=4.5, 1H)，9.91 (s，1H) ; MS (DCI/NH3)m/e314(M+H-16)+ ； 330(M+H)+. 順丁晞二酸鹽（190毫克）：對(：18112(^3〇2?.1.0(：4114〇4*1.1112〇 之分析計算值：c，57.88 ; H，5·53 ; N，8.80.實測值：C，57.49 ; H，5.56 ;Ν，8·72· 實例231 2-(M2-「(2-氟苽某）胺基1-2-酮基乙基卜4-六氫吡啶基）吡錠 N-氣化物 按照實例225B中所述之程序，以得自實例28A之產物取代 得自實例225A之產物，提供標題化合物。（126毫克，54% )。 1H NMR (300 MHz，DMSO-d6) δ 1.68 (m，2Η)，1.92 (d，J=6 Ηζ，2Η)，2.30 (m，2H)，3.01 (m，2H)，3·19 (s，2H)，3.25 (m，1H)，7.15 (m，1H)，7.30 (m，3H)， 7·42 (m，2H)，7.68 (m，1H)，8.26 (d，J=4.5,1H)，9.81 (s，1H) ; MS (DCI/NH3) m/e314(M+H-16)+ ； 330(M+H)+.Example 229B 2- (1- {1-methyl-24 (3-methylphenyl) amino group 1- 2-g with an ethyl} -4-hexahydropyridyl group) N-gas The procedure described in Example 225B replaced the product from Example 229A with the product from Example 225A to provide the title compound. (153 mg, 64.6%). 1H NMR (300 MHz, DMSO-d6) 5 1.20 (d, J = 6 Hz, 2H), 1.41 (d, J = 6 Hz, 1H), 1.65 (m, 2H), 1.91 (m, 2H), 2.28 (s, 3H), 2.29 (m, 1H), 2.45 (m, 1H), 3.30 (m, 3H), 6.88 (d, J = 7.5 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.31 (m, 2H), 7.45 (m, 3H), 8.24 (m, 1H), 9.68 (s, 1H), 9.94 (s, 1H); MS (DCI / NH3) m / e 324 (M + H-16) +; 340 (M + H) + 85228 -291- 200404539 maleic acid salt (187 mg): right (: 201125! ^ 〇2 · 1.2.0C4H404 · 1.2 · 20 Analytical calculated values: C, 60.42; H, 6.63; N, 8.81. Observed values: C, 60.41; H, 6.38; N, 8.01. Example 230 of-(1_ {24 (4-fluoromo ) A 1-ketoethyl M-hexahydroanido and a ratio of N-gases according to the procedure described in Example 225B, with N-chloroethanyl-4-fluoroaniline (Avacado ) In place of the product from Example 225A to provide the title compound (45% yield). 1H NMR (300 MHz, DMSO-d6) 5 1.68 (m, 2H), 1.92 (d5 J = 5.8 Hz, 2H), 2_30 (m, 2H), 3.01 (m, 2H), 3.19 (s, 2H), 3.25 (m, 1H), 6.89 (m, 1H), 7.35 (m, 3H), 7.42 (m 2H), 7.68 (m, 1H), 8.26 (d, J = 4.5, 1H), 9.91 (s, 1H); MS (DCI / NH3) m / e314 (M + H-16) +; 330 (M + H) +. Maleic acid dibasic acid salt (190 mg): Analytical calculation for (: 18112 (^ 3〇2? .1.0 (: 4114〇4 * 1.1112): c, 57.88; H, 5.53; N, 8.80. Found: C, 57.49; H, 5.56; N, 8.72. Example 231 2- (M2-"(2-fluorofluorene) amino 1--2 -ketoethyl ethyl 4-hexa Hydropyridyl) pyridinium N-gasate The procedure described in Example 225B was used to replace the product from Example 28A with the product from Example 225A to provide the title compound. (126 mg, 54%). 1H NMR (300 MHz, DMSO-d6) δ 1.68 (m, 2Η), 1.92 (d, J = 6 Ηζ, 2Η), 2.30 (m, 2H), 3.01 (m, 2H), 3.19 (s, 2H), 3.25 (m, 1H), 7.15 (m, 1H), 7.30 (m, 3H), 7.42 (m, 2H), 7.68 (m, 1H), 8.26 (d, J = 4.5, 1H), 9.81 (s , 1H); MS (DCI / NH3) m / e314 (M + H-16) +; 330 (M + H) +.

順丁烯二酸鹽（190 毫克）：對 C! 8H20N3O2F · l_0C4H4O4 · 0.2H2O 200404539 之分析計算值：C，58.84 ; Η，5·48 ; Ν，9·36_ 實測值：C，59.04 ; H，5.60 ;Ν，9·20· 實例232 N-(3_f基苯基）-2-{4-「3_(三氟甲基比淀基&quot;1-1-六氫p比咕某} 乙醯胺 實例232A 1-[3_(三氟甲基V2-?比淀基1六氳外h p并 將2-氯基-3-三氟甲基p比淀（6_57克，36.2毫莫耳）與六氫批p井 (31.48克’ 365.5 φ莫耳）在正-丁醇中之溶液，加熱至115它。48 小時後’使混合物冷卻至室溫，在減壓下移除溶劑，並使 殘留物於水與醋酸乙酯之間作分液處理。使有機相脫水乾 燥（硫酸鈉），過濾，及在減壓下濃縮。使殘留物於矽膠上 藉急騾式管柱層析純化（以15%甲醇：二氯甲烷溶離），提供 3.35克（40%產率）標題化合物，為黃褐色固體。1 η NMR β〇〇 MHz， DMSO-d6) 5 2.80 (m，4H)，3.10 (m，4H)，7·15 (ddd，1H，J=7.8, 4.7, 1.0 Hz)， 8.03 (dd，1H，J=7.8, 1.7 Hz)，8.50 (ddd，1H，J=4.8, 2.0, 0.7 Hz); MS (DCI/NH3) m/e 232(M+H)+.Maleic acid salt (190 mg): Analytical calculation for C! 8H20N3O2F · l_0C4H4O4 · 0.2H2O 200404539: C, 58.84; Η, 5.48; Ν, 9.36_ Found: C, 59.04; H, 5.60; N, 9 · 20 · Example 232 N- (3-f-phenylphenyl) -2- {4- "3_ (trifluoromethylpyridyl &quot; 1-1-hexahydrop-pyrolyl) acetamide Example 232A 1- [3_ (trifluoromethyl V2-? Than yttriol 1 hexafluoride hp and 2-chloro-3-trifluoromethyl p ylide (6_57 g, 36.2 mmol) and hexahydro Batch P (31.48 g of '365.5 phi mole) in n-butanol was heated to 115. After 48 hours, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the residue was dried at The solution was separated between water and ethyl acetate. The organic phase was dried (sodium sulfate), filtered, and concentrated under reduced pressure. The residue was purified on silica gel by flash column chromatography (15% Methanol: methylene chloride was dissolved) to provide 3.35 g (40% yield) of the title compound as a tan solid. 1 η NMR β 00 MHz, DMSO-d6) 5 2.80 (m, 4H), 3.10 (m, 4H ), 7.15 (ddd, 1H, J = 7.8, 4.7, 1.0 Hz), 8.03 (dd, 1 H, J = 7.8, 1.7 Hz), 8.50 (ddd, 1H, J = 4.8, 2.0, 0.7 Hz); MS (DCI / NH3) m / e 232 (M + H) +.

實例232B 处ί3·甲基苯基三氟甲..玉&gt;2_峨啶基1小六氤吡畊基^ 乙醯t 將得自實例33A之產物（1·30毫克，7·〇8毫莫耳）與n，N-二異 丙基胺（5.0毫升）在甲丰（50耄升）中，以得自實例232A之產物 (2.00 *克，8.65 *莫耳）處理，並加熱至6(^c，歷經18小時。 使混合物冷卻至室溫，轉移至分液漏斗，並以飽和碳酸氫 85228 -293 - 200404539 鈉水溶液洗滌。使有機相脫水乾燥（硫酸鋼），過滤，並使 濾液在減壓下濃縮。使殘留物於矽膠上藉急驟式管柱層析 純化（以25%至50%醋酸乙酯：己烷梯度溶離），提供標題化 合物，為白色固體。1 H NMR (300 MHz，DMSO-d6) 5 2.28 (s，3H)，2·67 (m，4Η)，3.18 (s，2Η)，3·27 (m，4Η)，6·88 (br d5 1Η，J=8.1 Ηζ)，7·18 (m，2Η)， 7.45 (m，2H)，8.06 (dd5 1H，J=7.8, 2.0 Hz)，8·53 (m，1H)，9·65 (br s，1H) ; MS (DCI/NH3) m/e 379 (M+H)+. 順丁烯二酸鹽2.45克，70%產率）··白色固體；iHNMR(300MHz， CD3 OD) δ 2.33 (s3 3Η)? 3.50 (m? 8Η), 4.06 (s, 2H)? 6.26 (s? 2H)? 6.97 (br d5 1H5 J=8.1 Hz)? 7.21 (dd? 1H51=7.8, 7.8 Hz)? 7.29 (ddd? 1H? J=7.83 5.1? 1.0 Hz), 7.40 (m，2H)，8.09 (dd，1H，J=7.8, 1.4 Hz)，8.57 (ddd，1H，J=4.8, 2.0, 0.7 Hz); 對(3191121卩3凡〇.1.0(34114〇4之分析計算值：c，55.87; H，5.10; N，11.33·實測值：C，55.55 ; H，5.00 ; N，10·99· 實例233 N二(3-甲基苯基）-244-(1,3-嘧唑-2-基V3,6-二氫吡啶-1(2HV基1乙醯胺 按照實例33C中所述之程序，以得自實例166B之產物取代 得自實例33B之產物，提供標題化合物，為黃色膠黏性殘留 物（450 毫克，62% )。1H NMR (300 MHz，CDC13) 5 2.3 (s，3H)，3.8 (m， 2H)，2.9 (m，2H)，3.31 (s，2H)，3.4 (m，2H)，6.6 (m，1H)，6.9 (m，1H)，7.2 (m， 1H)，7.25 (d，1H，J=3 Hz)，7.4 (m，2H)，7.8 (d，1H，J=3 Hz)，9.15 (br s，1H); MS (DCI/NH3) m/e 314 (M+H)+. 順丁烯二酸鹽：對c17h19n3os.i.oc4h4o4之分析計算值： C，58.73 ; H，5.40 ; N，9·78.實測值：C，58.69 ; Η，5·49 ; N，9_44. 實例234 85228 -294- 200404539 坠(3-甲基+基）-2-_(4-嘍.吩比啶_U2HV某）乙醯脖3. Methylphenyltrifluoromethyl in Example 232B: Jade> 2_Eridinyl 1 hexamethylpyridinyl ^ acetamidine The product obtained from Example 33A (1.30 mg, 7.08 Millimolar) and n, N-diisopropylamine (5.0ml) in methylphenidate (50ml), treated with the product obtained from Example 232A (2.00 * g, 8.65 * mol) and heated to 6 (^ c, over 18 hours. Allow the mixture to cool to room temperature, transfer to a separatory funnel, and wash with saturated aqueous sodium bicarbonate 85228 -293-200404539. The organic phase is dehydrated and dried (sulphate steel), filtered, and The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (25% to 50% ethyl acetate: hexane gradient) to provide the title compound as a white solid. 1 H NMR ( 300 MHz, DMSO-d6) 5 2.28 (s, 3H), 2.67 (m, 4Η), 3.18 (s, 2Η), 3.27 (m, 4Η), 6.88 (br d5 1Η, J = 8.1 Ηζ), 7.18 (m, 2Η), 7.45 (m, 2H), 8.06 (dd5 1H, J = 7.8, 2.0 Hz), 8.53 (m, 1H), 9.65 (br s, 1H ); MS (DCI / NH3) m / e 379 (M + H) +. Maleic acid salt 2.45 g, 70% yield) ·· White solid ; IHNMR (300MHz, CD3 OD) δ 2.33 (s3 3Η)? 3.50 (m? 8Η), 4.06 (s, 2H)? 6.26 (s? 2H)? 6.97 (br d5 1H5 J = 8.1 Hz)? 7.21 (dd 1H51 = 7.8, 7.8 Hz)? 7.29 (ddd? 1H? J = 7.83 5.1? 1.0 Hz), 7.40 (m, 2H), 8.09 (dd, 1H, J = 7.8, 1.4 Hz), 8.57 (ddd, 1H , J = 4.8, 2.0, 0.7 Hz); Analytical calculated value for (3191121 卩 3fan 0.0.1.0 (34114〇4: c, 55.87; H, 5.10; N, 11.33. Found: C, 55.55; H, 5.00; N, 10 · 99 · Example 233 N Di (3-methylphenyl) -244- (1,3-pyrazol-2-yl V3,6-dihydropyridine-1 (2HV group 1 acetamide) Following the procedure described in Example 33C, replacing the product from Example 33B with the product from Example 166B provided the title compound as a yellow tacky residue (450 mg, 62%). 1H NMR (300 MHz, CDC13 ) 5 2.3 (s, 3H), 3.8 (m, 2H), 2.9 (m, 2H), 3.31 (s, 2H), 3.4 (m, 2H), 6.6 (m, 1H), 6.9 (m, 1H) , 7.2 (m, 1H), 7.25 (d, 1H, J = 3 Hz), 7.4 (m, 2H), 7.8 (d, 1H, J = 3 Hz), 9.15 (br s, 1H); MS (DCI / NH3) m / e 314 (M + H) +. Maleic acid salt: Calculated value for analysis of c17h19n3os.i.oc4h4o4: C 58.73; H, 5.40; N, 9.78. Found: C, 58.69; Hf, 5.49; N, 9_44. Example 234 85228 -294- 200404539 Pendant (3-methyl + yl) -2 -_ ( 4- 喽 .phenpyridine _U2HV some) Acetyl neck

iJi234AiJi234A

土雍基冰嘍，_2_基六龙^酸第三-丁酯 將2-噻吩基鋰（27.6毫升，27_6毫莫耳）在四氫呋喃（3〇毫升） 中，於-78 C下，以15 *升四氫呋喃中之4_酮基-六氫吡啶_叛 酸第二-丁酯（5_0克’ 25耄莫耳）慢慢處理。使混合物溫熱至 室溫，並攪拌3.5小時。經由傾倒在冰上使反應淬滅，以醋 酸乙酯萃取’以硫酸鎂脫水乾燥，過濾，及在減壓下濃縮 ’而得綠油（5·68克’ 81% )，其係於靜置時固化。iHNMR (300 MHz，DMSO-d6) 5 1·4 (s，9H)，1.8 (m，4H)，3.10 (br s，2H)，3.8 (m，2H)， 5·5 (s，1H)，6.9 (m，2H)，7.38 (dd，1H，J=6, 3 Hz) ; MS (DCI/NH3) m/e 284 (M+H)'Tuyongyl borax, tert-butyl 2-hexaylhexanoate, 2-thienyl lithium (27.6 ml, 27_6 mmol) in tetrahydrofuran (30 ml) at -78 C, 15 * The 4-keto-hexahydropyridine-metanoic acid second-butyl ester (5_0 g '25 mol) in tetrahydrofuran is slowly processed. The mixture was allowed to warm to room temperature and stirred for 3.5 hours. The reaction was quenched by pouring on ice, extracted with ethyl acetate, 'dehydrated and dried with magnesium sulfate, filtered, and concentrated under reduced pressure' to give a green oil (5.68 g of 81%), which was left to stand When cured. iHNMR (300 MHz, DMSO-d6) 5 1.4 (s, 9H), 1.8 (m, 4H), 3.10 (br s, 2H), 3.8 (m, 2H), 5.5 (s, 1H), 6.9 (m, 2H), 7.38 (dd, 1H, J = 6, 3 Hz); MS (DCI / NH3) m / e 284 (M + H) '

實例234B 4_口塞吩_2-基_1，2,3,6_四氡卩比攻 將得自實例234A之產物（3克，10.59毫莫耳）以99%甲酸（7毫 升）處理，並於室溫下攪拌過夜。以飽和碳酸氫鈉（pH 8.5-9) 使混合物反應淬滅，以醋酸乙酯萃取，以硫酸鎂脫水乾燥 ，過濾，及在減壓下濃縮，而得帶紅色油（700毫克，40% ) 。1H NMR (300 MHz，CDC13) (5 2·45 (m，2H)，3.10 (t，2H，J=6 Hz)，2.45 (m， 2H)，6.18 (m，1H)，6·95 (d，2H，J=3 Hz)，7.18 (t，1H，J=3 Hz) ; MS (DCI/NH3) m/e 166 (M+H)+.Example 234B The 4-orthophenone_2-yl_1,2,3,6_tetrahydropyrene The product obtained from Example 234A (3 g, 10.59 mmol) was treated with 99% formic acid (7 ml) And stirred at room temperature overnight. The mixture was quenched with saturated sodium bicarbonate (pH 8.5-9), extracted with ethyl acetate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give a reddish oil (700 mg, 40%) . 1H NMR (300 MHz, CDC13) (5 2.45 (m, 2H), 3.10 (t, 2H, J = 6 Hz), 2.45 (m, 2H), 6.18 (m, 1H), 6.95 (d , 2H, J = 3 Hz), 7.18 (t, 1H, J = 3 Hz); MS (DCI / NH3) m / e 166 (M + H) +.

實例234C 甲基笨基V2-(4-4吩-2-某-3,6-二氫吡啶_1(2HV基）乙醯胺 按照實例33C中所述之程序，以得自實例234B之產物取代 85228 -295 - 200404539 得自實例33B之產物，提供標題化合物，為黃色固體（220毫 克，50% )。1 H NMR (300 MHz，DMSO-d6) 3 2.10 (s，3H)，2.45 (m，2H)， 2.75 (t，2H，J=6 Hz)，3.2 (m，4H)，6.1 (m，1H)，6.9 (d，1H，J=9 Hz)，7.0 (dd，1H， J=6, 4.5 Hz)，7.05 (dd，1H，J=3, 0·75 Hz)，7.18 (t，1H，J=7.5 Hz)，7.40 (dd，1H， J=3, 0.75 Hz)，7.5 (m，2H)，9.4 (s，1H) ; MS (DCI/NH3) m/e 313 (M+H)+ · 順丁烯二酸鹽··對 C18H20N2OS*l_0C4H4O4,0.4H2O 之分析計 算值：C，60.65 ; Η，5_74; Ν，6·43·實測值：C，60.44; H，5.44; Ν，6·18· 實例235 3-甲基-Ν-ΙΥ4-遠吩-2-基-3,6-二氫ρ比淀基）甲基1苯甲酿胺 按照實例200中所述之程序，以得自實例234Β之產物取代 得自實例119Α之產物，提供標題化合物，為黃色膠黏性殘 留物（84 毫克）。1H NMR (300 MHz，CDC13) 5 2.35 (s，3Η)，2.78 (t，2Η，J= 6 Hz)，3.2 (m，2H)，4.12 (d，1H，J=6 Hz)，4.7 (t，2H，J=6 Hz)，5·62 (t，1H，J=6 Hz)，6.1 (m，1H)，7.0 (m，2H)，7.38 (d，3H，J=6 Hz)，7.7 (m，2H)，9.0 (t，1H，J= 6Hz); MS(DCI/NH3)m/e313(M+H)+·順丁 晞二酸鹽：對C18H20N2OS • 1.0 C4H404 之分析計算值：C，61·67 ; H，5·65 ; N，6·54 ;實測值 :C，62.03, Η, 5.05, Ν，6·24· 實例236 2-(1-{2-|ϊ3-氣笨基）胺基1-2-酮某乙基}六氫吡啶冰基）吡錠 N-氣化物 ci^aVBrExample 234C Methylbenzyl V2- (4-4phen-2-a-3,6-dihydropyridine_1 (2HV group) acetamidinide Following the procedure described in Example 33C to obtain the product from Example 234B Substitution 85228 -295-200404539 The product from Example 33B provided the title compound as a yellow solid (220 mg, 50%). 1 H NMR (300 MHz, DMSO-d6) 3 2.10 (s, 3H), 2.45 (m , 2H), 2.75 (t, 2H, J = 6 Hz), 3.2 (m, 4H), 6.1 (m, 1H), 6.9 (d, 1H, J = 9 Hz), 7.0 (dd, 1H, J = 6, 4.5 Hz), 7.05 (dd, 1H, J = 3, 0.75 Hz), 7.18 (t, 1H, J = 7.5 Hz), 7.40 (dd, 1H, J = 3, 0.75 Hz), 7.5 ( m, 2H), 9.4 (s, 1H); MS (DCI / NH3) m / e 313 (M + H) + · Maleic acid salt · Analytical calculated value for C18H20N2OS * l_0C4H4O4, 0.4H2O: C , 60.65; H, 5_74; N, 6.43. Found: C, 60.44; H, 5.44; N, 6.18. Example 235 3-methyl-N-Ι-4-telephen-2-yl-3, 6-Dihydroρ-pyridyl) methyl 1 benzylamine Follow the procedure described in Example 200 to replace the product from Example 234B with the product from Example 119A to provide the title compound as a yellow tacky residue (84 mg)1H NMR (300 MHz, CDC13) 5 2.35 (s, 3Η), 2.78 (t, 2Η, J = 6 Hz), 3.2 (m, 2H), 4.12 (d, 1H, J = 6 Hz), 4.7 (t , 2H, J = 6 Hz), 5.62 (t, 1H, J = 6 Hz), 6.1 (m, 1H), 7.0 (m, 2H), 7.38 (d, 3H, J = 6 Hz), 7.7 (m, 2H), 9.0 (t, 1H, J = 6Hz); MS (DCI / NH3) m / e313 (M + H) + · Butanedioate: calculated and calculated for C18H20N2OS • 1.0 C4H404: C, 61 · 67; H, 5.65; N, 6.54; Found: C, 62.03, Η, 5.05, Ν, 6.24. Example 236 2- (1- {2- | ϊ3-Gaben Group) amine 1-2-one ethyl} hexahydropyridine ice group) pyridinium N-gas ci ^ aVBr

實例236A 2-溴-N-G-氣装基）乙醯胺 85228 -296- 200404539 按照實例1A中所述之程序，以3-氯苯胺取代3-甲基苯胺， 提供標題化合物，為白色固體。1HNMR(300MHz，DMSO_d6) 5 4.05 (s，2H)，7.15 (ddd，1H，J=7.8, 2.0, 1.4 Hz)，7.36 (dd，1H，J=7.8, 7.8 Hz)，7.4 4 (ddd，1H，J=8.1，2.0, 1.4 Hz)，7.79 (dd，1H，J=2.0, 2.0 Hz)，10.57 (br s，1H)·Example 236A 2-Bromo-N-G-gasoline) acetamide 85228 -296- 200404539 Following the procedure described in Example 1A, 3-methylaniline was replaced with 3-chloroaniline to provide the title compound as a white solid. 1HNMR (300MHz, DMSO_d6) 5 4.05 (s, 2H), 7.15 (ddd, 1H, J = 7.8, 2.0, 1.4 Hz), 7.36 (dd, 1H, J = 7.8, 7.8 Hz), 7.4 4 (ddd, 1H , J = 8.1, 2.0, 1.4 Hz), 7.79 (dd, 1H, J = 2.0, 2.0 Hz), 10.57 (br s, 1H) ·

實例236B 2-(1-丨2-R3-氪笨基）胺基1·2-酮某乙基丨六氤吡啶-4-基）吡錠 Ν-氧化物 按照實例225Β中所述之程序，以得自實例236Α之產物取代 付自貫例225Α之產物’提供標題化合物。（226毫克，66% )。 1H NMR (300 MHz, DMSO-d6) 5 1.68 (m5 2H)? 1.92 (d? J=5.7 Hz? 2H)5 2.30 (m，2H)，3.01 (m，2H)，3.19 (s，2H)，3.25 (m，1H)，6.89 (m，1H)，7.35 (m，3H)， 7.42 (m，2H)，7.68 (m，1H)，8.26 (d，J=4.5, 1H)，9.91 (s，1H) ; MS (DCI/NH3)， m/e330(M+H-16)+，346(M+H)+·順丁缔二酸鹽（294 毫克）：對 C18H2〇N302C1· 1.0C4H4〇4,0.2 H20 之分析計算值：C，57·21; Η，5·24 ; N，9.01·實測值：C，57·28 ; η，5·16 ; N, 8.7〇. 實例237 社4二(1-甲基-111-咪座_^ )_3,6_二氫吡啶-U2HV甚·^_(3_甲基笨基）Example 236B 2- (1- 丨 2-R3-fluorenyl) amino 1.2-ketoethyl hexamethylpyridin-4-yl) pyridine N-oxide Following the procedure described in Example 225B, The product from Example 236A was replaced with the product from Example 236A 'to provide the title compound. (226 mg, 66%). 1H NMR (300 MHz, DMSO-d6) 5 1.68 (m5 2H)? 1.92 (d? J = 5.7 Hz? 2H) 5 2.30 (m, 2H), 3.01 (m, 2H), 3.19 (s, 2H), 3.25 (m, 1H), 6.89 (m, 1H), 7.35 (m, 3H), 7.42 (m, 2H), 7.68 (m, 1H), 8.26 (d, J = 4.5, 1H), 9.91 (s, 1H); MS (DCI / NH3), m / e330 (M + H-16) +, 346 (M + H) + · maleic acid salt (294 mg): for C18H2ON302C1 · 1.0C4H4〇4 Analytical calculated value of 0.2, H20: C, 57 · 21; Η, 5.24; N, 9.01 · Measured value: C, 57 · 28; η, 5.16; N, 8.7〇. Example 237 社 社 二 二 ( 1-methyl-111-imido_ ^) _3,6_dihydropyridine-U2HV even ^ _ (3_methylbenzyl)

乙醯胺 會例237A 全魏基-4-(l_ 唑_2_基）六氫吡啶小勒酩第三_丁酉旨 將1甲基咪吐（4.1毫升，5〇毫莫耳）在無水四氫吱喃中，於 室溫下，以正—丁基鋰（25毫升，50毫莫耳）處理，並在4(^下 加熱3小時。使反應物冷卻至，並添加本酮基-六氫吡啶_ 1-羧酸第三_丁酯⑽克，5〇毫莫耳）。使混合物溫熱至室溫 85228 -297- 200404539 ，攪拌6小時，加熱至4(rc，再歷經3小時。使反應物冷卻至 1：溫’以水使反應淬滅，並以醋酸乙酯萃取。以硫酸鎂使 有機相脫水乾燥，過濾，及在減壓下濃縮。使粗製物質自 甲醇再結晶，提供標題化合物（8.2克，84% )，為白色固體。 1H NMR (300 MHz, CDC13) 5 1.45 (s5 9H)5 1.8 (d5 2H5 J=15 Hz)5 2.1 (m5 2H)5 3·3 (t，3H，J=15 Hz)，3·8 (s，4H)，6_8 (dd，2H，J=9, 3 Hz) ; MS (DCI/NH3) m/e 282 (M+H)+.Acetylamine Example 237A All-Wenyl-4- (l_azole_2_yl) hexahydropyridine oleyl tertiary butanidine Purpose 1 methylimidazole (4.1 ml, 50 mmol) in anhydrous tetrahydrate In hydrogen squeaking, treat with n-butyllithium (25 ml, 50 mmol) at room temperature, and heat at 4 ° C for 3 hours. Allow the reaction to cool to and add this keto-hexa Hydropyridine-1-carboxylic acid tert-butyl ester (50 g, 50 mmol). The mixture was allowed to warm to room temperature 85228-297-200404539, stirred for 6 hours, and heated to 4 ° C, followed by another 3 hours. The reaction was cooled to 1: warm 'the reaction was quenched with water, and extracted with ethyl acetate The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude material was recrystallized from methanol to provide the title compound (8.2 g, 84%) as a white solid. 1H NMR (300 MHz, CDC13) 5 1.45 (s5 9H) 5 1.8 (d5 2H5 J = 15 Hz) 5 2.1 (m5 2H) 5 3 · 3 (t, 3H, J = 15 Hz), 3 · 8 (s, 4H), 6_8 (dd, 2H, J = 9, 3 Hz); MS (DCI / NH3) m / e 282 (M + H) +.

實例237B 土0-甲基-1E_咪唑_2-基V3,6-二氤吡啶-1(2HV羧酸第三-丁酯 使得自實例237A之產物（5克，17.8毫莫耳）溶於甲苯中，並 以（甲氧羰基胺磺驢基）三乙基氫氧化銨内鹽（Burgess試劑，6.35 克，26.7毫莫耳）處理，及加熱至9〇°c，歷經6小時。使反應 物冷卻至室溫，並於醋酸乙酯/水之間作分液處理。以硫酸 鎂使有機相脫水乾燥，過濾，及在減壓下濃縮，而得41克（87 % )標題化合物，為褐色油狀殘留物。1H NMR (300 MHz，CDC13) 6 1.42 (s，9H)，2_63 (m，2H)，3.61 (t，2H，J=6 Hz)，3.7 (s，3H)，4.1 (d，2H，J= 3 Hz)，6.02 (br s，1H)，6.9 (d，1H，J=1.5 Hz)，7.1 (d，1H，J=1.5 Hz) ; MS (DCI/NH3) m/e 264 (M+H)+.Example 237B Ano-methyl-1E_imidazole_2-yl V3,6-dipyridine-1 (third-butyl carboxylic acid 2HV) solubilizes the product from Example 237A (5 g, 17.8 mmol) In toluene, and treated with (methoxycarbonylaminosulfonyl) triethylammonium hydroxide internal salt (Burgess reagent, 6.35 g, 26.7 mmol), and heated to 90 ° C for 6 hours. The reaction was allowed to react The product was cooled to room temperature and subjected to liquid separation between ethyl acetate / water. The organic phase was dehydrated and dried with magnesium sulfate, filtered, and concentrated under reduced pressure to obtain 41 g (87%) of the title compound as Brown oily residue. 1H NMR (300 MHz, CDC13) 6 1.42 (s, 9H), 2_63 (m, 2H), 3.61 (t, 2H, J = 6 Hz), 3.7 (s, 3H), 4.1 ( d, 2H, J = 3 Hz), 6.02 (br s, 1H), 6.9 (d, 1H, J = 1.5 Hz), 7.1 (d, 1H, J = 1.5 Hz); MS (DCI / NH3) m / e 264 (M + H) +.

實例237C 4-(1·甲基-1H-咪唑-2_某）-l，2,3,6-四氤吡啶 按照實例166B中所述之程序，以得自實例237B之產物取代 得自實例166A之產物，提供標題化合物，為黃色膠黏性殘 留物（1.28 克，41% )。1H NMR (300 MHz，CDC13) 5 2.6 (m，2H)，3.1 (t， 2H，J=6 Hz)，3.6 (m，2H)，3·7 (s，3H)，6.0 (m，1H)，6.82 (d，1H，J=1.5 Hz)，7.0 (d， 85228 -298- 200404539 1H, J=1.5 Hz) ； MS (DCI/NH3) m/e 164 (M+H)+.Example 237C 4- (1.methyl-1H-imidazole-2_some) -1,2,3,6-tetrapyridine Following the procedure described in Example 166B, substituting the product from Example 237B for Example The product of 166A provided the title compound as a yellow tacky residue (1.28 g, 41%). 1H NMR (300 MHz, CDC13) 5 2.6 (m, 2H), 3.1 (t, 2H, J = 6 Hz), 3.6 (m, 2H), 3.7 (s, 3H), 6.0 (m, 1H) , 6.82 (d, 1H, J = 1.5 Hz), 7.0 (d, 85228 -298- 200404539 1H, J = 1.5 Hz); MS (DCI / NH3) m / e 164 (M + H) +.

實例237D 2-「4-(l-甲基_1H-味吨-2-基）-3,6-二氮p比淀基甲基苯基） 乙醯胺 按照實例33C中所述之程序，以得自實例237C之產物取代 得自實例33Β之產物，提供標題化合物300毫克（51% )，為黃 色油；1H NMR (300 MHz，DMSO-d6) δ 2·30 (s，3Η)，2.5 (s，2Η)，2·6 (br s， 2Η)，2·75 (m，2Η)，3·20 (s，3Η)，3·75 (s，2Η)，6·3 (br s，1Η)，6·9 (m，2Η)，7.2 (m， 2H)，7.42 (m，2H)，9.65 (s，1H) ; MS (DCI/NH3) m/e 311 (M+H)+ · 順丁 晞二酸鹽：對（：181122仏0*1.3(：411404 “.71120之分析計 算值：C，56·65 ; Η，6·27 ; Ν，11·39·實測值：C，56.57 ; H，6.53 ; N，11.23. 實例238 N-(3_甲基笨基V2-「4-(3-硝基吡啶_2-基）六氫吡畊小基1乙醯胺Example 237D 2- "4- (l-Methyl_1H-amiton-2-yl) -3,6-diazolium p-methylmethylphenyl) Acetylamine Follow the procedure described in Example 33C, Replaced the product from Example 33B with the product from Example 237C to provide 300 mg (51%) of the title compound as a yellow oil; 1H NMR (300 MHz, DMSO-d6) δ 2.30 (s, 3Η), 2.5 (s, 2Η), 2.6 (br s, 2Η), 2.75 (m, 2Η), 3.20 (s, 3Η), 3.75 (s, 2Η), 6.3 (br s, 1Η), 6.9 (m, 2Η), 7.2 (m, 2H), 7.42 (m, 2H), 9.65 (s, 1H); MS (DCI / NH3) m / e 311 (M + H) + · Maleic acid dibasic acid salt: Calculated value: (181122 仏 0 * 1.3 (: 411404 ".71120"): C, 56 · 65; Η, 6.27; Ν, 11.39 · Measured value: C, 56.57 H, 6.53; N, 11.23. Example 238 N- (3-methylbenzyl V2- "4- (3-nitropyridin_2-yl) hexahydropyridine 1 acetamide

實例238A H3-硝基吡啶-2-基）六氫吡畊 於2-氯基-3-硝基吡啶（10.05克，63.39毫莫耳）在異丙醇（350毫 升）中之溶液内，於室溫下，以一份添加六氫吡畊（27.48克， 319.0毫莫耳）。2小時後，於減壓下移除溶劑，並使殘留物 於水與二氯甲烷之間作分液處理。使有機相脫水乾燥（硫酸 鈉），過濾及濃縮成鮮明黃色固體。使用此物質而無需進一 步純化。1 H NMR (300 MHz，CDC13) 51.74 (s，1H)，2.98 (m，4H)，3.43 (m， 4H), 6.73 (dd? 1H? J=8.1? 4.8 Hz)5 8.11 (dd? 1H? J=8.1? 1.7 Hz)? 8.32 (dd? 1H? J= 4.45 1.7 Hz) ； MS (DCI/NH3) m/e 209 (M+H)+.Example 238A H3-nitropyridin-2-yl) hexahydropyridine was dissolved in a solution of 2-chloro-3-nitropyridine (10.05 g, 63.39 mmol) in isopropanol (350 ml), and Hexamine (27.48 g, 319.0 mmol) was added in one portion at room temperature. After 2 hours, the solvent was removed under reduced pressure, and the residue was partitioned between water and dichloromethane. The organic phase was dried (sodium sulfate), filtered and concentrated to a bright yellow solid. This material was used without further purification. 1 H NMR (300 MHz, CDC13) 51.74 (s, 1H), 2.98 (m, 4H), 3.43 (m, 4H), 6.73 (dd? 1H? J = 8.1? 4.8 Hz) 5 8.11 (dd? 1H? J = 8.1? 1.7 Hz)? 8.32 (dd? 1H? J = 4.45 1.7 Hz); MS (DCI / NH3) m / e 209 (M + H) +.

實例238B 85228 -299- 200404539 N-(3-甲基本基）·2-「4_(3-硝基ρ比淀-2-基）7Τ氮p比呼_1·基1乙酿胺 按照實例23邡中所述之程序，以得自實例238Α之產物取代 得自實例232Α之產物，提供標題化合物（84%產率），為黃色 固體。WNMRPOOMHaCDCU) 5 2.36(s，3H)，2.74(m，4H)，3.20(s， IB), 3.56 (m5 4H), 6.80 (dd5 1H? J=8.1,4.4 Hz), 6.94 (br d5 1H5 J=7.8 Hz)5 7.23 (dd，1H，J=7.5, 7.5 Hz)，7.39 (m，2H)，8.15 (dd，1H，J=8.1，1.7 Hz)，8.35 (dd，1H， J=4.8, 2.0 Hz)，9.01 (br s，1H) ; MS (DCI/NH3) m/e 356 (M+H)+ ; 對 C18H21N503之分析計算值：c，60.83; H，5.96; N，19.71_ 實測 值：C，60.66 ; H，5·97 ; N，19.70. 實例239 2-『4-(3-氯基叶1：淀-2-基）六氫吡畊-1-某甲基笨基）乙醯胺Example 238B 85228 -299- 200404539 N- (3-methylbenzyl) · 2- "4_ (3-nitropapido-2-yl) 7T nitrogen pbihu_1 · yl 1 ethyl amine according to Example 23 The procedure described in (i) replaces the product from Example 238A with the product from Example 238A to provide the title compound (84% yield) as a yellow solid. WNMRPOOMHaCDCU) 2.36 (s, 3H), 2.74 (m, 4H), 3.20 (s, IB), 3.56 (m5 4H), 6.80 (dd5 1H? J = 8.1, 4.4 Hz), 6.94 (br d5 1H5 J = 7.8 Hz) 5 7.23 (dd, 1H, J = 7.5, 7.5 Hz), 7.39 (m, 2H), 8.15 (dd, 1H, J = 8.1, 1.7 Hz), 8.35 (dd, 1H, J = 4.8, 2.0 Hz), 9.01 (br s, 1H); MS (DCI / NH3) m / e 356 (M + H) +; Analysis and calculation of C18H21N503: c, 60.83; H, 5.96; N, 19.71_ Found: C, 60.66; H, 5.97; N, 19.70. Example 239 2- "4- (3-Chloroyl leaf 1: Yodo-2-yl) hexahydropyridine-1-a methylbenzyl) acetamide

實例239A 1-(3-氣基峨咬-2-基）六氫比啡 使六氫吡啡（29.1克，338毫莫耳）、2,3-二氣吡啶（5.00克，33.8 毫莫耳）及正-丁醇（220毫升）之溶液回流3天。使反應混合物 冷卻至23°C，及在減壓下濃縮。以醋酸乙酯與水將殘留物配 成漿液。將醋酸乙酯層倒出，並以硫酸鈉脫水乾燥，過濾 及濃縮，而得4·8克（72%產率）標題化合物。iHNMR(3〇〇MHz， DMSO-d6) (5 2.83 (m，4H)，3.15 (m，4H)，6.97 (dd，1H，J=4.5, 7.5 Ηζ)，7·77 (dd， 1H，J-1.5, 7.5 Hz)，8_21 (dd，1H，J=1.5, 4.5 Hz) ; MS (ESI) m/e 198 (M+H)+·Example 239A 1- (3-Aminopyridin-2-yl) hexahydrobiphane Hexahydropyridine (29.1 g, 338 mmol), 2,3-digas pyridine (5.00 g, 33.8 mmol) ) And n-butanol (220 ml) were refluxed for 3 days. The reaction mixture was cooled to 23 ° C and concentrated under reduced pressure. The residue was slurried with ethyl acetate and water. The ethyl acetate layer was decanted, dried over sodium sulfate, filtered, and concentrated to give 4.8 g (72% yield) of the title compound. iHNMR (300 MHz, DMSO-d6) (5 2.83 (m, 4H), 3.15 (m, 4H), 6.97 (dd, 1H, J = 4.5, 7.5 Ηζ), 7.77 (dd, 1H, J -1.5, 7.5 Hz), 8_21 (dd, 1H, J = 1.5, 4.5 Hz); MS (ESI) m / e 198 (M + H) + ·

f 例 239B 2-「4_(3-氯基吡啶-2-基）六氫吡畊-i-某甲基茉某）乙酸胺 按照實例232B中所述之程序，以得自實例239A之產物取代 得自實例232A之產物。使反應混合物在減壓下濃縮，並使 85228 -300- 200404539 殘留物藉層析純化（預備之Nova-PakHRC18管柱，6米 60 A，25 X 100毫米，溶離劑梯度液25%至95%乙腈：水，具有 ► 固定0.1%三氟醋酸），而得109毫克（23%產率）三氟醋酸鹽： 非晶質固體，熔點 45-55°C。iHNMROOOMHz’DMSO-cy 5 2.29 (s，3H)，3·40 (br m，8H)，3.80 (br m，1H)，4.19 (br m，1H)，6·96 (br d，1H，J=7.5 Hz)，7.09 (dd，1H，J=4.5, 7.5 Hz)，7.24 (dd，1H，J=7.8, 7.8 Hz)，7.40 (m，2H)， 7.88 (dd?lH?J=2.1? 8.1 Hz)5 8.28 (dd5lH?J=2.1? 4.8 Hz) ； MS (ESI) m/e 345 (]^+11)+.對(：181121€^40.1.1(：2册302之分析計算值：（：，51.59; H，4.74 ; N，11.91.實測值：C, 51.58 ; Η，4·81; N，11.99. 實例240 2-(l-{2_酮基-2-ΙΪ2Α6-三溴基-3-甲基笨基）胺基1乙基丨六氫吡啶_4-f Example 239B 2- "4- (3-chloropyridin-2-yl) hexahydropyridine-i-methylammoxamide" Acetyl acetate was replaced with the product obtained from Example 239A following the procedure described in Example 232B. Product from Example 232A. The reaction mixture was concentrated under reduced pressure, and the 85228-300-200404539 residue was purified by chromatography (prepared Nova-PakHRC18 column, 6 m 60 A, 25 X 100 mm, eluent Gradient solution 25% to 95% acetonitrile: water with ► fixed 0.1% trifluoroacetic acid) to give 109 mg (23% yield) trifluoroacetate: amorphous solid, melting point 45-55 ° C. IHNMROOOMHz ' DMSO-cy 5 2.29 (s, 3H), 3.40 (br m, 8H), 3.80 (br m, 1H), 4.19 (br m, 1H), 6.96 (br d, 1H, J = 7.5 Hz ), 7.09 (dd, 1H, J = 4.5, 7.5 Hz), 7.24 (dd, 1H, J = 7.8, 7.8 Hz), 7.40 (m, 2H), 7.88 (dd? LH? J = 2.1? 8.1 Hz) 5 8.28 (dd5lH? J = 2.1? 4.8 Hz); MS (ESI) m / e 345 (] ^ + 11) +. Pair (: 181121 € ^ 40.1.1 (: 2 302 analysis and calculation value: (: , 51.59; H, 4.74; N, 11.91. Found: C, 51.58; Hf, 4.81; N, 11.99. Example 240 2- (l- {2_keto-2-IΪ2A6-tribromo-3 -Methylbenzyl ) Amino 1-ethyl piperidine _4- Shu

基）吡錠N-氣化物 實例240A 2_、/臭-N-(2,4,6-三溪基_3_甲基苯基）乙酿胺 於3-甲基-2,4,6-三溴苯胺(4·36克，12.7毫莫耳）在甲苯(40毫升） 中之溶液内，於室溫下，添加氯化溴乙醯（1.20毫升，14.6毫 莫耳），並將漿液加熱至100°C，歷經24小時。使反應物冷卻 ，過濾，洗滌，並置於高真空泵上，提供2·88克（49% )標題 化合物，為白色固體。熔點 207-209°C ; 1H NMR (300 MHz，DMSO-d6) (5 2.52 (s，3H) 4.07 (s，2H) 8.05 (s，1H) 10.38 (s，1H) ; 13 C NMR (100 MHz， DMSO-d6) 3 24.2, 28.6, 121.3, 123.4, 127·2, 134·3, 134.9, 137.6, 164.4 ; MS(DCI/NH3)m/e482(M+NH4 + );對 C9H7Br4NO之分析計算值： C，23.26 ; H，1·52 ; N，3.01.實測值：C，23.30 ; H，1.45 ; N，2·94_Example) Pyridinium N-Gas Example 240A 2-A //-O-N- (2,4,6-trisyl_3-methylphenyl) ethylamine in 3-methyl-2,4,6-tris To a solution of bromoaniline (4.36 g, 12.7 mmol) in toluene (40 ml) was added ethyl bromide chloride (1.20 ml, 14.6 mmol) at room temperature, and the slurry was heated to 100 ° C for 24 hours. The reaction was cooled, filtered, washed, and placed on a high vacuum pump to provide 2.88 g (49%) of the title compound as a white solid. 207-209 ° C; 1H NMR (300 MHz, DMSO-d6) (5 2.52 (s, 3H) 4.07 (s, 2H) 8.05 (s, 1H) 10.38 (s, 1H); 13 C NMR (100 MHz , DMSO-d6) 3 24.2, 28.6, 121.3, 123.4, 127.2, 134.3, 134.9, 137.6, 164.4; MS (DCI / NH3) m / e482 (M + NH4 +); Analytical calculation for C9H7Br4NO : C, 23.26; H, 1.52; N, 3.01. Found: C, 23.30; H, 1.45; N, 2.94_

實例240B 85228 -301- 秦 200404539 MW2_酮基_2_RZ4,6-三漆基-3_甲基笨基）胺基1乙某丨六氫吡啶斗 基）吡键N-氫化物 按照實例225B中所述之程序，以得自實例240A之產物取代 得自實例225A之產物，提供標題化合物。（290毫克，51% )。 1H NMR (300 MHz，DMSO-d6) 6 1.75 (m，2H)，1.92 (m，2H)，2.30 (m，2H)， 2.54 (s，3H)，3.12 (m，1H)，3.15 (s，2H)，3.31 (m，1H)，7.30 (m5 3H)，7.40 (m， 2H)，8.26 (dd，J=4.5, 1·5 Hz，1H)，9.78 (s，1H) ; MS (DCI/NH3) m/e 545 (M+H-16)+ ； m/e563 (M+H)+. 順丁晞二酸鹽（294 毫克）：對C25H16N302Br3 ·1·(Κ：4Η404之分析 計算值：C，40.60; Η，3·；59; Ν，7·48·實測值：C，40.85 ; Η，3·54; Ν，7.27. 實例241 2-{443-(胺基甲基）吡啶_2-基1六氤吡畊-1-基丨-Ν-(3-甲基苯某） 乙醯胺 於20毫升20%無水氨中之實例5 (349毫克，1.04毫莫耳）在 甲醇中之溶液内，添加Raney®鎳（1.51克），並將反應物於室 溫及60 psi氫壓力下攪拌16小時。然後過濾混合物，及在減 壓下濃縮。使殘留物於矽膠上藉急騾式管柱層析純化（以10 %甲醇：二氯甲烷溶離），提供標題化合物（340毫克，96% 產率），為淡黃色半固體。1HNMR(300MHz，DMSαd6)5 2·33(s， 3H)，2.79 (m，4H)，3.20 (m，4H)，3.25 (s，2H)，3.87 (s，2H)，6·94 (br d，1H，J= 7.5 Hz)，7.09 (dd，1H，J=7.5, 4_8 Hz)，7.20 (dd，1H，J=7.5, 7.5 Hz)，7.40 (m，2H)， 7.79 (d，1H，J=7.5 Hz)，8.17 (dd，1H，4.8, 1.7 Hz) ; MS (DCI/NH3) m/e 340. 順丁烯二酸鹽··白色固體；1HNMR(300MHz，CD3OD)(52.33(s， 3H)，2.96 (m，4H)，3.27 (m，4H)，3.43 (s，2H)，4·25 (s，2H)，6.25 (s，2H)，6.95 85228 -302- 200404539 (br d，1H，J=7.5 Hz)，7·21 (m，2H)，7·40 (m，2H)，7.81 (dd, 1H，J=7_5, 1.7 Hz)， 8.38(dd，lH，J，4.8，1.7Hz) ; 13CNMR(100MHz，DMSO-d6) 5 21·1，37·8, 49.7, 52.5, 116.5, 118.8, 119.9, 121.8, 124.2, 128.2, 128.5, 135.8, 137.4, 137.9, 138.3, 147.5, 160.5, 167.1;對 C19H25N50· 1.2 C4H404 ·0·2Η2Ο(：4Η4Ο4 之分析計算值：C，59·27 ; Η ; 6·31 ; N，14.52·實測值：C，59.61 ; H，6·48 ; N，14.42. 實例242 Μ4-(2-異丙氧基笨基）六氤吡畊小基甲基笨基）乙醯胺Example 240B 85228 -301- Qin 200404539 MW2_keto_2_RZ4,6-trilacyl-3_methylbenzyl) amino 1 ethyl hexahydropyridinyl) pyridine bond N-hydride according to Example 225B The procedure described replaces the product from Example 240A with the product from Example 225A to provide the title compound. (290 mg, 51%). 1H NMR (300 MHz, DMSO-d6) 6 1.75 (m, 2H), 1.92 (m, 2H), 2.30 (m, 2H), 2.54 (s, 3H), 3.12 (m, 1H), 3.15 (s, 2H), 3.31 (m, 1H), 7.30 (m5 3H), 7.40 (m, 2H), 8.26 (dd, J = 4.5, 1.5 Hz, 1H), 9.78 (s, 1H); MS (DCI / NH3) m / e 545 (M + H-16) +; m / e563 (M + H) +. Maleic acid diacid salt (294 mg): Analytical calculation for C25H16N302Br3 · 1 · (Κ: 4Η404): C, 40.60; H3, 59; N, 7.48. Found: C, 40.85; H, 3.54; N, 7.27. Example 241 2- {443- (aminomethyl) pyridine_2 -Hexyl-1-hexapyrine-1-yl 丨 -N- (3-methylbenzene) acetamide in 20 ml of 20% anhydrous ammonia Example 5 (349 mg, 1.04 mmol) in methanol To the solution, Raney® nickel (1.51 g) was added, and the reaction was stirred at room temperature under 60 psi hydrogen pressure for 16 hours. The mixture was then filtered and concentrated under reduced pressure. The residue was quenched on silica gel. Purified by column chromatography (dissolved in 10% methanol: dichloromethane) to provide the title compound (340 mg, 96% yield) as a pale yellow semi-solid. 1HNMR (300MHz, DMSαd6) 5 2 · 33 (s, 3 H), 2.79 (m, 4H), 3.20 (m, 4H), 3.25 (s, 2H), 3.87 (s, 2H), 6.94 (br d, 1H, J = 7.5 Hz), 7.09 (dd, 1H, J = 7.5, 4_8 Hz), 7.20 (dd, 1H, J = 7.5, 7.5 Hz), 7.40 (m, 2H), 7.79 (d, 1H, J = 7.5 Hz), 8.17 (dd, 1H, 4.8 , 1.7 Hz); MS (DCI / NH3) m / e 340. Maleic acid ·· white solid; 1HNMR (300MHz, CD3OD) (52.33 (s, 3H), 2.96 (m, 4H), 3.27 ( m, 4H), 3.43 (s, 2H), 4.25 (s, 2H), 6.25 (s, 2H), 6.95 85228 -302- 200404539 (br d, 1H, J = 7.5 Hz), 7.21 ( m, 2H), 7.40 (m, 2H), 7.81 (dd, 1H, J = 7_5, 1.7 Hz), 8.38 (dd, 1H, J, 4.8, 1.7Hz); 13CNMR (100MHz, DMSO-d6) 5 21 · 1, 37 · 8, 49.7, 52.5, 116.5, 118.8, 119.9, 121.8, 124.2, 128.2, 128.5, 135.8, 137.4, 137.9, 138.3, 147.5, 160.5, 167.1; for C19H25N50 · 1.2 C4H404 · 0 · 2Η2〇 (: Calculated value of 4Η4Ο4: C, 59 · 27; Η; 6.31; N, 14.52 · Measured value: C, 59.61; H, 6.48; N, 14.42. Example 242 M4- (2-isopropyl Oxybenzyl) hexamethylpyridyl, methylbenzyl) acetamidine

實例242A 1-異丙氫某-2-硝某1 將2-硝基酚（10克，71.9毫莫耳）與碳酸鉀（21·85克，158.1毫 莫耳）在Ν，Ν-二甲基甲醯胺：丙酮（1 : 2，150毫升）中之溶液 ，於回流下加熱，並在回流期間，逐滴添加（於30分鐘内）2-溴丙烷（14.8毫升，158毫莫耳），且攪拌過夜。使反應物冷卻 至室溫，並於水與醋酸乙酯之間作分液處理。以硫酸鎂使 有機相脫水乾燥，過濾，及在減壓下濃縮。使殘留物於矽 膠上藉急驟式管柱層析純化（10%醋酸乙酯：己烷），提供標 題化合物，為金黃色油（11.5克，88%)。iHNMRpOOMHz'DCls) 5 1.4 (d，6H，J=6 Ηζ)，4.7 (七重峰，1H，J=6 Hz)，6.98 (m，1H)，7.09 (d，1H， J=9 Hz)，7.45 (m，1H)，7·78 (dd，1H，3 Hz) ; MS (DCI/NH3) m/e 182 (M+H)+ · f 例 242B 2·異丙氣基苯胺 使得自實例242A之產物（5·〇〇克，27.5)於氫壓力（60 psi)下， 使用10% Pd/C觸媒，在甲醇中還原。過漉觸媒，並使此溶液 44© 85228 -303 - 200404539 在減壓下濃縮，而得3.75克（90% )所要之產物，為褐色油。 1H NMR (400 MHz，CDC13) δ 1.35 (d，6Η，J=6.1 Ηζ)，3·77 (br s，2Η)，4.52 (m，1H)，6.75 (m，4H) ; MS (DCI/NH3 ) m/e 152 (M+H)+ ·Example 242A 1-Isopropylhydrogen-2-nitron-1 A 2-nitrophenol (10 g, 71.9 mmol) and potassium carbonate (21.85 g, 158.1 mmol) were added in Ν, Ν-dimethyl Methylformamide: a solution in acetone (1: 2,150 ml), heated under reflux, and during the reflux period, 2-bromopropane (14.8 ml, 158 mmol) was added dropwise (within 30 minutes). And stirred overnight. The reaction was allowed to cool to room temperature and was partitioned between water and ethyl acetate. The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (10% ethyl acetate: hexane) to provide the title compound as a golden yellow oil (11.5 g, 88%). iHNMRpOOMHz'DCls) 5 1.4 (d, 6H, J = 6 Ηζ), 4.7 (seventh peak, 1H, J = 6 Hz), 6.98 (m, 1H), 7.09 (d, 1H, J = 9 Hz), 7.45 (m, 1H), 7.78 (dd, 1H, 3 Hz); MS (DCI / NH3) m / e 182 (M + H) + · f Example 242B 2 · Isopropylaniline The product (5.0 g, 27.5) was reduced in methanol under hydrogen pressure (60 psi) using a 10% Pd / C catalyst. The catalyst was passed through the catalyst, and the solution was concentrated under reduced pressure to obtain 3.75 g (90%) of the desired product as a brown oil. 1H NMR (400 MHz, CDC13) δ 1.35 (d, 6Η, J = 6.1 Ηζ), 3.77 (br s, 2Η), 4.52 (m, 1H), 6.75 (m, 4H); MS (DCI / NH3 ) m / e 152 (M + H) + ·

實例242C 1-(2-異丙氣基笨基）六氫吡畊 將得自實例242B之產物（3_5克，23_2毫莫耳）於室溫下，慢 慢添加至雙-2-氯乙基胺鹽酸鹽（4.96克，27.78毫莫耳）中，並 回流48小時。使反應物冷卻至室溫，並添加碳酸鈉（9克）， 且再回流48小時。使混合物冷卻至室溫，過滤，並使白色 固體於二氯甲烷與3N氫氧化鈉之間作分液處理。以硫酸鎂 使有機相脫水乾燥，過濾，及在減壓下濃縮，而得3.2克（63 % )粉紅色油。1 H NMR (300 MHz，CDC13) ά1·4 (d，6H，J=6 Hz)，1.5-1.6 (m，4H)，2.45-2.65 (m，4H)，3.43 (m，1H)，6.6-6.8 (m，2H)，6.81-6.91 (m，2H); MS (DCI/NH3) m/e 221 (M+H)+.Example 242C 1- (2-Isopropylylbenzyl) hexahydropyridine The product from Example 242B (3-5 grams, 23_2 millimoles) was slowly added to bis-2-chloroethyl at room temperature. Amine hydrochloride (4.96 g, 27.78 mmol) and refluxed for 48 hours. The reaction was cooled to room temperature and sodium carbonate (9 g) was added and refluxed for another 48 hours. The mixture was allowed to cool to room temperature, filtered, and a white solid was separated between methylene chloride and 3N sodium hydroxide. The organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 3.2 g (63%) of a pink oil. 1 H NMR (300 MHz, CDC13) 1 · 4 (d, 6H, J = 6 Hz), 1.5-1.6 (m, 4H), 2.45-2.65 (m, 4H), 3.43 (m, 1H), 6.6- 6.8 (m, 2H), 6.81-6.91 (m, 2H); MS (DCI / NH3) m / e 221 (M + H) +.

實例242D 2-「4-(2-異丙氫基笨基）六氫吡畊小基甲基笨基）乙醯胺 按照實例33C中所述之程序，以得自實例242C之產物取代 得自實例33B之產物，提供標題化合物，為黃色油（223毫克 ，28% )。1H NMR (300 MHz，CDC13) δ 1.22 (d，6H，J=6 Hz)，2.25 (s，3H)， 2.65-2.70 (m，4H)，3.2-3.35 (m，4H)，3·38 (s，2H)，4_6 (m，1H)，6·85-6_91 (m， 5H)，7.2 (t，1H，J=9 Hz)，7.4-7.48 (m，2H)，9·62 (s，1H) ; MS (DCI/NH3) m/e 368 (M+H)+. 順丁烯二酸鹽：對〇221129%〇2,0.7€4114〇4之分析計算值：（：， 66.38 ; H，7.14 ; N，9.36.實測值：C，66.50 ; H，6.95 ;Ν，9·16· 85228 -304- 200404539 實例243 基苯基）胺基i_2_g同某乙基丨六，毗畊小基）於鹼醯胺 將得自實例5之產物（500毫克，ι·49毫莫耳）在2N氫氧化鈉 (15愛升）與乙醇（15毫升）中之溶液，加熱至1〇〇。〇，歷經16小 / 時。使反應物冷卻，濃縮，並使殘留物於醋酸乙酯與水之 間作分液處理。使有機相脫水乾燥（硫酸鈉），過濾，及在 減壓下濃縮，提供18毫克（3%產率）標題化合物，為黃色半 固體。hNMR(300 MHz，CD3〇D)占 2.32 (s，3H)，2.77 (m，4H)，3.23 (s， 2H)，3·42 (m，4H)，6.94 (br d，1H，J=7.8 Hz)，7.00 (dd，1H，J=7.5, 4.8 Hz), 7.19 (dd，1H，J=7.8, 7.8 Hz)，7.39 (m，2H)，7.95 (dd，1H，J=7.5, 2.0 Hz)，8.29 (dd，1H， J=4.7, 2.0 Hz) ; MS (DCI/NH3 ) m/e 354 (M+H)+ · 順丁烯二酸鹽：黃色固體；iHNMR(300 MHz，CD3OD) δ 2.33 〇， 3H)，3.44 (m，4H)，3.65 (m，4H)，4.03 (s，2H)，6.28 (s，2H)，6·98 (br d，1H，J= 7·5 Hz)，7.06 (dd，1H，J=7.8, 5·1 Hz)，7·21 (dd，1H，J=7.8, 7.8 Hz)，7.40 (m，2H), 7·94 (dd，1H，J=7.5, 1·7 Hz)，8.33 (dd，1H，J=4.8, 1.7 Hz);對 q 9H23N5 02 • 1.3C4H404 之分析計算值：C，57.64 ; H，5.64 ; N，13.89.實測值 :C，57.60 ; Η，5·61 ; N，13-61. 實例244 N-(3_甲某笨基）-2-[(2SV2-甲某-4-吡啶-2·基六氪吡畊-l-某1 乙烷硫醯胺 將得自實例214之產物（200毫克，0.62毫莫耳）在無水甲苯(6 毫升）中之溶液，以2,4-雙（4-甲氧苯基）-1，3-二硫-2,4-二磷四圜· 2,4-二硫化物（Lawesson氏試劑，125毫克，0·31毫莫耳）處理， 並於65°C下加熱1小時。使混合物冷卻至室溫，及在減壓下 85228 -305 - 200404539 濃縮。使殘留物於珍膠上藉急驟式管柱層析純化（以75%己 · 烷：醋酸乙酯溶離），提供173毫克（82%產率）標題化合物， 為黃色油。！11醒11(300]^取€〇0：13)61.17((15&gt;6.1取311)2.39(8， 3H) 2.75 (dd，J一 12_4, 9.8 Hz，1H) 2·81 (m，1H) 2.96 (m，2H) 3.26 (t，J=5_5 Hz， 1H) 3.56 (d，J=17.6 Hz，1H) 3.88 (d，J=17.6 Hz，1H) 4.04 (m，2H) 6.67 (t，J=6.1 Hz，1H) 6·69 (d，J=8.5 Hz，1H) 7.08 (d，J=7.5 Hz，1H) 7.30 (t，J=7.8 Hz，1H) 7.52 (ddd，J=8.7, 7.0, 2.0 Hz，1H) 7·67 (s，1H) 7.74 (d，J=8.1 Hz，1H) 8.22 (dd5 J=4.9, 1.9 Hz? 1H) 11.25 (s5 1H) ； MS (DCI/NH3) m/e 341.2 (M+H)+. φ 順丁晞二酸鹽：黃色固體；iHNMR(300MHz，DMSO-d6) (5 U3 (m，3H) 2.34 (s，3H) 3.06 (m，2H) 3.31 (m，3H) 3.79 (m，2H) 4.05 (m，2H) 6·22 (s，2H) 6.69 (m，1H) 6·94 (d5 J=7.8 Hz，1H) 7·11 (d，J=7.5 Hz，1H) 7_32 (t，J= 7.1 Hz，1H) 7.58 (d，J=6.8 Hz，1H) 7_63 (s，1H) 7.71 (d，J=7.5 Hz，1H) 8.11 (d， J=4.1 Hz，1H) 11.54(s，1H);對 C20H25N3O2 · L5C4H404之分析計算 值：C，58.35 ; Η, 5·88 ; N，10·89·實測值：C，58.35 ; H，5·99 ; N，10.41. 實例245 澳基-3_甲基苯甲驗基）胺基1甲基}六氮p比淀-4·基V比鍵 Ν-氧化物 按照實例200中所述之程序，以4-溴基-3-甲基苯甲醯胺 (Lancaster)取代3-甲基苯甲醯胺，提供標題化合物（10%產率） ，為白色固體。1HNMR(300MHz，DMSO·d6)(n·54(m，2H)1.89(m， 2H) 2.34 (m, 2H) 2.41 (s? 3H) 2.95 (m? 2H) 3.21 (m? 1H) 4.16 (d? J=5.8 Hz? 2H) 7.29 (m，2H) 7.39 (m，1H) 7.63 (dd，J=8.1，2.0 Hz，1H) 7.69 (d，J=8.1 Hz，1H) 7·87 (d，J=2.0 Hz，1H) 8.23 (m，1H) 8.80 (t，J=5.9 Hz，1H) ; MS (DCI/NH3) m/e404/406(M+H)+ ; 388/390(M-16)+;對€1911223办3〇2.0.8112〇之 85228 -306- 200404539 分析計算值：C，54·50 ; Η，5·68 ; N，10.04.實測值：c，54.38 ; H，5.15 ;Ν，9·75· 實例246 2·「4-(3-氰基毗啶-2-基）六氫吡畊小基l-N-「3彳甲硫基）苯基1乙醯胺 按照實例145中所述之程序，以2-氯-Ν_(3_甲硫基苯基）乙醯 胺取代得自實例143Β之產物，提供標題化合物，為黃色膠 黏性殘留物（420 毫克，82% )。1H NMR (300 MHz，CDC13) 5 2.5 (s， 3H)? 2.7 (t? 4H? J=6 Hz)? 3.22 (s? 2H)? 3.8 (t? 4H, J=6 Hz)? 6.82 (dd5 1H? J=95 6 Hz), 7.0-7.7 (m5 3H)? 7.55 (m5 1H)5 7.80 (dd5 1H3 J=95 3 Hz)? 8.38 (dd? 1H? J=6? 3 Hz)，9.07 (br s，1H) ; MS (DCI/NH3) m/e 368 (M+H)+ · 順丁烯二酸鹽：對(^911211^5〇5吐0(：4%〇4之分析計算值：c， 57·13 ; H，5.21 ; N，14.48.實測值：C，57·02 ; Η，5·20 ; N，14.45. 實例247 N-(3-弟二·丁基苯基）_2-『4-(3_氰基峨淀-2-基）六氫p比p井-i-基1乙醯胺 實例247Α Ν-(3-第三丁基笨基V2-氯乙醯胺 按照實例33Α中所述之程序，以3-第三-丁基苯胺取代3-甲 基苯胺，提供標題化合物（86%產率），為白色固體。iHNMR (300 MHz，DMSO-d6) 5 1·27 (s，9H)，4·23 (s，2H)，7.12 (ddd，1H，J=8_l，2.0, 1·4 Ηζ)，7.25 (dd，1Η，J=7.8, 7.8 Ηζ)，7_47 (ddd，1Η，J=8.1，2·0, 1·〇 Ηζ)，7·56 (dd，1Η，J=2_0, 2·0 Ηζ)，10.22 (br s，1Η) ; MS (DCI/NH3) m/e 225 (Μ+Η)+ ; 243 (M+NH4)+.Example 242D 2- "4- (2-Isopropylhydrobenzyl) hexahydropyridinylmethylbenzyl) acetamidinide Following the procedure described in Example 33C, substituting the product obtained from Example 242C from The product of Example 33B provided the title compound as a yellow oil (223 mg, 28%). 1H NMR (300 MHz, CDC13) δ 1.22 (d, 6H, J = 6 Hz), 2.25 (s, 3H), 2.65- 2.70 (m, 4H), 3.2-3.35 (m, 4H), 3.38 (s, 2H), 4_6 (m, 1H), 6.85-6_91 (m, 5H), 7.2 (t, 1H, J = 9 Hz), 7.4-7.48 (m, 2H), 9.62 (s, 1H); MS (DCI / NH3) m / e 368 (M + H) +. Maleic acid salt: para. % 〇2,0.7 € 4114〇4 Analytical calculation value: (:, 66.38; H, 7.14; N, 9.36. Found: C, 66.50; H, 6.95; N, 9.16. 85228 -304- 200404539 Examples 243 phenyl group) amine group i_2_g with an ethyl group, hexamethylene group, and stilbene group) in base hydrazine will be obtained from the product of Example 5 (500 mg, ι 49 mol) in 2N sodium hydroxide (15 A Liter) and ethanol (15 ml), heated to 100. 0, over 16 hours / hour. The reaction was cooled, concentrated, and the residue was dissolved in ethyl acetate and water. Interphase separation. The organic phase was dehydrated (sodium sulfate), filtered, and concentrated under reduced pressure to provide 18 mg (3% yield) of the title compound as a yellow semi-solid. HNMR (300 MHz, CD30D) ) Accounts for 2.32 (s, 3H), 2.77 (m, 4H), 3.23 (s, 2H), 3.42 (m, 4H), 6.94 (br d, 1H, J = 7.8 Hz), 7.00 (dd, 1H , J = 7.5, 4.8 Hz), 7.19 (dd, 1H, J = 7.8, 7.8 Hz), 7.39 (m, 2H), 7.95 (dd, 1H, J = 7.5, 2.0 Hz), 8.29 (dd, 1H, J = 4.7, 2.0 Hz); MS (DCI / NH3) m / e 354 (M + H) + · maleate: yellow solid; iHNMR (300 MHz, CD3OD) δ 2.33 〇, 3H), 3.44 (m, 4H), 3.65 (m, 4H), 4.03 (s, 2H), 6.28 (s, 2H), 6.98 (br d, 1H, J = 7.5 Hz), 7.06 (dd, 1H, J = 7.8, 5.1 Hz), 7.21 (dd, 1H, J = 7.8, 7.8 Hz), 7.40 (m, 2H), 7.94 (dd, 1H, J = 7.5, 1.7 Hz) , 8.33 (dd, 1H, J = 4.8, 1.7 Hz); Analytical calculated value for q 9H23N5 02 • 1.3C4H404: C, 57.64; H, 5.64; N, 13.89. Found: C, 57.60; 60, 5 · 61; N, 13-61. Example 244 N- (3-methylbenzyl) -2-[(2SV2-methylsome-4-pyridin-2 · ylhexapyridine -l- Certain 1 ethanethioamide is obtained from a solution of the product of Example 214 (200 mg, 0.62 mmol) in anhydrous toluene (6 ml), with 2,4-bis (4-methoxyphenyl) ) -1,3-disulfide-2,4-diphosphotetraphosphonium · 2,4-disulfide (Lawesson's reagent, 125 mg, 0.31 mmol), and heated at 65 ° C for 1 hour. The mixture was allowed to cool to room temperature and concentrated under reduced pressure 85228 -305-200404539. The residue was purified by flash column chromatography on gelatin (dissolved with 75% hexane: ethyl acetate) to provide 173 mg (82% yield) of the title compound as a yellow oil. !! 11 wake 11 (300) ^ take € 00: 13) 61.17 ((15 &gt; 6.1 take 311) 2.39 (8, 3H) 2.75 (dd, J-12_4, 9.8 Hz, 1H) 2.81 (m, 1H) 2.96 (m, 2H) 3.26 (t, J = 5_5 Hz, 1H) 3.56 (d, J = 17.6 Hz, 1H) 3.88 (d, J = 17.6 Hz, 1H) 4.04 (m, 2H) 6.67 (t, J = 6.1 Hz, 1H) 6.69 (d, J = 8.5 Hz, 1H) 7.08 (d, J = 7.5 Hz, 1H) 7.30 (t, J = 7.8 Hz, 1H) 7.52 (ddd, J = 8.7, 7.0 , 2.0 Hz, 1H) 7.67 (s, 1H) 7.74 (d, J = 8.1 Hz, 1H) 8.22 (dd5 J = 4.9, 1.9 Hz? 1H) 11.25 (s5 1H); MS (DCI / NH3) m / e 341.2 (M + H) +. φ maleate: yellow solid; iHNMR (300MHz, DMSO-d6) (5 U3 (m, 3H) 2.34 (s, 3H) 3.06 (m, 2H) 3.31 (m, 3H) 3.79 (m, 2H) 4.05 (m, 2H) 6.22 (s, 2H) 6.69 (m, 1H) 6.94 (d5 J = 7.8 Hz, 1H) 7.11 (d, J = 7.5 Hz, 1H) 7_32 (t, J = 7.1 Hz, 1H) 7.58 (d, J = 6.8 Hz, 1H) 7_63 (s, 1H) 7.71 (d, J = 7.5 Hz, 1H) 8.11 (d, J = 4.1 Hz, 1H) 11.54 (s, 1H); Analytical calculated value for C20H25N3O2 · L5C4H404: C, 58.35; Η, 5.88; N, 10.89 · Found: C, 58.35; H, 5.99 N, 10.41. Example 245 Ao-3methyl Group) amine 1 methyl} hexazine p ratio -4-group V ratio bond N-oxide Following the procedure described in Example 200, 4-bromo-3-methylbenzylamine (Lancaster) Substitution of 3-methylbenzidine provides the title compound (10% yield) as a white solid. 1HNMR (300 MHz, DMSO · d6) (n · 54 (m, 2H) 1.89 (m, 2H) 2.34 (m , 2H) 2.41 (s? 3H) 2.95 (m? 2H) 3.21 (m? 1H) 4.16 (d? J = 5.8 Hz? 2H) 7.29 (m, 2H) 7.39 (m, 1H) 7.63 (dd, J = 8.1, 2.0 Hz, 1H) 7.69 (d, J = 8.1 Hz, 1H) 7.87 (d, J = 2.0 Hz, 1H) 8.23 (m, 1H) 8.80 (t, J = 5.9 Hz, 1H); MS (DCI / NH3) m / e404 / 406 (M + H) +; 388/390 (M-16) +; For € 1911223, 3028.0.8112〇 85228 -306- 200404539 Analytical calculation value: C, 54 · 50; Hf, 5.68; N, 10.04. Found: c, 54.38; H, 5.15; N, 9.75. Example 246 2 "4- (3-Cyanopyridin-2-yl) hexa Hydropyridine 1N- "3-methylthio) phenyl 1acetamide was obtained by substitution with 2-chloro-N_ (3-methylthiophenyl) acetamide according to the procedure described in Example 145. Product of Example 143B, providing the title compound as a yellow tacky residue (420 mg, 82%) . 1H NMR (300 MHz, CDC13) 5 2.5 (s, 3H)? 2.7 (t? 4H? J = 6 Hz)? 3.22 (s? 2H)? 3.8 (t? 4H, J = 6 Hz)? 6.82 (dd5 1H? J = 95 6 Hz), 7.0-7.7 (m5 3H)? 7.55 (m5 1H) 5 7.80 (dd5 1H3 J = 95 3 Hz)? 8.38 (dd? 1H? J = 6? 3 Hz), 9.07 ( br s, 1H); MS (DCI / NH3) m / e 368 (M + H) + · Maleic acid salt: Analytical calculation for (^ 911211 ^ 5〇5 吐 0 (: 4% 〇4) : C, 57 · 13; H, 5.21; N, 14.48. Found: C, 57 · 02; Hf, 5.20; N, 14.45. Example 247 N- (3-Di-di-butylphenyl) _2 -"4- (3_cyanoamido-2-yl) hexahydro p ratio p well-i-yl 1 acetamide example 247A N- (3-Third-butylbenzyl V2-chloroacetamide according to The procedure described in Example 33A, replacing 3-methylaniline with 3-tert-butylaniline provided the title compound (86% yield) as a white solid. IHNMR (300 MHz, DMSO-d6) 5 1 · 27 (s, 9H), 4.23 (s, 2H), 7.12 (ddd, 1H, J = 8_l, 2.0, 1.4 Ηζ), 7.25 (dd, 1Η, J = 7.8, 7.8 Ηζ), 7_47 ( ddd, 1Η, J = 8.1, 2 · 0, 1 · 〇Ηζ), 7.56 (dd, 1Η, J = 2_0, 2 · 0 Ηζ), 10.22 (br s, 1Η); MS (DCI / NH3) m / e 225 (Μ + Η) +; 243 (M + NH4) +.

實例247B N-(3-t三-丁基笨某V2-〖4-(3-氰基吡啶-2·基）六氫吡畊小| 1乙醯胺 85228 -307- 200404539 將Η2·氰基吡啶基）六氬吡畊（850毫克，4·52毫莫耳，均 與N，N-二異丙基胺（5.0毫升）在甲苯（2〇毫升）中，以得自實例 247A之產物（810毫克，3.59毫莫耳）處理，並加熱至6〇艺，歷 經18小時。使混合物冷卻至室溫，轉移至分液漏斗，並以 飽和碳酸氫鈉水溶液洗滌。使有機相脫水乾燥（硫酸鈉）， 過濾、’並使滤液在減塵下濃縮。使殘留物於碎膠上夢參驟 式管柱層析純化（以25%醋酸乙酯：己烷溶離），提供984毫 克（73/產率）:^通化合物，為淡黃色固體。ipj nmr丨300 MHz， DMSO_d6) 5 1 ·27 (s，9H)，2·68 (m，4H)，3.20 (s，2H)，3.68 (m，4H)，6.93 (dd， 1H，J=7.5, 4.8 Hz)，7.09 (m，1H)，7.22 (dd，1H，J=7.8, 7.8 Hz)，7.52 (m，1H)， 7.63 (dd，1H, J=2O, 2.0 Hz)，8.07 (dd，1H，J=7.8, 2.0 Hz)，8.42 (dd，1H，J=4.7， 2.0Hz)，9.71(brs，lH); MS(DCI/NH3)m/e378 (M+H)+ ;對 c22H27N50 之分析計算值：C，70·00; H，7.21; N，18.55.實測值：c，69.76; H，7.16 ;N，18.29. 實例248 2-Γ4·(2-羥笨基）六氫吡畊小某甲某苽基）乙醯胺 按照實例232B中所述之程序，以2-(1-六氫p比呼基）紛取代得 自實例232A之產物，提供標題化合物（80%產率），為淡黃褐 色固體。1 H NMR (300 MHz，DMSO-d6) 5 2.28 (s，3H)，2·68 (m，4H)，3.01 (m，4H)，3·16 (s，2H)，6.78 (m，5H)，7.18 (dd，1H，J=7.8, 7·8 Hz)，7·45 (m，2H)， 8.90 (s，1H)，9.63 (s，1H); MS (DCI/NH3) m/e 326 (M+H)+ ;對 Q 9 H2 3 N3 02 之分析計算值：C，70.13 ; H，7.12; N，12.91.實測值：C，69.95 ; H，7.09 ;N，12.85. 實例249 85228 -308 - 200404539 244-(3-羥笨基）六氫吡啩_1-某1-N-G-甲基笨某）乙醯脖 · 按照實例232B中所述之程序，以3-(1-六氫吡畊基）酚取代得Example 247B N- (3-ttri-butylbenzyl) V2- [4- (3-cyanopyridine-2 · yl) hexahydropyridine | 1 Ethylamine 85228 -307- 200404539 Pyridyl) hexapyrine (850 mg, 4.52 mmol, both with N, N-diisopropylamine (5.0 ml) in toluene (20 ml) to give the product from Example 247A ( (810 mg, 3.59 mmol) and heated to 60 ° C over 18 hours. The mixture was allowed to cool to room temperature, transferred to a separatory funnel, and washed with saturated aqueous sodium bicarbonate solution. The organic phase was dehydrated and dried (sulfuric acid Sodium), filtered, and the filtrate was concentrated under reduced dust. The residue was purified by gel column chromatography (dissolved in 25% ethyl acetate: hexane) on crushed gel to provide 984 mg (73 / Yield): the compound is a pale yellow solid. Ipj nmr 丨 300 MHz, DMSO_d6) 5 1 · 27 (s, 9H), 2.68 (m, 4H), 3.20 (s, 2H), 3.68 (m , 4H), 6.93 (dd, 1H, J = 7.5, 4.8 Hz), 7.09 (m, 1H), 7.22 (dd, 1H, J = 7.8, 7.8 Hz), 7.52 (m, 1H), 7.63 (dd, 1H, J = 2O, 2.0 Hz), 8.07 (dd, 1H, J = 7.8, 2.0 Hz), 8.42 (dd, 1H, J = 4.7, 2.0Hz), 9.71 (brs, lH); MS (DCI / NH3) m / e378 (M + H) +; Analytical calculation for c22H27N50: C, 70 · 00; H, 7.21; N, 18.55 Measured values: c, 69.76; H, 7.16; N, 18.29. Example 248 2-Γ4 · (2-hydroxybenzyl) hexahydropyroxymethyl, some methyl, some methyl, and some ethyl) acetamide as described in Example 232B. Procedure, substituting the product from Example 232A with 2- (1-hexahydrop-pyhyl) to provide the title compound (80% yield) as a pale yellow-brown solid. 1 H NMR (300 MHz, DMSO-d6) 5 2.28 (s, 3H), 2.68 (m, 4H), 3.01 (m, 4H), 3.16 (s, 2H), 6.78 (m, 5H) , 7.18 (dd, 1H, J = 7.8, 7.8 Hz), 7.45 (m, 2H), 8.90 (s, 1H), 9.63 (s, 1H); MS (DCI / NH3) m / e 326 (M + H) +; Analytical calculated values for Q 9 H2 3 N3 02: C, 70.13; H, 7.12; N, 12.91. Found: C, 69.95; H, 7.09; N, 12.85. Example 249 85228- 308-200404539 244- (3-Hydroxybenzyl) hexahydropyridine_1-some 1-NG-methylbenzyl) acetamidine · Follow the procedure described in Example 232B, using 3- (1-hexahydro Pyridyl) phenol substitution

V 自實例232A之產物，提供標題化合物（77%產率），為白色固 體。1HNMR(300 MHz，DMSad6)62.27 (s，3H)，2.64 (m，4H)，3.14 (m， 4H)，3.16 (s，2H)，6.20 (dd，1H，J=8.5, 2_7 Hz)，6.31 (dd，1H，J=2.0, 2.0 Hz)， 6.38 (dd，1H，J=8.1，2.0 Hz)，6.87 (d，1H，J=7.5 Hz)，6.98 (dd，1H，J=8.1，8·1 Hz)，7.18 (dd，1H，J=7.8, 7.8 Hz)，7.44 (m，2H)，9.09 (s，1H)，9·64 (s，1H) ; MS (DCI/NH3)m/e326(M+H)+ ;對(：191123化02之分析計算值：C，70.13 _ ;H，7·12 ; N，12·91·實測值：C，69·91 ; H，7·19 ; N，12.69. 實例250 244-(4-蕤苯某）六氫吡畊小某甲基苯基）乙醯胺 按照實例232B中所述之程序，以4-(1-六氫吡畊基）酚取代得 自實例232A之產物，提供標題化合物（39%產率），為淡黃色 固體。1H NMR (300 MHz，DMSO-d6) δ 2.27 (s，3H)，2_64 (m，4H)，3.03 (m， 4H)，3·15 (s，2H)，6·64 (AA’BB’，2H，J=8.8 Hz), 6·79 (AA’BB，，2H，J=8.8 Hz)， 6.87 (d，1H，J=7.5 Hz)，7.18 (dd，1H，J=7.8, 7.8 Hz)，7.44 (m，2H)，8.79 (s，1H)， 0 9·63 (s，1H) ; MS (DCI/NH3) m/e 326 (M+H)+ ;對 C! 9 H2 3 N3 02 之分析 計算值：C，70.13 ; H，7.12 ; N，12.91·實測值：C，69·82 ; H，7.21 ; N, 12.81. 實例251 244-(2•乙氣笨某）六氫哄畊小基1_Ν·(3·甲基笨基）乙醯胺 按照實例232Β中所述之程序，以1-(2-乙氧苯基）六氫吡畊取 代得自實例232A之產物，提供標題化合物（84%產率），為白 色固體。1 H NMR (300 MHz，DMSO-d6) 51.34 (t，3H，J=6.8 Ηζ)，2·28 (s， 85228 •309- 200404539 3H)，2·67 (m，4H)，3.06 (m，4H)，3·17 (s，2H)，4.01 (q，2H，J=7.1 Hz)，6.90 (m， · 5H)，7.18 !：dd，1H，J=7.5, 7.5 Hz)，7.45 (m，2H)，9.64 (s，1H) ; MS (DCI/NH3)V The product from Example 232A provided the title compound (77% yield) as a white solid. 1HNMR (300 MHz, DMSad6) 62.27 (s, 3H), 2.64 (m, 4H), 3.14 (m, 4H), 3.16 (s, 2H), 6.20 (dd, 1H, J = 8.5, 2_7 Hz), 6.31 (dd, 1H, J = 2.0, 2.0 Hz), 6.38 (dd, 1H, J = 8.1, 2.0 Hz), 6.87 (d, 1H, J = 7.5 Hz), 6.98 (dd, 1H, J = 8.1, 8 · 1 Hz), 7.18 (dd, 1H, J = 7.8, 7.8 Hz), 7.44 (m, 2H), 9.09 (s, 1H), 9.64 (s, 1H); MS (DCI / NH3) m / e326 (M + H) +; Analytical calculation value for (: 191123 Hua02: C, 70.13 _; H, 7.12; N, 12.91. Found: C, 69.91; H, 7.19 N, 12.69. Example 250 244- (4-Benzophenone) Hexahydropyroxymethylmethylphenyl) acetamidine Following the procedure described in Example 232B, The product obtained from Example 232A was substituted with phenol to provide the title compound (39% yield) as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 2.27 (s, 3H), 2_64 (m, 4H), 3.03 (m, 4H), 3.15 (s, 2H), 6.64 (AA'BB ', 2H, J = 8.8 Hz), 6.79 (AA'BB ,, 2H, J = 8.8 Hz), 6.87 (d, 1H, J = 7.5 Hz), 7.18 (dd, 1H, J = 7.8, 7.8 Hz) , 7.44 (m, 2H), 8.79 (s, 1H), 0 9 · 63 (s, 1H); MS (DCI / NH3) m / e 326 (M + H) +; for C! 9 H2 3 N3 02 Analytical and calculated values: C, 70.13; H, 7.12; N, 12.91. Measured values: C, 69.82; H, 7.21; N, 12.81. Example 251 244- (2 • Ethylbenzyl) Hexahydro Small 1-N · (3 · methylbenzyl) acetamidinide was substituted for the product obtained from Example 232A with 1- (2-ethoxyphenyl) hexahydropyridine according to the procedure described in Example 232B to provide the title compound (84% yield) as a white solid. 1 H NMR (300 MHz, DMSO-d6) 51.34 (t, 3H, J = 6.8 Ηζ), 2.28 (s, 85228 • 309- 200404539 3H), 2.67 (m, 4H), 3.06 (m, 4H), 3.17 (s, 2H), 4.01 (q, 2H, J = 7.1 Hz), 6.90 (m, · 5H), 7.18 !: dd, 1H, J = 7.5, 7.5 Hz), 7.45 (m , 2H), 9.64 (s, 1H); MS (DCI / NH3)

A m/e354(M+H)+·對（^2〇%5巧0 · 0·20Η2〇之分析計算值：C，70.64 ♦ * . , 《 · ;H，7·73 ; N，11 ·77·實測值：C，70.74 ; H，7·56 11.78· 實例252 -» ♦ N-(3-甲基笨某V2-{442-(甲硫基）苯某1六氫吡畊小基}乙醯胺 按照實例232B中所述之程序，以1-(2-甲硫基苯基）六氫吡畊 取代得自實例232A之產物，提供標題化合物（84%產率），為 籲 黃色油。1 H NMR (300 MHz，DMSO-d6) 5 2.28 (s，3H)，2.36 (s，3H)，2.68 (m，4H)，2.97 (m，4H)，3·18 (s，2H)，6.88 (d，1H，J=7.8 Ηζ)，7·12 (m，5H) 7.45 (m，2H)，9·64 (s，1H) ; MS (DCI/NH3) m/e 356 (M+H)+. 順丁晞二酸鹽：白色固體；對〇201125^[3〇3，1.00：4114〇4之分析 計算值·· C，61.13 ; H，6.20 ; N，8.91.實測值：C，60·78 ; Η，6·11; Ν，8·81· 實例253 2-「4-(2-氟笨基V六氫吡畊小某甲基笨基）乙醯胺 按照實例232Β中所述之程序，以1-(2-氟苯基）六氫吡畊取代 φ 得自實例232A之產物，提供標題化合物（84%產率），為黃褐 色固體。1 H NMR (300 MHz，DMSO-d6) 5 2.28 (s，3H)，2.69 (m，4H)，3.09 (m，4H)，3.18 (s，2H)，6.88 (d，1H，J=7.8 Hz)，7.06 (m，4H)，7.18 (dd，1H，J=7.8， 7.8 Hz)? 7.45 (m5 2H)? 9.65 (s5 1H) ； MS (DCI/NH3) m/e 328 (M+H)+ ；對 C19H22FN30 之分析計算值：c，69.70 ; H，6.77 ; N，12.83.實測值 ·· C，69.52 ; H，6·73 ; N，12.80. 實例254 2-「4-(3-氰基吡啶-2-基）六氫吡畊小基氟笨基）乙醯胺 85228 -310- 200404539A m / e354 (M + H) + · Analytical calculation value for (^ 20% 50% 0 · 20 · 20Η20): C, 70.64 ♦ *., "·; H, 7.73; N, 11 · 77 · Measured value: C, 70.74; H, 7.56 11.78 · Example 252-»♦ N- (3-methylbenzyl V2- {442- (methylthio) benzene 1 hexahydropyridine small group} Acetylamine was substituted for the product from Example 232A with 1- (2-methylthiophenyl) hexahydropyridine according to the procedure described in Example 232B to provide the title compound (84% yield) as a yellow oil 1 H NMR (300 MHz, DMSO-d6) 5 2.28 (s, 3H), 2.36 (s, 3H), 2.68 (m, 4H), 2.97 (m, 4H), 3.18 (s, 2H), 6.88 (d, 1H, J = 7.8 Ηζ), 7.12 (m, 5H) 7.45 (m, 2H), 9.64 (s, 1H); MS (DCI / NH3) m / e 356 (M + H ) +. Maleic acid salt: white solid; analytically calculated value for 2011201 ^ [3〇3, 1.00: 4114〇4 · C, 61.13; H, 6.20; N, 8.91. Found: C, 60 · 78; hydrazone, 6.11; Ν, 8 · 81 · Example 253 2- "4- (2-Fluorobenzyl V hexahydropyridine methylmethylbenzyl) acetamidamine as described in Example 232B Procedure, replacing φ with 1- (2-fluorophenyl) hexahydropyridine. Product from Example 232A The title compound was provided (84% yield) as a tan solid. 1 H NMR (300 MHz, DMSO-d6) 5 2.28 (s, 3H), 2.69 (m, 4H), 3.09 (m, 4H), 3.18 ( s, 2H), 6.88 (d, 1H, J = 7.8 Hz), 7.06 (m, 4H), 7.18 (dd, 1H, J = 7.8, 7.8 Hz)? 7.45 (m5 2H)? 9.65 (s5 1H); MS (DCI / NH3) m / e 328 (M + H) +; Analytical calculated value for C19H22FN30: c, 69.70; H, 6.77; N, 12.83. Measured value · C, 69.52; H, 6.73; N, 12.80. Example 254 2- "4- (3-Cyanopyridin-2-yl) hexahydropyridine small fluorobenzyl) acetamide 85228 -310- 200404539

實例254A 1 氯氯苯基）乙醯胺 按照實例33A中所述之程序，以3_氟苯基胺取代3-甲基笨 胺’提供標題化合物，為白色固體。1H NMR (3〇〇 mHz，CDC13) δ 4·19 (s，2H)，6.88 (dddd，1H，J=8.1，8.1，2.7, 1·0 Hz)，7·19 (ddd，1H，J=8.1， 2.0, 1·0 Hz)，7·31 (ddd，1H，J=8.1，8.1，6.4 Hz)，7.52 (ddd，1H，J=10.6, 2.3, 2·3 Hz)，8·26 (br s，1H) ; MS (DCI/NH3 ) m/e 187 (M+H)+ ; 205 (M+NH4)+ ·Example 254A 1 Chlorochlorophenyl) acetamide Following the procedure described in Example 33A, substituting 3-fluorophenylamine for 3-methylbenzylamine 'provided the title compound as a white solid. 1H NMR (300mHz, CDC13) δ 4.19 (s, 2H), 6.88 (dddd, 1H, J = 8.1, 8.1, 2.7, 1.0 Hz), 7.19 (ddd, 1H, J = 8.1, 2.0, 1.0 Hz), 7.31 (ddd, 1H, J = 8.1, 8.1, 6.4 Hz), 7.52 (ddd, 1H, J = 10.6, 2.3, 2.3 Hz), 8.26 ( br s ， 1H); MS (DCI / NH3) m / e 187 (M + H) +; 205 (M + NH4) + ·

實例254B 2-PH3-氰基吡啶-2-基）六氫吡畊—μ基氟茉基）乙醯胺 按照實例247B中所述之程序，以得自實例254A之產物取代 得自實例247A之產物，提供標題化合物（81%產率），為黃褐 色固體。1 H NMR (300 MHz, DMSOd6) 5 2.68 (m，4H)，3.23 (s, 2H)，3.68 (m，4H)，6·89 (m，1H)，6·93 (dd，1H，J=7.8, 4·8 Hz)，7.34 (ddd，1H，J=8.0, 8.0， 6·6 Hz)，7.42 (ddd，1H，J=8.1，1.5, 1.5 Hz)，7.65 (ddd，1H，J=11.7, 2.4, 2·4 Hz)， 8.07 (dd，1H，J=7.5, 2·0 Hz)，8.42 (dd，1H，J=4.8, 2.0 Hz)，9.98 (br s，1H) ; MS (DCI/NH3) m/e 340 (M+H)+ ;對 Ci 8 Hi 8 FN5 O 之分析計算值：C，63.71 ;H，5·35; N，20.64.實測值：C，63.59 ; H，5.11; N，20.56. 實例255 N_G-溴苯某）-244-(3-氰基吡啶-2-基）六氫吡畊小基1乙醯胺Example 254B 2-PH3-Cyanopyridin-2-yl) hexahydropyridine- [mu] fluorofluoromolyl) acetamide Follow the procedure described in Example 247B, replacing the product from Example 254A with the product from Example 247A. The product provided the title compound (81% yield) as a tan solid. 1 H NMR (300 MHz, DMSOd6) 5 2.68 (m, 4H), 3.23 (s, 2H), 3.68 (m, 4H), 6.89 (m, 1H), 6.93 (dd, 1H, J = 7.8, 4 · 8 Hz), 7.34 (ddd, 1H, J = 8.0, 8.0, 6.6 Hz), 7.42 (ddd, 1H, J = 8.1, 1.5, 1.5 Hz), 7.65 (ddd, 1H, J = 11.7, 2.4, 2.4 Hz), 8.07 (dd, 1H, J = 7.5, 2.0 Hz), 8.42 (dd, 1H, J = 4.8, 2.0 Hz), 9.98 (br s, 1H); MS ( DCI / NH3) m / e 340 (M + H) +; Analytical calculation for Ci 8 Hi 8 FN5 O: C, 63.71; H, 5.35; N, 20.64. Found: C, 63.59; H, 5.11; N, 20.56. Example 255 N_G-Bromobenzene) -244- (3-cyanopyridine-2-yl) hexahydropyridine 1 acetamide

實例255A I * f Ν-(3-溴笨基V2-氣乙醯胺 按照實例33Α中所述之程序，以3-溴苯基胺取代3-甲基苯 胺，提供標題化合物（100%產率），為白色固體。iHNMR (300 MHz，CDC13) 5 4·19 (s，2H)，7.24 (m，1H)，7·31 (m，1H)，7.47 (m，1H)， 85228 -311 - 200404539 7.81 (dd; 1H，J=1.9, 1.9 Hz)，8.20 (br s，1Η) ; MS (DCI/NH3 ) m/e 248/250 (M+H)+ ； 263/265 (M+NH4)+.Example 255A I * f Ν- (3-Bromobenzyl V2-ptoethylammoniumamine Following the procedure described in Example 33A, 3-methylaniline was replaced with 3-bromophenylamine to provide the title compound (100% yield ) As a white solid. IHNMR (300 MHz, CDC13) 5 4 · 19 (s, 2H), 7.24 (m, 1H), 7.31 (m, 1H), 7.47 (m, 1H), 85228 -311- 200404539 7.81 (dd; 1H, J = 1.9, 1.9 Hz), 8.20 (br s, 1Η); MS (DCI / NH3) m / e 248/250 (M + H) +; 263/265 (M + NH4) +.

* 實例255B 攻溴苯基）_2-[4_(3-氰基峨淀_2_基）六氫峨啡_i_某i乙醯胺 按照實例247B中所述之程序，以得自實例255A之產物取代 得自實例247A之產物，提供標題化合物（84%產率），為黃褐 色固體。1 H NMR (300 MHz，DMSO-d6) δ 2·68 (m，4H)，3.22 (s，2H)，3.69 (m，4Η)，6·93 (dd，J=7.5, 4.8 Ηζ，1Η)，7.26 (m5 2Η)，7.62 (ddd，J=7.1，2.0, 2·0* Example 255B Tacrobromophenyl) _2- [4_ (3-cyanoedian_2_yl) hexahydroerphine_i_some i acetamide Follow the procedure described in Example 247B to obtain from Example 255A This product replaced the product from Example 247A to provide the title compound (84% yield) as a tan solid. 1 H NMR (300 MHz, DMSO-d6) δ 2.68 (m, 4H), 3.22 (s, 2H), 3.69 (m, 4Η), 6.93 (dd, J = 7.5, 4.8 Ηζ, 1Η) , 7.26 (m5 2Η), 7.62 (ddd, J = 7.1, 2.0, 2.0

Hz? 1H), 8.00 (m5 1H)? 8.07 (dd? 1H5 J=7.5? 1.7 Hz)5 8.42 (dd? 1H5 J=4.7, 1.7 Hz )，9.94 (br s，1H) ; MS (DCI/NH3) m/e 400/402 (M+H)+ ;對 q 8 氏 8 BrN5 O 之分析計算值：C54.01 ; H，4·53 ; N，17.50·實測值：C，54.02; H，4.37 ;N，17.63. 實例256 N-(3-甲基苯基）-2_(4-p比違_2-基六氫峨$ -1-基）乙燒硫縫脸 將得自實例4之產物（250毫克，0.81毫莫耳）在無水甲苯（6 毫升）中之溶液，以2,4·雙（4-甲氧苯基）_1，3_二硫·2,4·二磷四圜-2,4-二硫化物（Lawesson氏試劑，163毫克，0.4毫莫耳）處理， 並於65°C下加熱1小時。使混合物冷卻至室溫，及在減壓下 濃縮。使殘留物於矽膠上藉急騾式管柱層析純化（以75%己 燒；：醋酸乙酯溶離），提供185毫克（70%產率）標題化合物， 為灰白色固體。1 H NMR (300 MHz，CDC13) 5 2.39 (s，3H) 2.77 (m，4H) 3.65 (m，6H) 6·68 (m，2H) 7.08 (d，J=7.5 Hz，1H) 7.30 (t，J=7.8 Hz，1H) 7·51 (ddd，J=8.7, 7.0, 2·0 Hz，1H) 7.67 (s，1H) 7.75 (d，J=8.1 Hz，1H) 8.21 (ddd，J= 4.9, 1.9, 0.7 Hz，1H) 11.04 (br s，1H) ; MS (DCI/NH3) m/e 327 (M+H)+ ;對 85228 -312- 200404539 q 8H22N4S 之分析計算值：c，66.22 ; H，6.79 ; N，17.16.實測值： C，66.15 ; Η，6·79 ; N，17.00· 實例257 胺4苯基）六氳吨j7井·1_基甲葚节其祕胺 將得自實例7之產物（299毫克，0.636毫莫耳）在f醇(20毫升） 中之溶液，以10%鈀/碳處理，並於6〇批氫及室溫下放置8〇 分鐘。過滤不均勻之混合物，在減壓下濃縮，並使殘留物 於2N氫氧化鈉與二氯甲烷之間分配。使有機相脫水乾燥（硫 酸鋼）’過濾，及在減壓下濃縮，提供標題化合物（160毫克 ，78%產率），為淡黃褐色固體，其係於靜置時變暗色。 iHNMRpOOMHADMSO-c^) 5 2.28 (s，3H)，2.69 (m，4H)，2.87 (m，4H)， 3.17 (s，2H)，4·69 (s，2H)，6.55 (ddd，1H，J=7.5, 7.5, 1·7 Hz)，6.66 (dd，1H，J=7.8, 1.4 Hz)，6.80 (ddd，1H，J=7.5, 7.5, 1.4 Hz)，6.88 (m，1H)，6.92 (dd，1H，J=7.8， 1.4 Hz)，7.19 (dd，1H，J=7.8, 7.8 Hz)，7.46 (m，2H)，9_63 (s，1H); MS (DCI/NH3) m/e325 (M+H)+，對(^9Η24Ν40·0·〇5〇Η2α2 之分析計算值：c，69.62 ;H，7.39 ; N，17.05.實測值·· C，69.52 ; Η，7·32 ; N，17.13. 實例258 N-(3-硝基苯基V2-(4-峨淀·2·基六氫p比呼-1_基）己酼脸 將1-(2•吡啶基）六氫吡畊（0.65毫升，4.3毫莫耳，Aldrich)與N，N-二異丙基胺（5.0毫升）在甲苯(20毫升）中，以2-氯-N-(3-硝基苯 基）乙醯胺（750毫克，3.49毫莫耳，Lancaster)處理，並加熱至6〇 °C，歷經18小時。使混合物冷卻至室溫，轉移至分液漏斗， 並以飽和碳酸氫鈉水溶液洗滌。使有機相脫水乾燥（硫酸姜内） ，過滤，並使濾液在減壓下濃縮。使殘留物於碎膠上藉急Hz? 1H), 8.00 (m5 1H)? 8.07 (dd? 1H5 J = 7.5? 1.7 Hz) 5 8.42 (dd? 1H5 J = 4.7, 1.7 Hz), 9.94 (br s, 1H); MS (DCI / NH3 ) m / e 400/402 (M + H) +; Analytical calculated value for q 8 s 8 BrN5 O: C54.01; H, 4.53; N, 17.50. Found: C, 54.02; H, 4.37 ; N, 17.63. Example 256 N- (3-methylphenyl) -2_ (4-p bis_2-ylhexahydroe $ -1-yl) ethoxysulfur suture face will be obtained from the product of Example 4 (250 mg, 0.81 mmol) in anhydrous toluene (6 ml) with 2,4 · bis (4-methoxyphenyl) _1,3_disulfide · 2,4 · diphosphotetraphosphonium- Treated with 2,4-disulfide (Lawesson's reagent, 163 mg, 0.4 mmol) and heated at 65 ° C for 1 hour. The mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was purified on silica gel by flash column chromatography (75% hexane; ethyl acetate) to provide 185 mg (70% yield) of the title compound as an off-white solid. 1 H NMR (300 MHz, CDC13) 5 2.39 (s, 3H) 2.77 (m, 4H) 3.65 (m, 6H) 6.68 (m, 2H) 7.08 (d, J = 7.5 Hz, 1H) 7.30 (t , J = 7.8 Hz, 1H) 7.51 (ddd, J = 8.7, 7.0, 2.0 Hz, 1H) 7.67 (s, 1H) 7.75 (d, J = 8.1 Hz, 1H) 8.21 (ddd, J = 4.9, 1.9, 0.7 Hz, 1H) 11.04 (br s, 1H); MS (DCI / NH3) m / e 327 (M + H) +; Analysis and calculation of 85228 -312- 200404539 q 8H22N4S: c, 66.22 H, 6.79; N, 17.16. Measured values: C, 66.15; Hf, 6.79; N, 17.00. Example 257 Amine 4phenyl) Hexatonium j7 well 1-methylformamidine. A solution of the product of Example 7 (299 mg, 0.636 mmol) in f-alcohol (20 ml) was treated with 10% palladium / carbon and left in 60 batches of hydrogen at room temperature for 80 minutes. The heterogeneous mixture was filtered, concentrated under reduced pressure, and the residue was partitioned between 2N sodium hydroxide and dichloromethane. The organic phase was dried (sulphate) and filtered and concentrated under reduced pressure to provide the title compound (160 mg, 78% yield) as a pale yellow-brown solid which darkened upon standing. iHNMRpOOMHADMSO-c ^) 5 2.28 (s, 3H), 2.69 (m, 4H), 2.87 (m, 4H), 3.17 (s, 2H), 4.69 (s, 2H), 6.55 (ddd, 1H, J = 7.5, 7.5, 1.7 Hz), 6.66 (dd, 1H, J = 7.8, 1.4 Hz), 6.80 (ddd, 1H, J = 7.5, 7.5, 1.4 Hz), 6.88 (m, 1H), 6.92 ( dd, 1H, J = 7.8, 1.4 Hz), 7.19 (dd, 1H, J = 7.8, 7.8 Hz), 7.46 (m, 2H), 9_63 (s, 1H); MS (DCI / NH3) m / e325 ( M + H) +, Analytical calculated value for (^ 9Η24N40 · 0 · 〇50〇2α2: c, 69.62; H, 7.39; N, 17.05. Measured value · C, 69.52; Η, 7.32; N, 17.13. Example 258 N- (3-Nitrophenyl V2- (4-Edo · 2 · Hydroxyhexahydropaphu-1_yl) Hexylacetate 1- (2 • pyridyl) hexahydropyridine (0.65 ml, 4.3 mmol, Aldrich) with N, N-diisopropylamine (5.0 ml) in toluene (20 ml) with 2-chloro-N- (3-nitrophenyl) acetamidine Amine (750 mg, 3.49 mmol, Lancaster) was treated and heated to 60 ° C. for 18 hours. The mixture was cooled to room temperature, transferred to a separatory funnel, and washed with a saturated aqueous sodium bicarbonate solution. Phase dehydrated (inside ginger sulfate), filtered, and The filtrate was concentrated under reduced pressure. The residue was broken by the acute gum

85228 -313- 200404539 驟式管柱層析純化（以25%醋酸乙酯：己烷溶離），提供900 - 毫克（76%產率）標題化合物，為黃褐色固體。IjjnMR (3〇〇mHz， DMSO-d6) δ 2·62 (m，4H)，3·24 (s，2H)，3·56 (m，4H)，6.63 (ddd，1H，J=7.1， • , 4·7, O·7 Hz)，6·83 (d，1H，J=8.8 Hz)，7.52 (ddd，1H，J=8.5, 7.1，2.0)，7.61 (dd， 1H，J=8.5, 8.5 Hz)，7.92 (ddd，1H，J=8.1，2·4, 1.0 Hz)，8.04 (ddd，1H，J=8.5, 2.4， 1.0 Hz)，8·11 (ddd，1H，J=4.8, 1.7, 0.7 Hz)，8.70 (dd，1H，J=2.0, 2.0 Hz)，10.27 (br s，1H) ; MS (DCI/NH3) m/e 342 (M+H)+ ;對 q 79 N5 03 之分析計 算值：C，59.81 ; H，5·61 ; N，20.52.實測值：C，59.61 ; H，5·55 ; N，20.23.⑩ 實例259 2-『4-(2-氯基苯基）六氫峨_ -1-基梢基笨基）乙酸胺 按照實例258中所述之程序，以2-六氫吡畊-1-基苯甲腈（Chess) 取代1-(2-吡啶基）六氫吡畊，提供標題化合物（58%產率），為 白色固體。1HNMR(300MHz，DMSOd6)5 2·74(m，4H)，3·24(m，4H)， 3.29 (s，2H)，7.10 (ddd，1H，J=7.5, 7.5, 0·7 Hz)，7.19 (d，1H，J=8.5 Hz)，7.61 (m， 2H)，7.70 (dd，1H，J=7.8, 1.7 Hz)，7.93 (ddd，1H，J=8.5, 2.4, 1.0 Hz)，8.04 (ddd5 1H，J=8.5, 2.4, 1.0 Hz)，8.70 (dd，1H，J=2.0, 2.0 Hz)，10.28 (br s，1H) ; MS _ (DCI/NH3) m/e 366 (M+H)+ ;對 Q 9 9N5 03 之分析計算值：C，62.46 ;H，5·24 ; N，19.17·實測值·· C，62_41 ; H，5·02 ; N，19·08_ , 實例260 氯某笨基^比淀·2-基六氮p比呼_1-基）乙酿胺 按照實例258中所述之程序，以2-氯-N-(3-氰基苯基）乙醯胺 (Maybridge)取代2-氯-N-(3-硝基苯基）乙醯胺，提供標題化合物（79 % 產率），為白色固體。4 NMR (300 MHz，DMSO-d6) 5 2.61 (m，4H)， 3·22 (s，2H)，3.56 (m，4H)，6.63 (ddd，1H，J=7.1，5.1，0·7 Ηζ)，6·83 (d，1H，J= 85228 -314- 200404539 〜8·5 Hz)，7.52 (m，3H)，7.95 (m，1Η)，8·11 (ddd，1H，J=4.7, 2.0, 0.7 Hz)，8.15 (m， 1H)，10_10 (br s，1H) ; MS (DCI/NH3) m/e 322 (M+H)+ ;對 Q 8氏 9N5 O 之分析計算值：C，67.27; H，5.96; N，21·79·實測值：C，67.27; H，5.97 ；N? 21.73. t ♦ 實例261 Ν-(3·氰基笨基）_2-[4-(2-氰某苽基）六氫吡畊-1-基1乙醯胺 按照實例258中所述之程序，以2-氯-N-(3-氰基苯基）乙醯胺 (Maybridge)取代2-氯-N-(3_硝基苯基）乙醯胺，並以2-六氫吡畊-1_ 基苯甲腈（Chess)取代1-(2-吡啶基）六氫吡畊，提供標題化合物 (74% 產率），為白色固體。iHNMRpOOMHADMSOc^) 5 2.73 (m， 4H)，3.23 (m，4H)，3.27 (s，2H)，7.10 (ddd，1H，J=7.8, 7.8, 1.0 Hz)，7.19 (d，1H， J=8.5 Hz), 7.53 (m5 2H)5 7.61 (ddd5 1H5 J=8.5? 7.5, 1.7 Hz), 7.70 (dd5 1H5 J=7.85 1·7 Hz)，7_94 (m, 1H), 8.14 (m，1H)，10.11 (br s，1H); MS (DCI/NH3) m/e 346 (M+H)+ ;對 C2〇H19N50 · 0.1 H20 · 0.05 CH2C12 之分析計算值： C，68.52 ; H，5.54 ; N，19.93·實測值：C，68·52 ; H，5.52 ; N，19_81· 實例262 L[4-(3-氰基吡啶-2·基）六氫吡畊小基l-N-(五氟笨基）乙醯胺85228 -313- 200404539 Purification by flash column chromatography (isolated with 25% ethyl acetate: hexane) provided 900-mg (76% yield) of the title compound as a tan solid. IjjnMR (300mHz, DMSO-d6) δ 2.62 (m, 4H), 3.24 (s, 2H), 3.56 (m, 4H), 6.63 (ddd, 1H, J = 7.1, • , 4 · 7, O · 7 Hz), 6.83 (d, 1H, J = 8.8 Hz), 7.52 (ddd, 1H, J = 8.5, 7.1, 2.0), 7.61 (dd, 1H, J = 8.5, 8.5 Hz), 7.92 (ddd, 1H, J = 8.1, 2.4, 1.0 Hz), 8.04 (ddd, 1H, J = 8.5, 2.4, 1.0 Hz), 8.11 (ddd, 1H, J = 4.8, 1.7, 0.7 Hz), 8.70 (dd, 1H, J = 2.0, 2.0 Hz), 10.27 (br s, 1H); MS (DCI / NH3) m / e 342 (M + H) +; for q 79 N5 03 Analytical calculated values: C, 59.81; H, 5.61; N, 20.52. Found: C, 59.61; H, 5.55; N, 20.23. ⑩ Example 259 2- 『4- (2-Chlorobenzene Base) Hexahydro-1--1-ylpyridyl) amine acetate Substitute 1- (2-pyridine) with 2-hexahydropyrine-1-ylbenzonitrile (Chess) according to the procedure described in Example 258. Hexahydropyracine provided the title compound (58% yield) as a white solid. 1HNMR (300MHz, DMSOd6) 5 2.74 (m, 4H), 3.24 (m, 4H), 3.29 (s, 2H), 7.10 (ddd, 1H, J = 7.5, 7.5, 0.7 Hz), 7.19 (d, 1H, J = 8.5 Hz), 7.61 (m, 2H), 7.70 (dd, 1H, J = 7.8, 1.7 Hz), 7.93 (ddd, 1H, J = 8.5, 2.4, 1.0 Hz), 8.04 (ddd5 1H, J = 8.5, 2.4, 1.0 Hz), 8.70 (dd, 1H, J = 2.0, 2.0 Hz), 10.28 (br s, 1H); MS _ (DCI / NH3) m / e 366 (M + H) +; Analytical calculated values for Q 9 9N5 03: C, 62.46; H, 5.24; N, 19.17. Measured value. C, 62_41; H, 5.02; N, 19.08_, Example 260 A chlorobenzyl bispyridine · 2-ylhexaaza ppyhyl-1-yl) ethylamine was prepared according to the procedure described in Example 258 with 2-chloro-N- (3-cyanophenyl) acetamidine The amine (Maybridge) replaced 2-chloro-N- (3-nitrophenyl) acetamidamine to provide the title compound (79% yield) as a white solid. 4 NMR (300 MHz, DMSO-d6) 5 2.61 (m, 4H), 3.22 (s, 2H), 3.56 (m, 4H), 6.63 (ddd, 1H, J = 7.1, 5.1, 0.7 Ηζ ), 6.83 (d, 1H, J = 85228 -314- 200404539 to 8.5 Hz), 7.52 (m, 3H), 7.95 (m, 1Η), 8.11 (ddd, 1H, J = 4.7, 2.0, 0.7 Hz), 8.15 (m, 1H), 10_10 (br s, 1H); MS (DCI / NH3) m / e 322 (M + H) +; Analytical calculated value for Q 8's 9N5 O: C , 67.27; H, 5.96; N, 21 · 79 · Measured values: C, 67.27; H, 5.97; N? 21.73. T ♦ Example 261 Ν- (3 · cyanobenzyl) _2- [4- (2- Substitute 2-chloro-N- (3-cyanophenyl) acetamide (Maybridge) for 2-chloro-N- (3-cyanophenyl) acetamide (Maybridge) following the procedure described in Example 258. Chloro-N- (3-nitrophenyl) acetamidine and replacing 1- (2-pyridyl) hexahydropyridine with 2-hexahydropyridine-1_ylbenzonitrile (Chess) to provide the title compound (74% yield) as a white solid. iHNMRpOOMHADMSOc ^) 5 2.73 (m, 4H), 3.23 (m, 4H), 3.27 (s, 2H), 7.10 (ddd, 1H, J = 7.8, 7.8, 1.0 Hz), 7.19 (d, 1H, J = 8.5 Hz), 7.53 (m5 2H) 5 7.61 (ddd5 1H5 J = 8.5? 7.5, 1.7 Hz), 7.70 (dd5 1H5 J = 7.85 1 · 7 Hz), 7_94 (m, 1H), 8.14 (m, 1H), 10.11 (br s, 1H); MS (DCI / NH3) m / e 346 (M + H) +; Analytical calculated value for C20H19N50 · 0.1 H20 · 0.05 CH2C12: C, 68.52; H, 5.54; N, 19.93. Found: C, 68.52; H, 5.52; N, 19_81. Example 262 L [4- (3-cyanopyridine-2.yl) hexahydropyridine 1N- (pentafluorobenzyl) Acetamide

實例262A 2-氯-N-(五氟笨基）乙醯胺 按，照實例22A中所述之程序，以五氟苯基胺取代3,4,5-三甲 氧基苯胺，提供標題化合物（94%產率），為黃褐色固體。1Η NMR(300 MHz? DMSO-d6) δ 3.31 (s? 2H)? 10.48 (br s? 1H)； MS (DCI/NH3) m/e259(M+H)+ ； 277(M+NH4)+.Example 262A 2-Chloro-N- (pentafluorobenzyl) acetamide Following the procedure described in Example 22A, 3,4,5-trimethoxyaniline was replaced with pentafluorophenylamine to provide the title compound ( 94% yield) as a tan solid. 1Η NMR (300 MHz? DMSO-d6) δ 3.31 (s? 2H)? 10.48 (br s? 1H); MS (DCI / NH3) m / e259 (M + H) +; 277 (M + NH4) +.

實例262B 85228 -315- 200404539 2-「4_(3-氰基批啶-2-基）六氫吡畊小基1-N-(五氟笨基）乙醯胺 · 按照實例247B中所述之程序，以得自實例262A之產物取代 得自貪例247A之產物，提供標題化合物（71%產率），為油狀 物。1HNMR(300MHz，DMSO-d6) 5 2.69 (m，4H)，3.32 (s，2H)，3.69 (m， 4H)5 6.93 (dd? 1H? J=7.8, 4.8 Hz)? 8.07 (dd5 1H? J=7.8? 2.0 Hz)? 8.42 (dd, 1¾ J= 4.8, 1.7 Hz)，9.93 (br s，1H) ; MS (DCI/NH3) m/e 412. 順丁烯二酸鹽：白色固體；1HNMR(300MHz，CD3OD)53.18(m， 4H)，3.84 (s，2H)，3.87 (m，4H)，6·28 (s，2H)，6.98 (dd，1H，J=7.8, 5.1 Hz)，7.99 φ (dd，1H，J=7.8, 2.0 Hz), 8.42 (dd，1H，J=4.7, 1.7 Hz);對 q 8 呒 4 F5 N5 O · 1.0C4H4O4之分析計算值：c，50.10; Η，3·44; Ν，13·28.實測值： C，49.81 ; Η，3·41 ; N，12.90· 實例263 2-[4-(3-氰基外I：淀-2-基）六氫叶1：喷-1-基 二甲基-1H-外I： 4 -5- 基）乙醯胺 按照實例247B中所述之程序，以2-氯_Ν·(2,5-二甲基-2H·吡唑-3-基）乙醯胺（Maybridge)取代得自實例247Α之產物，提供標題 化合物（84%產率），為油狀物。MS(DCI/NH3)m/e340(M+H)+· 順丁晞二酸鹽：白色固體；iHNMR(300MHz，CD3OD) (52.19(s，3H)， 3.26 (m，4H)，3.67 (s，3H)，3.88 (m，6H)，6.12 (s，1H)，6.27 (s, 2H)，7.00 (dd，1H， J=7.5, 4.7 Hz)? 8.00 (dd? 1H? J=7.8? 2.0 Hz)? 8.43 (dd? 1H5 J=5.1? 2.0 Hz) ； ^ C17H21N7CUl.0C4H4O4之分析計算值：C，55.38 ; H，5·53; Ν，21·53· 實測值：C，55.07 ; H，5·65; N，21.30. 實例264 坠(3-芊基笨基）-244-G-氰基吡啶-2-基）六氫吡畊·1-基）乙醯胺 85228 -316-Example 262B 85228 -315- 200404539 2- "4- (3-Cyanopyridin-2-yl) hexahydropyridine 1-N- (pentafluorobenzyl) acetamidamine as described in Example 247B Procedure to replace the product from Example 247A with the product from Example 262A to provide the title compound (71% yield) as an oil. 1HNMR (300 MHz, DMSO-d6) 5 2.69 (m, 4H), 3.32 (s, 2H), 3.69 (m, 4H) 5 6.93 (dd? 1H? J = 7.8, 4.8 Hz)? 8.07 (dd5 1H? J = 7.8? 2.0 Hz)? 8.42 (dd, 1¾ J = 4.8, 1.7 Hz), 9.93 (br s, 1H); MS (DCI / NH3) m / e 412. Maleic acid salt: white solid; 1HNMR (300MHz, CD3OD) 53.18 (m, 4H), 3.84 (s, 2H ), 3.87 (m, 4H), 6.28 (s, 2H), 6.98 (dd, 1H, J = 7.8, 5.1 Hz), 7.99 φ (dd, 1H, J = 7.8, 2.0 Hz), 8.42 (dd , 1H, J = 4.7, 1.7 Hz); Analytical calculation for q 8 呒 4 F5 N5 O · 1.0C4H4O4: c, 50.10; Η, 3.44; Ν, 13.28. Found: C, 49.81; Rhenium, 3.41; N, 12.90. Example 263 2- [4- (3-Cyanoexo I: Yodo-2-yl) hexahydro leaf 1: Ethyl-1-yldimethyl-1H-exo I: 4-5-yl) acetamidamine followed the procedure described in Example 247B with 2-chloro-N · (2 5,5-Dimethyl-2H.pyrazol-3-yl) acetamide (Maybridge) substituted the product from Example 247A to provide the title compound (84% yield) as an oil. MS (DCI / NH3 ) m / e340 (M + H) + · maleic acid salt: white solid; iHNMR (300MHz, CD3OD) (52.19 (s, 3H), 3.26 (m, 4H), 3.67 (s, 3H), 3.88 (m, 6H), 6.12 (s, 1H), 6.27 (s, 2H), 7.00 (dd, 1H, J = 7.5, 4.7 Hz)? 8.00 (dd? 1H? J = 7.8? 2.0 Hz)? 8.43 ( dd? 1H5 J = 5.1? 2.0 Hz); ^ C17H21N7CUl.0C4H4O4: Calculated value: C, 55.38; H, 5.53; Ν, 21.53. Found: C, 55.07; H, 5.65; N , 21.30. Example 264 (3-fluorenylbenzyl) -244-G-cyanopyridine-2-yl) hexahydropyridine · 1-yl) acetamidine 85228 -316-

200404539 V 實例264A - N-(3-字基笨某V2-氯乙jfe脖 按照實例33A中所述之程序，以3-苄基苯胺取代3-甲基苯 胺，提供標題化合物（84%產率），為白色固體。iHNMRpOOMHz， DMSO-d6) (5 3.92 (s，2H)，4.21 (s，2H)，6·98 (d，1H，J=7.5 Ηζ)，7·24 (m，6H)， 7.39 (m，1H)，7.44 (d，1H，J=8· 1 Hz)，10.22 (br s，1H) ； MS (DCI/NH3) m/e 260(M+H)+ ； 277(M+NH4)+. 實例264B · N_(3-字基苯基）-2-[~4-(3-散基峨淀_2_基）六氫峨p井小基1乙疏胺 按照實例247B中所述之程序，以得自實例264A之產物取代 得自實例247A之產物，提供標題化合物（86%產率），為油狀 物。1HNMR(300MHz，DMSO-d6) (52.67(m，4H)，3.18(s，2H)，3.67(m， 4H)，3·90 (s，2H)，6.92 (m, 2H)，7·22 (m，6H)，7·50 (m，2H)，8.07 (dd，1H，J=7.8， 2.0 Hz)，8·41 (dd，1H，J=4.7, 2·0 Hz)，9·72 (br s，1H); MS (DCI/NH3) m/e 412 (M+H)+. 順丁晞二酸鹽：白色固體；1HNMR(300MHz，DMSO·d6)5 3·35(m，鲁 4H)，3.90 (m，6H)，3.95 (s，2H)，6.26 (s，2H)，7.01 (m5 2H)，7.21 (m，6H)，7.44 (m，2H)，8.01 (dd，1H，J=7.5,1.7 Hz)，8.43 (dd，1H，J=5.1，2.0 Hz);對 C25H25N5O.1.0C4H4O4之分析計算值：C，66.02 ; H，5.54; Ν，13·27· 實測值：C65.68 ; H，5·49 ; N，13.08. 實例265 2_「4-(2-氣笨基）六氫吡畊_1-某1·Ν-(3-甲基笨基）乙醯胺 按照實例232Β中所述之程序，以μ(2-氯苯基）六氫吡畊取代 得自實例232A之產物，提供標題化合物（92%產率），為淡黃 85228 -317- 200404539 色固體。1 H NMR (300 MHz，DMSO-d6) (5 2.28 (s，3H)，2.71 (m，4H)，3.05 (m，4H)，3.20 (s，2H)，6.87 (br d，1H，J=7.7 Hz)，7.04 (ddd，1H，J=8.0, 7.4, 1.5 Hz)，7.19 (m，2H)，7.30 (ddd，1H，J=8.0, 7.4, 1.5 Hz)，7.40 (dd，1H，J=8.0, 1.5 Hz) 7.46 (m，2H)，9.64 (br s，1H) ; MS (DCI/NH3) m/e 344 (M+H)+ ; 對(：191122〇^30之分析計算值：（：，66.37;11，6.45;凡12.22.實測 值·· C，66.40 ; H，6_50 ; N，12.22· 實例266 2_「4-(3-亂基峨呼-2-基）7T氮？比喷-1-基甲基笨基）乙酿胺 按照實例232B中所述之程序，以3,4,5,6-四氫-2H-[l，2f]雙吡畊 基-3’-甲腈取代得自實例232A之產物，提供標題化合物（82% 產率），為淡黃色固體。111丽11(300]\«^，〇]^〇_(16)52.28(8,311)， 2.69 (m，4H)，3.20 (s，2H)，3.80 (m，4H)，6.88 (br d，1H，J=7.5 Hz)，7.18 (dd，1H， J=7_8, 7.8 Hz)，7.44 (br d，1H，J=7.8 Hz)，7.47 (br s，1H)，8·11 (d，1H，J=2.4 Hz)5 8.45(d，1H，J=2.0Hz)，9.69(brs，1H) ; MS (DCI/NH3) m/e 337 (M+H)+ ； 對 C18H2()N60之分析計算值·· C，64.27; H，5·99; N，24.98.實測值200404539 V Example 264A-N- (3-Benzylbenzyl V2-chloroethyl jfe neck Follow the procedure described in Example 33A to replace 3-methylaniline with 3-benzylaniline to provide the title compound (84% yield ) As a white solid. IHNMRpOOMHz, DMSO-d6) (5 3.92 (s, 2H), 4.21 (s, 2H), 6.98 (d, 1H, J = 7.5 Ηζ), 7.24 (m, 6H) , 7.39 (m, 1H), 7.44 (d, 1H, J = 8.1 Hz), 10.22 (br s, 1H); MS (DCI / NH3) m / e 260 (M + H) +; 277 (M + NH4) +. Example 264B · N_ (3-WordPhenyl) -2- [~ 4- (3-Scattered Edo_2_yl) Hexahydrop-well small group 1 Ethylamine according to Example 247B The procedure described in the above replaced the product from Example 247A with the product from Example 264A to provide the title compound (86% yield) as an oil. 1HNMR (300 MHz, DMSO-d6) (52.67 (m, 4H ), 3.18 (s, 2H), 3.67 (m, 4H), 3.90 (s, 2H), 6.92 (m, 2H), 7.22 (m, 6H), 7.50 (m, 2H), 8.07 (dd, 1H, J = 7.8, 2.0 Hz), 8.41 (dd, 1H, J = 4.7, 2.0 Hz), 9.72 (br s, 1H); MS (DCI / NH3) m / e 412 (M + H) +. maleic acid salt: white solid; 1HNMR (300MHz, DMSO · d6) 5 3 · 35 (m, Lu 4H), 3. 90 (m, 6H), 3.95 (s, 2H), 6.26 (s, 2H), 7.01 (m5 2H), 7.21 (m, 6H), 7.44 (m, 2H), 8.01 (dd, 1H, J = 7.5 , 1.7 Hz), 8.43 (dd, 1H, J = 5.1, 2.0 Hz); Analysis and calculation of C25H25N5O.1.0C4H4O4: C, 66.02; H, 5.54; Ν, 13.27. Found: C65.68; H, 5.49; N, 13.08. Example 265 2_ "4- (2-Alkyl) hexahydropyridine_1-a certain 1 · N- (3-methylbenzyl) acetamide according to Example 232B The procedure described replaces the product from Example 232A with μ (2-chlorophenyl) hexahydropyridine to provide the title compound (92% yield) as a pale yellow 85228-317-200404539 color solid. 1 H NMR (300 MHz, DMSO-d6) (5 2.28 (s, 3H), 2.71 (m, 4H), 3.05 (m, 4H), 3.20 (s, 2H), 6.87 (br d, 1H, J = 7.7 Hz) , 7.04 (ddd, 1H, J = 8.0, 7.4, 1.5 Hz), 7.19 (m, 2H), 7.30 (ddd, 1H, J = 8.0, 7.4, 1.5 Hz), 7.40 (dd, 1H, J = 8.0, 1.5 Hz) 7.46 (m, 2H), 9.64 (br s, 1H); MS (DCI / NH3) m / e 344 (M + H) +; Analytical calculation for (: 191122〇 ^ 30: (:, 66.37; 11, 6.45; Where 12.22. Measured values · C, 66.40; H, 6_50; N, 12.22 · Example 26 6 2_ "4- (3-Ranyl ehu-2-yl) 7T nitrogen? Bifen-1-ylmethylbenzyl) ethylamine was prepared according to the procedure described in Example 232B with 3,4,5,6-tetrahydro-2H- [l, 2f] bispyridyl-3'- The nitrile substituted the product from Example 232A to provide the title compound (82% yield) as a pale yellow solid. 111 Li 11 (300) \ «^, 〇] ^ 〇_ (16) 52.28 (8,311), 2.69 (m, 4H), 3.20 (s, 2H), 3.80 (m, 4H), 6.88 (br d, 1H , J = 7.5 Hz), 7.18 (dd, 1H, J = 7_8, 7.8 Hz), 7.44 (br d, 1H, J = 7.8 Hz), 7.47 (br s, 1H), 8.11 (d, 1H, J = 2.4 Hz) 5 8.45 (d, 1H, J = 2.0Hz), 9.69 (brs, 1H); MS (DCI / NH3) m / e 337 (M + H) +; Analysis and calculation of C18H2 () N60 Value ·· C, 64.27; H, 5.99; N, 24.98. Measured value

:C，64.04 ; H，6.10 ; N，24.60. 實例267 2-(4-吡啶·2-基六氫吡畊小基VN-(2-丨ΙΪ4-吡啶_2·基六新.吡畊-1-基） 乙醯基1胺基丨笨基）乙醯胺 按照實例181中所述之程序，以2-氯-Ν-[2-(2-氯基乙醯胺基） 苯基]乙醯胺（Aldrich)取代Ν-(2,5-二甲基苯基）-2-氯乙醯胺，並 使用2.4當量之1-吡啶-2-基_六氫吡畊，提供標題化合物（74% 產率），為淡黃褐色固體。1^^1\/111(3001^2,〇]\^〇-(16)5 2.59(111， 8H)5 3.18 (s? 4H)? 3.52 (m? 8H), 6.63 (dd? 2H? J=5.1? 5.1 Hz), 6.78 (d? 2H? J=8.5 85228 -318- 200404539: C, 64.04; H, 6.10; N, 24.60. Example 267 2- (4-Pyridine · 2-ylhexahydropyridine small base VN- (2- 丨 ΙΪ4-pyridine_2 · ylhexaxin. Pycnogenol- 1-yl) ethanyl 1 amine Benzyl) ethanyl amine According to the procedure described in Example 181, using 2-chloro-N- [2- (2-chloroethanylamino) phenyl] ethyl Aldrich replaced N- (2,5-dimethylphenyl) -2-chloroacetamidine and used 2.4 equivalents of 1-pyridin-2-yl_hexahydropyridine to provide the title compound (74 % Yield) as a pale yellow-brown solid. 1 ^^ 1 \ / 111 (3001 ^ 2, 〇) \ ^ 〇- (16) 5 2.59 (111, 8H) 5 3.18 (s? 4H)? 3.52 (m? 8H), 6.63 (dd? 2H? J = 5.1? 5.1 Hz), 6.78 (d? 2H? J = 8.5 85228 -318- 200404539

Hz)，7.20 (dd，2H，J=5.8, 3·4 Hz)，7.51 (dd，2H，J=8.5, 8·5 Hz)，7.60 (dd，2H，: 5.8, 3·7 Hz)，8.10 (d，2H，J=3.7 Hz)，9.64 (br s，2H) ; MS (DCI/NH3)m/e 515 (M+H)+ ;對 C28H34N802 · 0.4C4H8O2 · 0.1 H20 之分析計算值： C，64.44 ; H，6·83 ; N，20.31.實測值：C，64.42 ; H，6.67 ; N，20.12. 實例268 N-(3-甲基本基比淀-2_基7T现外b矣-1-基）乙燒硫酿胺 將得自實例36D之產物（77毫克，0.25毫莫耳）在無水甲苯（3 毫升）中溶液，以2,4-雙（4-甲氧苯基）-1，3-二硫-2,4_二磷四圜-2,4· _ 二硫化物（Lawesson氏試劑，51毫克，0.13毫莫耳）處理，並於 65°C下加熱1小時。使混合物冷卻至室溫，及在減壓下濃縮 。使殘留物於矽膠上藉急驟式管柱層析純化（以5%甲醇：二 氯甲烷溶離），提供40毫克（0.12毫莫耳，49%產率）標題化合 物，為黃色油。1H NMR (300 MHz，DMSO-d6 ) 51.85 (m，2H) 1.96 (dq, J= 12.4, 12.4, 12.4, 3·6 Hz，2H) 2.34 (s，3H) 2.39 (m，2H) 2_70 (tt，J=11.8, 11.8, 3·7， 3·9 Hz, 1H) 2·96 (m，2H) 3·55 (s，2H) 7·09 (d, J=7.80 Hz，1H) 7·22 (ddd，J=7.5， 4.7, 1.0 Hz，1H) 7.31 (t，J=7.7 Hz，1H) 7.32 (d，J=7.8 Hz，1H) 7.65 (s，1H) 7.71 % (dd，J=7.8, 1·7 Hz，1H) 7.73 (dt，J=7.8, 7.8, 1·7 Hz，1H) 8.50 (dd，J=5.0,1·2 Hz， 1H) 11 _34 (s，1H) ; MS (DCI/NH3) m/e 326· 1 (M+H)+ ·對 Q 9 H2 3 N3 S 之 分析計算值：C，70.12 ; H，7·12; N，12.91·實測值：C，69.87 ; H，7.11 ;N，12.78. 實例269 2-『4-(l-甲基-1H-味1:7坐-2-基）氮p比淀_1-基甲基苯基）乙龜胺 按照實例224中所述之程序，以得自實例237D之產物取代 得自實例166C之產物，提供標題化合物，為淡黃色油（13毫 85228 -319- 200404539 克）。iHNMRpOOMHADMSO-A) 5 1.7-1.85 (m，4H)，2.5-2.35 (m，4H)， - 2.75 (m，1H)，2.85-2.95 (m，2H)，3.1 (s，3H)，3.6 (s，3H)，6.65 (d，1H，J=3 Hz)， 6.85-6.95 (m，1H)，6.95 (d，1H，J=3 Hz)，7·2 (m，1H)，7.5 (m，2H)，9.6 (s，1H); MS (DCI/NH3) m/e 313 (M+H)+. 事 實例270 N-(3-甲基笨基）-2-「4_(1，3-口塞口坐-2_基）ττ氮p比淀-1-基1乙酿胺 按照實例224中所述之程序，以得自實例233之產物取代得 自實例166C之產物，提供標題化合物（35毫克），為淡黃色油 φ 。1H NMR (300 MHz，DMSO-d6) 6 1.8-1.95 (m，2H)，2·0·2·15 (m，2H)，2.22 (s，3H)，2.25-2.35 (m，2H)，2.85-2.98 (m，2H)，3.0 (m，1H)，3·15 (s，2H)，6.82 (d， 1H，J=9 Hz)，7.18 (t，1H，J=7.5 Hz)，7.45 (m，2H)，7.6 (d，1H，J=3 Hz)，7.7 (d， 1H，J=3 Hz)，9.6 (br s51H) ; MS (DCI/NH3 ) m/e 316 (M+H)+ · 實例271 N-(4-蛾基-3-甲基苯基比淀-2-基六氫p比淀-1-基）乙酿胺Hz), 7.20 (dd, 2H, J = 5.8, 3.4 Hz), 7.51 (dd, 2H, J = 8.5, 8.5 Hz), 7.60 (dd, 2H ,: 5.8, 3.7 Hz), 8.10 (d, 2H, J = 3.7 Hz), 9.64 (br s, 2H); MS (DCI / NH3) m / e 515 (M + H) +; Analytical calculations for C28H34N802 · 0.4C4H8O2 · 0.1 H20: C, 64.44; H, 6.83; N, 20.31. Found: C, 64.42; H, 6.67; N, 20.12. Example 268 N- (3-methylbenzylpyridine-2_yl 7T is now b 现1-I-yl) ethanesulfanil The solution of the product from Example 36D (77 mg, 0.25 mmol) in anhydrous toluene (3 ml) was added to 2,4-bis (4-methoxyphenyl). Treated with -1,3-disulfide-2,4_diphosphotetrahydrazone-2,4 · _ disulfide (Lawesson's reagent, 51 mg, 0.13 mmol) and heated at 65 ° C for 1 hour. The mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (dissolved with 5% methanol: methylene chloride) to provide 40 mg (0.12 mmol, 49% yield) of the title compound as a yellow oil. 1H NMR (300 MHz, DMSO-d6) 51.85 (m, 2H) 1.96 (dq, J = 12.4, 12.4, 12.4, 3.6 Hz, 2H) 2.34 (s, 3H) 2.39 (m, 2H) 2_70 (tt , J = 11.8, 11.8, 3 · 7, 3 · 9 Hz, 1H) 2 · 96 (m, 2H) 3 · 55 (s, 2H) 7 · 09 (d, J = 7.80 Hz, 1H) 7 · 22 (ddd, J = 7.5, 4.7, 1.0 Hz, 1H) 7.31 (t, J = 7.7 Hz, 1H) 7.32 (d, J = 7.8 Hz, 1H) 7.65 (s, 1H) 7.71% (dd, J = 7.8 , 1 · 7 Hz, 1H) 7.73 (dt, J = 7.8, 7.8, 1 · 7 Hz, 1H) 8.50 (dd, J = 5.0, 1.2 · 1 Hz, 1H) 11 _34 (s, 1H); MS ( DCI / NH3) m / e 326 · 1 (M + H) + · Analytical calculated value for Q 9 H2 3 N3 S: C, 70.12; H, 7 · 12; N, 12.91. Found: C, 69.87; H, 7.11; N, 12.78. Example 269 2- "4- (l-methyl-1H-taste 1: 7-s--2-yl) nitrogen p-pyridine_1-ylmethylphenyl) ethidamine according to The procedure described in Example 224 replaced the product from Example 166C with the product from Example 237D to provide the title compound as a pale yellow oil (13 mmol 85228-319-200404539 g). iHNMRpOOMHADMSO-A) 5 1.7-1.85 (m, 4H), 2.5-2.35 (m, 4H),-2.75 (m, 1H), 2.85-2.95 (m, 2H), 3.1 (s, 3H), 3.6 (s , 3H), 6.65 (d, 1H, J = 3 Hz), 6.85-6.95 (m, 1H), 6.95 (d, 1H, J = 3 Hz), 7.2 (m, 1H), 7.5 (m, 2H), 9.6 (s, 1H); MS (DCI / NH3) m / e 313 (M + H) +. Example 270 N- (3-methylbenzyl) -2- "4_ (1,3- Mouth plug mouth seat -2-base) τ τ nitrogen p ratio 1-1-1 ethyl amine according to the procedure described in Example 224, replacing the product from Example 233 with the product from Example 233 to provide the title compound ( 35 mg) as a pale yellow oil φ. 1H NMR (300 MHz, DMSO-d6) 6 1.8-1.95 (m, 2H), 2.0 · 2 · 15 (m, 2H), 2.22 (s, 3H), 2.25-2.35 (m, 2H), 2.85-2.98 (m, 2H), 3.0 (m, 1H), 3.15 (s, 2H), 6.82 (d, 1H, J = 9 Hz), 7.18 (t, 1H, J = 7.5 Hz), 7.45 (m, 2H), 7.6 (d, 1H, J = 3 Hz), 7.7 (d, 1H, J = 3 Hz), 9.6 (br s51H); MS (DCI / NH3 ) m / e 316 (M + H) + · Example 271 N- (4-Methyl-3-methylphenylpyridine-2-ylhexahydrop-pyridine-1-yl) ethylamine

實例271A 2-邊-N-(4-蛾基-3-甲基茉基）乙醯胺 _ 按照實例1A中所述之程序，以4-碘基-3-甲基苯胺取代3-甲 基苯胺，提供標題化合物，為白色固體。1HNMR(300MHz， DMSO-d6) δ 2·33 (s，3H)，4_02 (s，2H)，7.20 (dd，1H，J=8_5, 2·4 Hz)，7.56 (d， 1H5 J=2A Hz)5 7.74 (d5 1H? J=8.5 Hz)? 10.40 (br s? 1H) ； MS (DCI/NH3) m/e 353/355 (M+H)+ ; 371.373 (M+NH4)+·Example 271A 2-Edge-N- (4-pyridyl-3-methylmosyl) acetamidinide_ Follow the procedure described in Example 1A to replace 3-methyl with 4-iodo-3-methylaniline Aniline provided the title compound as a white solid. 1HNMR (300MHz, DMSO-d6) δ 2.33 (s, 3H), 4_02 (s, 2H), 7.20 (dd, 1H, J = 8_5, 2.4 Hz), 7.56 (d, 1H5 J = 2A Hz ) 5 7.74 (d5 1H? J = 8.5 Hz)? 10.40 (br s? 1H); MS (DCI / NH3) m / e 353/355 (M + H) +; 371.373 (M + NH4) + ·

實例271B N-(4-破基-3-甲基苯基^比淀-2-基六氫p比淀_i_基）乙酸胺 按照實例225B中所述之程序，以得自實例271A之產物取代 85228 -320- 200404539 得自實例225A之產物，提供標題化合物。（290毫克，51%)。 1H NMR (300 MHz, DMSO-d6) δ 1·83 (m，4Η)，2·28 (m，2Η)，2·33 (s，3Η)， 2·64 (m，1Η)，2.98 (m，2Η)，3· 12 (s，2Η)，7.20 (m，2Η)，7.30 (m，2Η)，7.65 (d，J= 3 Hz，1H)，7.73 (m，2H)，9.76 (br s，1H) ; MS (DCI/NH3) m/e 436 (M+H)+ ; 對(3191122^01 之分析計算值：C，52.42; H，5.09; N，9.65.實測值 :C，52.30 ; Η, 5·14 ; Ν，9·29· 實例272 2_(4-氣基-4-苯基ττ氫峨淀-1-基）甲基笨基）乙酿胺Example 271B N- (4-Hydroxy-3-methylphenyl ^ pyridine-2-ylhexahydrop-pyridine_i_yl) amine Acetic acid was obtained according to the procedure described in Example 225B to obtain Product substitution 85228-320-200404539 The product from Example 225A provided the title compound. (290 mg, 51%). 1H NMR (300 MHz, DMSO-d6) δ 1.83 (m, 4Η), 2.28 (m, 2Η), 2.33 (s, 3Η), 2.64 (m, 1Η), 2.98 (m , 2Η), 3.12 (s, 2Η), 7.20 (m, 2Η), 7.30 (m, 2Η), 7.65 (d, J = 3 Hz, 1H), 7.73 (m, 2H), 9.76 (br s , 1H); MS (DCI / NH3) m / e 436 (M + H) +; Analytical calculated value for (3191122 ^ 01: C, 52.42; H, 5.09; N, 9.65. Found: C, 52.30; Η, 5 · 14; Ν, 9 · 29 · Example 272 2_ (4-Amino-4-phenylττ Hydrogenide-1-yl) methylbenzyl) ethylamine

實例272A 4-#垔基-4-苯基六氫说啶_1_藏酸第三-丁酯 按照實例234A中所述之程序，以苯基鋰取代2-嘧吩基鋰， 提供標題化合物，為淡黃色油（6克，87%)。iHNMROOOMHz， CDC13) δ 1.5 (s5 9H)? 1.65-1.71 (m5 2H)5 1.9-1.98 (m5 1H)5 2.42 (t? 1H, J=6 Hz)5 3.22-3.25 (m，1H)，3.43 (d，2H，J=3 Hz)，3.7 (t，1H，J=6 Hz)，7.30-7.39 (m，2H)， 7_43-7_48 (m，2H)，7.58-7.60 (m，1H) ; MS (DCI/NH3 ) m/e 278 (M+H)+.Example 272A 4- # fluorenyl-4-phenylhexahydropyridin-1-triazine tert-butyl ester Following the procedure described in Example 234A, the 2-pyridyllithium was replaced with phenyllithium to provide the title compound As a pale yellow oil (6 g, 87%). iHNMROOOMHz, CDC13) δ 1.5 (s5 9H)? 1.65-1.71 (m5 2H) 5 1.9-1.98 (m5 1H) 5 2.42 (t? 1H, J = 6 Hz) 5 3.22-3.25 (m, 1H), 3.43 ( d, 2H, J = 3 Hz), 3.7 (t, 1H, J = 6 Hz), 7.30-7.39 (m, 2H), 7_43-7_48 (m, 2H), 7.58-7.60 (m, 1H); MS (DCI / NH3) m / e 278 (M + H) +.

實例272B 氟基_4-苯基六氫p比啶鮝酸第三_丁酯 於（二乙胺基）三氟化硫（〇_9毫升，7.2毫莫耳）在二氯甲烷中 之溶液内，於-70°C下，以在二氯甲烷中之溶液（1〇毫升）添加 得自貫例272A之產物（1克，3.6毫莫耳）。1小時後，使混合 物慢慢溫熱至-10°C，並攪拌2小時。以水（2〇毫升）與飽和碳 酸鉀（7毫升）使反應淬滅，接著以乙醚萃取。將合併有機相 以鹽水洗滌，以硫酸鎂脫水乾燥，過濾，及在減壓下濃縮 。使殘留物於矽膠上藉急騾式管柱層析純化（3〇%醋酸乙酯 85228 -321- 200404539 :己烷），而得標題化合物，為黃色油（200毫克，25% )。iHNMR / (300 MHz，CDC13) δ 1.5 (s5 9Η)5 1.9-1.96 (m? 2Η), 2.0-2.10 (m, 2H)? 3.18-3:26 (m，2H)，3.5-3.62 (m，2H)，7.3 (m，1H)，7.35-7.4 (m，4H); MS (DCI/NH3) rn/e 280 (M+H)+.Example 272B Fluoro-4-phenylhexahydrop-pyridinate tertiary-butyl ester in (diethylamino) sulfur trifluoride (0-9 ml, 7.2 mmol) in dichloromethane Then, the product obtained from Example 272A (1 g, 3.6 mmol) was added as a solution in dichloromethane (10 ml) at -70 ° C. After 1 hour, the mixture was slowly warmed to -10 ° C and stirred for 2 hours. The reaction was quenched with water (20 ml) and saturated potassium carbonate (7 ml), followed by extraction with ether. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (30% ethyl acetate 85228-321-200404539: hexane) to give the title compound as a yellow oil (200 mg, 25%). iHNMR / (300 MHz, CDC13) δ 1.5 (s5 9Η) 5 1.9-1.96 (m? 2Η), 2.0-2.10 (m, 2H)? 3.18-3: 26 (m, 2H), 3.5-3.62 (m, 2H), 7.3 (m, 1H), 7.35-7.4 (m, 4H); MS (DCI / NH3) rn / e 280 (M + H) +.

實例272C 4-氟基-4-苯基六氤毗啶 按照實例166B中所述之程序，以得自實例272B之產物取代 得自實例166A之產物，提供標題化合物，為黃色油狀殘留 物（200 毫克）。111丽11(300]^112,〇〇(：13)5 2.20-2.30(111，211)，2.45-2.55 (m，2H)，3.10 (t，2H，J=6 Hz)，3.50-3.55 (m，1H)，7.30-7.40 (m，4H) ； MS (DCI/NH3) m/e 180 (M+H)+.Example 272C 4-Fluoro-4-phenylhexapyridine According to the procedure described in Example 166B, the product from Example 272B was replaced with the product from Example 166A to provide the title compound as a yellow oily residue ( 200 mg). 111 Li 11 (300) ^ 112, 00 (: 13) 5 2.20-2.30 (111,211), 2.45-2.55 (m, 2H), 3.10 (t, 2H, J = 6 Hz), 3.50-3.55 ( m, 1H), 7.30-7.40 (m, 4H); MS (DCI / NH3) m / e 180 (M + H) +.

實例272D 2-(4-氟基-4-笨基六氫吡啶-1_基）-N_(3_甲基笨基）乙醯胺 按照實例33C中所述之程序，以得自實例272C之產物取代 得自實例33B之產物，提供標題化合物，為黃色油（155毫克 ，42% )。1H NMR (300 MHz，CDC13) K48 (br s，1H)，2.35 (m，4H)，2.65 (m，2H)，2·85 (t，2H，J=6 Hz)，3.22 (s，2H)，3.38 (m，2H)，6·85 (m，1H)，7·2 (m， 1H), 7.35-7.45 (m5 7H), 9.2 (br s? 1H) ； MS (DCI/NH3) m/e 327 (M+H)+ ； 對C2〇H23FN20之分析計算值：c，73.59; Η，7·10; Ν，8·58·實測 值：C，73.70 ; Η，7·19 ; Ν，8·80. 實例273 2-ΡΚ5_:輕基咐淀-2-基）六氫ρ比啶-1-基甲基笨基）乙醯胺 實例273Α 芊氣基V2-溴某毗嗆 85228 -322- 200404539 將6-氯基吡啶_3_醇（6克，46毫莫耳）在N，N-二甲基甲醯胺（50 笔升）中’以溴化芊（5.5毫升，46毫莫耳）與碳酸鉀（12·8毫莫 耳）處理’並將反應混合物加熱至4〇°c，歷經18小時。使反 應物冷卻至室溫，倒入鹽水（2〇〇毫升）中，並以醋酸乙酯（2⑻ 毫升）萃取。將有機層以鹽水（3χ1〇〇毫升）洗滌，以硫酸鎂脫 水乾燥，過濾，及在減壓下濃縮，獲得5-苄氧基_2-氯吡啶。 使此粗產物溶於丙腈（5〇毫升）中，並以溴化三甲基矽烷（12 36 毫升’ 92毫莫耳）處理，並將反應混合物在i〇(rc下加熱113 小時。使反應混合物冷卻至室溫，並倒入2〇 Μ氫氧化鈉溶 液中，於其中已添加50克冰。以乙醚（3 X 75毫升）萃取此水 相。將有機層合併，並以水（2χ 1〇〇毫升）及鹽水（75毫升）洗 滌’以硫酸鎂脫水乾燥，過濾，及在減壓下濃縮。使粗製 殘留物（淡褐色油）於矽膠上藉急驟式管柱層析純化，使用8 %醋酸乙酯：己烷作為溶離劑，而得4.72克標題化合物，為 淡黃色固體。1H NMR (300 MHz，DMSO-d6) 5 5.19 (s，2Η)，7·42 (m，6Η)， 7·57 (d，J=6 Ηζ，1Η)，8·19 (d，J=3 Ηζ，1Η)，MS (DCI/NH3) m/e 365 (Μ+Η)+.Example 272D 2- (4-Fluoro-4-benzylhexahydropyridin-1-yl) -N_ (3-methylbenzyl) acetamidinide Following the procedure described in Example 33C to obtain the compound from Example 272C The product replaced the product from Example 33B to provide the title compound as a yellow oil (155 mg, 42%). 1H NMR (300 MHz, CDC13) K48 (br s, 1H), 2.35 (m, 4H), 2.65 (m, 2H), 2.85 (t, 2H, J = 6 Hz), 3.22 (s, 2H) , 3.38 (m, 2H), 6.85 (m, 1H), 7.2 (m, 1H), 7.35-7.45 (m5 7H), 9.2 (br s? 1H); MS (DCI / NH3) m / e 327 (M + H) +; Analytical calculation for C20H23FN20: c, 73.59;;, 7.10; Ν, 8.58. Found: C, 73.70; Η, 7.19; Ν, 8 · 80. Example 273 2-PKK5_: light radical yodo-2-yl) hexahydroρ than pyridin-1-ylmethylbenzyl) acetamido amine Example 273A fluorenyl group V2-bromopyrimidine 85228 -322- 200404539 Place 6-chloropyridine_3_ol (6 g, 46 mmol) in N, N-dimethylformamide (50 liters) with phosphonium bromide (5.5 ml, 46 mmol) ) Treated with potassium carbonate (12.8 mmol) and the reaction mixture was heated to 40 ° C. for 18 hours. The reaction was cooled to room temperature, poured into brine (200 ml), and extracted with ethyl acetate (2⑻ ml). The organic layer was washed with brine (3 × 100 ml), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to obtain 5-benzyloxy_2-chloropyridine. This crude product was dissolved in propionitrile (50 mL) and treated with trimethylsilane bromide (12 36 mL '92 mmol), and the reaction mixture was heated at 110 ° C for 113 hours. The reaction mixture was cooled to room temperature, and poured into a 20 M sodium hydroxide solution, to which 50 g of ice had been added. The aqueous phase was extracted with ether (3 X 75 ml). The organic layers were combined and washed with water (2 x 100 ml) and brine (75 ml) were washed 'dehydrated with magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue (light brown oil) was purified on silica gel by flash column chromatography using 8% ethyl acetate: hexane was used as eluent to obtain 4.72 g of the title compound as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6) 5 5.19 (s, 2Η), 7.42 (m, 6Η) , 7 · 57 (d, J = 6 Ηζ, 1Η), 8.19 (d, J = 3 Ηζ, 1Η), MS (DCI / NH3) m / e 365 (Μ + Η) +.

實例273B 氫-2,4’-聯吡啶讀酸第三丁酯 將在乙醚（10毫升）中而得自實例273A之產物（〇·33克，17·7 毫莫耳）迅速添加至2.5Μ正-丁基鋰（0.98毫升，1.56毫莫耳）在 乙醚（8毫升）中，於_78°C下之溶液内。將所形成之褐色溶液 於-78°C下攪拌1〇分鐘。於其中添加〇·5Μ氯化鋅溶液（2·75毫升 ’ 07毫莫耳），並使反應混合物溫熱至0°C，及在0°C下攪拌15 分鐘。於此反應混合物中，添加4_三氟甲烷磺醯氧基_3,6_二 85228 -323 - 200404539 氫-2H-吡途小叛酸第三·丁酯（Bursavich，μ G 等人；〇rg· Lett 2〇〇1，3, 2317 ’ 0.5克’ 1.5毫莫耳）與肆（三苯膦）免⑼(175毫克，〇15毫 莫耳.）t將反應物加熱至60t：，歷經4小時。使混合物冷卻至 室溫’及在減壓下移除溶劑。使殘留物於醋酸乙酯（5()毫升） 與1N氫氧化鈉（50毫升）之間作分液處理。過濾無機鹽，並將 濾液以鹽水（50毫升）洗滌，脫水乾燥（硫酸鎂），及在迴轉式 蒸發為上濃縮，獲得褐色油。使粗製化合物於♦膠上藉急 驟式管柱層析純化，使用80%己烷：醋酸乙酯作為溶離劑， 而得0.209克（47%產率）所要之產物，為白色固體。ihnmrExample 273B Hydrogen-2,4'-bipyridine tert-butyl ester The product from Example 273A (0.33 g, 17.7 mmol) was quickly added to 2.5M in diethyl ether (10 ml). A solution of n-butyllithium (0.98 ml, 1.56 mmol) in ether (8 ml) at -78 ° C. The resulting brown solution was stirred at -78 ° C for 10 minutes. To this was added a 0.5M zinc chloride solution (2.75 ml '07 mmol), and the reaction mixture was warmed to 0 ° C and stirred at 0 ° C for 15 minutes. To this reaction mixture was added 4-trifluoromethanesulfonyloxy-3,6_di 85228-323-200404539 hydrogen-2H-pyridine tertiary acid tert-butyl ester (Bursavich, μG, etc .; rg · Lett 20001, 3, 2317 '0.5 g' 1.5 mM) and triphenylphosphine (175 mg, 015 mol.) t The reaction was heated to 60t :, after 4 hours. The mixture was allowed to cool to room temperature 'and the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (5 () ml) and 1N sodium hydroxide (50 ml). The inorganic salt was filtered, and the filtrate was washed with brine (50 ml), dried (MgSO4), and concentrated on a rotary evaporator to obtain a brown oil. The crude compound was purified by flash column chromatography on a gel using 80% hexane: ethyl acetate as the eluent to give 0.209 g (47% yield) of the desired product as a white solid. ihnmr

(300 MHz，DMSO-d6) (5 1.42 (s5 9H)，2.52 (m，2H)，3.51 (t，J=6 Hz，2H)，4.01 (m，2H)，5·19 (s，2H)，6.52 (m，1H)，7.41 (m，7H)，8.31 (d，J=1.5 Hz，1H)，MS (DCI/NH3 ) m/e 367 (M+H)+.(300 MHz, DMSO-d6) (5 1.42 (s5 9H), 2.52 (m, 2H), 3.51 (t, J = 6 Hz, 2H), 4.01 (m, 2H), 5.19 (s, 2H) , 6.52 (m, 1H), 7.41 (m, 7H), 8.31 (d, J = 1.5 Hz, 1H), MS (DCI / NH3) m / e 367 (M + H) +.

實例273C M苄氧基Vr，2\3W·四氫-2,4T-聯吡啶 使得自實例273B之產物（200毫克，0.54毫莫耳）在二氯甲烷（8 毫升）中，冷卻至0°C，並以三氟醋酸（〇·35毫升，4.3毫莫耳）φ 處理2小時；溫熱至室溫，歷經2小時，並藉迴轉式蒸發器 移除〉谷劑。將甲冬添加至殘留物中’然後在減壓下移除（2 X 50 毫升），獲得所要之產物，為無色油。iHNMRQOOMHz，DMSO-d6) (5 2.72 (m，2H)，3·32 (m，2H)，3.79 (m，2H)，5.20 (s，2H)，6.55 (m，1H)，7.41 (m， 6H)，7.59 (d，J=9 Hz，1H)，8_34 (d，J=1.5 Hz，1H)，8.82 (s，1H); MS (DCI/NH3) m/e 267 (M+H)+.Example 273C M benzyloxy Vr, 2 \ 3W · tetrahydro-2,4T-bipyridine. The product from Example 273B (200 mg, 0.54 mmol) was cooled to 0 ° in dichloromethane (8 ml). C, and treated with trifluoroacetic acid (0.35 ml, 4.3 mmol) for 2 hours; warmed to room temperature for 2 hours, and removed by a rotary evaporator> cereal. Adding winter to the residue ’was then removed under reduced pressure (2 X 50 ml) to obtain the desired product as a colorless oil. iHNMRQOOMHz, DMSO-d6) (5 2.72 (m, 2H), 3.32 (m, 2H), 3.79 (m, 2H), 5.20 (s, 2H), 6.55 (m, 1H), 7.41 (m, 6H ), 7.59 (d, J = 9 Hz, 1H), 8_34 (d, J = 1.5 Hz, 1H), 8.82 (s, 1H); MS (DCI / NH3) m / e 267 (M + H) +.

實例273D 245-(爷氧基二氫·2,4’_聯外1：淀基甲基笨基） 85228 -324- 200404539 乙醯胺 將得自實例273C之產物（175毫克，0.46毫莫耳）、得自實例1A 之產物（125毫克’ 0.54毫莫耳）及碳酸钟（164毫克，I」毫莫耳） 在N，N-二甲基甲醯胺（8毫升）中之混合物，於室溫下擾拌18 小時。將反應混合物倒入水（30亳升）中，並以醋酸乙酿（3〇 毫升）萃取。將有機層以鹽水（2x30毫升）洗滌，並以硫酸鎂 脫水乾燥，過濾，及在減壓下濃縮，並藉急驟式管柱層析 純化，使用70%己烷：醋酸乙酯，而得所要之產物1〇5毫克（55 % 產率）。iHNMRpOOMHsDMSOO 5 2.27(s，3H)，2.60(m，2H)， 2.76 (t，J=4.5 Hz，2H)，3.27 (m，2H)，3.97 (d，J=6 Hz, 2H)，5.19 (s，2H)，6.54 (m， 1H)，6.87 (m，2H)，7.18 (t，J=6 Hz，2H)，7.42 (m，7H)，8.31 (d，J=3 Hz，1H)， 9.52 (s，0.5H)，9.64 (s，0.5H) ; MS (DCI/NH3) m/e 414 (M+H)+ ·Example 273D 245- (Ethoxydihydro-2,4'_exo 1: Hexylmethylbenzyl) 85228 -324- 200404539 Acetylamine will be obtained from the product of Example 273C (175 mg, 0.46 mmol) ), A mixture of the product from Example 1A (125 mg '0.54 mmol) and bell carbonate (164 mg, 1 "mmol) in N, N-dimethylformamide (8 ml) at Stir for 18 hours at room temperature. The reaction mixture was poured into water (30 ml) and extracted with ethyl acetate (30 ml). The organic layer was washed with brine (2x30 ml), dried over magnesium sulfate, filtered, and concentrated under reduced pressure, and purified by flash column chromatography using 70% hexane: ethyl acetate to get the desired The product was 105 mg (55% yield). iHNMRpOOMHsDMSOO 5 2.27 (s, 3H), 2.60 (m, 2H), 2.76 (t, J = 4.5 Hz, 2H), 3.27 (m, 2H), 3.97 (d, J = 6 Hz, 2H), 5.19 (s , 2H), 6.54 (m, 1H), 6.87 (m, 2H), 7.18 (t, J = 6 Hz, 2H), 7.42 (m, 7H), 8.31 (d, J = 3 Hz, 1H), 9.52 (s, 0.5H), 9.64 (s, 0.5H); MS (DCI / NH3) m / e 414 (M + H) + ·

實例273E 羥基吡啶-2-基）六氫吡啶小基甲基苽某）乙醯胺 將得自實例273D之產物（105毫克，0.2毫莫耳）在甲醇（50毫 升）中，於60 psi下，以10% Pd/C (58毫克）處理16小時。過濾 觸媒，並使濾液在減壓下濃縮，獲得淡黃色泡沫狀固體。 使此粗產物於矽膠上藉急驟式管柱層析純化，使用4%乙醇 :醋酸乙酯，而得標題化合物，50毫克（64%產率）。^NMR (300 MHz，CDC13) (5 1.93 (m，4H)，2·31 (s，3H)，2·41 (m，2H)，2.71 (m，1H)， 3·04 (m，2H)，3·16 (s，2H)，6_92 (d，J=7.5 Hz, 1H)，)，7.20 (m，4H)，7·40 (d，J= 9 Hz，2H)，8·26 (m，1H)，9.24 (br s，1H) ; MS (DCI/NH3) m/e 326 (M+H)+ ; 對(：191123叫02之分析計算值：C，70.13 ; H，7.12; N，12.91·實測 值：C，69.97 ; H，7.17 ; N，12.68. 85228 -325 - 200404539 實例274 ·· 氟基-U-苯# 4唑-2-基V2_f4-(3-甲氣笨基）六氤毗哧-ui 1 乙醯胺 按照,實例247B中所述之程序，以2-溴-N-(5-氟基苯并嘧唑_2_ 基）乙醯胺（Maybridge)取代得自實例247A之產物，並以1-(2-甲 氧苯基）六氫吡啡取代1-(2-氰基吡啶基）六氫吡畊，提供標題 化合物（62% 產率），為油狀物。1^^]\411(300]\«^，〇〇3〇〇);(5 2.77_ 2.86 (m, 4H)5 3.10-3.19 (m? 4H)5 3.32 (s5 2H)? 3.86 (s? 3H), 6.86-7.06 (m5 3H)5 · 7.08-7.25 (m，2H)，7·65 (dd，J=3.0, 6·0 Hz，1.0H)，7.70-7.76 (m5 1H); MS(DCI/NH3)m/e401;對 C2〇H21N402SF 之分析計算值：C，59.98 ;H，5.29 ; N，14·12·實測值：C，60.12 ; H，5.58 ; N，14.12. 實例275 2-『4-(2·甲氧苯基）六氫外-1-基1-Ν-Π-甲基-1H-笨并咪吐_2-某） 乙醯胺 按照實例247B中所述之程序，以2-氯-N-(l-甲基-1H-苯并咪 唑-2·基）乙醯胺（Caroti，P·等人；Farmaco 1989, 44, 227)取代得自實 · 例247A之產物，並以1-(2-甲氧苯基）六氫吡畊取代1_(2_氰基吡 啶基）六氫吡畊，提供標題化合物（44%產率），為黃色油。 1H NMR (300 MHz? CD3 OD) ； δ 2.81-2.84 (m? 4H)? 3.05-3.10 (m? 4H)5 3.38 (s，2H)，3.75(s，3H)，3.85(s，3H)，6.85-7.05(m，4H)，7.22-7.37(m，2H)，7.42-7.58(m，2H); MS(DCI/NH3)m/e380;對 C21H25N502 之分析計算值 :C，65.82 ; Η, 6·61 ; N，17.87·實測值·· C，65.69 ; H，6·69 ; N，18.24. 實例276 N-(3-甲基苯基）-2-「4-(3_甲基嘧吩-2_基V3,6·二氫吡啶基1 85228 -326- 200404539Example 273E Hydroxypyridin-2-yl) hexahydropyridine small methylmethyl} acetamidine The product obtained from Example 273D (105 mg, 0.2 mmol) in methanol (50 ml) at 60 psi Treated with 10% Pd / C (58 mg) for 16 hours. The catalyst was filtered, and the filtrate was concentrated under reduced pressure to obtain a pale yellow foamy solid. This crude product was purified by flash column chromatography on silica gel using 4% ethanol: ethyl acetate to give the title compound, 50 mg (64% yield). ^ NMR (300 MHz, CDC13) (5 1.93 (m, 4H), 2.31 (s, 3H), 2.41 (m, 2H), 2.71 (m, 1H), 3.04 (m, 2H) , 3.16 (s, 2H), 6_92 (d, J = 7.5 Hz, 1H),), 7.20 (m, 4H), 7.40 (d, J = 9 Hz, 2H), 8.26 (m , 1H), 9.24 (br s, 1H); MS (DCI / NH3) m / e 326 (M + H) +; Analytical calculation for (: 191123 called 02: C, 70.13; H, 7.12; N, 12.91 · Measured values: C, 69.97; H, 7.17; N, 12.68. 85228 -325-200404539 Example 274 · · Fluoro-U-benzene # 4azole-2-yl V2_f4- (3-methylbenzyl) hexa Pyridoxine-ui 1 Acetylamine Obtained from Example 247A by substituting 2-bromo-N- (5-fluorobenzopyrazol_2_yl) acetamide (Maybridge) according to the procedure described in Example 247B. The product was replaced with 1- (2-cyanopyridyl) hexahydropyridine with 1- (2-methoxyphenyl) hexahydropyridine to provide the title compound (62% yield) as an oil. 1 ^^] \ 411 (300) \ «^ ， 〇〇3〇〇); (5 2.77_ 2.86 (m, 4H) 5 3.10-3.19 (m? 4H) 5 3.32 (s5 2H)? 3.86 (s? 3H), 6.86-7.06 (m5 3H) 5 · 7.08-7.25 (m, 2H), 7.65 (dd, J = 3.0, 6.0 Hz, 1.0H), 7.70-7.76 (m5 1H); MS ( DCI / NH3) m / e401; yes Analytical calculated value for C20H21N402SF: C, 59.98; H, 5.29; N, 14.12. Measured value: C, 60.12; H, 5.58; N, 14.12. Example 275 2- "4- (2 · methoxybenzene Yl) hexahydroexo-1-yl 1-N-Π-methyl-1H-benzimidazole_2-some) acetamidine Follow the procedure described in Example 247B with 2-chloro-N- (l -Methyl-1H-benzimidazole-2 · yl) acetamide (Caroti, P. et al .; Farmaco 1989, 44, 227) substituted the product obtained from Example · 247A, and replaced by 1- (2-methyl Oxyphenyl) hexahydropyridine replaces 1- (2-cyanopyridyl) hexahydropyridine to provide the title compound (44% yield) as a yellow oil. 1H NMR (300 MHz? CD3 OD); δ 2.81- 2.84 (m? 4H)? 3.05-3.10 (m? 4H) 5 3.38 (s, 2H), 3.75 (s, 3H), 3.85 (s, 3H), 6.85-7.05 (m, 4H), 7.22-7.37 ( m, 2H), 7.42-7.58 (m, 2H); MS (DCI / NH3) m / e380; Analytical calculation for C21H25N502: C, 65.82; Η, 6.61; N, 17.87 · Measured value ·· C , 65.69; H, 6.69; N, 18.24. Example 276 N- (3-methylphenyl) -2- "4- (3-methylpyridin-2-yl V3,6 · dihydropyridyl 1 85228 -326- 200404539

乙醯胺 實例276A 4-G-甲某嘧吩-2_基_3,6_二氫吡啶_1(2HV翁酸第三·丁酯 按照實例143A中所述之程序，以3-甲基-2-嘧吩基溴化鋅取 代3:甲基-2-吡啶基溴化鋅，提供標題化合物，為黃色油（2.67 克，54%)。iHNMRpOOMHiCDC^) 5 1.5(s，9H)，1.6(s，3H)，2.5(m， 2H)，3.6 (t，2H，J=6 Hz)，4.03 (m，2H)，5·8 (m，1H)，6.8 (d，1H，J=6 Hz)，7.15 (d， 1H5 J=6 Hz) ； MS (DCI/NH3) m/e 280 (M+H)+.Acetylamine Example 276A 4-G-Methylpyrimidin-2_yl_3,6_dihydropyridine_1 (2HV Oncony tert-butyl ester) Follow the procedure described in Example 143A, using 3-methyl 2-Pyrimidinyl zinc bromide substituted 3: methyl-2-pyridyl zinc bromide to provide the title compound as a yellow oil (2.67 g, 54%). IHNMRpOOMHiCDC ^) 5 1.5 (s, 9H), 1.6 (s, 3H), 2.5 (m, 2H), 3.6 (t, 2H, J = 6 Hz), 4.03 (m, 2H), 5.8 (m, 1H), 6.8 (d, 1H, J = 6 Hz), 7.15 (d, 1H5 J = 6 Hz); MS (DCI / NH3) m / e 280 (M + H) +.

實例276B 4_(3-甲基嘧吩-2-基）·1，2,3,6•四氫吡啶 按照實例166Β中所述之程序，以得自實例276Α之產物取代 得自實例166Α之產物，提供標題化合物，為黃色油（450毫克 ，46%)。1HNMR(300 MHz，CDC13)5 2.22 (s，3H)，2.78-2.80(m，2H)， 3.44-3.47 (m，2H)，3.85-3.90 (m，2H)，5.79-5.81 (m，1H)，6.83 (d，1H，J=6 Hz)， 7.18 (d，1H，J=6 Hz)，9.6 (br s，1H) ; MS (DCI/NH3) m/e 180 (M+H)+ ·Example 276B 4- (3-methylpyrimin-2-yl) · 1,2,3,6 · tetrahydropyridine Following the procedure described in Example 166B, the product from Example 276A was replaced with the product from Example 166A Provide the title compound as a yellow oil (450 mg, 46%). 1HNMR (300 MHz, CDC13) 5 2.22 (s, 3H), 2.78-2.80 (m, 2H), 3.44-3.47 (m, 2H), 3.85-3.90 (m, 2H), 5.79-5.81 (m, 1H) , 6.83 (d, 1H, J = 6 Hz), 7.18 (d, 1H, J = 6 Hz), 9.6 (br s, 1H); MS (DCI / NH3) m / e 180 (M + H) + ·

實例276CExample 276C

N-(3-甲基笨基V2-「4-(3-甲基嘧吩_2-基V3,6-二氫吡啶-U2HV 基1乙醯胺 按照實例33C中所述之程序，以得自實例272C之產物取代 . 得自實例33B之產物，提供標題化合物，為無色油（370毫克 ，49% )。1H NMR (300 MHz，CDC13) (5 2.30 (s，3H)，2.35 (s，3H)，2.61 (m， 2H)，2·83 (t，2H，J=6 Hz)，3·25 (s，2H)，3.38 (m，2H)，5·82 (m，1H)，6.82 (d，1H， J;6 Hz)，6·95 (d，1H，J=9 Hz)，7.10 (d，1H，J=6 Hz)，7.20 (d，1H，J=9 Hz)，7.40 (m，2H)，9.15 (br s，1H) ; MS (DCI/NH3) m/e 327 (M+H)+. 200404539 順丁婦二酸酯鹽：對c19h22n2os*i.oc4h4o4之分析計算值： C，62.42 ; H，5.92 ; N，6.33 ;實測值：C，62.23, H，5.96, N，6.18. 實例277 2-(1-丨2-「(3,5-二氣笨襄）胺基1-2-S同基乙基丨ττ氮峨淀-4-基V比键 Ν-氣化物 按照實例225Β中所述之程序，以2·溴_Ν-(3,5-二氯苯基）乙醯 胺（Maybridge)取代得自實例225Α之產物，提供標題化合物。 單離為醋酸鹽（36 毫克，34% )。iHNMRpOOMHADMSO-dJ 5 1·71 (m，2H)，1·92 (m，2H)，2.30 (m，2H)，2·98 (m，2H)，3·19 (s，2H)，3.25 (m， 1H)，7.30 (m，2H)，7.42 (m，1H)，7.80 (d，J=3 Hz，2H)，8.26 (d，J=4.5, 1H)， 10.05 (s，1H) ; MS (DCI/NH3) m/e 365 (M+H-16)+ ； 381 (M+H)+ ;對 Ci 8H19C12N302 · L0C2H4O2 之分析計算值：C，54·55; H，5·26; N，9·54· 實測值：C, 54_85 ; H，5.02 ; N，10.23· 實例278 2-(1-丨2-[Y2,3-二氯苯基）胺基基乙基}六氮峨淀_4-基V比鍵； N-氣化物 按照實例225B中所述之程序，以2-溴-N-(2,3-二氯苯基）乙醯 胺取代得自實例225A之產物，提供標題化合物。單離為醋 酸鹽（25 毫克，22% )。iHNMRpOOMHsDMSOO 5 1.71 (m，2H)， 1.99 (m，2H)，2.43 (m，2H)，3.03 (m，2H)，3.25 (s，2H)，3.35 (m，1H)，7.38 (m， 5H)，8.26 (dd，J=4.5,1.5, 2H)，10.15 (s，1H) ; MS (DCI/NH3) m/e 365 (M+H-16)+ ; 381(M+H)+ ;之分析計 算值：C，54·55 ; H，5·26 ; N，9.54·實測值：C，55_62 ; H，4_92 ; N，10.50· 實例279 85228 -328- 200404539N- (3-methylbenzyl V2- "4- (3-methylpyridin_2-yl V3,6-dihydropyridine-U2HV group 1 acetamide) Follow the procedure described in Example 33C to obtain Substitution from the product of Example 272C. The product from Example 33B provided the title compound as a colorless oil (370 mg, 49%). 1H NMR (300 MHz, CDC13) (5 2.30 (s, 3H), 2.35 (s, 3H), 2.61 (m, 2H), 2.83 (t, 2H, J = 6 Hz), 3.25 (s, 2H), 3.38 (m, 2H), 5.82 (m, 1H), 6.82 (d, 1H, J; 6 Hz), 6.95 (d, 1H, J = 9 Hz), 7.10 (d, 1H, J = 6 Hz), 7.20 (d, 1H, J = 9 Hz), 7.40 (m, 2H), 9.15 (br s, 1H); MS (DCI / NH3) m / e 327 (M + H) +. 200404539 Maleic acid ester salt: Analytical calculation for c19h22n2os * i.oc4h4o4 : C, 62.42; H, 5.92; N, 6.33; Found: C, 62.23, H, 5.96, N, 6.18. Example 277 2- (1- 丨 2-"(3,5-Digasbenzyl) amine Iso-2-1-S isopropylethyl ττ azelide-4-yl V ratio bond N-Gas Follow the procedure described in Example 225B, using 2 · bromo_N- (3,5-dichlorobenzene Methyl) acetamide (Maybridge) substituted the product from Example 225A to provide the title compound. 36 mg, 34%). IHNMRpOOMHADMSO-dJ 5 1.71 (m, 2H), 1.92 (m, 2H), 2.30 (m, 2H), 2.98 (m, 2H), 3.19 (s , 2H), 3.25 (m, 1H), 7.30 (m, 2H), 7.42 (m, 1H), 7.80 (d, J = 3 Hz, 2H), 8.26 (d, J = 4.5, 1H), 10.05 ( s, 1H); MS (DCI / NH3) m / e 365 (M + H-16) +; 381 (M + H) +; Analytical calculation for Ci 8H19C12N302 · L0C2H4O2: C, 54 · 55; H, 5.26; N, 9.54. Found: C, 54_85; H, 5.02; N, 10.23. Example 278 2- (1- 丨 2- [Y2,3-dichlorophenyl) aminoethyl } Hexazine_4-based V ratio bond; N-Gas was obtained from the example by substituting 2-bromo-N- (2,3-dichlorophenyl) acetamidine according to the procedure described in Example 225B. Product of 225A to provide the title compound. Isolated as acetic acid (25 mg, 22%). iHNMRpOOMHsDMSOO 5 1.71 (m, 2H), 1.99 (m, 2H), 2.43 (m, 2H), 3.03 (m, 2H), 3.25 (s, 2H), 3.35 (m, 1H), 7.38 (m, 5H) , 8.26 (dd, J = 4.5, 1.5, 2H), 10.15 (s, 1H); MS (DCI / NH3) m / e 365 (M + H-16) +; 381 (M + H) +; Analysis Calculated: C, 54 · 55; H, 5.26; N, 9.54. Found: C, 55_62; H, 4_92; N, 10.50. Example 279 85228 -328- 200404539

將2-甲氧基-6-甲基苯胺（4當量）在二氯甲烷（0·2 M)中之溶液 ’以吨淀（8當量），接著以氯化溴乙醯（丨當量）處理。在室溫 下j小時後，將混合物以碳酸鈉當量）與得自實例n9A之 產物（3當量）在二氧陸圜：水(2 : 1)中處理。將不均勻混合物 加熱至40 C過夜。使反應混合物冷卻至室溫，在減壓下濃縮 ’並將殘留物以5%甲醇：二氯甲烷研製。過濾固體無機物 質，並使已過濾物濃縮，及藉HPLC純化。單離為醋酸鹽。（45 毫克，44% )。1H NMR (300 MHz，DMSO-d6) 51.71 (m，2H)，1.99 (m，4H)， 2.15 (m5 3HX 2.30 (m5 2H), 3.10 (m? 1H), 3.15 (s5 2H)? 3.75 (s? 3H)5 6.86 (dd5 J= 9? 1.5 Hz, 2H)? 7.16 (t5 J=9 Hz, 1H)5 7.30 (m? 2H), 7.45 (m? 1H), 8.26 (dd? J=4.5, 1.5 Hz，1H)，8.95 (s，1H); MS (DCI/NNH3) m/e 340 (M+H-16)+ ; 356 (M+H)+ · 實例280 2-{1-[~2-(1，1|-聯笨_3-基胺基）-2_酮基乙基1六氫？比淀_4-基卜比錠A solution of 2-methoxy-6-methylaniline (4 equivalents) in dichloromethane (0.2 M) was treated in tons (8 equivalents) and then treated with ethyl bromide chloride (丨 equivalent) . After j hours at room temperature, the mixture was treated with sodium carbonate equivalents) and the product (3 equivalents) obtained from Example n9A in dioxolane: water (2: 1). The heterogeneous mixture was heated to 40 C overnight. The reaction mixture was cooled to room temperature, concentrated under reduced pressure and the residue was triturated with 5% methanol: dichloromethane. The solid inorganic material was filtered, and the filtered material was concentrated and purified by HPLC. Isolated as acetate. (45 mg, 44%). 1H NMR (300 MHz, DMSO-d6) 51.71 (m, 2H), 1.99 (m, 4H), 2.15 (m5 3HX 2.30 (m5 2H), 3.10 (m? 1H), 3.15 (s5 2H)? 3.75 (s 3H) 5 6.86 (dd5 J = 9? 1.5 Hz, 2H)? 7.16 (t5 J = 9 Hz, 1H) 5 7.30 (m? 2H), 7.45 (m? 1H), 8.26 (dd? J = 4.5, 1.5 Hz, 1H), 8.95 (s, 1H); MS (DCI / NNH3) m / e 340 (M + H-16) +; 356 (M + H) + · Example 280 2- {1- [~ 2 -(1,1 | -biben_3-ylamino) -2_ketoethyl 1 hexahydro? Biyodo_4-kibbibilide

N-氣化物 實例280A Ν-1，Γ_聯笨_3-某-2-氣乙醯胺 按照實例22Α中所述之程序，以聯苯-3-基胺取代3,4,5-三甲 氧基苯胺，提供標題化合物。MS(DCI)m/e346(M+H)+.N-Gas Example 280A Ν-1, Γ_biben_3-a-2--2-acetamidine Follow the procedure described in Example 22A to replace 3,4,5-trimethyl with biphenyl-3-ylamine Oxyaniline to provide the title compound. MS (DCI) m / e346 (M + H) +.

實例280B 旒苽_3_基胺基）_2_酮基乙基1六氫吡啶冬某}毗錠 Ν-氧化物 按照實例225Β中所述之程序，以得自實例280Α之產物取代 85228 -329- 200404539 得自實例225A之產物，提供標題化合物，為非晶質固體。（38.5 · 毫克，26%)。iHNMRpOOMHACDClOdimCmJHy.i^CmJH) 2.55 (m5 2H) 3.08 (m? 2H) 3.22 (s? 2H) 3.48 (m? 1H) 7.19 (m5 4H) 7.39 (m5 3H) 7.61 (m5 5H) 8.28 (d5 J=6.10 Hz? 1H) 9.21 (s5 1H) ； MS (ESI) m/e 390 (M+H)+ ;對 C24H25N302 之分析計算值：C，74.39 ; H，6·50 ; N，10.80.實 測值：C，73.87 ; Η，7·13; N，10.58. 實例281 2-(l-{2-『(3-乙基苯基）月安基1-2-酉同基乙基}ττ氮外匕淀-4-基V比键Example 280B 旒 苽 _3_ylamino) _2_ketoethyl 1 hexahydropyridine} Pyridin N-oxide Following the procedure described in Example 225B, the product from Example 280A was substituted for 85228 -329 -200404539 Product from Example 225A, providing the title compound as an amorphous solid. (38.5 · mg, 26%). iHNMRpOOMHACDClOdimCmJHy.i ^ CmJH) 2.55 (m5 2H) 3.08 (m? 2H) 3.22 (s? 2H) 3.48 (m? 1H) 7.19 (m5 4H) 7.39 (m5 3H) 7.61 (m5 5H) 8.28 (d5 J = 6.10 Hz? 1H) 9.21 (s5 1H); MS (ESI) m / e 390 (M + H) +; Analysis and calculation of C24H25N302: C, 74.39; H, 6.50; N, 10.80. Measured value: C , 73.87; Hf, 7.13; N, 10.58. Example 281 2- (l- {2-"(3-ethylphenyl) monthlyl1-2-fluorenylethyl} ττ nitrogen nitrogen -4-base V ratio bond

Ν-氣化物 實例281A 2-氣-Ν·(3-乙基苯基）乙酸月矣 按照實例22Α中所述之程序，以3-乙基苯胺取代3,4,5-三甲 氧基苯胺，提供標題化合物（8.0克，100%)。iHNMROOOMHz， CDC13) δ 1 _25 (m，3Η)，2·68 (m，2Η)，4·35 (m，2Η)，7·02 (d，J=5_4 Ηζ，1Η)， 7.40 (m，3H)，8.18 (br s，1H) ; MS (DCI/NH3 ) m/e 198 (M+H)+ · 實例281B 鲁 2-(l]2-「(3-乙基笨基）胺基1-2-酮基乙基}六氫吡啶-4-基）吡錠 Ν-氧化物 按照實例225Β中所述之程序，以得自實例281Α之產物取代 得自實例225Α之產物，提供標題化合物，為非晶質固體。（38 毫克，26% )。1H NMR (300 MHz，CDC13) (5 1.24 (t，J=7.6 Ηζ，3Η)，1.70 (m， 8H)，2.64 (m，3H)，4·26 (s，2H)，6_91 (s，1H)，7.25 (m，3H)，7.42 (m，2H)，7.60 (m，1H)，8.28 (d，J=6.1 Hz，1H) ; MS (ESI) m/e 340 (M+H)+. 實例282 85228 -330- 200404539 胺基乙基1六氤毗冷丄 . 吡錠N-氲化腩 、.將5_胺基氫印（19〇毫克，143€莫耳）在二氯甲燒(7毫升）中 之溶液，以吡啶（300微升，3·71毫莫耳），接著以氯化溴乙醯 (3〇獗升，0·36毫莫耳）處理。在室溫下3小時後，將混合物 以碳酸鈉（450毫克，4·25毫莫耳）與得自實例η9Α之產物（225 毛克，1.05耄莫耳）在二氧陸圜：水（2:丨，7毫升）中處理。 將不均勻混合物加熱至4(rc過夜。使混合物冷卻，並以二氯 甲烷稀釋。藉過濾移除碳酸鉀，並使濾液在減壓下濃縮。 將殘留物使用20%乙醇水溶液，以1 : 1〇稀釋，並裝填於強 酸性離子交換樹脂（Biorad AG50W-X2)上。將樹脂以水洗滌至 中性’並將產物以20%乙醇水溶液中之10毫升5%氫氧化銨 落離。使此溶液凍乾，提供（5〇%產率）標題化合物，為白色 固體。iHNMROOOMHiDMSOc^) 5 1.69(ddd，J=12.3，12.3，12.1，3.7N-Gas Example 281A 2-Gas-N · (3-ethylphenyl) acetic acid, according to the procedure described in Example 22A, replacing 3,4,5-trimethoxyaniline with 3-ethylaniline, The title compound (8.0 g, 100%) was provided. iHNMROOOMHz, CDC13) δ 1 _25 (m, 3Η), 2.68 (m, 2Η), 4.35 (m, 2Η), 7.02 (d, J = 5_4 Ηζ, 1Η), 7.40 (m, 3H ), 8.18 (br s, 1H); MS (DCI / NH3) m / e 198 (M + H) + · Example 281B Lu 2- (l) 2-"(3-ethylbenzyl) amino 1- 2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide Following the procedure described in Example 225B, the product from Example 281A was substituted for the product from Example 225A to provide the title compound as Amorphous solid. (38 mg, 26%). 1H NMR (300 MHz, CDC13) (5 1.24 (t, J = 7.6 Ηζ, 3Η), 1.70 (m, 8H), 2.64 (m, 3H), 4 26 (s, 2H), 6_91 (s, 1H), 7.25 (m, 3H), 7.42 (m, 2H), 7.60 (m, 1H), 8.28 (d, J = 6.1 Hz, 1H); MS ( ESI) m / e 340 (M + H) +. Example 282 85228 -330- 200404539 Aminoethyl 1 hexamethylpyridine. Pyridinium N-pyridine,. Mg, 143 € mol) in dichloromethane (7 ml), with pyridine (300 μl, 3.71 mmol), followed by acetamidine bromide (30 μl, 0 · 36 mmol). After 3 hours at room temperature, mix Treatment with sodium carbonate (450 mg, 4.25 mmol) and the product obtained from Example η9A (225 g, 1.05 mol) in dioxin: water (2: 丨, 7 ml). The heterogeneous mixture was heated to 4 ° C overnight. The mixture was cooled and diluted with dichloromethane. The potassium carbonate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was taken with a 20% aqueous ethanol solution at 1: 1 〇Dilution and loading on a strongly acidic ion exchange resin (Biorad AG50W-X2). The resin was washed with water to neutrality and the product was dropped off with 10 ml of 5% ammonium hydroxide in a 20% ethanol aqueous solution. Let this The solution was lyophilized to provide (50% yield) of the title compound as a white solid. IHNMROOOMHiDMSOc ^) 5 1.69 (ddd, J = 12.3, 12.3, 12.1, 3.7

Hz，2H)，1.91 (d，J=11.5 Hz，2H)，2.00 (dq，J=7.6, 7.4 Hz，2H)，2.30 (t，J=11.5 Hz，2H)，2·81 (q，J=7.8 Hz，4H)，2.99 (d，J=11.2 Hz，2H)，3.13 (s，2H)，3.28 (m， 1H)，7.14 (d，J=8.1 Hz，1H)，7.33 (m，3H)，7.45 (dd，J=7.5, 2·4 Hz，1H)，7.55 (s，1H)，8.25 (dd，J=6.3, 1·5 Hz，1H), 9·57 (s，1H) ; MS (DCI/NH3) m/e 352 (M+H)+ ;對 C21H25N302 · 0.2K2CO3 · 0_4H2O 之分析計算值： C，65.92 ; H，6·73 ; N，10.88.實測值：C，66.07 ; H，6·65 ; N，10.75. 實例283 2-{l_嗣基-「2-ί5·6·7,8-四鼠奈-1-基胺基）乙基1六氮外途-4-農比鍵 N-氧化物 按照實例282中所述之程序，以5,6,7,8-四氫萘-1-基胺取代5- 85228 •331- 200404539 胺基氫茚，提供標題化合物（70%產率），為白色固體。 · 1H NMR (300 MHz, DMSO-d6) δ 1.71 (m，6H)，1.96 (d，J=11.5 Hz，2H)，2.37 (t: J=10.7 Hz，2H)，2_61 (t，J=6.1 Hz，2H)，2.72 (t，J=5_9 Hz，2H)，3·04 (d，J= 11.2 Hz，2H)，3.16 (s5 2H)，3.29 (m，1H)，6.87 (d，J=7.8 Hz，1H)，7.07 (t，J=7.8 Hz，1H)，7.33 (m，2H)，7.42 (dd5 J=8.8, 2·4 Hz，1H)，7.61 (d，J=7.8 Hz，1H)，8·2 7 (d，J=6.1 Hz，1H)，9.34 (s，1H) ； MS (DCI/NH3) m/e 366 (M+H)+ ；對 (322Η27Ν302 ·0·3Κ2Ο)3·1·0Η20 之分析計算值：C，63.03; Η，6·88 ;Ν，9.89·實測值：C，62·82 ; Η，6·79 ; Ν，9·71· φ 實例284 2_(1-丨2-『(3-異丙氣基苯基）胺基1_2-嗣基乙基丨7^氮0比症-4-基）0比鍵 Ν-氣化物 按照實例279中所述之程序，以3-異丙氧基苯胺取代2-甲氧 基各甲基苯胺，提供標題化合物。（74毫克，52.8% )。hNMR (300 MHz? DMSO-d6) δ 1 _26 (d，J=6 Ηζ，6Η)，1.70 (m5 2Η)，1 ·91 (m，2Η)， 2·30 (m，2Η)，3·01 (m，2Η)，3.15 (m，1Η)，3.31 (m，1Η)，4·55 (m，1Η)，6.62 (m， 1H)，7.16 (m，2H)，7_30 (m，3H)，7.45 (m，1H)，8.15 (dd，J=6,1.5 Hz，1H)，9.65 _ (s，1H); MS(DCI/NH3)m/e354(M+H-16)+; 370 (M+H)+;對 C21H27N303 • 0.4 H20 之分析計算值：C，66·96; H，7·44; N，11.16·實測值：C，66.69 ;Η，7·56; N，10_80. 實例285 2-(1-(24(3,5-二甲基笨基）胺基1-2-酮某乙基}六氫吡啶-4-基）吡錠Hz, 2H), 1.91 (d, J = 11.5 Hz, 2H), 2.00 (dq, J = 7.6, 7.4 Hz, 2H), 2.30 (t, J = 11.5 Hz, 2H), 2.81 (q, J = 7.8 Hz, 4H), 2.99 (d, J = 11.2 Hz, 2H), 3.13 (s, 2H), 3.28 (m, 1H), 7.14 (d, J = 8.1 Hz, 1H), 7.33 (m, 3H ), 7.45 (dd, J = 7.5, 2.4 Hz, 1H), 7.55 (s, 1H), 8.25 (dd, J = 6.3, 1.5 Hz, 1H), 9.57 (s, 1H); MS (DCI / NH3) m / e 352 (M + H) +; Analytical calculated values for C21H25N302 · 0.2K2CO3 · 0_4H2O: C, 65.92; H, 6.73; N, 10.88. Found: C, 66.07; H, 6 · 65; N, 10.75. Example 283 2- {l_fluorenyl- "2-ί5 · 6 · 7,8-tetramurazin-1-ylamino) ethyl 1hexazine -Nongbi bond N-oxide. Follow the procedure described in Example 282, replacing 5-85228 with 5,6,7,8-tetrahydronaphthalen-1-ylamine. 331-200404539 Aminohydroindene to provide the title compound. (70% yield) as a white solid. · 1H NMR (300 MHz, DMSO-d6) δ 1.71 (m, 6H), 1.96 (d, J = 11.5 Hz, 2H), 2.37 (t: J = 10.7 Hz , 2H), 2_61 (t, J = 6.1 Hz, 2H), 2.72 (t, J = 5_9 Hz, 2H), 3.04 (d, J = 11.2 Hz, 2H), 3.16 (s5 2H), 3.29 ( m, 1H), 6.8 7 (d, J = 7.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 7.33 (m, 2H), 7.42 (dd5 J = 8.8, 2.4 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 8 · 2 7 (d, J = 6.1 Hz, 1H), 9.34 (s, 1H); MS (DCI / NH3) m / e 366 (M + H) +; for (322Η27N302) · 0 · 3Κ2Ο) 3 · 1 · 0Η20 Analytical calculated values: C, 63.03; Η, 6.88; N, 9.89 · Found: C, 62 · 82; Η, 6.79; Ν, 9.71 · φ Example 284 2_ (1- 丨 2-"(3-Isopropylaminophenyl) amino group 1_2-fluorenylethyl 丨 7 ^ nitrogen 0 ratio syndrome-4-yl) 0 ratio bond N-Gas according to the example The procedure described in 279 replaced 3-methoxyisomethylaniline with 3-isopropoxyaniline to provide the title compound. (74 mg, 52.8%). hNMR (300 MHz? DMSO-d6) δ 1 _26 (d, J = 6 Ηζ, 6Η), 1.70 (m5 2Η), 1.91 (m, 2Η), 2.30 (m, 2Η), 3.01 (m, 2Η), 3.15 (m, 1Η), 3.31 (m, 1Η), 4.55 (m, 1Η), 6.62 (m, 1H), 7.16 (m, 2H), 7_30 (m, 3H), 7.45 (m, 1H), 8.15 (dd, J = 6, 1.5 Hz, 1H), 9.65 _ (s, 1H); MS (DCI / NH3) m / e354 (M + H-16) +; 370 (M + H) +; Analytical calculated value for C21H27N303 • 0.4 H20: C, 66 · 96; H, 7.44; N, 11.16. Found: C, 66.69; H, 7.56; N, 10_80. Example 285 2- (1- (24 (3,5-Dimethylbenzyl) amino 1-one-one ethyl} hexahydropyridin-4-yl) pyridine

N-氣化物 實例285A 2-氪-N-(3,5-二甲基茉某）乙醯胺 85228 -332 200404539 按照實例22A中所述之程序，以3,5-二甲基笨胺取代3,4,5- · 三甲氧基苯胺，提供標題化合物（6.38克，79% )。iHNMR (300MHz，CDC13) (5 2.34 (s，6H)，4.17 (s，2H)，6.82 (s，1H)，7.17 (s，1H)，7.26 (s，1H)，8_11 (s，1H) ; MS (ESI) m/e 198 (M+H)+ ·Example of N-Gas 285A 2-fluorene-N- (3,5-dimethyl jasmine) acetamide 85228 -332 200404539 Substituted with 3,5-dimethylbenzylamine according to the procedure described in Example 22A 3,4,5- · trimethoxyaniline to provide the title compound (6.38 g, 79%). iHNMR (300MHz, CDC13) (5 2.34 (s, 6H), 4.17 (s, 2H), 6.82 (s, 1H), 7.17 (s, 1H), 7.26 (s, 1H), 8_11 (s, 1H); MS (ESI) m / e 198 (M + H) +

實例285B 2-(1-丨2-「(3,5-二甲某笨基）胺基1_2-酮基乙基}六氫吡啶-4-基）吡錠 N-氣化物 按照實例225B中所述之程序，以得自實例285A之產物取代 _ 得自實例225A之產物，提供標題化合物，為非晶質固體。（38 毫克，26% )。1H NMR (300 MHz，CDC13) (5 1.88 (d，J=3.39 Hz，2H)，2.05 (d，J=12.55 Hz，2H)，2.28 (s，6H)，2.43 (m，2H)，3.11 (m5 3H)，3·21 (s，2H)，6.78 (s，1H)，7_21 (s，2H)，7.41 (m，2H)，7.60 (d，J=4.07 Hz，1H)，8.34 (d，J=6.44 Hz， 1H) ； MS (ESI) m/e 340 (M+H)+. 實例286 2-(1-丨2-f(4-溪基-2-甲基苯基胺基1-2•嗣基乙基丨六氮p比淀-4-基) 口比錠Ν-氣化物 _ 按照實例282中所述之程序，以4-溴基_2_甲基苯基胺取代5-胺基氫茚，提供標題化合物（60%產率），為白色固體。 1H NMR (300 MHz，DMSO-d6) 6 1.67(ddd，J=24.6, 12.2, 3.6 Ηζ，2Η)，1.96 (d，J=12.5 Hz，2H)，2·25 (s，3H)，2.37 (t，J=11.7 Hz，2H)，3.04 (d，J=11.5 Hz， 2H)5 3.18 (s5 2H)? 3.26 (m? 1H)5 7.37 (m, 5H)? 7.76 (d5 J=8.8 Hz, 1H), 8.26 (m? 1H)，9.46 (s，1H); MS (DCI/NH3) m/e 404/406 (M+H)+ ;對 q 9 H2 2 BrN3 02 • 0.1 K2C03 之分析計算值：c，54·87 ; H，5·30 ; N, 10.05.實測值： C，54.72 ; H，5·38 ; N，9.73. 85228 -333 - 200404539 實例287Example 285B 2- (1- 丨 2-"(3,5-Dimethylbenzyl) amino 1_2-ketoethyl} hexahydropyridin-4-yl) pyridine N-gas, as described in Example 225B The procedure described above was replaced with the product from Example 285A_ The product from Example 225A provided the title compound as an amorphous solid. (38 mg, 26%). 1H NMR (300 MHz, CDC13) (5 1.88 ( d, J = 3.39 Hz, 2H), 2.05 (d, J = 12.55 Hz, 2H), 2.28 (s, 6H), 2.43 (m, 2H), 3.11 (m5 3H), 3.21 (s, 2H) , 6.78 (s, 1H), 7_21 (s, 2H), 7.41 (m, 2H), 7.60 (d, J = 4.07 Hz, 1H), 8.34 (d, J = 6.44 Hz, 1H); MS (ESI) m / e 340 (M + H) +. Example 286 2- (1- 丨 2-f (4-Cryl-2-methylphenylamino 1-2 • fluorenylethyl) hexazine p ratio -4-yl) N-Gas bismuth_ Follow the procedure described in Example 282 to replace 5-aminohydroindane with 4-bromo-2-methylphenylamine to provide the title compound (60% yield Ratio) as a white solid. 1H NMR (300 MHz, DMSO-d6) 6 1.67 (ddd, J = 24.6, 12.2, 3.6 Ηζ, 2Η), 1.96 (d, J = 12.5 Hz, 2H), 2.25 ( s, 3H), 2.37 (t, J = 11.7 Hz, 2H), 3.04 (d, J = 11.5 Hz, 2H) 5 3.1 8 (s5 2H)? 3.26 (m? 1H) 5 7.37 (m, 5H)? 7.76 (d5 J = 8.8 Hz, 1H), 8.26 (m? 1H), 9.46 (s, 1H); MS (DCI / NH3 ) m / e 404/406 (M + H) +; Analytical calculation for q 9 H2 2 BrN3 02 • 0.1 K2C03: c, 54 · 87; H, 5.30; N, 10.05. Found: C, 54.72; H, 5.38; N, 9.73. 85228 -333-200404539 Example 287

2-「l-(2-酮基-2-彳『3-Γ三氟甲氧基）笨基Ί胺某}乙某）六氪吡啶4-基J 吡錠N-氣化物 按照實例282中所述之程序，以3-三氟甲氧苯基胺取代5-胺基政茚，提供標題化合物（77%產率），為白色固體。 ^NMRCBOOMHz^DMSO-^) δ 1.68 (q? J=11.9 Hz, 1H)? 1.69 (q? J=12.4 Hz? 1H)，1.91 (d，J=11.9 Hz，2H)，2.31(t，J=11.5 Hz，2H)，3.00 (d，J=11.5 Hz，2H)， 3.19 (s，2H)，3.28 (m，1H)，7.05 (m，J=8.3, 2.4, 1.0, 〇·9 Hz，1H)，7.31 (m，2H)， φ 7.44 (m，2H)，7.62 (ddd，J=8.2, 2.0, 1·0 Hz，1H)，7.85 (s，1H)，8.26 (d，J=5.8 Hz， 1H)，10.01 (s，1H) ; MS (DCI/NH3) m/e 396 (M+H)+ ;對 q 9 H2 〇 F3N3 03 • 0·4Η2Ο 之分析計算值：C，56·69; H，5.21; N，10.44.實測值：C，56.71 ;H，5.04; N，10-19. 實例288 2-(1-丨2-「(5-甲基-2-硝基苯基）胺基&quot;1-2-酉同基乙基}六獻it比淀-4-基） 外匕錠N-氣化物 按照實例282中所述之程序，以2-甲基-5-硝基苯基胺取代5- % 胺基氫茚，提供標題化合物（75%產率），為黃色固體。ifi NMR (300 MHz, CDC13) δ 1.70 (q? J=11.9 Hz? 1H)5 1.71 (q5 J=12.4 Hz? 1H)? 2.21 (d5 J=13.2 Hz，2H)，2.40 (s，3H)，2.62 (t，J=11.9 Hz，2H)，3·11 (d，J=11.9 Hz，2H)， 3.28 (s，2H)，3_55 (tt，J=12.0, 3.4 Hz，1H)，7.19 (ddd，J=12_9, 6.4, 2.7 Hz，1H)， 7.31 (m，2H)，7.91 (dd，J=8.1，2.4 Hz，1H)，8.28 (d，J=6.4 Hz，1H)，9.08 (d，J= 2·4 Hz，1H)，9.55 (s，1H); MS (DCI/NH3) m/e 371 (M+H)+ ;對 q 9 H2 2 N4 04 • 1.1 H20 之分析計算值：c，58·48; H，6·25; N，1436·實測值·· C，58.44 ;H，6.20 ; N，14.30. 85228 -334- 200404539 € 實例289 2-(1-(24(2,6-二甲某笨基）胺基1-2-酮某乙某}六氫吡啶-4-基）吡錠 ^ N-氧化物2- "l- (2-keto-2-fluorene" 3-Γtrifluoromethoxy) benzylamine} ethyl}) hexapyridine 4-ylJ pyridinium N-gas The procedure described replaces 5-aminoindene with 3-trifluoromethoxyphenylamine to provide the title compound (77% yield) as a white solid. ^ NMRCBOOMHz ^ DMSO- ^) δ 1.68 (q? J = 11.9 Hz, 1H)? 1.69 (q? J = 12.4 Hz? 1H), 1.91 (d, J = 11.9 Hz, 2H), 2.31 (t, J = 11.5 Hz, 2H), 3.00 (d, J = 11.5 Hz, 2H), 3.19 (s, 2H), 3.28 (m, 1H), 7.05 (m, J = 8.3, 2.4, 1.0, 0.9 Hz, 1H), 7.31 (m, 2H), φ 7.44 (m , 2H), 7.62 (ddd, J = 8.2, 2.0, 1.0 Hz, 1H), 7.85 (s, 1H), 8.26 (d, J = 5.8 Hz, 1H), 10.01 (s, 1H); MS ( DCI / NH3) m / e 396 (M + H) +; Analytical calculated value for q 9 H2 〇F3N3 03 • 0 · 4Η2Ο: C, 56 · 69; H, 5.21; N, 10.44. Found: C, 56.71; H, 5.04; N, 10-19. Example 288 2- (1- 丨 2-"(5-methyl-2-nitrophenyl) amino &quot; 1-2-fluorenylethyl} Rokushin Itabi-Yen-4-yl) Outer dagger N-gassing Substituting 2-methyl-5-nitrophenylamine for 5-% amino hydrogen according to the procedure described in Example 282 Provide the title compound (75% yield) as a yellow solid. Ifi NMR (300 MHz, CDC13) δ 1.70 (q? J = 11.9 Hz? 1H) 5 1.71 (q5 J = 12.4 Hz? 1H)? 2.21 (d5 J = 13.2 Hz, 2H), 2.40 (s, 3H), 2.62 (t, J = 11.9 Hz, 2H), 3.11 (d, J = 11.9 Hz, 2H), 3.28 (s, 2H), 3_55 ( tt, J = 12.0, 3.4 Hz, 1H), 7.19 (ddd, J = 12_9, 6.4, 2.7 Hz, 1H), 7.31 (m, 2H), 7.91 (dd, J = 8.1, 2.4 Hz, 1H), 8.28 (d, J = 6.4 Hz, 1H), 9.08 (d, J = 2.4 Hz, 1H), 9.55 (s, 1H); MS (DCI / NH3) m / e 371 (M + H) +; pair q 9 H2 2 N4 04 • 1.1 Analytical calculated value of H20: c, 58 · 48; H, 6.25; N, 1436 · Measured value ·· C, 58.44; H, 6.20; N, 14.30. 85228 -334- 200404539 € Example 289 2- (1- (24 (2,6-Dimethylbenzyl) amino-1-2-one-ketomethyl} hexahydropyridin-4-yl) pyridine ^ N-oxide

實例289A 2-氯-N-(2,6-二甲某茉基）乙醯胺 按照實例22A中所述之程序，以2,6-二甲基苯胺取代3,4,5-三甲氧基苯胺，提供標題化合物（7.21克，δΡ^^ΗΝΜΙΐρΟΟΜΗζ， CDC13) ά 2.25 (s，6H)，4.26 (s，2H)，6.65 (t，J=7.46 Hz，1H)，6.95 (d，J=7.46 Hz， 2H)，7.84 (s，3H) ; MS (ESI) m/e 198 (M+H)+ ·Example 289A 2-Chloro-N- (2,6-dimethylmosyl) acetamidine Following the procedure described in Example 22A, 3,4,5-trimethoxy was replaced with 2,6-dimethylaniline Aniline, providing the title compound (7.21 g, δP ^^ ΗΝΜΙΐρΟΟΜΗζ, CDC13) ά 2.25 (s, 6H), 4.26 (s, 2H), 6.65 (t, J = 7.46 Hz, 1H), 6.95 (d, J = 7.46 Hz, 2H), 7.84 (s, 3H); MS (ESI) m / e 198 (M + H) + ·

實例289B 2-(1-{2-|~(2,6-二甲基苯基）胺某1-2-酮基乙基}六氫外1：淀-4-基）外1：鍵 N-氣化物 按照實例225B中所述之程序，以得自實例289A之產物取代 得自實例225A之產物，提供標題化合物，為非晶質固體。（27 毫克，8% )。1H NMR (300 MHz，CD3 OD) 61.88 (dd，J=12.4, 3·6 Hz，2H)， 2.07 (m，2H)，2·22 (s，6H)，2.50 (m，2H)，3.11 (m, 3H) 3.21 (s，2H)，7.10 (m， 1H)，7.42 (m，2H)，7.58 (m，1H)，7.86 (m，1H)，7.93 (d，J=2.0 Hz，1H)，8.34 (d， J=6.4 Hz, ； 1H) ； MS (ESI) m/e 354 (M+H)+. 實例290 2-(l-{2-「(2,6-七氯-3-甲基盖基）胺基i_2-酮某基！六新毗啶_4_基） 外匕錠N-氫化物 按照實例282中所述之程序，以2,6_二氯_3_甲基苯基胺取代孓 胺基氫茚，提供標題化合物（64%產率”為灰白色固體。 1H NMR (300 MHz? CDC13) δ 1.72 (q? J=12.4 Hz? 1H)? 1.73 (q? J=12.3 Hz? 85228 -335 - 200404539 1H)，2.17 (d，J=12.9 Hz，2H)，2.39 (s，3H)，2.56 (t，J=11.9 Hz，2H)，3.25 (d，J= 12.2 Hz，2H)，3.27 (s，2H)，3.58 (t，JN12.2, 3·3 Hz，1H)，6.57 (d，J=8.1 Hz，1H)， 7.17 (m，4H)，8.27 (d，J=6.4 Hz，1H)，9.03 (s，1H) ; MS (DCI/NH3) m/e 394 (]\4+11)+;對(：1911210：12^〇”1.3112〇之分析計算值：(：，54.63;11，5.69 ;N，10.06.實測值：C，54·51 ; H，5·13 ; N，9·70. ’ 實例291 2-{l-[2-(l，3-苯并二氧伍圜烯-5-某胺基）-2-酮基乙基1六氪吡啶-4-Example 289B 2- (1- {2- | ~ (2,6-dimethylphenyl) amine 1-2-ketoethyl} hexahydroex 1: Hodo-4-yl) Ex 1: Bond N -The gaseous product was replaced with the product from Example 289A by the procedure described in Example 225B to provide the title compound as an amorphous solid. (27 mg, 8%). 1H NMR (300 MHz, CD3 OD) 61.88 (dd, J = 12.4, 3.6 Hz, 2H), 2.07 (m, 2H), 2.22 (s, 6H), 2.50 (m, 2H), 3.11 ( m, 3H) 3.21 (s, 2H), 7.10 (m, 1H), 7.42 (m, 2H), 7.58 (m, 1H), 7.86 (m, 1H), 7.93 (d, J = 2.0 Hz, 1H) , 8.34 (d, J = 6.4 Hz,; 1H); MS (ESI) m / e 354 (M + H) +. Example 290 2- (l- {2-「(2,6-heptachloro-3- Methyl capryl) amine i_2-one keto! Hexa neopyridine_4_yl) outer dagger N-hydride Follow the procedure described in Example 282 with 2,6_dichloro_3_methyl Phenylamine substituted sulfinylindane to provide the title compound (64% yield) as an off-white solid. 1H NMR (300 MHz? CDC13) δ 1.72 (q? J = 12.4 Hz? 1H)? 1.73 (q? J = 12.3 Hz? 85228 -335-200404539 1H), 2.17 (d, J = 12.9 Hz, 2H), 2.39 (s, 3H), 2.56 (t, J = 11.9 Hz, 2H), 3.25 (d, J = 12.2 Hz , 2H), 3.27 (s, 2H), 3.58 (t, JN12.2, 3.3 Hz, 1H), 6.57 (d, J = 8.1 Hz, 1H), 7.17 (m, 4H), 8.27 (d, J = 6.4 Hz, 1H), 9.03 (s, 1H); MS (DCI / NH3) m / e 394 (] \ 4 + 11) +; Analysis and calculation of (: 1911210: 12 ^ 〇 "1.3112〇: (:, 54.63; 11, 5.69; N, 10.06. Found: C, 54 · 51; H, 5.13; N, 9.70. 'Example 291 2- {l- [2- (l, 3-benzodioxolene) -5-Amino group) -2-ketoethyl 1 hexapyridine-4-

基}吡錠N-氫化物 實例291A Ν-1，3·苯并二氣伍圜烯-5-基-2-氣乙醯胺 按照實例33Α中所述之程序，以苯并[1，3]二氧伍圜晞基-5-基 胺取代3-甲基苯胺，提供標題化合物（92%產率），為褐色固 體。1 H NMR (300 MHz，CDC13) 5 4.2 (s，2Η)，5.98 (s，2Η)，6.78 (d，1Η，J=9 Hz), 6·83 (dd，1H，J=9 Hz，3 Hz)，7.22 (d，1H，J=3 Hz)，8.10 (br s，1H) ; MS (DCI/NH3) m/e 213 (M+H)+.Example} Pyridinium N-Hydride Example 291A N-1,3 · Benzodiazepine-5-yl-2-aminoacetamidinide Following the procedure described in Example 33A, benzo [1,3 ] Dioxo-5-ylamine substituted 3-methylaniline to provide the title compound (92% yield) as a brown solid. 1 H NMR (300 MHz, CDC13) 5 4.2 (s, 2Η), 5.98 (s, 2Η), 6.78 (d, 1Η, J = 9 Hz), 6.83 (dd, 1H, J = 9 Hz, 3 Hz), 7.22 (d, 1H, J = 3 Hz), 8.10 (br s, 1H); MS (DCI / NH3) m / e 213 (M + H) +.

實例291B 2-{l-『2-(l，3-苯并二氧伍圜烯-5-某胺基）-2-酮基乙基1六氫吡啶-4- 基）吡錠N-氫化物^ 按照實例22兄中所述之程序，以實例291A中之產物取代得 自實例225A之產物，提供標題化合物，為白色固體（25毫克 ，21%)。iHNMR(300MHz，CDC13) δ 1.65-L7(m，2H)，2.15-2.19 (m， 2H)5 2.45 (t? 2¾ J=12 Hz)5 3.05 (m? 2H)? 3.10-3.15 (m? 2H)? 3.45 (m； 1H)? 5.9 (s5 2H)，6.76 (d，1H，J=9 Hz)，6.75-6.85 (m，1H)，7.12-7.18 (m，1H)，7.32-7.38 (m， 3H)，8.25 (d，1H，J=6 Hz)，9.08 (br s，1H) ; MS (DCI/NH3) m/e 356 (M+H)+ 85228 -336- 200404539 ;對 Ci 9H2 i N3 04 · 0·5 H20 之分析計算值：c, 62.63; H，6.09; N，11.53·-實測值：C，63.01 ; Η，5·96; N，11.12. 實例292 2-『l-(2-{|~3-(甲硫基）笨基1胺基丨-2-酮基乙某）六氫P比淀-4-基比錠 N-氣化物 按照實例225B中所述之程序，以2_氯·Ν-(3_甲硫基苯基）乙醯 胺取代得自實例225Α之產物’提供標題化合物，為淡黃色 油（Π 毫克，21% )。iHNMRGOOMHz’DMSOO 5 1.60-1.78 (m，2H)， φ 1.63-1.95 (m，2Η)，2.12-2.18 (m，2Η)，2.70 (s，3Η)，2.9-3.12 (m，2Η)，3.22-3.30 (m，3H)，6.9-7.0 (m，1H)，7·2-7·3 (m，2H)，7.3-7.35 (m，2H)，7.62 (t，1H，J=3 Hz)，7.8 (s，1H)，8.23-8.27 (m，1H)，9.75 (s，1H) ； MS (DCI/NH3)m/e 358 (M+H)+· 實例293 2-(1•丨2_「(5_氯某_2-甲基苯基）胺基1_2-酮基乙基丨六氫吡啶斗甚、 吡錠N_氣化物Example 291B 2- {l- "2- (l, 3-benzodioxolene-5-aminyl) -2-ketoethyl 1 hexahydropyridin-4-yl) pyridine N-hydrogenated Compound ^ The procedure described in Example 22 was used to replace the product from Example 225A with the product from Example 291A to provide the title compound as a white solid (25 mg, 21%). iHNMR (300MHz, CDC13) δ 1.65-L7 (m, 2H), 2.15-2.19 (m, 2H) 5 2.45 (t? 2¾ J = 12 Hz) 5 3.05 (m? 2H)? 3.10-3.15 (m? 2H )? 3.45 (m; 1H)? 5.9 (s5 2H), 6.76 (d, 1H, J = 9 Hz), 6.75-6.85 (m, 1H), 7.12-7.18 (m, 1H), 7.32-7.38 (m , 3H), 8.25 (d, 1H, J = 6 Hz), 9.08 (br s, 1H); MS (DCI / NH3) m / e 356 (M + H) + 85228 -336- 200404539; for Ci 9H2 i Analytical calculation value for N3 04 · 0 · 5 H20: c, 62.63; H, 6.09; N, 11.53 · -Measured value: C, 63.01; Η, 5.96; N, 11.12. Example 292 2- 『l- ( 2- {| ~ 3- (methylthio) benzyl 1amino group-2--2-ketoethyl group) hexahydro P ratio lake 4-yl ratio ingot N-gasification according to the procedure described in Example 225B, Substitution of the product from Example 225A with 2-chloro.N- (3-methylthiophenyl) acetamide provided the title compound as a pale yellow oil (Π mg, 21%). iHNMRGOOMHz'DMSOO 5 1.60-1.78 (m, 2H), φ 1.63-1.95 (m, 2Η), 2.12-2.18 (m, 2Η), 2.70 (s, 3Η), 2.9-3.12 (m, 2Η), 3.22- 3.30 (m, 3H), 6.9-7.0 (m, 1H), 7.2-7 · 3 (m, 2H), 7.3-7.35 (m, 2H), 7.62 (t, 1H, J = 3 Hz), 7.8 (s, 1H), 8.23-8.27 (m, 1H), 9.75 (s, 1H); MS (DCI / NH3) m / e 358 (M + H) + · Example 293 2- (1 • 丨 2_ 「 (5-Chlorin-2-methylphenyl) amino 1_2-ketoethyl 丨 Hydroxypyridine, pyridinium N_gas

實例293A 2-讀.氯基_2_甲基笨基）乙醯胺 按照實例33A中所述之程序，以5-氯基-2-甲基苯基胺取代3-甲基苯胺，提供標題化合物（1.7克，55% )，為白色固體。 1H NMR (300 MHz? DMSO-d6) 5 2.0 (s，3H)，5.10 (s，2H)，6.42 (dd，1H，J= 9, 3 Hz)，6_60 (d，1H，J=3 Hz)，6.90 (d，1H，J=9 Hz) ; MS (DCI/NH3) m/e 219 (M+H)' 實例293B 氯某-2-甲基笨基）胺基1-2-酮基乙基}六氫啤 85228 -337- 200404539 叶匕鍵N-氳化物 按照實例225B中所述之程序，以得自實例293A之產物取代 得自實例225A之產物，提供標題化合物，為褐色粉末（15毫 克，13% )。1H NMR (300 MHz，CDC13) 5 1.68-1.73 (m，2H)，2.15-2.22 (m， 2H)，2.25(s，3H)，2.6(t，2H，J=12Hz)，3.05-3.18(m，2H)，3.22(s，2H)，3.50-3·60 (m，1H)，7.05 (dd，1H，J=6 Hz，3 Hz)，7.10 (d，1H，9 Hz)，7.18-7.2 (m，1H)， 7.22-7.28 (m，2H)，8.22 (d，2H，J=6 Hz)，9.38 (br s，1H) ; MS (DCI/NH3) m/e 360(^4+«〇+;對0：191122(：1化02.〇.51120之分析計算值：（：，61.87 ;H，6·28 ; N，11·39·實測值：C，61.76 ; H，6·22 ; N，11.10. 實例294 2-(l-{2-[~(2,5-二甲氣基苯基）胺某l—2_嗣基乙基}六氫叶1：淀-4-基） 吡鍵N-氲化物Example 293A 2-Reading. Chloro_2-methylbenzyl) acetamidin. Follow the procedure described in Example 33A to replace 3-methylaniline with 5-chloro-2-methylphenylamine to provide the title. Compound (1.7 g, 55%) as a white solid. 1H NMR (300 MHz? DMSO-d6) 5 2.0 (s, 3H), 5.10 (s, 2H), 6.42 (dd, 1H, J = 9, 3 Hz), 6_60 (d, 1H, J = 3 Hz) , 6.90 (d, 1H, J = 9 Hz); MS (DCI / NH3) m / e 219 (M + H) 'Example 293B Chlor-2-methylbenzyl) amino 1-2-ketoethyl Hexahydro beer 85228 -337- 200404539 The leaf N-phosphonium compound was replaced with the product from Example 293A by the procedure described in Example 225B to provide the title compound as a brown powder (15 mg, 13%). 1H NMR (300 MHz, CDC13) 5 1.68-1.73 (m, 2H), 2.15-2.22 (m, 2H), 2.25 (s, 3H), 2.6 (t, 2H, J = 12Hz), 3.05-3.18 (m , 2H), 3.22 (s, 2H), 3.50-3 · 60 (m, 1H), 7.05 (dd, 1H, J = 6 Hz, 3 Hz), 7.10 (d, 1H, 9 Hz), 7.18-7.2 (m, 1H), 7.22-7.28 (m, 2H), 8.22 (d, 2H, J = 6 Hz), 9.38 (br s, 1H); MS (DCI / NH3) m / e 360 (^ 4 + « 〇 +; Analytical calculation value for 0: 191122 (1: 02.0.05.1202: (:, 61.87; H, 6.28; N, 11.39. Found: C, 61.76; H, 6.22 N, 11.10. Example 294 2- (l- {2- [~ (2,5-Dimethylaminophenyl) amine 1-2_fluorenylethyl} hexahydro leaf 1: Yodo-4-yl ) N-pyridine

實例294A 2-氯-N-(2,5-二甲藍，某笨基）乙醯胺 按照實例33A中所述之程序，以2-氯-N-(2,5-二甲氧基苯基） 苯胺取代3-甲基苯胺，提供標題化合物（1·6克，55%產率）， 為褐色固體。1H NMR (300 MHz, CDC13) δ 3.73 (s，3Η), 3.8 (s，3Η)，4·4 (s，2H)，6.33 (dd，1H，J=9,3 Hz)，6.45 (d，1H，J=3 Ηζ)，6·65 (dd，1H，J=9,3 Hz) ；MS(DCI/NH3)m/e230(M+H)+.Example 294A 2-Chloro-N- (2,5-dimethyl blue, a benzyl) acetamidamine Following the procedure described in Example 33A, ) Aniline substituted 3-methylaniline to provide the title compound (1.6 g, 55% yield) as a brown solid. 1H NMR (300 MHz, CDC13) δ 3.73 (s, 3Η), 3.8 (s, 3Η), 4.4 (s, 2H), 6.33 (dd, 1H, J = 9, 3 Hz), 6.45 (d, 1H, J = 3 Ηζ), 6.65 (dd, 1H, J = 9, 3 Hz); MS (DCI / NH3) m / e230 (M + H) +.

實例294B 二甲氧基_苯基）胺某]_2·酮基乙基}六氫吡啶斗基） 口比錠N-氧化物 按照實例22犯中所述之程序，以得自實例294A之產物取代 得自實例225A之產物，提供標題化合物，為淡黃色油卩7毫 85228 -338- 200404539 克，77%)。WNMR(300MHz，CDC13)5 1.40-1.51 (m，2H)，1.65-1.80 (m，2H)，2.15-2.20 (m，2H)，2.50-2.60 (m，2H)，3.10-3.18 (m，2H)，3.50-3.60 (m， 1H)，3·8.0 (s，3H)，3.85 (s，3H)，6.60 (dd，1H，J=6 Hz，3 Hz)，6·80 (d，1H，J=9 Hz)，7.20-7.25 (m，1H)，7.30-7.39 (m，2H)，8.15 (d，1H，J=3 Hz)，8·38 (d，1H， J=6 Hz)，9.8 (br s，1H) ; MS (DCI/NH3) m/e 372 (M+H)+ · 順丁烯二酸酯鹽：對 C2〇H25N304 .2.0C4H404，1.3H20 之分析 計算值：C，53·64; H，5·72 ; N，6.70.實測值：C，53.26 ; H，5.95 ; N，6.45. 實例295Example 294B Dimethoxy_phenyl) amine] _2 · ketoethyl} hexahydropyridinyl) Oral ingot N-oxide Follow the procedure described in Example 22 to obtain the product from Example 294A In place of the product obtained from Example 225A, the title compound was provided as a pale yellow oil (75 mmol 85228-338-200404539 g, 77%). WNMR (300MHz, CDC13) 5 1.40-1.51 (m, 2H), 1.65-1.80 (m, 2H), 2.15-2.20 (m, 2H), 2.50-2.60 (m, 2H), 3.10-3.18 (m, 2H) ), 3.50-3.60 (m, 1H), 3.8.0 (s, 3H), 3.85 (s, 3H), 6.60 (dd, 1H, J = 6 Hz, 3 Hz), 6.80 (d, 1H, J = 9 Hz), 7.20-7.25 (m, 1H), 7.30-7.39 (m, 2H), 8.15 (d, 1H, J = 3 Hz), 8.38 (d, 1H, J = 6 Hz), 9.8 (br s, 1H); MS (DCI / NH3) m / e 372 (M + H) + · Maleic acid salt: Analytical calculation for C20H25N304 .2.0C4H404, 1.3H20: C, 53 · 64; H, 5.72; N, 6.70. Found: C, 53.26; H, 5.95; N, 6.45. Example 295

2-α-丨24(3,5-二甲氣基笨基）胺某1-2-酮基乙基丨六氫吡啶-4-D2-α- 丨 24 (3,5-dimethylaminobenzyl) amine 1-2-ketoethyl 丨 hexahydropyridine-4-D

吡錠N_氣化物 實例295A 2-氯-N-(3,5-二甲氧基笨基）乙醯胺 按照實例33A中所述之程序，以2-氯-N-(3,5-二甲氧基苯基） 苯胺取代3-甲基苯胺，提供標題化合物（1.8克，60%產率）， 為白色固體。iHNMRpOOMHiCDCU) 5 3.80(s，6H)，4.20(s，2H)， 6.15 (t，1H，J=3 Hz)，6.78 (d，2H，J=3 Ηζ)，8·15 (br s，1H); MS (DCI/NH3) m/e 230(M+H)+.Pyridine N_Gas Example 295A 2-Chloro-N- (3,5-dimethoxybenzyl) acetamidamine Following the procedure described in Example 33A, 2-chloro-N- (3,5- Dimethoxyphenyl) aniline substituted 3-methylaniline to provide the title compound (1.8 g, 60% yield) as a white solid. iHNMRpOOMHiCDCU) 5 3.80 (s, 6H), 4.20 (s, 2H), 6.15 (t, 1H, J = 3 Hz), 6.78 (d, 2H, J = 3 Ηζ), 8.15 (br s, 1H) ; MS (DCI / NH3) m / e 230 (M + H) +.

實例295B 2-(1-丨2-「(3,5_二甲乳基苯基）胺基Ί-2-酉同基乙基}六氫p比淀-4-基） 外匕錠N-氣化物 按照實例225B中所述之程序，以得自實例295A之產物取代 得自實例225A之產物，提供標題化合物，為黃色固體（5〇毫 克）。1H NMR (300 MHz，CDC13) 5 1.42 (d，2H，J=6 Hz)，1.50-1.60 (m，2H)， 2.20-2.50 (m，2H)，3.10-3.18 (m，1H)，3.22-3.41 (m，2H)，3·62_3·70 (m，2H)， 85228 -339- 200404539 3.80 (s，6H)，6·15 (m，1H)，6.82 (s，1Η)，7.20-7.35 (m，4H)，8.02 (s，1H)，8.25 (d， 1H，J=6 Hz); MS (DCI/NH3) m/e 372 (M+H)+ ;對 C2 〇 H2 5 N3 04 · 2.24 H2 O 之分析計算值：C，58.34; H，7·22; N，10.20·實測值：C，58.73 ; H，7.50 ；N,9.79. 實例296 241-(2-丨「3-(二甲胺基）笨基1胺基丨-2-酮基乙某）六氫吡啶斗基1 吡錠N-氣化物 按照實例282中所述之程序，以N，N-二甲苯-1，3-二胺取代5-胺基氫茚。使殘留物於矽膠上藉急驟式管柱層析純化（以5% 甲醇：二氯甲烷溶離），提供60毫克（48%產率）標題化合物 ，為透明油。1H NMR (300 MHz, CDC13) 5 1.70 (q，J=12.4 Hz，1H)，1.71 (q，J=12.2 Hz，1H)，2.15 (d，J=12.9 Hz，2H)，2.53 (t，J=1L9 Hz，2H)，2.96 (s， 6H)? 3.08 (d5 J=13.6 Hz? 2H)? 3.18 (s? 2H)? 3.55 (tt? J=12.0? 3.4 Hz, 1H)? 6.49 (dd5 J=8.05 2.2 Hz? 1H)? 6.72 (d5 J=8.1 Hz, 1H)? 7.17 (m? 2H)5 7.24 (t5 J=2.4 Hz? 1H)，7.28 (d，J=4.4 Hz，2H)，9_05 (s，1H) ; MS (DCI/NH3) m/e 355 (M+H)+ ; 對 C20H26N4O2 · 0.3CH2C12之分析計算值：c，64.18; H，7.06; N，14.75. 實測值：C，64.32 ; H，7.04 ; N，14_79. 實例297 ?-(l-丨2-|&quot;(3-異丙基苯基）胺基1-2-酮基乙基丨六氫峨咬-4-基V比錠Example 295B 2- (1- 丨 2-"(3,5_dimethyllactylphenyl) aminofluorenyl-2-fluorenylethyl} hexahydrop-pyridol-4-yl) Outer dagger N- The gaseous product was replaced with the product from Example 295A by the procedure described in Example 225B to provide the title compound as a yellow solid (50 mg). 1H NMR (300 MHz, CDC13) 5 1.42 ( d, 2H, J = 6 Hz), 1.50-1.60 (m, 2H), 2.20-2.50 (m, 2H), 3.10-3.18 (m, 1H), 3.22-3.41 (m, 2H), 3.62_3 · 70 (m, 2H), 85228 -339- 200404539 3.80 (s, 6H), 6.15 (m, 1H), 6.82 (s, 1Η), 7.20-7.35 (m, 4H), 8.02 (s, 1H) , 8.25 (d, 1H, J = 6 Hz); MS (DCI / NH3) m / e 372 (M + H) +; Analytical calculated value for C2 〇H2 5 N3 04 · 2.24 H2 O: C, 58.34; H, 7.22; N, 10.20. Found: C, 58.73; H, 7.50; N, 9.79. Example 296 241- (2- 丨 "3- (Dimethylamino) benzyl 1amino 丨 -2 -Ketoethoxy) hexahydropyridyl 1 pyridinium N-gasate Substituting N, N-xylene-1,3-diamine with 5-aminohydroindene according to the procedure described in Example 282. The residue was purified by flash column chromatography on silica gel (using 5% methanol: methylene chloride) to provide 60 mg (48% yield) of the title compound as a clear oil. 1H NMR (300 MHz, CDC13) 5 1.70 (q, J = 12.4 Hz, 1H), 1.71 (q , J = 12.2 Hz, 1H), 2.15 (d, J = 12.9 Hz, 2H), 2.53 (t, J = 1L9 Hz, 2H), 2.96 (s, 6H)? 3.08 (d5 J = 13.6 Hz? 2H) 3.18 (s? 2H)? 3.55 (tt? J = 12.0? 3.4 Hz, 1H)? 6.49 (dd5 J = 8.05 2.2 Hz? 1H)? 6.72 (d5 J = 8.1 Hz, 1H)? 7.17 (m? 2H ) 5 7.24 (t5 J = 2.4 Hz? 1H), 7.28 (d, J = 4.4 Hz, 2H), 9_05 (s, 1H); MS (DCI / NH3) m / e 355 (M + H) +; Yes C20H26N4O2 · 0.3CH2C12 Analytical calculation value: c, 64.18; H, 7.06; N, 14.75. Found: C, 64.32; H, 7.04; N, 14_79. Example 297?-(L- 丨 2- | &quot; ( 3-Isopropylphenyl) amino 1-2-ketoethyl 丨 Hexahydro-4-enyl V ratio ingot

N-氧化物 實例297A 2-氯-N_(3-異丙基茉某）乙醯胺 按照實例22A中所述之程序，以3-異丙基苯胺取代3,4,5-三 甲氧基苯胺，提供標題化合物（7.12克，92% )。1H NMR (300 MHz， 85228 -340- 200404539 CDC13) 5 1.24 (dd，J=10.3, 7.0 Hz，6H)，2.91 (m，1Η)，4·19 (s，2H)，7·05 (d，J二 7.8 Hz，1H)，7·39 (m，3H)，8·18 (s，1H) ; MS (ESI) m/e 212 (M+H)+.N-oxide Example 297A 2-Chloro-N_ (3-isopropylammonium) acetamide Follow the procedure described in Example 22A to replace 3,4,5-trimethoxyaniline with 3-isopropylaniline Provide the title compound (7.12 g, 92%). 1H NMR (300 MHz, 85228 -340- 200404539 CDC13) 5 1.24 (dd, J = 10.3, 7.0 Hz, 6H), 2.91 (m, 1Η), 4.19 (s, 2H), 7.05 (d, J 2 7.8 Hz, 1H), 7.39 (m, 3H), 8.18 (s, 1H); MS (ESI) m / e 212 (M + H) +.

實例297B 異丙基笨基）胺基1-2-酮基乙基丨六氤吡啶-4-基）吡錠 • N-氧化物 按照實例225B中所述之程序，以得自實例297A之產物取代 得自實例225A之產物，提供標題化合物，為非晶質固體。（160 毫克，30% )。1H NMR (300 MHz，CD3 OD) 5 1.25 (d，J=6.8 Hz，6H)，1.86 (dd，J=12.7, 3_6 Hz，2H)，2·05 (m，2H)，2.44 (m，2H)，2.89 (m，1H)，3.13 (m， 3H)5 3.23 (s5 2H)5 7.00 (d5 J=7.8 Hz? 1H)5 7.24 (t, J=7.8 Hz, 1H)5 7.40 (m5 3H), 7.48 (s，1H)，7·60 (d，J=4.4 Hz，1H)，8.34 (d，J=6.4 Hz，1H); MS (ESI) m/e 354 (M+H)+ ;對 C21H27N302 · 0.4CH2C12 · 2.0H2O 之分析計算值： C，52.29 ; Η，6·15; N，7.82·實測值：c，52.21 ; H，6.14; N，8.15. 實例298 2-(l-{2-[(3-氯基-2-甲基苯基）胺某i_2-酮基乙基}六氫p比啶_4_基）Example 297B Isopropylbenzyl) amino 1-2-ketoethyl 丨 hexapyridin-4-yl) pyridine • N-oxide The procedure described in Example 225B was used to obtain the product from Example 297A Instead of the product from Example 225A, the title compound was provided as an amorphous solid. (160 mg, 30%). 1H NMR (300 MHz, CD3 OD) 5 1.25 (d, J = 6.8 Hz, 6H), 1.86 (dd, J = 12.7, 3_6 Hz, 2H), 2.05 (m, 2H), 2.44 (m, 2H ), 2.89 (m, 1H), 3.13 (m, 3H) 5 3.23 (s5 2H) 5 7.00 (d5 J = 7.8 Hz? 1H) 5 7.24 (t, J = 7.8 Hz, 1H) 5 7.40 (m5 3H) , 7.48 (s, 1H), 7.60 (d, J = 4.4 Hz, 1H), 8.34 (d, J = 6.4 Hz, 1H); MS (ESI) m / e 354 (M + H) +; pair C21H27N302 · 0.4CH2C12 · 2.0H2O Analytical calculated value: C, 52.29; Η, 6.15; N, 7.82 · Found: c, 52.21; H, 6.14; N, 8.15. Example 298 2- (l- {2 -[(3-Chloro-2-methylphenyl) amine i_2-ketoethyl} hexahydrop than pyridin_4_yl)

吡錠N-氧化物 實例298APyridium N-oxide Example 298A

M -N-C3-氯基_2_甲基笨基）乙醯胺 按照實例22Α中所述之程序，以3_氯基冬甲基苯基胺取代 3,4,5-三甲氧基苯胺，提供標題化合物（7.3克，95% )。iHNMR (300 MHz，CDC13) δ 2.35 (s，3H)，4.26 (s，2H)，7.19 (m，1H)，7.26 (m，1H)， 7.73 (d，J=8.1 Hz，1H)，8.26 (s，1H) ; MS (ESI) m/e 219 (M+H)+ ·M -N-C3-Chloro_2_methylbenzyl) acetamidine Follow the procedure described in Example 22A to replace 3,4,5-trimethoxyaniline with 3-chlorobenzylmethylphenylamine Provide the title compound (7.3 g, 95%). iHNMR (300 MHz, CDC13) δ 2.35 (s, 3H), 4.26 (s, 2H), 7.19 (m, 1H), 7.26 (m, 1H), 7.73 (d, J = 8.1 Hz, 1H), 8.26 ( s, 1H); MS (ESI) m / e 219 (M + H) + ·

f 例 298B 2-(1-{Μ3_氯基-2_.里安基1-2-酮某乙基}六氫吡啶斗基） 85228 -341 - 200404539 吡錠N-氲化物 按照實例225B中所述之程序，以得自實例298A之產物取代 得自賞例225A之產物，提供標題化合物，為非晶質固體。（25 毫克，18% )。1H NMR (300 MHz，CD3 OD) 61.64 (dd，J=12.2, 3·7 Hz，2H)， 1·87 (m，2H)，2·05 (d，JN12.9 Hz，2H)，2·33 (s，3H)，2·89 (m，2H)，3.21 (m，3H)， 7.23 (m，2H)，7·39 (m，2H)，7.58 (m，2H)，8·34 (d，J=6.4 Hz，1H) ； MS (ESI) m/e360 (M+H)+. 實例299 3-甲基-N-|~2-(4-吡啶-2-基六氫吡畊-l-基）乙基i笨甲醯胺 於3-甲基苯甲醯胺（360毫克，5.0毫莫耳）在二氯甲烷(5毫升） 中之溶液内，於0°C下，添加1-(3-二甲胺基丙基）_3•乙基碳化 一亞胺鹽版鹽（1·〇6克’ 5.5愛莫耳）。15分鐘後，添加乙醇胺（333 微升，5.5毫莫耳），並將混合物於室溫下攪拌6小時。將混 合物以50毫升醋酸乙酯稀釋。將有機層以2χ飽和氯化銨水 溶液(25毫升）、2χ飽和碳酸氫鈉水溶液（25毫升）、2Χ鹽水（25 毫升）洗滌，以硫酸鎂脫水乾燥，過濾，及蒸發。產物為白 色固體（476毫克，53% )。於所形成之醇（55毫克，0.31毫莫耳） 與吡啶（33微升，〇·37毫莫耳）在二氯甲烷（〇·5毫升）中之溶液 内’於0°C下，添加氯化甲烷磺醯（43毫克，〇·37毫莫耳）。在 罜溫下1小時後，以1〇毫升醋酸乙酯稀釋混合物。將有機層 以2x氯化按稀水溶液(5毫升）、2χ鹽水(5毫升）洗條，以硫酸 鎂脫水乾燥，過濾，及蒸發。使殘留物溶於Ν，Ν-二甲基甲醯 胺（1笔升）中，並以丨_吡啶_2_基六氫吡畊⑽微升，0.31毫莫耳） 與Ν，Ν-二異丙基乙胺（155微升，〇·78毫莫耳）處理。在繼。c下 85228 -342- 200404539 24小時後，使混合物冷卻，及濃縮。使殘留物於珍膠上藉 急驟式管柱層析純化（以1-2.5%甲醇··二氯甲燒溶離），提供 45毫克（45%產率）標題化合物，為白色固體。1 H NMR (300 MHz， CDC13) 5 2·40 (s，3H)，2.66 (m，6H)，3.60 (m，6H)，6.65 (m，2H)，6.84 (s，1H)， 7.31 (m，2H)，7.49 (ddd，J=8.7, 7.0, 2.0 Hz，1H)，7_55 (m，1H)，7.63 (s，1H)， 8.20 (cidd，J=5.0, 2.0, 0_9 Hz，1H) ; MS (DCI/NH3) m/e 325 (M+H)+ ；對 C19H24N40· 0.2 H20之分析計算值：C，69·57 ; Η，7·50; N, 17.08· 實測值：C，69_41 ; H，7.21 ; N，17.10· 實例300 ^1-{「(2,3-二溴基-5-甲某笨甲醯基）胺基1甲基}六氫吡啶-4_某）f Example 298B 2- (1- {M3_Chloro-2_.Rianyl1-2-one-one ethyl} hexahydropyridinyl) 85228 -341-200404539 The procedure described replaces the product from Example 298A with the product from Example 298A to provide the title compound as an amorphous solid. (25 mg, 18%). 1H NMR (300 MHz, CD3 OD) 61.64 (dd, J = 12.2, 3.7 Hz, 2H), 1.87 (m, 2H), 2.05 (d, JN12.9 Hz, 2H), 2 · 33 (s, 3H), 2.89 (m, 2H), 3.21 (m, 3H), 7.23 (m, 2H), 7.39 (m, 2H), 7.58 (m, 2H), 8.34 ( d, J = 6.4 Hz, 1H); MS (ESI) m / e360 (M + H) +. Example 299 3-methyl-N- | ~ 2- (4-pyridin-2-ylhexahydropyridine- l-yl) ethyl benzamidine in 3-methylbenzamide (360 mg, 5.0 mmol) in dichloromethane (5 ml) at 0 ° C, add 1 -(3-Dimethylaminopropyl) -3 ethyl ethylcarbodiimide salt (1.06 g '5.5 Emole). After 15 minutes, ethanolamine (333 μl, 5.5 mmol) was added and the mixture was stirred at room temperature for 6 hours. The mixture was diluted with 50 ml of ethyl acetate. The organic layer was washed with a 2 × saturated aqueous ammonium chloride solution (25 ml), a 2 × saturated aqueous sodium bicarbonate solution (25 ml), and 2 × brine (25 ml), dried over magnesium sulfate, filtered, and evaporated. The product was a white solid (476 mg, 53%). In a solution of the formed alcohol (55 mg, 0.31 mmol) and pyridine (33 μl, 0.37 mmol) in dichloromethane (0.5 mL) was added at 0 ° C. Methanesulfonium chloride (43 mg, 0.37 mmol). After 1 hour at a high temperature, the mixture was diluted with 10 ml of ethyl acetate. The organic layer was washed with dilute aqueous solution (5 ml) of 2x chloride and 2x brine (5 ml), dried over magnesium sulfate, filtered, and evaporated. The residue was dissolved in Ν, Ν-dimethylformamide (1 liter), and π-pyridin-2-ylhexahydropyridine (0.31 mmol) and Ν, Ν- 二Isopropylethylamine (155 μl, 0.78 mmol) was treated. Following on. 85228 -342- 200404539 under c. After 24 hours, the mixture was cooled and concentrated. The residue was purified by gel column chromatography on gelatin (dissolved in 1-2.5% methanol · dichloromethane) to provide 45 mg (45% yield) of the title compound as a white solid. 1 H NMR (300 MHz, CDC13) 5 2.40 (s, 3H), 2.66 (m, 6H), 3.60 (m, 6H), 6.65 (m, 2H), 6.84 (s, 1H), 7.31 (m , 2H), 7.49 (ddd, J = 8.7, 7.0, 2.0 Hz, 1H), 7_55 (m, 1H), 7.63 (s, 1H), 8.20 (cidd, J = 5.0, 2.0, 0_9 Hz, 1H); MS (DCI / NH3) m / e 325 (M + H) +; Analytical calculation for C19H24N40 · 0.2 H20: C, 69 · 57; Η, 7.50; N, 17.08 · Found: C, 69_41; H, 7.21; N, 17.10 · Example 300 ^ 1-{"(2,3-dibromo-5-methylbenzylmethylamino) amino 1methyl} hexahydropyridine-4_some)

吡錠N-氣化物 實例300A 2,3-二溴基-5-甲基笨甲酸 於3-溴基-5-甲基鄰胺基苯甲酸(2.3克，10毫莫耳）在醋酸（12 毫升）中之溶液内，於〇°C下，添加18%氫溴酸（30毫升，30毫 莫耳），接著逐滴添加亞硝酸鈉（690毫克，10毫莫耳）在水（5 毫升）中之溶液。10分鐘後，將此溶液於〇°C下，添加至溴化 銅（1)(2.15克’ 15毫莫耳）在48%氫溴酸（7毫升）中之混合物内 。使混合物溫熱至環境溫度（15分鐘），然後在5〇l下回流， 直到N2完全釋出為止。接著將混合物以醋酸乙酯萃取，以 水、鹽水洗滌，以無水硫酸鎂脫水乾燥，及在減壓下濃縮 ’提供2.8克粗製標題化合物。iHNMR(300MHz，DMSO-d6) 5 2.27 (s，3H)，7·43 (s5 1H)，7.72 (s，1H)，13_60 (br s，1H) ; MS (DCI/NH3)m/e 310(Μ+ΝΗ4)+· 85228 -343 - 200404539Example of Pyridin N-Gas 300A 2,3-Dibromo-5-methylbenzylcarboxylic acid in 3-bromo-5-methyl-o-aminobenzoic acid (2.3 g, 10 mmol) in acetic acid (12 To the solution in 18 mL of hydrobromide (30 mL, 30 mmol) at 0 ° C, add sodium nitrite (690 mg, 10 mmol) in water (5 mL) dropwise. ) In solution. After 10 minutes, this solution was added to a mixture of copper (1) (2.15 g &apos; 15 mmol) in 48% hydrobromic acid (7 ml) at 0 ° C. The mixture was allowed to warm to ambient temperature (15 minutes) and then refluxed at 501 until N2 was completely released. The mixture was then extracted with ethyl acetate, washed with water, brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to provide 2.8 g of the crude title compound. iHNMR (300MHz, DMSO-d6) 5 2.27 (s, 3H), 7.43 (s5 1H), 7.72 (s, 1H), 13_60 (br s, 1H); MS (DCI / NH3) m / e 310 ( Μ + ΝΗ4) + 85228 -343-200404539

實例300B 2,3-二漠基_5-甲基苯甲酿胺 將得自實例300A之產物（L5克，5毫莫耳）、i_(3_二甲胺基 丙基）-3-乙基碳化二亞胺鹽酸鹽（EDCI，1.43克，7.5毫莫耳）及 1-羥基苯并三唑（675毫克，5毫莫耳）在氯仿（30毫升）中之混 合物，攪拌90分鐘，然後添加至10%氫氧化銨（1〇毫升）中， 並再持續攪:拌6小時。接著於減恩下移除氯仿，並將已沉澱 之固體過濾，以水洗滌，及在減壓下乾燥，提供1.45克標題 化合物。1 H NMR (300 MHz，DMSO_d6) 5 2.27 (s，3H)，7.20 (m，1H)，7·60 (br s，1H)，7.64 (m，1H)，7·89 (br s，1H) ; MS (DCI/NH3) m/e 309 (M+NH4)+ ·Example 300B 2,3-Dimethynyl-5-methylbenzylamine The product from Example 300A (L5 g, 5 mmol), i_ (3-dimethylaminopropyl) -3-ethyl Of carbodiimide hydrochloride (EDCI, 1.43 g, 7.5 mmol) and 1-hydroxybenzotriazole (675 mg, 5 mmol) in chloroform (30 ml), stir for 90 minutes, Then add to 10% ammonium hydroxide (10 ml), and continue stirring: mix for 6 hours. Then, chloroform was removed under reduced gravity, and the precipitated solid was filtered, washed with water, and dried under reduced pressure to provide 1.45 g of the title compound. 1 H NMR (300 MHz, DMSO_d6) 5 2.27 (s, 3H), 7.20 (m, 1H), 7.60 (br s, 1H), 7.64 (m, 1H), 7.89 (br s, 1H) ; MS (DCI / NH3) m / e 309 (M + NH4) + ·

實例300C 2-(1-{ΙΤ2,3-二澳基_5-甲基苯甲gj基）胺某l甲基}六氫p比淀_4_某） 吡錠N-氣化物 按照實例200中所述之程序，以得自實例300B之產物取代3-甲基苯甲醯胺，而得標題化合物（30%產率），為白色固體。 1H NMR (300 MHz，DMSO-d6) 5 1.53 (m，2H)，1 ·90 (m，2H)，2.30 (s，3H)， 2.47 (m，2H)，2.93 (m，2H)，3.22 (m，1H)，4·15 (d，2H，J=6.1 Hz)，7.29 (m，4H)， 7.66 (dd，1H，J=2_0, 1.0 Hz)，8.24 (m，1H)，8.77 (t，1H，J=6.1 Hz) ; MS (DCI/NH3) m/e 484 (M+H)+. 實例301 2·{1-『(笨甲醯胺基）甲基1六氫p比淀-4_基]^比鍵N-氧化物 按照實例200中所述之程序，以苯甲醯胺取代3-甲基苯甲 醯胺，提供標題化合物（27毫克，30%產率）。iHNMRQOOMHz， CD3 0D) (5 1.71 (dd，J=12.4, 3.6 Hz，2H)，2·04 (m，2H)，2.54 (m，2H)，3.12 (m， 85228 -344- 200404539 3H)，3.37 (s，2H)，7.46 (m，5H)，7.87 (m，3H)，8.33 (d，J=6.4 Hz，1H) ; MS - (ESI)m/e312(M+H)+ ;對 C18H21N302 ·2·0Η2Ο之分析計算值： C，62.23 ; H，7·25 ; N，12.10.實測值：C，61·91 ; H，7.27 ; N，12·03· 實例302 2- (MIY4-氯某-3-甲基苯甲酸基）胺基1甲基}六氫吡啶-4-基 &gt;比鍅 N-氧化物 按照實例200中所述之程序，以4-氯基-3-甲基苯甲醯胺取代 3- 甲基苯甲醯胺，提供標題化合物（60毫克，56%產率）。 _ 1H NMR (300 MHz，DMSO-d6) δ 2.38 (m，6H)，2·51 (m，2H)，2.73 (m，1H)， 2.88 (s，3H)，4·80 (s，2Η)，7·34 (m，1H)，7.52 (m，2H)，7.71 (m，2H)，7.90 (m， 2H)，9.21 (br s，1H) ; MS (ESI) m/e 360 (M+H)+ ;對 q 9 H2 2 C1N3 O · 1.0 C2HF3 02 之分析計算值：c，53.23 ; H，4·89 ; N，8.87.實測值： C，52.84 ; H，4.57 ; N，8.62. 764284 實例 303 氟基-3-甲基笨甲醯基）胺基1甲基}六氪吡啶-4-基）吡錠 N-氧化物 鬌 按照實例200中所述之程序，以4-氟基-3-甲基苯甲醯胺 (Oakwood)取代3-甲基苯甲醯胺，提供標題化合物。（82毫克 ，82.8%)。iHNMR(300 MHz, DMSO-d6)(5 1.52 (m，2H)，l_89(d，J=12Example 300C 2- (1- {ΙΤ2,3-Dioxo_5-methylbenzyl gjyl) amine 1 methyl} hexahydro p ratio_4_some) pyridinium N-gas according to Example 200 The procedure described in this example replaced the 3-methylbenzamide with the product from Example 300B to give the title compound (30% yield) as a white solid. 1H NMR (300 MHz, DMSO-d6) 5 1.53 (m, 2H), 1.90 (m, 2H), 2.30 (s, 3H), 2.47 (m, 2H), 2.93 (m, 2H), 3.22 ( m, 1H), 4.15 (d, 2H, J = 6.1 Hz), 7.29 (m, 4H), 7.66 (dd, 1H, J = 2_0, 1.0 Hz), 8.24 (m, 1H), 8.77 (t ， 1H ， J = 6.1 Hz); MS (DCI / NH3) m / e 484 (M + H) +. Example 301 2 · {1-『(benzylmethylamino) methyl 1 hexahydro p ratio lake- 4-Alkyl bond N-oxide Following the procedure described in Example 200, 3-methylbenzamide was replaced with benzamidine to provide the title compound (27 mg, 30% yield). iHNMRQOOMHz, CD3 0D) (5 1.71 (dd, J = 12.4, 3.6 Hz, 2H), 2.04 (m, 2H), 2.54 (m, 2H), 3.12 (m, 85228 -344- 200404539 3H), 3.37 (s, 2H), 7.46 (m, 5H), 7.87 (m, 3H), 8.33 (d, J = 6.4 Hz, 1H); MS-(ESI) m / e312 (M + H) +; For C18H21N302 · Analytical calculated values from 2 · 0Η20: C, 62.23; H, 7.25; N, 12.10. Found: C, 61 · 91; H, 7.27; N, 12.03. Example 302 2- (MIY4-chlorine 3-Methylbenzoate) amino 1methyl} hexahydropyridin-4-yl &gt; Pyridyl N-oxide Following the procedure described in Example 200, 4-chloro-3-methylbenzene Formamidine replaced 3-methylbenzidine to provide the title compound (60 mg, 56% yield). _ 1H NMR (300 MHz, DMSO-d6) δ 2.38 (m, 6H), 2.51 (m , 2H), 2.73 (m, 1H), 2.88 (s, 3H), 4.80 (s, 2Η), 7.34 (m, 1H), 7.52 (m, 2H), 7.71 (m, 2H), 7.90 (m, 2H), 9.21 (br s, 1H); MS (ESI) m / e 360 (M + H) +; Analytical calculation for q 9 H2 2 C1N3 O · 1.0 C2HF3 02: c, 53.23; H, 4.89; N, 8.87. Found: C, 52.84; H, 4.57; N, 8.62. 764284 Example 303 Fluorine Methyl-3-methylbenzylidene) amino 1methyl} hexapyridin-4-yl) pyridine N-oxide- Follow the procedure described in Example 200, using 4-fluoro-3-formyl Substituted 3-methylbenzamide with Oakwood to provide the title compound. (82 mg, 82.8%). iHNMR (300 MHz, DMSO-d6) (5 1.52 (m, 2H), l_89 (d, J = 12

Hz，2H)，2.29 (s，3H)，2·36 (t，J=12 Hz，2H)，2.95 (d，J=12 Hz，2H)，3·19 (m， 1H)，4.17 (d，J=6 Hz, 2H)，7.27 (m，3H)，7.39 (dd, J=7.5, 1.5 Hz，1H)，7·75 (m， 1H)，7.85 (dd，7.5, 1·5 Hz，1H)，8.23 (dd，J=6, 1·5 Hz，1H)，8.72 (t，J=6 Hz, 1H) ;MS(DCI/NH3)m/e328 (M+H-16)+ ; 344(M+H)+ ;對 C19H22N3F02 之分析計算值：C，66.54; H，6·46; N，12.24.實測值：C，66.20; H，6.31 85228 -345- 200404539 ;N，12.18. 實例304 2-「l-(丨「3-氯基-4-Γ三氣甲氧基）笨甲醯基1胺基丨甲基）六氫吡啶-4- 基1吡錠N-氣化物 按照實例200中所述之程序，以3-氯基-4-甲氧基苯甲醯胺 (Oakwood)取代3-甲基苯甲醯胺。（98毫克，62% )。iHNMR (300 MHz，DMSO-d6) (51.52 (m5 2H)，1·89 (d，J=12 Hz，2H)，2·36 (t，J=12 Hz， 2H)，2.95 (d，J=12 Hz，2H)，3.20 (m，1H)，4·18 (d，J=6 Hz，2H)，7_27 (m，3H)， 7.39 (dd? J=7.5? 1.5 Hz? 1H)? 7.75 (m? 1H)5 7.85 (dd? 7.5, 1.5 Hz? 1H)? 8.23 (dd5 J=6，1.5HZ，lH)，8.72(t，J=6Hz，lH) ； MS (DCI/NH3) m/e 414 (M+H-16)+ ;430(]\4+11)+;對（：191119(：1?303之分析計算值：0；53.09;11，4.46 ;N，9·78·實測值 C，52.73 ; H，4.34 ; N，9·51· 實例305 2-Π4ΙΥ3-乙氫某苯甲醯基）胺基1甲基i六氫吡啶-4-基）吡錠 Ν-氣化物 按照實例200中所述之程序，以3-乙氧基苯甲醯胺取代3-甲基苯甲醯胺。（65 毫克，47% )。WNMRPOOMHaDMSOA) δ 1.34 (t5 J=7.5 Hz, 3H)? 1.52 (m? 2H)? 1.89 (d? J=12 Hz5 2H)5 2.36 (t? J=12 Hz, 2H)，2.95 (d5J=12 Hz，2H)，3_20 (m，1H)，4_08 (q，J=6 Hz, 2H)，4·18 (d，J=6 Hz， 2H)，7_08 (m，1H)，7.27 (m，2H)，7.39 (m，4H)，8.23 (dd，J=6 Hz，1·5 Hz，1H)， 8.72 (t5 J=6 Hz? 1H) ； MS (DCI/NH3) m/e 340 (M+H-16)+ ； 356 (M+H)+ ； 對 C2〇H25N303 · 0.75 H20 之分析計算值：C，65.11; H，7.24; N，11.39. 實測值：C，65·00 ; H，7.08 ; N，11.01· 實例306 85228 -346- 200404539 2-α·{ΙΪ3,5-二氯笨甲_基）胺基1甲基}六氫说淀-4-基 &gt;比錠 · Ν-氧化物 按照實例200中所述之程序，以3,5-二氯苯甲酸胺（Lancaster) 取代3-甲基苯甲醯胺。（46毫克，33.3% )。iHNMROOOMHz， DMSO-d6) 6 1.52 (m，2H)，1·89 (d，J=12 Hz，2H)，2·36 (t，J=12 Hz，2H)，2·95 (d，J=12 Hz，2H)，3·20 (m，1H)，4.18 (d，J=6 Hz，2H)，7.29 (m，2H)，7·39 (m， 1H)，7.83 (t，J=L5 Hz，1H)，7.92 (d，J=1 ·5 Hz，2H)，8.23 (dd，J=6 Hz，1.5 Hz， 1H)? 8.98 (t5 J=6 Hz? 1H) ； MS (DCI/NH3) m/e 365 (M+H-16)+ ； 381 (M+H)+ φ ;對0：181119&lt;：12叫〇2之分析計算值：C，56.85; H，5.04; Ν，11·05_ 實測值：C，56.56 ; H，5·20 ; N，10·79· 實例307 2-Γ1-川4-甲基-3彳三氟甲基）笨甲醯某1胺基}甲基）六氫吡啶-4-基1 吡錠Ν-氣化物 按照實例200中所述之程序，以4-甲基-3_三氟甲基苯甲醯胺 (Apollo)取代3-甲基苯甲醯胺。（75毫克，66.3%)。iHNMRpOO MHz，DMSO-d6) (5 1.52 (m，2H)，1 ·89 (d，J=12 Hz，2H)，2.36 (t，J=12 Hz，2H)， φ 2.95 (d，J=12 Hz，2H)，3·20 (m，1H)，3.25 (s，3H)，4·18 (d，J=6 Hz，2H)，7.29 (m， 2H)，7.39 (m，1H)，7.58 (d，J=9 Hz，1H)，8.08 (d，J=9 Hz，1H)，8.19 (s，1H)， 8.23 (dd，J=6,1.5 Hz，1H)，8.98 (t，J=6 Hz，1H) ; MS (DCI/NH3) m/e 378 (M+H-16)+ ; 394(M+H)+ ;對 C20H22F3N3O2 · 0·3Η2Ο 之分析計算 值：C，60.23 ; H，5·71 ; N，10.53·實測值：C，60.03 ; H，5.62 ; N，10·18· 實例308 2-(1-丨「(3,4_二甲笨甲酿基）胺基1甲基}六氫T?比淀-4-基V比鍵 Ν-氧化物Hz, 2H), 2.29 (s, 3H), 2.36 (t, J = 12 Hz, 2H), 2.95 (d, J = 12 Hz, 2H), 3.19 (m, 1H), 4.17 (d , J = 6 Hz, 2H), 7.27 (m, 3H), 7.39 (dd, J = 7.5, 1.5 Hz, 1H), 7.75 (m, 1H), 7.85 (dd, 7.5, 1.5 Hz, 1H), 8.23 (dd, J = 6, 1.5 Hz, 1H), 8.72 (t, J = 6 Hz, 1H); MS (DCI / NH3) m / e328 (M + H-16) +; 344 (M + H) +; Analysis and calculation of C19H22N3F02: C, 66.54; H, 6.46; N, 12.24. Found: C, 66.20; H, 6.31 85228 -345- 200404539; N, 12.18. Example 304 2- "l- (丨" 3-Chloro-4-Γtrifluoromethoxy) benzylidene 1amino 丨 methyl) hexahydropyridin-4-yl 1pyridine N-gas according to Example 200 Procedure described in Substitution of 3-methylbenzamide with 3-chloro-4-methoxybenzamide (Oakwood). (98 mg, 62%). IHNMR (300 MHz, DMSO-d6 ) (51.52 (m5 2H), 1.89 (d, J = 12 Hz, 2H), 2.36 (t, J = 12 Hz, 2H), 2.95 (d, J = 12 Hz, 2H), 3.20 ( m, 1H), 4 · 18 (d, J = 6 Hz, 2H), 7_27 (m, 3H), 7.39 (dd? J = 7.5? 1.5 Hz? 1H)? 7.75 (m? 1H) 5 7.85 (dd ? 7.5, 1.5 Hz? 1H)? 8.23 (dd5 J = 6, 1.5HZ, lH), 8.72 (t J = 6Hz, lH); MS (DCI / NH3) m / e 414 (M + H-16) +; 430 (] \ 4 + 11) +; Analysis and calculation of (191191 (: 1? 303): 0; 53.09; 11, 4.46; N, 9.78. Found C, 52.73; H, 4.34; N, 9.51. Example 305 2-Π4ΙΠ3-ethylhydrogen benzamidine) amino 1methyli Hexahydropyridin-4-yl) pyridine N-gasate Follow the procedure described in Example 200 to replace 3-methylbenzamide with 3-ethoxybenzamide. (65 mg, 47%) .WNMRPOOMHaDMSOA) δ 1.34 (t5 J = 7.5 Hz, 3H)? 1.52 (m? 2H)? 1.89 (d? J = 12 Hz5 2H) 5 2.36 (t? J = 12 Hz, 2H), 2.95 (d5J = 12 Hz, 2H), 3_20 (m, 1H), 4_08 (q, J = 6 Hz, 2H), 4.18 (d, J = 6 Hz, 2H), 7_08 (m, 1H), 7.27 (m, 2H ), 7.39 (m, 4H), 8.23 (dd, J = 6 Hz, 1.5 Hz, 1H), 8.72 (t5 J = 6 Hz? 1H); MS (DCI / NH3) m / e 340 (M + H-16) +; 356 (M + H) +; Analytical calculation for C20H25N303 · 0.75 H20: C, 65.11; H, 7.24; N, 11.39. Found: C, 65 · 00; H, 7.08 N, 11.01 · Example 306 85228 -346- 200404539 2-α · {ΙΪ3,5-dichlorobenzyl-methyl) amino 1methyl} hexahydrosulfonyl-4-yl &gt; Bi ingot · Ν- Oxide Following the procedure described in Example 200, 3-methylbenzylamine was replaced with 3,5-dichlorobenzoate (Lancaster). (46 mg, 33.3%). iHNMROOOMHz, DMSO-d6) 6 1.52 (m, 2H), 1.89 (d, J = 12 Hz, 2H), 2.36 (t, J = 12 Hz, 2H), 2.95 (d, J = 12 Hz, 2H), 3.20 (m, 1H), 4.18 (d, J = 6 Hz, 2H), 7.29 (m, 2H), 7.39 (m, 1H), 7.83 (t, J = L5 Hz, 1H), 7.92 (d, J = 1 · 5 Hz, 2H), 8.23 (dd, J = 6 Hz, 1.5 Hz, 1H)? 8.98 (t5 J = 6 Hz? 1H); MS (DCI / NH3 ) m / e 365 (M + H-16) +; 381 (M + H) + φ; Analytical calculated value for 0: 181119 &lt;: 12 is 〇2: C, 56.85; H, 5.04; Ν, 11 · 05_ Measured value: C, 56.56; H, 5.20; N, 10 · 79. Example 307 2-Γ1-Chuan 4-methyl-3 彳 trifluoromethyl) Benzobenzyl 1 amino} methyl) Hexahydropyridin-4-yl 1 pyridinium N-gasate Substituting 4-methyl-3_trifluoromethylbenzylamine (Apollo) for 3-methylbenzylamine according to the procedure described in Example 200 amine. (75 mg, 66.3%). iHNMRpOO MHz, DMSO-d6) (5 1.52 (m, 2H), 1.89 (d, J = 12 Hz, 2H), 2.36 (t, J = 12 Hz, 2H), φ 2.95 (d, J = 12 Hz, 2H), 3.20 (m, 1H), 3.25 (s, 3H), 4.18 (d, J = 6 Hz, 2H), 7.29 (m, 2H), 7.39 (m, 1H), 7.58 (d, J = 9 Hz, 1H), 8.08 (d, J = 9 Hz, 1H), 8.19 (s, 1H), 8.23 (dd, J = 6, 1.5 Hz, 1H), 8.98 (t, J = 6 Hz, 1H); MS (DCI / NH3) m / e 378 (M + H-16) +; 394 (M + H) +; Analytical calculation for C20H22F3N3O2 · 0 · 3Η2〇: C, 60.23; H, 5.71; N, 10.53. Measured values: C, 60.03; H, 5.62; N, 10.18. Example 308 2- (1- 丨 "(3,4_Dimethylbenzyl) amino 1A Base} hexahydro T? Bito-4-yl V ratio bond N-oxide

85228 -347- 200404539 按照實例200中所述之程序，以3,4-二甲基苯甲酿胺（Lancaster) · 耳又代3_甲基苯甲醯胺。（85毫克，89% )。iHNMRpOOMHz， DMSO-d6) 5 1 ·52 (m，2H)，1.89 (d，J=12 Hz，2H)，2·28 (s，6H)，2·36 (m，2H)， 2.95 (d，J=12 Hz，2H)，3.20 (m，1H)，4·18 (d，J=6 Hz，2H)，7.21 (d，J=9 Hz，1H)， 7.29 (m，2H)，7.39 (m，1H)，7·62 (d，J=9 Hz，1H)，7.68 (s，1H)，8.23 (dd，J=6， 1.5 Hz，1H)，8.64 (t，J=6 Hz，1H) ; MS (DCI/NH3) m/e 324 (M+H-16)+ ; 340 (M+H)+ ;對 C2〇H25N302 · 0·3 H20 之分析計算值：C，69·66 ; H，7.48 ;N，12.19.實測值：C，69.39 ; H，7.41 ; N，11.94· φ 實例309 氯基-4-氣笨甲醯基）胺某1甲基丨六氫吡啶-4-基）吡錠 Ν-氣化物 按照實例200中所述之程序，以3-氯基-4-氟基苯甲醯胺 (Maybridge)取代3-甲基苯甲醯胺。（85毫克，89% )。iHNMR (300 MHz, DMSO-d6 ) δ 1 ·52 (m，2Η)，1.89 (d，J=12 Ηζ，2Η)，2·36 (m，2Η)， 2.95 (d，J=12 Hz, 2Η)，3.20 (m，1Η)，4.18 (d，J=6 Ηζ，2Η)，7.24 (m，2Η)，7_39 (dd，J=6, 1.5 Hz，1H)，7·53 (t，J=9 Hz，1H)，7.93 (m，1H)，8·13 (dd，J=6,1·5 Hz， · 1H)，8.23 (dd，J=6, 1·5 Hz，1H)，8·90 (t，J=6 Hz，1H); MS (DCI/NH3) m/e 348 (M+H-16)+ ; 364(M+H)+ ;對&lt;^181119&gt;13〇2(^.0.8112〇之分析計算 值：C，57.16 ; H，5.49; N，11.11.實測值：C，57.26 ; Η，5·40; Ν，10·53· 實例310 2-(l-{『(吡啶-2-某韃基）胺基1甲基}六氫吡啶4-基）吡錠N-氣化物 按照實例200中所述之程序，以甲基吡啶醯胺取代3-甲基 苯甲酸胺。（51 毫克，57% )。1H NMR (300 MHz，DMSO-d6 ) 5 1·52 (m， 2Η)，1·89 (d，J=12 Ηζ，2Η)，2.36 (m，2Η)，2·98 (d，J=12 Ηζ，2Η)，3.18 (m，1Η)， 85228 -348- 200404539 ^ 4.22 (d5 J=6 Hz5 2H)? 7.27 (m? 2H)5 7.28 (dd? J=6? 1.5 Hz? 1H)5 7.63 (m5 1H)5 8.03 (m? 1H)? 8.22 (dd5 J=65 1.5 Hz? 1H), 8.23 (dd5 J=65 1.5 Hz5 1H), 8.68 (dd5 'J=6; 1.5 Hz，1H)，9.02 (t，J=6 Hz，1H) ; MS (DCI/NH3) m/e 297 (M+H-16)+ ;313 (M+H)+ ;對 C17H2〇N402 · 0.3 H20 之分析計算值·· C，64.25 ;H，6.53 ; N，17.63·實測值：C，64.10 ; H，6·51 ; N，17.35. 實例311 2-α-{「(3,5-二甲苯甲醯基）胺基1甲基i六氫吡啶-4-基）吡錠 N-氣化物 按照實例200中所述之程序，以3,5-二甲基苯甲醯胺取代3-甲基苯甲醯胺。（140 毫克，60% )。iHNMRpOOMHz/DsOD) 5 1·76 (dd，J=12.4, 3·6 Hz，2H)，2.11 (d，J=12.6 Hz，2H)，2·36 (s，6H)，2.66 (m， 2H)5 3.23 (d5 J=12.2 Hz, 2H), 3.47 (m, 1H)5 4.38 (s5 2H)5 7.22 (s, 1H), 7.41 (m5 1H)，7.52 (m，2H)，7·56 (m，2H)，8.34 (d，J=6.4 Hz，1H) ； MS (ESI) m/e 340 (M+H)+. 實例312 2-(ΜΙΪ3-乙烯基笟甲醯基）胺基甲基i六氫吡啶-4-基）吡錠 N-氣化物 按照實例200中所述之程序，以3-乙烯基苯甲醯胺取代3-甲基苯甲醯胺。（84 毫克，67% )。WNMRGOOMHz'DsOD) 5 1.75 (dd，J=12.6, 3.7 Hz，2H)，2.10 (d，J=12.6 Hz，2H)，2.63 (m，2H)，3.21 (m， &lt; 2H)，3.46 (m，1H)，4.38 (s，2H)，5.34 (d，J=11.2 Hz，1H)，5.90 (d，J=17.3 Hz， 1HX 6.81 (dd5 J=17.6? 10.9 Hz? 1H)? 7.50 (m? 5H)5 7.76 (d5 J=7.5 Hz? 1H)5 7.95 (s，1H)，8.33 (d，J=6_4 Hz，1H)，MS(ESI) m/e 338 (M+H)+ · 實例313 85228 -349- 200404539 2-(M「(4_溴基-3-甲某苽甲醯基）胺基1甲基MZ3,6-四氫吡啶_4_笔」 '85228 -347- 200404539 Following the procedure described in Example 200, 3,4-dimethylbenzamide was substituted with 3-methylbenzamide. (85 mg, 89%). iHNMRpOOMHz, DMSO-d6) 5 1 · 52 (m, 2H), 1.89 (d, J = 12 Hz, 2H), 2.28 (s, 6H), 2.36 (m, 2H), 2.95 (d, J = 12 Hz, 2H), 3.20 (m, 1H), 4.18 (d, J = 6 Hz, 2H), 7.21 (d, J = 9 Hz, 1H), 7.29 (m, 2H), 7.39 ( m, 1H), 7.62 (d, J = 9 Hz, 1H), 7.68 (s, 1H), 8.23 (dd, J = 6, 1.5 Hz, 1H), 8.64 (t, J = 6 Hz, 1H ); MS (DCI / NH3) m / e 324 (M + H-16) +; 340 (M + H) +; Analytical calculation for C20H25N302 · 0 · 3 H20: C, 69 · 66; H , 7.48; N, 12.19. Found: C, 69.39; H, 7.41; N, 11.94 · φ Example 309 Chloro-4-aminobenzylmethyl) amine 1 methyl 1 hexahydropyridin-4-yl) Pyridoxine N-gasate was replaced with 3-chlorobenzylamine (Maybridge) by the procedure described in Example 200. (85 mg, 89%). iHNMR (300 MHz, DMSO-d6) δ 1 · 52 (m, 2Η), 1.89 (d, J = 12 Ηζ, 2Η), 2.36 (m, 2Η), 2.95 (d, J = 12 Hz, 2Η ), 3.20 (m, 1Η), 4.18 (d, J = 6 Ηζ, 2Η), 7.24 (m, 2Η), 7_39 (dd, J = 6, 1.5 Hz, 1H), 7.53 (t, J = 9 Hz, 1H), 7.93 (m, 1H), 8.13 (dd, J = 6, 1.5 Hz, · 1H), 8.23 (dd, J = 6, 1.5 Hz, 1H), 8 · 90 (t, J = 6 Hz, 1H); MS (DCI / NH3) m / e 348 (M + H-16) +; 364 (M + H) +; pair &lt; ^ 181119 &gt; 13〇2 (^ Analytical calculated value: 0.81120: C, 57.16; H, 5.49; N, 11.11. Found: C, 57.26; H, 5.40; Ν, 10.53. Example 310 2- (l- {"(pyridine -2-Amidino) amino 1methyl} hexahydropyridine 4-yl) pyridine N-gasate The procedure described in Example 200 was used to replace 3-methylbenzoic acid amine with methylpyridiniumamine. (51 mg, 57%). 1H NMR (300 MHz, DMSO-d6) 5 1.52 (m, 2Η), 1.89 (d, J = 12 Ηζ, 2Η), 2.36 (m, 2Η), 2 · 98 (d, J = 12 Ηζ, 2Η), 3.18 (m, 1Η), 85228 -348- 200404539 ^ 4.22 (d5 J = 6 Hz5 2H)? 7.27 (m? 2H) 5 7.28 (dd? J = 6 ? 1.5 Hz? 1H) 5 7.63 (m5 1H) 5 8.03 (m? 1H)? 8.2 2 (dd5 J = 65 1.5 Hz? 1H), 8.23 (dd5 J = 65 1.5 Hz5 1H), 8.68 (dd5 'J = 6; 1.5 Hz, 1H), 9.02 (t, J = 6 Hz, 1H); MS (DCI / NH3) m / e 297 (M + H-16) +; 313 (M + H) +; Analytical calculated value for C17H20N402 · 0.3 H20 · C, 64.25; H, 6.53; N, 17.63 · Measured values: C, 64.10; H, 6.51; N, 17.35. Example 311 2-α-{"(3,5-Xylylenemethyl) amino 1methylihexahydropyridin-4-yl ) Pyridoxine N-Gas Follow the procedure described in Example 200 to replace 3-methylbenzylamine with 3,5-dimethylbenzylamine. (140 mg, 60%). iHNMRpOOMHz / DsOD) 5 1 · 76 (dd, J = 12.4, 3.6 Hz, 2H), 2.11 (d, J = 12.6 Hz, 2H), 2.36 (s, 6H), 2.66 (m, 2H) 5 3.23 (d5 J = 12.2 Hz, 2H), 3.47 (m, 1H) 5 4.38 (s5 2H) 5 7.22 (s, 1H), 7.41 (m5 1H), 7.52 (m, 2H), 7.56 (m , 2H), 8.34 (d, J = 6.4 Hz, 1H); MS (ESI) m / e 340 (M + H) +. Example 312 2- (ΜΙΪ3-vinylamidinyl) aminomethyli Hexahydropyridin-4-yl) pyridine N-gasate. The procedure described in Example 200 was used to replace 3-methylbenzylamine with 3-vinylbenzidine. (84 mg, 67%). WNMRGOOMHz'DsOD) 5 1.75 (dd, J = 12.6, 3.7 Hz, 2H), 2.10 (d, J = 12.6 Hz, 2H), 2.63 (m, 2H), 3.21 (m, &lt; 2H), 3.46 (m , 1H), 4.38 (s, 2H), 5.34 (d, J = 11.2 Hz, 1H), 5.90 (d, J = 17.3 Hz, 1HX 6.81 (dd5 J = 17.6? 10.9 Hz? 1H)? 7.50 (m? 5H) 5 7.76 (d5 J = 7.5 Hz? 1H) 5 7.95 (s, 1H), 8.33 (d, J = 6_4 Hz, 1H), MS (ESI) m / e 338 (M + H) + · Example 313 85228 -349- 200404539 2- (M "((4-bromo-3-methylsulfanylmethylamino) amino 1methyl MZ3,6-tetrahydropyridine_4_pen" ''

叶匕鍵N-氧化物 實例313A 2-[1-(第三-丁氧羰基）-4邊基六氫吡啶-4-基 &gt;比錠N-氧化物 於4’-羥基_3’，4’，5’，6’-四氫-2Ή-[2,4]聯吡啶基-1’-羧酸第三-丁酯 (Saari，WS.等人；J. Med· Chem· 1984, 27,1182，4.00 克，14.4 毫莫 耳）在二氯甲烷（100毫升）中之溶液内，於室溫下，添加間一 氣過冬甲版（4.70克’ 27.3毫莫耳）’並將反應物揽掉16小時 _ 。以偏亞硫酸氫鈉溶液使反應淬滅，並以飽和碳酸鈉洗務 。使有機相脫水乾燥（硫酸鈉），過濾，及在減壓下濃縮。 使殘留物於矽膠上藉急騾式管柱層析純化（以二氯甲烷至1〇 %甲醇：二氣甲烷梯度溶離），提供標題化合物（94%產率） ，為白色固體。1 H NMR (300 MHz，DMSO-d6) (5 1.41 (s，9H)，1.84 (br d， 2H? J=11.5 Hz)5 2.13 (ddd5 2H? J=12.9, 12.9, 4.7 Hz)5 3.17 (br s5 2H), 3.87 (br s? 2H)，7·30 (br s，1H)，7.43 (m，1H)，7.51 (ddd，1H，J=7.5, 7.5, 1.4 Hz)，7.64 (dd， 1H，J=7.8, 1.7 Hz)，8.32 (dd，1H，J=6.5, 1.4 Hz) ; MS (DCI/NH3 ) m/e 295 · (M+H)+.Example of dagger bond N-oxide 313A 2- [1- (Third-butoxycarbonyl) -4 side group hexahydropyridin-4-yl> 4'-Hydroxy-3 ', 4' than indium N-oxide , 5 ', 6'-tetrahydro-2Ή- [2,4] bipyridyl-1'-carboxylic acid tertiary-butyl ester (Saari, WS. Et al .; J. Med · Chem · 1984, 27,1182 , 4.00 g, 14.4 mmol) in a solution of dichloromethane (100 ml), at room temperature, add Infraventricular Winter A (4.70 g '27 .3 mmol) 'and remove the reaction 16 Hours_. The reaction was quenched with sodium metabisulfite solution and washed with saturated sodium carbonate. The organic phase was dried (sodium sulfate), filtered, and concentrated under reduced pressure. The residue was purified on silica gel by flash column chromatography (gradient elution with dichloromethane to 10% methanol: digas methane) to provide the title compound (94% yield) as a white solid. 1 H NMR (300 MHz, DMSO-d6) (5 1.41 (s, 9H), 1.84 (br d, 2H? J = 11.5 Hz) 5 2.13 (ddd5 2H? J = 12.9, 12.9, 4.7 Hz) 5 3.17 ( br s5 2H), 3.87 (br s? 2H), 7.30 (br s, 1H), 7.43 (m, 1H), 7.51 (ddd, 1H, J = 7.5, 7.5, 1.4 Hz), 7.64 (dd, 1H, J = 7.8, 1.7 Hz), 8.32 (dd, 1H, J = 6.5, 1.4 Hz); MS (DCI / NH3) m / e 295 · (M + H) +.

實例313B 2-「1-(第三_丁氧黢基）_1，2,3,6-四氫峨淀冰基1?比鉸&gt;1-氧化物 按照實例237B中所述之程序，以得自實例313A之產物取代 得自實例237A之產物，提供標題化合物（40%產率），為黃色 油。1HNMR(300MHz，DMSO-d6) 5 1.43 (s，9H)，3.32 (m，2H)，3.49 (m， 2H)，4.01 (br s，2H)，6·27 (br s，1H)，7·36 (m5 3H)，8.20 (m，1H); MS (DCI/NH3) m/e261(M+H-16)+ ; 277(M+H)+. 85228 -350- 200404539Example 313B 2- "1- (Third_butoxyfluorenyl) _1,2,3,6-tetrahydroedian ice-based 1? Hinge &gt; 1-oxide Following the procedure described in Example 237B, The product from Example 313A replaced the product from Example 237A to provide the title compound (40% yield) as a yellow oil. 1HNMR (300 MHz, DMSO-d6) 5 1.43 (s, 9H), 3.32 (m, 2H) , 3.49 (m, 2H), 4.01 (br s, 2H), 6.27 (br s, 1H), 7.36 (m5 3H), 8.20 (m, 1H); MS (DCI / NH3) m / e261 (M + H-16) +; 277 (M + H) +. 85228 -350- 200404539

實例313C 2-〔1，2,3,6-四盧i 口比淀，4-基）口比J足N-氣化物 按照實例166B中所述之程序，以得自實例313B之產物取代 得自實例166A之產物，提供標題化合物，為黃色油。iHNMR (300 MHz，DMSO-d6) 5 2.78 (m，2H)，3_28 (m，2H)，3.79 (m，2H)，6·36 (s，1H)， 7.38 (m，3H)，8_26 (m，1H); MS (DCI/NH3) m/e 161 (M+H-16)+ ; 177 (M+H)+ ·Example 313C 2- [1,2,3,6-Tetrahydropyrene, 4-base) Orthopyrene J-N-Gas Follow the procedure described in Example 166B, substituting the product from Example 313B to obtain From the product of Example 166A, the title compound was provided as a yellow oil. iHNMR (300 MHz, DMSO-d6) 5 2.78 (m, 2H), 3_28 (m, 2H), 3.79 (m, 2H), 6.36 (s, 1H), 7.38 (m, 3H), 8_26 (m ， 1H); MS (DCI / NH3) m / e 161 (M + H-16) +; 177 (M + H) + ·

實例313D 2-Π-(ΙΪ4-溴基-3-甲基笨甲醯基）胺某1甲基M,2,3,6- · 四氫吡啶-4-基）吡鉸 按照實例200中所述之程序，以得自實例313C醯胺之產物 取代得自實例119A之產物，並以4-溴基-3-甲基苯甲醯胺 (Lancaster)取代3-甲基苯甲醯胺，提供標題化合物（6%產率）， 為黃色固體。1H NMR (300 MHz，CD3 OD) ; (5 2.63-2.75 (m，2H)，2.86- 2.99(m，2H)，3.30(s，3H)，3.36-3.44(m，2H)，4.39(s，2H)，6.23(m，lH)，7.37-7·51 (m，2H)，7.52-7.61 (m，2H)，7_66 (d，J=9.0 Hz，1H)，7.68 (d，J=3.6 Hz，1H)， 8.27 (d，J=8.0 Hz，1H) ; MS (DCI/NH3)m/e 386/388 (M+H-16)+ ; 402/404 # (M+H)+. 實例314 2-{l-「(2-荃甲醯基胺基）甲基1六氪吡啶斗基}吡錠N-氣化物 按照實例200中所述之程序，以萘-2·羧酸醯胺取代3-甲基苯 曱醯胺，提供標題化合物（75毫克，56%產率），為白色固體 。iHNMRpOOMHADMSacy 5 1.56(q，J=12.2Hz，lH)，1.57(q，J=11.9Example 313D 2-II- (l-4-Bromo-3-methylbenzylidene) amine 1 methyl M, 2,3,6-tetrahydropyridin-4-yl) pyrimidine The procedure described above replaces the product from Example 119A with the product from Example 313C and the 3-methylbenzylamine with 4-bromo-3-methylbenzamide, providing The title compound (6% yield) as a yellow solid. 1H NMR (300 MHz, CD3 OD); (5 2.63-2.75 (m, 2H), 2.86- 2.99 (m, 2H), 3.30 (s, 3H), 3.36-3.44 (m, 2H), 4.39 (s, 2H), 6.23 (m, 1H), 7.37-7 · 51 (m, 2H), 7.52-7.61 (m, 2H), 7_66 (d, J = 9.0 Hz, 1H), 7.68 (d, J = 3.6 Hz , 1H), 8.27 (d, J = 8.0 Hz, 1H); MS (DCI / NH3) m / e 386/388 (M + H-16) +; 402/404 # (M + H) +. Example 314 2- {l-"(2-Trimethylmethylamino) methyl1hexamethylpyridinyl} pyridine N-gasate was replaced with naphthalene-2 · carboxylic acid hydrazine according to the procedure described in Example 200 3-Methylbenzidine provides the title compound (75 mg, 56% yield) as a white solid. IHNMRpOOMHADMSacy 5 1.56 (q, J = 12.2 Hz, 1H), 1.57 (q, J = 11.9

Hz，1H)，1.92 (d，J=11.2 Hz，2H)，2.41 (t，J=11.2 Hz，2H)，3.02 (d，J=11.5 Hz, 2H)，3.25 (m，J=12.9 Hz，1H)，4.24 (d，J=5.8 Hz，2H)，7.30 (m，2H)，7.40 (dd，J= 85228 -351- 200404539 7.5, 2·4 Hz，1H)，7.62 (m，2H)，8·01 (m，4H)，8.24 (d，J=5.8 Hz，1H)，8.51 (s， ^ 1H)，8.97 (s，1H); MS (DCI/NH3) m/e 362 (M+H)+ ;對 C2 2 H2 3 N3 02 · 0.2 CH2C12 · 1.2 H20 之分析計算值：C，66.65 ; H，6.50 ; N，10.50.實測 值：C，66.62 ; H, 6.20 ; N，10.19. 實例315 2-α-丨ΙΪ碟吩基）胺基1甲基丨六氫吡啶-4-基）吡錠N-氫化物 ♦ 按照實例200中所述之程序，以噻吩-2-羧酸醯胺取代3-甲 基苯甲醯胺。（100 毫克，56.6%)。WNMRPOOMHaDMSO·^)占 φ 1.52 (m，2Η)，1·89 (d，J=12 Ηζ，2Η)，2·36 (m，2Η)，2.98 (d，J=12 Hz, 2Η)，3.18 (m，1H)，4·12 (d，J=6 Hz，2H)，7·18 (dd，J=4.5, 3.0, 1H)，7.28 (m，2H)，7.39 (dd， J=9_0, 3 Hz，1H)，7.78 (dd，J=4_5, 1.5 Hz，1H)，7.85 (dd，J=4.5, 1.5 Hz，1H)， 8.22 (dd，J=6, 1·5 Hz，1H)，8_79 (t，J=6 Hz，1H) ; MS (DCI/NH3) m/e 297 (M+H_16)+ ; 313(M+H)+. 實例316 丨「(6_氯某毗啶-3-基）羰基Ί胺基丨甲基）六氫吡啶-4_基1吡錠 N-氧化物 · 按照實例200中所述之程序，以6-氯基菸鹼醯胺取代3-甲 基苯甲醯胺。1H NMR (300 MHz，DMSO-d6) 6 1.52 (m，2H)，1.89 (d，J= 12 Hz，2H)，2_36 (m，2H)，2.98 (d，J=12 Hz，2H)，3.22 (m，1H)，4.19 (d，J=6 Hz， 2H)，7.29 (m，2H)，7.30 (dd，J=6, 1.5 Hz，1H)，7.65 (d，J=9 Hz，1H)，8.26 (m， 2H)，8.88 (d，J=3 Hz，1H)，9.02 (t，J=6 Hz，1H) ; MS (DCI/NH3) m/e 331 (M+H-16)+ ;對 C17H19N4O2CN0.4H2O 之分析計算值·· C，57.68; H，5.64 ; N，15.83.實測值·· C，57.63 ; H，65.45 ; N，15.60. 實例317 85228 -352- 200404539 2-α-(『(3-氰基1甲醯基）胺基1甲基丨六氫吡啶-4·某Vth鏜N-氫化物 按照實例200中所述之程序，以3-氰基苯甲醯胺取代3-甲 基苯 T 醯胺。（55 毫克，55% )。1H NMR (300 MHz，CD3 OD) (5 1·73 (dd， J=12.5, 3·6 Ηζ，2Η)，2·11 (m，2Η)，2.69 (d，J=2.0 Ηζ，2Η)，3.27 (m，2Η)，3.46 (m， 1H)，4.43 (s，2H)，7·41 (d，J=2.4 Hz，1H)，7.56 (m，2H)，7.70 (t5 J=7.8 Hz，1H)， 7.96 (d，J=8.8 Hz，1H)，8.18 (d，J=8.1 Hz, 1H)，8.24 (s，1H)，8.34 (d，J=6.4 Hz， 1H)，MS (ESI) m/e 337 (M+H)+. 實例318 2-α]「(2,3-二溴某-5_甲基笨甲醯基）胺基1甲某丨-1丄3,6-四氤吡啶- 4-基V比鍵Ν-氣化物 按照實例200中所述之程序，以得自實例300Β之產物取代3-甲基苯甲醯胺，並以得自實例313C之產物取代得自實例119Α 之產物，而得標題化合物（4%產率），為黃色固體。iHNMR (300 MHz，CD3 OD) ; 5 2·35 (s，3H)，2.65-2.73 (m，2H)，2.80-2.85 (s，2H)， 3.10 (t，J=9 Hz，2H)，3.45-3.58 (m，2H)，6.21 (m，1H)，7.21 (d，J=3.1 Hz，1H)， 7.40-7.65 (m，4H)，8.25 (d，J=9.0 Hz，1H) ; MS (ESI-) m/e 479 (M_H)+ · 實例319 2-(M「(4-溴某苽甲醯基)胺基1甲基}六氫吡啶-4-基）吡錠N-氣化物 按照實例200中所述之程序，以4-溴基苯甲醯胺取代3-甲 基苯甲醯胺，提供標題化合物（87毫克，60%產率），為白色 固體。iHNMRpOOMHADMSO-dd 5 1.55(q，J=11.9Hz，2H)，1.90(d， J=11.9 Hz? 2H)5 2.36 (t? J=11.9 Hz? 2H)? 2.98 (d5 J=11.5 Hz? 2H)5 3.24 (m? 1H)? 4.18 (d，J=4.8 Hz，2H)，7.29 (m，2H)，7.39 (dd，J=7.8, 2·7 Hz，1H)，7.69 (m，2H)， 7.84 (m，2H)，8.24 (d，J=5.8 Hz，1H)，8.89 (br s，1H) ; MS (DCI/NH3) m/e 85228 -353 - 200404539 390/392 (M+H)+. 實例320 2_(1_{「(3-氯基-4_甲基苯甲酸基）胺基1甲基}六氫比咬_4-基V比錄 N-氧化物 按照實例200中所述之程序，以3-氯基冬甲基苯甲醯胺取代 3-甲基苯甲醯胺，提供標題化合物（66毫克，50%產率），為 白色固體。1 H NMR (300 MHz，DMSO_d6) 61.55 (q，J=11 ·9 Hz，2H)，1.90 (d，J=11.9 Hz，2H)，2.36 (t，JM11.9 Hz，2H)，2.39 (s，3H)，2.98 (d，J=11.5 Hz， 2H)5 3.24 (m5 1H)? 4.18 (d5 J=4.8 Hz, 2H)? 7.29 (m? 2H)? 7.39 (dd5 J=7.85 2.7 Hz, 1H)，7.48 (d，J=6.7 Hz，1H)，7.80 (d，J=6.8 Hz，1H)，7.94 (s，1H)，8.24 (d，J=5.8 Hz，1H)，8.89 (br s，1H) ; MS (DCI/NH3) m/e 360 (M+H)+ · 實例321 MHf甲基（3_甲基苯甲醯基）胺某1甲基}六i.吡啶斗某V比錠 N-氧化物 於得自實例200之產物（90毫克，0.28毫莫耳）在N，N-二甲基 甲醯胺（4毫升）中，冷卻至〇°C之溶液内，添加氫化鈉（121毫 克，0.88毫莫耳）。於此混合物中添加破化甲烷（1〇6毫克，0.35 毫莫耳）。在室溫下40分鐘後，以醋酸使混合物中和，及濃 縮。使殘留物於矽膠上藉急驟式管柱層析純化（以5-10%甲 醇：二氯甲烷溶離），提供85毫克（60%產率）標題化合物， 為白色固體。iHNMRpOOMHz’DMSO-c^) 5 1.52(q，J=11.8，Hz，2H)， 1_89 (d，J=9.2 Hz，2H)，2·04 (t，J=11.5 Hz，2H)，2.35 (s，3H)，2.77 (d，J=4.4 Hz， 3H)，2.92 (m，2H)，3.16 (m，1H)，3.32 (s，2H)，7.24 (m，1H)，7.30 (m，4H)，7.40 (m，1H)，7.62 (m，1H)，8.24 (d，J=6.1 Hz，1H) ; MS (DCI/NH3) m/e 340 85228 -354- 200404539 (Μ+Η)+· 實例322 2-(1-{|~(3-硝基苯甲醯基）胺基1甲基丨六氫吡啶斗基）吡錠Ν-氣化物 按照實例200中所述之程序，以3-硝基苯甲醯胺取代3-甲 基苯甲醯胺，提供標題化合物（28毫克，26%產率），為油狀 物。1 H NMR (300 MHz，CD3 OD) 51.74 (m，2Η)，2.11 (m，2Η)，2.69 (m，2Η)， 3·26 (m，2H)，3.45 (m，1H)，4.35 (s，2H)，7·50 (m，4H)，7.73 (m，3H)，7.87 (d，J= 8.1 Hz，1H)，8·34 (d，J=6.4 Hz，1H) ; MS (ESI) m/e 357 (M+H)+ ; 對匸18%〇：^404 *2.00：2证302之分析計算值：C，45.21; H，3.79; N，9·59_ 實測值：C，45.58 ; H, 4.00 ; N，9.72. 實例323 2-(l-m2-氯基-5-甲基笨甲醯基）胺基1甲基丨六氫吡啶-4-基）吡錠 N-氧化物 按照實例200中所述之程序，以2-氯基-5-甲基苯甲醯胺取代 3-甲基苯甲醯胺，提供標題化合物（31毫克，29%產率），為 油狀物。1 H NMR (300 MHz，CD3 OD) .74 (m，2H)，2.08(d，J=11.9 Hz， # 1H)，2.35 (m，2H)，2·67 (m，2H)，2.84 (m，1H)，3.15 (m，2H)，3.42 (m，2H)，4.34 (m5 2H)，7.34 (m，4H)，7·55 (m，2H)，7_71 (s，1H)，8.34 (d，J=6.4 Hz，1H) ; MS (ESI) m/e 360 (M+H)+ ;對 q 9 H2 2 C1N3 02 · 2.0 C2 HF3 02 之分析計算 值·· C，46.99; Η，4·11 ; Ν，7·15·實測值：C，47.23; Η，3·96; Ν，7·02. 實例324 2-(Μ「(3-甲氫某-2-甲基苯甲醯基）胺基1甲基丨六氪吡啶·4·某、 吡錠Ν_氣化物 實例324ΑHz, 1H), 1.92 (d, J = 11.2 Hz, 2H), 2.41 (t, J = 11.2 Hz, 2H), 3.02 (d, J = 11.5 Hz, 2H), 3.25 (m, J = 12.9 Hz, 1H), 4.24 (d, J = 5.8 Hz, 2H), 7.30 (m, 2H), 7.40 (dd, J = 85228 -351- 200404539 7.5, 2.4 Hz, 1H), 7.62 (m, 2H), 8.01 (m, 4H), 8.24 (d, J = 5.8 Hz, 1H), 8.51 (s, ^ 1H), 8.97 (s, 1H); MS (DCI / NH3) m / e 362 (M + H ) +; Analytical calculations for C2 2 H2 3 N3 02 · 0.2 CH2C12 · 1.2 H20: C, 66.65; H, 6.50; N, 10.50. Found: C, 66.62; H, 6.20; N, 10.19. Example 315 2-α- 丨 Iphenidyl) amino 1methyl 丨 hexahydropyridin-4-yl) pyridine N-hydride ♦ Substituted with thiophene-2-carboxylic acid phosphonium amine according to the procedure described in Example 200 3-methylbenzamide. (100 mg, 56.6%). WNMRPOOMHaDMSO · ^) accounts for φ 1.52 (m, 2Η), 1.89 (d, J = 12 Ηζ, 2Η), 2.36 (m, 2Η), 2.98 (d, J = 12 Hz, 2Η), 3.18 ( m, 1H), 4 · 12 (d, J = 6 Hz, 2H), 7 · 18 (dd, J = 4.5, 3.0, 1H), 7.28 (m, 2H), 7.39 (dd, J = 9_0, 3 Hz, 1H), 7.78 (dd, J = 4_5, 1.5 Hz, 1H), 7.85 (dd, J = 4.5, 1.5 Hz, 1H), 8.22 (dd, J = 6, 1.5 Hz, 1H), 8_79 (t, J = 6 Hz, 1H); MS (DCI / NH3) m / e 297 (M + H_16) +; 313 (M + H) +. Example 316 丨 "(6_chlorosome pyridin-3- Group) carbonylamidoaminomethyl) hexahydropyridin-4-yl1pyridine N-oxide · Follow the procedure described in Example 200 to replace 3-methylbenzyl with 6-chloronicotinylpyridineamine Amidine. 1H NMR (300 MHz, DMSO-d6) 6 1.52 (m, 2H), 1.89 (d, J = 12 Hz, 2H), 2_36 (m, 2H), 2.98 (d, J = 12 Hz, 2H ), 3.22 (m, 1H), 4.19 (d, J = 6 Hz, 2H), 7.29 (m, 2H), 7.30 (dd, J = 6, 1.5 Hz, 1H), 7.65 (d, J = 9 Hz , 1H), 8.26 (m, 2H), 8.88 (d, J = 3 Hz, 1H), 9.02 (t, J = 6 Hz, 1H); MS (DCI / NH3) m / e 331 (M + H- 16) +; Analytical calculated value for C17H19N4O2CN0.4H2O · C, 57.68; H, 5.64; N, 1 5.83. Measured values: C, 57.63; H, 65.45; N, 15.60. Example 317 85228 -352- 200404539 2-α-("(3-cyano 1methylfluorenyl) amino 1methyl 丨 hexahydropyridine -4. A Vth boring N-hydride Substituting 3-cyanobenzamide with 3-methylbenzidine in accordance with the procedure described in Example 200. (55 mg, 55%). 1H NMR (300 MHz, CD3 OD) (5 1 · 73 (dd, J = 12.5, 3 · 6 Ηζ, 2Η), 2.11 (m, 2Η), 2.69 (d, J = 2.0 Ηζ, 2Η), 3.27 (m, 2Η), 3.46 (m, 1H), 4.43 (s, 2H), 7.41 (d, J = 2.4 Hz, 1H), 7.56 (m, 2H), 7.70 (t5 J = 7.8 Hz, 1H), 7.96 (d, J = 8.8 Hz, 1H), 8.18 (d, J = 8.1 Hz, 1H), 8.24 (s, 1H), 8.34 (d, J = 6.4 Hz, 1H), MS (ESI) m / e 337 (M + H) +. Example 318 2-α] "(2,3-dibromo-5 -methylbenzylidene) amino 1methyl 1-1-3, 6-tetrapyridine-4 -Base V ratio bond N-Gas Follow the procedure described in Example 200 to replace 3-methylbenzamide with the product from Example 300B and the product from Example 119A with the product from Example 313C. The title compound was obtained (4% yield) as a yellow solid. iHNMR (300 MHz, CD3 OD); 5 2.35 (s, 3H), 2.65-2.73 (m, 2H), 2.80-2.85 (s, 2H), 3.10 (t, J = 9 Hz, 2H), 3.45 -3.58 (m, 2H), 6.21 (m, 1H), 7.21 (d, J = 3.1 Hz, 1H), 7.40-7.65 (m, 4H), 8.25 (d, J = 9.0 Hz, 1H); MS ( ESI-) m / e 479 (M_H) + · Example 319 2- (M "(4-bromo-methanemethyl) amino 1methyl} hexahydropyridin-4-yl) pyridine N-gas The procedure described in Example 200, replacing 3-methylbenzamide with 4-bromobenzamide provided the title compound (87 mg, 60% yield) as a white solid. IHNMRpOOMHADMSO-dd 5 1.55 ( q, J = 11.9Hz, 2H), 1.90 (d, J = 11.9 Hz? 2H) 5 2.36 (t? J = 11.9 Hz? 2H)? 2.98 (d5 J = 11.5 Hz? 2H) 5 3.24 (m? 1H )? 4.18 (d, J = 4.8 Hz, 2H), 7.29 (m, 2H), 7.39 (dd, J = 7.8, 2.7 Hz, 1H), 7.69 (m, 2H), 7.84 (m, 2H) , 8.24 (d, J = 5.8 Hz, 1H), 8.89 (br s, 1H); MS (DCI / NH3) m / e 85228 -353-200404539 390/392 (M + H) +. Example 320 2_ (1_ {"(3-Chloro-4-methylbenzoate) amino 1methyl} Hexahydro- 4-methyl V-Record N-oxide Follow the procedure described in Example 200, starting with 3- -Methylbenzylamine replaced 3-methylbenzylamine to provide the title compound (66 mg, 50% yield) as a white solid. 1 H NMR (300 MHz, DMSO_d6) 61.55 (q, J = 11 · 9 Hz, 2H), 1.90 (d, J = 11.9 Hz, 2H), 2.36 (t, JM11.9 Hz, 2H), 2.39 (s, 3H), 2.98 (d, J = 11.5 Hz, 2H) 5 3.24 (m5 1H)? 4.18 (d5 J = 4.8 Hz, 2H)? 7.29 (m? 2H)? 7.39 (dd5 J = 7.85 2.7 Hz, 1H), 7.48 (d, J = 6.7 Hz, 1H), 7.80 (d, J = 6.8 Hz, 1H), 7.94 (s, 1H), 8.24 (d, J = 5.8 Hz, 1H), 8.89 (br s, 1H); MS (DCI / NH3) m / e 360 (M + H) + · Example 321 MHf methyl (3-methylbenzyl) amine 1 methyl} hexa i. Pyridine bucket V than ingot N-oxide in the product obtained from Example 200 (90 mg, 0.28 mmol) in N, N-dimethylformamide (4 ml), cooled to 0 ° C, and sodium hydride (121 mg, 0.88 mmol) was added. To this mixture was added decomposed methane (106 mg, 0.35 mmol). After 40 minutes at room temperature, the mixture was neutralized with acetic acid and concentrated. The residue was purified by flash column chromatography on silica gel (dissolved with 5-10% methanol: dichloromethane) to provide 85 mg (60% yield) of the title compound as a white solid. iHNMRpOOMHz'DMSO-c ^) 5 1.52 (q, J = 11.8, Hz, 2H), 1_89 (d, J = 9.2 Hz, 2H), 2.04 (t, J = 11.5 Hz, 2H), 2.35 (s , 3H), 2.77 (d, J = 4.4 Hz, 3H), 2.92 (m, 2H), 3.16 (m, 1H), 3.32 (s, 2H), 7.24 (m, 1H), 7.30 (m, 4H) , 7.40 (m, 1H), 7.62 (m, 1H), 8.24 (d, J = 6.1 Hz, 1H); MS (DCI / NH3) m / e 340 85228 -354- 200404539 (Μ + Η) + · Examples 322 2- (1- {| ~ (3-Nitrobenzylidene) amino 1methyl 丨 hexahydropyridinyl) pyridine N-gasate Follow the procedure described in Example 200, using 3-nitrate Substituted 3-methylbenzylamine to give the title compound (28 mg, 26% yield) as an oil. 1 H NMR (300 MHz, CD3 OD) 51.74 (m, 2Η), 2.11 (m, 2Η), 2.69 (m, 2Η), 3.26 (m, 2H), 3.45 (m, 1H), 4.35 (s , 2H), 7.50 (m, 4H), 7.73 (m, 3H), 7.87 (d, J = 8.1 Hz, 1H), 8.34 (d, J = 6.4 Hz, 1H); MS (ESI) m / e 357 (M + H) +; For 匸 18% 〇: ^ 404 * 2.00: Analysis value of 2 certificate 302: C, 45.21; H, 3.79; N, 9.59_ Found: C, 45.58; H, 4.00; N, 9.72. Example 323 2- (l-m2-chloro-5-methylbenzylidene) amino 1methyl 丨 hexahydropyridin-4-yl) pyridine N-oxide according to The procedure described in Example 200 was used to replace 3-methylbenzamide with 2-chloro-5-methylbenzamide to provide the title compound (31 mg, 29% yield) as an oil. 1 H NMR (300 MHz, CD3 OD) .74 (m, 2H), 2.08 (d, J = 11.9 Hz, # 1H), 2.35 (m, 2H), 2.67 (m, 2H), 2.84 (m , 1H), 3.15 (m, 2H), 3.42 (m, 2H), 4.34 (m5 2H), 7.34 (m, 4H), 7.55 (m, 2H), 7_71 (s, 1H), 8.34 (d , J = 6.4 Hz, 1H); MS (ESI) m / e 360 (M + H) +; Analytical calculated value for q 9 H2 2 C1N3 02 · 2.0 C2 HF3 02 ·· C, 46.99; Η, 4 · 11; Ν, 7.15. Found: C, 47.23; Η, 3.96; Ν, 7.02. Example 324 2- (M "(3-methylhydro-2-methylbenzyl) Amino 1methyl 丨 Hexapyridine · 4 ·, Pyridine N_Gas Example 324A

85228 -355 - 200404539 k甲氧基-2-甲墓茉甲醯胺 將含有 &gt;甲氧基1甲基苯甲酸（2克，12.04毫莫耳）、ι_(3_二 甲，月文墓丙基）-3_乙基碳化二亞胺鹽酸鹽（2·76克，M·4毫莫耳） 、1-羥基苯并三唑水合物（1·95克，144毫莫耳）在氯仿中之反 應混合物，於室溫下攪拌！小時。以3〇%氫氧化銨溶液卬毫 升）使反應淬滅，並再持續攪拌15小時。分離液層，以硫酸 鎂使有機相脫水乾燥，過濾，及在減壓下濃縮。使殘留物 於碎膠上藉急騾式管柱層析純化（5〇%醋酸乙酯/己烷），而 得白色粉末（1.2 克，60% )。1H NMR (300 MHz，CDC13) 5 2.3 (s，3H)， 3.82 (s，3H)，6.9 (d5 1H，J=9 Hz)，7.02 (d，1H，J=9 Hz)，7·18 (t，1H，J=9 Hz); MS (DCI/NH3) m/e 166 (M+H)+.85228 -355-200404539 k methoxy-2-methyl tomb jasminamine will contain &gt; methoxy 1 methylbenzoic acid (2 g, 12.04 mmol), ι_ (3_dimethyl, Yuewen Tomb Propyl) -3_ethylcarbodiimide hydrochloride (2.76 g, M.4 mmol), 1-hydroxybenzotriazole hydrate (1.95 g, 144 mmol) The reaction mixture in chloroform was stirred at room temperature! hour. The reaction was quenched with 30% ammonium hydroxide solution (mL) and stirring was continued for another 15 hours. The layers were separated, the organic phase was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified on a gel by flash column chromatography (50% ethyl acetate / hexane) to give a white powder (1.2 g, 60%). 1H NMR (300 MHz, CDC13) 5 2.3 (s, 3H), 3.82 (s, 3H), 6.9 (d5 1H, J = 9 Hz), 7.02 (d, 1H, J = 9 Hz), 7.18 ( t, 1H, J = 9 Hz); MS (DCI / NH3) m / e 166 (M + H) +.

實例324B 2JHK3-甲氧基-2-甲基笨甲醯某）胺基1甲基}六氫吡啶斗某） 吡錠N-氣化物 按照實例200中所述之程序，以實例325A中之產物取代3-甲基苯甲醯胺，提供標題化合物（45毫克，16% )，為白色固 體。1 H NMR (300 MHz，CDC13) (5 1·45-1·55 (m，2H)，2.05-2.15 (m，2H)，2·25 (s，3H)，2·55_2·65 (m，2H)，3.05-3.10 (m，2H), 3·40_3·50 (m，1H)，3.81 (s，3H)， 4_40 (d，2H，J=6 Hz)，6.4 (br s，1H)，6.85 (d，1H，J=9 Hz)，7.0 (d，1H，J=9 Hz)， 7.10-7.20 (m，2H)，7.25_7·32 (m，2H)，8.20 (d，1H，J=6 Hz) ; MS (DCI/NH3) m/e 356 (M+H)+ ;對 C2〇H25N303之分析計算值：C，67.58; Η，7·09 ;N, 11.82.實測值：C，67.29 ; H，7·20 ; N，11.87. 實例325 2-(1-丨「(4-氯甚-3-甲氣笨甲醯基）胺基1甲基丨六氫吡淀二4-基 &gt;比錠 85228 -356- 200404539Example 324B 2JHK3-Methoxy-2-methylbenzidine, a) Amine 1methyl} Hexahydropyridine, a) Pyridinium N-Gas Follow the procedure described in Example 200, using the product from Example 325A Substitution of 3-methylbenzidine provides the title compound (45 mg, 16%) as a white solid. 1 H NMR (300 MHz, CDC13) (5 1.45-1 · 55 (m, 2H), 2.05-2.15 (m, 2H), 2.25 (s, 3H), 2.55_2 · 65 (m, 2H), 3.05-3.10 (m, 2H), 3.40_3 · 50 (m, 1H), 3.81 (s, 3H), 4_40 (d, 2H, J = 6 Hz), 6.4 (br s, 1H), 6.85 (d, 1H, J = 9 Hz), 7.0 (d, 1H, J = 9 Hz), 7.10-7.20 (m, 2H), 7.25_7 · 32 (m, 2H), 8.20 (d, 1H, J = 6 Hz); MS (DCI / NH3) m / e 356 (M + H) +; Analytical calculated value for C20H25N303: C, 67.58; Η, 7.09; N, 11.82. Found: C, 67.29; H, 7 · 20; N, 11.87. Example 325 2- (1- 丨 "(4-chloroeven-3-methylbenzylmethyl) amino group 1methyl 丨 hexahydropyridine di 4-yl &gt; Ingot 85228 -356- 200404539

N-氧化物 實例325A 氣基-3-甲氧基苯甲醒胺 按照實例325A中所述之程序，以3-甲氧基氯苯甲酸取代3-甲氧基-2-甲基苯甲酸，提供標題化合物（1.5克，75%產率）’ 為白色固體。1HNMR(300 MHz，DMSO_d6) 5 3.9 (s，3H)，7.42-7.52 (m， 2H)，7.6 (d，1H，J=3 Hz)，8·08 (s，2H) ; MS (DCI/NH3) m/e 203 (M+NH4 疒·N-oxide Example 325A Gasoyl-3-methoxybenzylamine Follow the procedure described in Example 325A to replace 3-methoxy-2-methylbenzoic acid with 3-methoxychlorobenzoic acid The title compound (1.5 g, 75% yield) was provided 'as a white solid. 1HNMR (300 MHz, DMSO_d6) 5 3.9 (s, 3H), 7.42-7.52 (m, 2H), 7.6 (d, 1H, J = 3 Hz), 8.08 (s, 2H); MS (DCI / NH3 ) m / e 203 (M + NH4 疒 ·

實例325B 2-(ΜΙΪ4-着.甚甲氫笨甲醯基）胺某1甲基}六氫吡啶-4-基）吡錠 Ν-氧化物 按照實例200中所述之程序，以實例326Α中之產物取代3-甲基苯甲醯胺，提供標題化合物（75毫克，17% )，為黃色固 體。1HNMR(300MHz，CDα3)5 1·6-l·68(m52H)，2·05-2·20(m，2H)，2_50- 2·65 (m，2Η)，3.05-3.20 (m，2Η)，3.42-3.55 (m，1Η)，3_98 (s，3Η)，4·40 (d，2Η， J=6 Hz)，6.65 (br s，1H)，7.15 (m，1H)，7·2·7·35 (m，3H)，7.40 (d，1H，J=9 Hz)， 7.45 (d? 1H, J=3 Hz)? 8.22 (d5 1H, J=6 Hz) ； MS (DCI/NH3) m/e 376 (M+H)+ ;對(：191122(^[303之分析計算值：c，60.72 ; H，5·90; N，11.18.實 測值：C，60.44 ; H，5.84 ; N, 10.97. 實例326 Ν·(3-甲基苯基）·2-(3-ρ比淀-2-基六1?比淀·1_基）乙硫胺 實例326Α 5f，6^二氫-2,3’-聯吡啶酸第三-丁酯 按照實例328C中所述之程序，以2-吡啶基溴化鋅取代2-嘧 唑基溴化鋅，提供標題化合物（92% )。MS (DCI/NH3)m/e 261 85228 -357 - 200404539 (M+H)+ ·Example 325B 2- (ΜΙΪ4- by. Very methylhydrobenzylmethyl) amine 1methyl} hexahydropyridin-4-yl) pyridine N-oxide Following the procedure described in Example 200, using Example 326A The product replaced 3-methylbenzidine to provide the title compound (75 mg, 17%) as a yellow solid. 1HNMR (300MHz, CDα3) 5 1.6-1.668 (m52H), 2.05--2.20 (m, 2H), 2-50-2.65 (m, 2Η), 3.05-3.20 (m, 2Η) , 3.42-3.55 (m, 1Η), 3_98 (s, 3Η), 4 · 40 (d, 2Η, J = 6 Hz), 6.65 (br s, 1H), 7.15 (m, 1H), 7 · 2 · 7.35 (m, 3H), 7.40 (d, 1H, J = 9 Hz), 7.45 (d? 1H, J = 3 Hz)? 8.22 (d5 1H, J = 6 Hz); MS (DCI / NH3) m / e 376 (M + H) +; for (: 191122 (^ [303 analysis calculated value: c, 60.72; H, 5.90; N, 11.18. Found: C, 60.44; H, 5.84; N , 10.97. Example 326 N · (3-methylphenyl) · 2- (3-ρ Biyodo-2-ylhexa 1-pyridine · 1-yl) ethionamine Example 326A 5f, 6 ^ dihydro- Tertiary-butyl 2,3'-bipyridine was substituted for 2-pyrazolyl zinc bromide by 2-pyridyl zinc bromide following the procedure described in Example 328C to provide the title compound (92%). MS ( DCI / NH3) m / e 261 85228 -357-200404539 (M + H) + ·

實例326B 3-口比淀-2-基六氮外匕淀-1-幾酸第三-丁酉旨 按照實例328D中所述之程序，以得自實例326A之產物取代 得自實例328C之產物，提供標題化合物（93% )。MS (DCI/NH3) m/e 263 (M+H)+. 實例326C 氮口比淀-3-基口比淀 按照實例328E中所述之程序，以得自實例326B之產物取代 得自實例328D之產物，提供標題化合物。Example 326B 3-Hydroxypyridine-2-ylhexazideexo-1--1-chitoic acid tertiary-butyrate The procedure described in Example 328D was used to replace the product from Example 328A with the product from Example 328C, Provided the title compound (93%). MS (DCI / NH3) m / e 263 (M + H) +. Example 326C Nitrogen ratio of 3--3-biphenyl ratio. Follow the procedure described in Example 328E to replace the product from Example 326B. Product of 328D, providing the title compound.

實例326D N-(3-甲基苯基）-2-(3-口比淀-2-基六氮口比淀-1-基）乙酉盛月安 按照實例33C中所述之程序，以得自實例326C之產物取代 得自實例33B之產物，提供標題化合物（XX% )。1 HNMR(300 MHz, CDC13) 5 1.71 (m，4H)，2.04 (m，1H)，2.36 (s5 3H)，2.43 (m，1Η)，2.65 (m，1H)， 2.92 (m，1H)，3_15 (m，3H)，6.91 (d，J=7.5 Hz，1H)，7.19 (m，3H)，7·39 (m，2H)， 7.638 (t，J=7.5 Hz，1H)，8·53 (m，1H)，9.25 (bs，1H) ; MS (DCI顯3) m/e 310 (M+H)+ ;對 Q 9 H2 3 N3 O 之分析計算值：C，73.76 ; H，7.49 ; N，13.58· 實測值：C，73.93 ; H，7·42 ; N，13.53· 實例327 甲 I i )-2-(3一比 四 i 口比 口各一1_|)乙 _ # 按照實例232B中所述之程序，以2-四氫吡咯-3_基吡啶取代 得自實例232A之產物，提供標題化合物（21%產率），為黃色 油。1 H NMR (300 MHz, CD3 OD); 5 2.06-2.12 (m，1H)，2.15-2.23 (m，4H)， 85228 - 358 - 200404539 2.84_2·98 (m，1H)，3.0-3.10 (m，2H)，3.12-3.20 (m，1Η)，3.25 (d，J=12_0 Hz，1H)， 3.45 (d，J=12.0 Hz，1H)，3.50-3.65 (m，1H)，6_93 (d，J=9_0 Hz，1H)，7.06-7.13 (m，2H)，7.18-7.23 (m，2H)，7·62 (ddd，J=6.5, 6·1，3·3 Hz，1H)· 8.59 (d，6.0 Hz， 1H)，7.38 (s，1H) ; MS (DCI/NH3) m/e 296 ;對 Q 8 H2 ! N3 O 之分析計 算值：C，73·19 ; H，7·17 ; N，14.23.實測值：C，72.88 ; H，7.01; N，13.91. 實例328 N-(l-甲基-1H-笨并味嗤-2-基）_2-「3-(l，3-口塞唆-2-基）六氮外匕淀-1-基1Example 326D N- (3-methylphenyl) -2- (3-Hydroxypyridine-2-ylhexazylpyridyl-1-yl) acetamidineYueyue An Follow the procedure described in Example 33C to obtain the example The product of 326C replaced the product from Example 33B to provide the title compound (XX%). 1 HNMR (300 MHz, CDC13) 5 1.71 (m, 4H), 2.04 (m, 1H), 2.36 (s5 3H), 2.43 (m, 1Η), 2.65 (m, 1H), 2.92 (m, 1H), 3_15 (m, 3H), 6.91 (d, J = 7.5 Hz, 1H), 7.19 (m, 3H), 7.39 (m, 2H), 7.638 (t, J = 7.5 Hz, 1H), 8.53 (m, 1H), 9.25 (bs, 1H); MS (DCI shows 3) m / e 310 (M + H) +; Analytical calculated values for Q 9 H2 3 N3 O: C, 73.76; H, 7.49; N, 13.58 · Measured value: C, 73.93; H, 7.42; N, 13.53 · Example 327 A I i) -2- (3 one to four i each one 1_ |) B_ # According to example 232B The procedure described in substituting the product from Example 232A with 2-tetrahydropyrrole-3-ylpyridine provided the title compound (21% yield) as a yellow oil. 1 H NMR (300 MHz, CD3 OD); 5 2.06-2.12 (m, 1H), 2.15-2.23 (m, 4H), 85228-358-200404539 2.84_2 · 98 (m, 1H), 3.0-3.10 (m , 2H), 3.12-3.20 (m, 1Η), 3.25 (d, J = 12_0 Hz, 1H), 3.45 (d, J = 12.0 Hz, 1H), 3.50-3.65 (m, 1H), 6_93 (d, J = 9_0 Hz, 1H), 7.06-7.13 (m, 2H), 7.18-7.23 (m, 2H), 7.62 (ddd, J = 6.5, 6 · 1, 3 · 3 Hz, 1H) · 8.59 ( d, 6.0 Hz, 1H), 7.38 (s, 1H); MS (DCI / NH3) m / e 296; Analytical calculated values for Q 8 H2! N3 O: C, 73 · 19; H, 7.17; N, 14.23. Found: C, 72.88; H, 7.01; N, 13.91. Example 328 N- (l-methyl-1H-benzylidene-2-yl) _2- "3- (l, 3- Moxa-2-yl) hexazine outer 1-yl-1

乙醯胺 實例328A 3-酮基六氫吡啶-1-羧酸第三-丁酯 將1-苄基六氫吡啶-3-酮（22.06克，116.6毫莫耳，Acros)、20% 氫氧化鈀/碳（2·50克）、二碳酸二-第三-丁酯（22.37克，102.5 毫莫耳）及三乙胺（13·9毫升）在甲醇（200毫升）中之溶液，於 60 psi氫及50°C下，放置40分鐘。使此溶液冷卻至室溫，過濾 ，及濃縮，提供標題化合物。iHNMRpOOMHADMSOO 31_48 (s，9H)，1.99 (m，2H)，2.47 (m，2H)，3.59 (m，2H)，4.00 (s，2H); MS (DCI/NH3) m/e 200 (M+H)+ ； 217(M+NH4)+.Example of acetamidine 328A 3-ketohexahydropyridine-1-carboxylic acid third-butyl ester 1-benzylhexahydropyridin-3-one (22.06 g, 116.6 mmol, Acros), 20% hydroxide A solution of palladium / carbon (2.50 g), di-tertiary-butyl dicarbonate (22.37 g, 102.5 mmol) and triethylamine (13.9 ml) in methanol (200 ml) at 60 psi hydrogen and 50 ° C for 40 minutes. The solution was allowed to cool to room temperature, filtered, and concentrated to provide the title compound. iHNMRpOOMHADMSOO 31_48 (s, 9H), 1.99 (m, 2H), 2.47 (m, 2H), 3.59 (m, 2H), 4.00 (s, 2H); MS (DCI / NH3) m / e 200 (M + H ) +; 217 (M + NH4) +.

實例328B 乏-{「(三氟甲基）確酸基1氧基丨-3,6-二氫峨淀-1(2HV複酸第三-丁酉旨 使二異丙基胺（13.1毫升，110毫莫耳）與四氫呋喃（15〇毫升） 之混合物冷卻至-_l〇°C。於此混合物中，經由注射器添加正_ 丁基鋰（2.5M，在己烷中，44毫升，110毫莫耳）。將混合物 攪拌30分鐘，冷卻至-78t，並以在四氫呋喃（50毫升）中之溶 液，添加得自實例328A之產物溶液（16克，80毫莫耳）。將混 85228 -359- 200404539 合物攪拌15分鐘，然後添加已溶於四氳呋喃（6〇毫升）中之N_ 苯基-雙_三氟甲烷磺醯胺（35·〇克，110毫莫耳）之溶液。使反 應/I2L熱至室溫，以飽和碳酸氫鈉溶液（乃毫升）使反應淬滅， 並以乙駿稀釋。分離液層，並將有機相以鹽水洗滌，以硫 酸鎂脫水乾燥，及在減壓下濃縮。使殘留物藉急驟式管柱 層析純化（矽膠，5%醋酸乙酯：己烷），獲得所要之三氟甲 ^ 石買故鹽’為油狀物（7.8 克，24% )。MS (DCI/NH3) m/e 333 (Μ+Η)+.Example 328B-((trifluoromethyl) acidyloxyl-3,6-dihydroeodo-1 (2HV polyacid tertiary-butyridine) diisopropylamine (13.1 ml, 110 The mixture of millimolar) and tetrahydrofuran (150 ml) was cooled to-10 ° C. To this mixture, n-butyllithium (2.5M in hexane, 44 ml, 110 mmol) was added via a syringe. ). The mixture was stirred for 30 minutes, cooled to -78t, and a solution in tetrahydrofuran (50 ml) was added to the solution of the product from Example 328A (16 g, 80 mmol). The mixture was stirred for 15 minutes, and then a solution of N-phenyl-bis-trifluoromethanesulfonamide (35.0 g, 110 mmol) in tetramethylenefuran (60 ml) was added. I2L was warmed to room temperature, and the reaction was quenched with saturated sodium bicarbonate solution (nanoliter) and diluted with Ethane. The layers were separated and the organic phase was washed with brine, dried over magnesium sulfate, and under reduced pressure Concentrated. The residue was purified by flash column chromatography (silica gel, 5% ethyl acetate: hexane) to obtain the desired trifluoromethane. So salt ’is an oil (7.8 g, 24%). MS (DCI / NH3) m / e 333 (Μ + Η) +.

實例328C i(l，3-魂唾_2_基）_3,6-二氫叶1:淀-1(2HV#酸第三-丁酉旨 於2-嘍吐基溴化鋅（20毫升，10毫莫耳）在無水四氫呋喃（3〇 毫升）中之混合物内，於(TC下，添加得自實例328B之產物（3.3 克’ 10毫莫耳）與肆（三苯膦）免（0)(10%莫耳，i」克）。將混合 物於50°C下加熱1小時，冷卻至室溫，以鹽水使反應淬滅， 並以醋酸乙酯萃取。使有機層以硫酸鎂脫水乾燥，過濾， 及在減壓下濃縮。使殘留物藉急騾式管柱層析純化（矽膠，25 %醋酸乙酯：己烷），獲得所要之產物，1.4克（60%)，為無 色油。MS (DCI/NH3) m/e 265 (M+H)+ ·Example 328C i (l, 3-somalin_2_yl) _3,6-dihydro leaf 1: Yodo-1 (2HV # acid third-butyrate is intended for 2-oxetyl zinc bromide (20 ml, 10 In a mixture of anhydrous tetrahydrofuran (30 ml), the product obtained from Example 328B (3.3 g '10 mmol) and triphenylphosphine (0) ( 10% mole, i "g). The mixture was heated at 50 ° C for 1 hour, cooled to room temperature, the reaction was quenched with brine, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and filtered , And concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 25% ethyl acetate: hexane) to obtain the desired product, 1.4 g (60%) as a colorless oil. MS (DCI / NH3) m / e 265 (M + H) + ·

實例328D 3-(1,3-嘧唑-2-基）六氫吡啶小勒酸第三·丁酉旨 將得自實例328C之產物在甲醇（50毫升）與20%鈀/碳(0·7克） 中之溶液，於1個氫大氣壓力及室溫下，放置4天。將反應 物過滤，及在減壓下濃縮，提供標題化合物（1.42克，100%) 0 MS(DCI/NH3)m/e267(M+H)+.Example 328D 3- (1,3-pyrimazol-2-yl) hexahydropyridine oleyl acid tert-butyrate The product from Example 328C was obtained in methanol (50 ml) and 20% palladium / carbon (0.7 G), the solution was left at room temperature for 4 days under an atmosphere of hydrogen pressure. The reaction was filtered and concentrated under reduced pressure to provide the title compound (1.42 g, 100%). MS (DCI / NH3) m / e267 (M + H) +.

實例328E 85228 -360- 200404539 3-Π,3-嶁唑-2-某）六氤吡啶 將得自實例328D之產物（1.2克，4.5毫莫耳）在25%三氟醋酸 /二氯甲烷（10毫升）中之溶液，於室溫下攪拌2小時。使反 應物在減壓下濃縮，提供標題化合物，0.70克（76% )，為黃 色油。將此化合物直接使用在下一反應中。 實例328Ε 士(1_甲基·1Η-茉并咪唑-2-基嘧唑-2-墓）六氫吡啶小甚1 乙醯胺Example 328E 85228 -360- 200404539 3-Π, 3-oxazole-2-some) Hexapyridine 10 ml), and stirred at room temperature for 2 hours. The reaction was concentrated under reduced pressure to provide the title compound, 0.70 g (76%) as a yellow oil. This compound was used directly in the next reaction. Example 328E Shi (1-methyl · 1Η-mobenzimidazole-2-ylpyrazole-2-grave) hexahydropyridine 1 acetamidine

按照實例247B中所述之程序，以2-氯-N-(l-甲基_1H-苯并咪 峻_2_基）乙酿胺（Caroti，P·;等人Farmaco 1989,44, 227)取代得自實 例247A之產物，並以得自實例328E之產物取代1-(2-氰基吡啶 基）六氫吡畊，提供標題化合物（23% )，為黃色油。IhNMR (300 MHz，CD3 OD) ; 5 1.80-1.88 (m，1H)，1.90-1.95 (m，2H)，2.05-2.10 (m， 1H)，2.45-2.68 (m，4H)，2_98_3·05 (m，2H)，3.21-3.26 (m，1H)，3.65 (s，3H)， 7.20-7.38 (m，2H)，7.42-7.58 (m，3H)，7.65 (d，J=3.1 Hz，1H); 對Q 8吒之分析計算值：C，6021 ; H，6.01 ; N，19.50.實測 值：C，60.20 ; Η，5·84 ; N，19.16. 實例329 N_=C,l:_.f ,基_1H-苯并咪峻-2-基）-2_「3_α,3-,塞唑基^氫峨哈小某1 乙醯胺Following the procedure described in Example 247B, 2-chloro-N- (l-methyl_1H-benzimidazol-2-yl) ethylamine (Caroti, P .; et al. Farmaco 1989, 44, 227 ) Substituting the product from Example 247A and substituting 1- (2-cyanopyridyl) hexahydropyridine with the product from Example 328E to provide the title compound (23%) as a yellow oil. IhNMR (300 MHz, CD3 OD); 5 1.80-1.88 (m, 1H), 1.90-1.95 (m, 2H), 2.05-2.10 (m, 1H), 2.45-2.68 (m, 4H), 2_98_3 · 05 ( m, 2H), 3.21-3.26 (m, 1H), 3.65 (s, 3H), 7.20-7.38 (m, 2H), 7.42-7.58 (m, 3H), 7.65 (d, J = 3.1 Hz, 1H) ; Analytical calculated values for Q 8 吒: C, 6021; H, 6.01; N, 19.50. Found: C, 60.20; Η, 5.84; N, 19.16. Example 329 N_ = C, l: _. F , Yl_1H-benzimidazol-2-yl) -2_ "3_α, 3-, Setazolyl ^ Hydroxy-1, 1 acetamide

實例329A 3_酮基四氫吡咯-1-讀醢第 按照實例撒巾所述之程序m細氫料_3_酮(Acros) 取代1-爷基六氯峨唉-3-嗣，提供標題化合物。Ms (dq/nh3 &gt; 85228 •361- 200404539 186(M+H)+ ; 203 (M+NH4)+.Example 329A 3_ketotetrahydropyrrole-1-reading procedure According to the procedure described in the example, m fine hydrogen material_3_one (Acros) is substituted for 1-hexadecylhexachloroethan-3-pyrene, providing the title Compounds. Ms (dq / nh3 &gt; 85228 • 361- 200404539 186 (M + H) +; 203 (M + NH4) +.

實例329B 3-{「(三氟甲基）績醯基1氧基丨-2,5-二氫-1H-吡咯-1-羧酸第三丁酯 按照實例328B中所述之程序，以得自實例329A之產物取代 得自實例328A之產物，提供標題化合物。iHNMROOOMHz， CDC13 ) δ 5.71-5.76 (m, 1H), 4.22 (m5 4H)5 1.48 (s, 9H) ； MS (DCI/NH3) m/e 318(M+H)+.Example 329B 3-{"(trifluoromethyl) fluorenyl 1oxy--2,5-dihydro-1H-pyrrole-1-carboxylic acid third butyl ester Follow the procedure described in Example 328B to obtain The product from Example 329A replaced the product from Example 328A to provide the title compound. IHNMROOOMHz, CDC13) δ 5.71-5.76 (m, 1H), 4.22 (m5 4H) 5 1.48 (s, 9H); MS (DCI / NH3) m / e 318 (M + H) +.

實例329C 3-(1,3-嘧唑-2-基V2,5-二氫-1H-吡咯_1·羧酸第三-丁酯 按照實例143Α中所述之程序，以2-嘧唑基溴化鋅取代3-甲 基-2-吡啶基溴化鋅，並以得自實例329Β之產物取代4_三氟甲 烷磺醯氧基·3,6-二氫-2Η-吡啶小羧酸第三丁酯，提供標題化 合物。MS(DCI/NH3)m/e253 (M+H)+ ; 270(Μ+ΝΗ4)+·Example 329C 3- (1,3-pyrazol-2-yl V2,5-dihydro-1H-pyrrole_1 · carboxylic acid tert-butyl ester Following the procedure described in Example 143A, Zinc bromide was substituted for 3-methyl-2-pyridylzinc bromide and 4-trifluoromethanesulfonyloxy · 3,6-dihydro-2Η-pyridine small carboxylic acid was substituted with the product obtained from Example 329B. Tributyl ester to provide the title compound. MS (DCI / NH3) m / e253 (M + H) +; 270 (Μ + ΝΗ4) + ·

實例329D 3-(1,3-ρ塞唑-2-基）四氫吡咯-1-羧酸第三-丁酯 按照實例224中所述之程序，以得自實例329B之產物取代 得自實例166C之產物，提供標題化合物（45%產率），為黃色 油。1HNMR(300 MHz，DMSO-d6) 5 1.47 (s，9H)，2.36 (m，2H)，3.73 (m， 5H)，7·25 (d5 1H，J=3.4 Hz)，7.71 (d，1H，J=3.1 Hz) ; MS (DCI/NH3) m/e 255 (M+H)+_Example 329D 3- (1,3-ρ thiazolyl-2-yl) tetrahydropyrrole-1-carboxylic acid tert-butyl ester The procedure described in Example 224 was used to replace the product from Example 329B. The product of 166C provided the title compound (45% yield) as a yellow oil. 1HNMR (300 MHz, DMSO-d6) 5 1.47 (s, 9H), 2.36 (m, 2H), 3.73 (m, 5H), 7.25 (d5 1H, J = 3.4 Hz), 7.71 (d, 1H, J = 3.1 Hz); MS (DCI / NH3) m / e 255 (M + H) + _

實例329E 2-四氮p比洛-3_基-1,3&lt;裳峡 按照實例166B中所述之程序，以得自實例329C之產物取代 得自實例166A之產物，提供標題化合物（81%產率），為黃色 85228 -362- 200404539 固體。1H NMR (300 MHz，DMSO-d6 ) (5 2.12 (m，1H)，2.43 (m，1H)，3.35 (m，： 3H)，3.64 (m，1H)，3.98 (m，1H)，7.71 (d，1H，J=3.4 Hz)，7.78 (d，1H，J=3.1 Hz)， 8.99 (br s，1H) ; MS (DCI/NH3 ) m/e 155 (M+H)+ ·Example 329E 2-tetrazolium pilo-3-3-yl-1,3 &lt; Shangxia was replaced with the product from Example 329C by the procedure described in Example 166B to provide the title compound (81% Yield) as a yellow 85228-362-200404539 solid. 1H NMR (300 MHz, DMSO-d6) (5 2.12 (m, 1H), 2.43 (m, 1H), 3.35 (m ,: 3H), 3.64 (m, 1H), 3.98 (m, 1H), 7.71 ( d, 1H, J = 3.4 Hz), 7.78 (d, 1H, J = 3.1 Hz), 8.99 (br s, 1H); MS (DCI / NH3) m / e 155 (M + H) + ·

實例329F Ν-(1·甲基-1H-笨并咪唑_2-基V2-f3-(l，3-嘧唑-2-基）四氫吡咯甚1 乙醯胺 按照實例247Β中所述之程序，以2-氯-N-(l-甲基-1Η_苯并咪 唑-2-基）乙醯胺（Caroti, R ;等人Farmaco 1989, 44, 227)取代得自實 _ 例247A之產物，並以得自實例329D之產物取代1-(2-氰基吡啶 基）六氫吡畊，提供標題化合物（23%產率），為黃色油。1HNMR (300 MHz，CD3 OD) ; 5 2.51-2.65 (m，1H)，2·68_3·25 (m，1H)，3.62 (s，2H)， 3.85 (t，J=3.0 Hz，1H)，4.15-4.24 (m，4H)，4·92 (s，3H)，7.13-7.25 (m，4H)，7.58 (d，J=3.0 Hz，1H)，7.80 (d，J=3.0 Hz，1H) ； MS (DCI/NH3 ) m/e 242 ；對 C17H19N5OS之分析計算值·· C，59.80; Η，5·61; Ν，20·51·實測值 :C，59.61 ; Η，5·42 ; Ν，20·86· 實例330 · 2-(2-字基四氮ρ比洛-1_基氣苯基）乙酿胺 按照實例247B中所述之程序，以得自實例254A之產物取代 得自實例247A之產物，並以3-爷基四氫it比洛(Array)取代1-(2-氰 基吡啶基）六氫吡畊，提供標題化合物（21%產率），為黃色油 。iHNMRpOOMHACDsOD) ; 5 1.58-1.92 (m，4H)，2.38-2.42 (m，1H)， 2.58-2.70 (m，1H)，2.83-3.02 (m，2H)，3·10 (d，J=12.0 Hz，1H)，3.09-3.23 (m， 1HX 3.25-3.31 (m? 1H)? 3.58 (d5 J=12.0 Hz5 1H)? 6.80-6.85 (m, 1H)? 7.12-7.37 (m，6H)，7.55 (dt，J=9.0, 3.0 Hz，1H) ; MS (DCI/NH3) m/e 313 ; 85228 -363 - 200404539 對€191121]^20卩.0.101120 之分析計算值：C 7263; H68〇; N892 實測值：C，72.51 ; Η, 6.88 ; N，8.82. 實例331 N-(4-氟苯基）-2-(3-嘍吩-2-基四氫吡咯_；[_基）乙醯胺Example 329F Ν- (1.methyl-1H-benzimidazole_2-yl V2-f3- (l, 3-pyrimazol-2-yl) tetrahydropyrrole and 1 acetamidine were as described in Example 247B The procedure was replaced with 2-chloro-N- (l-methyl-1Η_benzimidazol-2-yl) acetamide (Caroti, R; et al. Farmaco 1989, 44, 227). Example 247A Product and substituting 1- (2-cyanopyryl) hexahydropyridine with the product from Example 329D to provide the title compound (23% yield) as a yellow oil. 1HNMR (300 MHz, CD3 OD); 5 2.51-2.65 (m, 1H), 2.68_3 · 25 (m, 1H), 3.62 (s, 2H), 3.85 (t, J = 3.0 Hz, 1H), 4.15-4.24 (m, 4H), 4 · 92 (s, 3H), 7.13-7.25 (m, 4H), 7.58 (d, J = 3.0 Hz, 1H), 7.80 (d, J = 3.0 Hz, 1H); MS (DCI / NH3) m / e 242 ; Analysis and calculation value for C17H19N5OS ·· C, 59.80; Η, 5.61; Ν, 20.51 · Measured value: C, 59.61; Η, 5.42; Ν, 20 · 86 · Example 330 · 2- ( 2-Fytyltetrazol pilo-1-yl-phenylphenyl) ethylamine was replaced with the product from Example 254A by the procedure described in Example 247B, and replaced with the Tetrahydro it Billo (Array) replaces 1- (2-cyano Pyridyl) hexahydropyridine to provide the title compound (21% yield) as a yellow oil. IHNMRpOOMHACDsOD); 5 1.58-1.92 (m, 4H), 2.38-2.42 (m, 1H), 2.58-2.70 (m , 1H), 2.83-3.02 (m, 2H), 3.10 (d, J = 12.0 Hz, 1H), 3.09-3.23 (m, 1HX 3.25-3.31 (m? 1H)? 3.58 (d5 J = 12.0 Hz5 1H)? 6.80-6.85 (m, 1H)? 7.12-7.37 (m, 6H), 7.55 (dt, J = 9.0, 3.0 Hz, 1H); MS (DCI / NH3) m / e 313; 85228 -363- 200404539 Analytical calculated value for € 191121] ^ 20 卩 .0.101120: C 7263; H68〇; N892 Found: C, 72.51; Thallium, 6.88; N, 8.82. Example 331 N- (4-fluorophenyl) -2 -(3-fluoren-2-yltetrahydropyrrole_; [_yl) acetamidin

實例331AExample 331A

3-遠吩-2-基-2,5-二氫-111-咐^各-1-幾酸第三-丁酉旨 於得自實例329B之產物（3.65克，11_5毫莫耳）在四氫呋喃（2〇 毫升）中之溶液内，於惰性大氣及室溫下，添加2_嘧吩基溴 化鋅（40毫升，20毫莫耳，0.5M溶液）在無水四氫呋喃中之溶 液，接著添加肆（三苯膦）把（0)(9%莫耳，ΐ·2〇克）。將混合物 於50°C下加熱2小時。使反應物冷卻至室溫，以碳酸氫鈉水 溶液使反應淬滅，並以醋酸乙酯（3 X 30毫升）萃取。將有機 層合併，以鹽水洗滌，以硫酸鈉脫水乾燥，在減壓下濃縮 ’並藉急驟式管柱層析純化（碎膠，10 : 1己燒：酷酸乙酉旨） ’提供所要之化合物，為油狀物（1·50克，54% )。iHNMR (300 MHz，CDC13) 5 7.23 (d，J=5 Hz，1H)，7·00 (dd，J=5 Hz，3 Hz，1H)，6.94 (m，1H)，5.93-5.99 (m，1H)，4.25-4.49 (m，4H)，1_50 (m，9H) ; MS (DCI/NH3) m/e 252 (M+H)+.3-Fenphen-2-yl-2,5-dihydro-111-b-^^-1--1-acid tertiary-butyrate was intended to be the product obtained from Example 329B (3.65 g, 11_5 mmol) in tetrahydrofuran ( 20 ml) of the solution in an inert atmosphere and room temperature, add a solution of 2-pyrimidinyl zinc bromide (40 ml, 20 mmol, 0.5M solution) in anhydrous tetrahydrofuran, and then add ( Triphenylphosphine) (0) (9% mole, ΐ · 20 g). The mixture was heated at 50 ° C for 2 hours. The reaction was allowed to cool to room temperature, the reaction was quenched with aqueous sodium bicarbonate solution, and extracted with ethyl acetate (3 X 30 mL). The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure, and purified by flash column chromatography (crumb, 10: 1 hexane: ethyl acetate) to provide the desired compound. , As an oil (1.50 g, 54%). iHNMR (300 MHz, CDC13) 5 7.23 (d, J = 5 Hz, 1H), 7.0 (dd, J = 5 Hz, 3 Hz, 1H), 6.94 (m, 1H), 5.93-5.99 (m, 1H), 4.25-4.49 (m, 4H), 1_50 (m, 9H); MS (DCI / NH3) m / e 252 (M + H) +.

實例33IB 3-口塞吩-2-基四氫外|：哈小羧酸第三-丁酯 將得自實例331A之產物（1.25克，5毫莫耳）在甲醇（1〇〇毫升） 中之溶液，以20%鈀/碳（〇_7克）處理，並於60 psi氫壓力及室 溫下放置過夜。將此溶液過濾，及濃縮，而得所要之化合 物（1.10 克，92% )。1H NMR (300 MHz，CDC13) 5 7·17 (d，J=5，l Hz，1H)， 85228 -364- 200404539 6.95 (dd，J=5,4 Hz，1H)，6.87 (m，1H)，3.39-3.82 (m，5H)，2.32 (m，1Η)，2·02 (m，1H)，1.47 (m，9H) ; MS (DCI/NH3) m/e 254 (M+H)+.Example 33IB 3-Osphenphen-2-yltetrahydroexo |: The third-butyl harbinate carboxylic acid The product obtained from Example 331A (1.25 g, 5 mmol) in methanol (100 ml) The solution was treated with 20% palladium / carbon (0-7 g) and left overnight at 60 psi hydrogen pressure and room temperature. This solution was filtered and concentrated to obtain the desired compound (1.10 g, 92%). 1H NMR (300 MHz, CDC13) 5 7 · 17 (d, J = 5, 1 Hz, 1H), 85228 -364- 200404539 6.95 (dd, J = 5, 4 Hz, 1H), 6.87 (m, 1H) , 3.39-3.82 (m, 5H), 2.32 (m, 1Η), 2.02 (m, 1H), 1.47 (m, 9H); MS (DCI / NH3) m / e 254 (M + H) +.

實例331C 3-口塞吩-2-基四氮口比洛 將得自實例331B之產物（1.3克，5.13毫莫耳）於室溫下，以50 %三氟醋酸/二氯甲烷（20毫升）處理2小時。使反應物在減 壓下濃縮，以2N氫氧化鈉鹼化，並以二氯甲烷（3 X 20毫升） 萃取。將有機層合併，以鹽水洗滌，並乾燥，而得所要之 產物（0.62 克，79% )，為黃色油。1 H NMR (300 MHz, CDC13) 5 7.14 (d， J=5, 1 Hz，1H)，6·93 (dd，J=5, 4 Hz，1H)，6.83 (m，1H)，3·51 (m，1H)，3.33 (m， 1H)，3·14 (m，1H)，3.05 (m，1H)，2.91 (m，1H)，2.28 (m，1H)，1.91 (m，1H); MS (DCI/NH3) m/e 154 (M+H)+.Example 331C 3-ordephen-2-yltetraazapyrazole The product from Example 331B (1.3 g, 5.13 mmol) was obtained at room temperature with 50% trifluoroacetic acid / dichloromethane (20 ml ) Processing for 2 hours. The reaction was concentrated under reduced pressure, basified with 2N sodium hydroxide, and extracted with dichloromethane (3 × 20 mL). The organic layers were combined, washed with brine, and dried to give the desired product (0.62 g, 79%) as a yellow oil. 1 H NMR (300 MHz, CDC13) 5 7.14 (d, J = 5, 1 Hz, 1H), 6.93 (dd, J = 5, 4 Hz, 1H), 6.83 (m, 1H), 3.51 (m, 1H), 3.33 (m, 1H), 3.14 (m, 1H), 3.05 (m, 1H), 2.91 (m, 1H), 2.28 (m, 1H), 1.91 (m, 1H); MS (DCI / NH3) m / e 154 (M + H) +.

實例33 ID 氣苯基遠吩-2-基四氮p比哈-1-基）乙酿胺 按照實例247B中所述之程序，以得自實例331C之產物取代 1-(2-氰基吡啶基）六氫吡畊，並以2-氯-N-(4-氟苯基）乙醯胺 (Maybridge)取代247A，提供標題化合物（23%產率）。iHNMR (300 MHz，DMSO_d6 ) δ 2·14 (m，1H)，3.20-4.00 (m，6H)，4·33 (s，2H)，7.03 (m，2Η)，7.21 (dd，2Η，J=8.8, 8·8 Ηζ)，7·46 (dd，1Η，J=5.1，1·0 Ηζ)，7·61 (m，2Η)， 10.50 (br s5 1Η)5 10.66 (s? 1Η) ； MS (DCI/NH3) m/e 305 (M+H)+. 活體外數據 Da之功能性活性 本發明化合物對人類D4受體之功效與藥效，係使用含有人 類〇4受體與嵌合G蛋白質於HEK-293細胞中之安定細胞系進 85228 -365- 200404539 行測定。此細胞系允許強效鈣信號，可使用鈣螢光染料與 螢光照影板讀取器（FLIPR)(Coward 等人，Anal. Biochem· 270 : 242-248, 1999)偵測。將此等細胞覆蓋（20000 /井）至96井培養m中 ，並培養48小時。移除培養基，添加Fluo-4染料，並使細胞 在室溫下培養1小時。將細胞以磷酸鹽緩衝之鹽水洗滌，以 移除過量染料，並將欲被測試之化合物添加至井中，及在 FLIPR中度量信號。功效百分比為被化合物產生之最大回應 ，與10 /ZM多巴胺之最大作用有關聯。EC50為會造成化合物 最大回應之50%之化合物有效濃度。 嵌合G-蛋白質係允許Gi-偶合受體之高通過量發出訊息檢 測，P. Coward, S. Chan? H. Wada5 G. Humpries Ά. B. Conklin, Biochemistry 270,242-248 (1999)。 本發明之代表性化合物顯示EC5〇在約0.8 nM至約5200 nM之 範圍内。 活體内數據 大白鼠陰莖勃起模式 使用Wistai·大白鼠作為研究活體内陰莖勃起之主要動物模 式。所有實驗均在使用紅光之漫射照明測試室中，於9: 00 AM 與3 : 00 PM之間進行。將動物稱重，並在實驗開始之前，使 其適應測試室60分鐘。於藥物注射後，將大白鼠個別置於 透明籠子（20x30x30公分）中。於藥物服用後，藉由直接觀察 ，記錄陰莖勃起次數，歷經60分鐘，並將顯示1次或更多次 勃起之動物數目，以發生率（％)表示。使用鹽水中之（L)-抗 壞血酸（1毫克/毫升）作為媒劑，及使用阿樸嗎啡，在0.1微 85228 -366- 200404539 莫耳/公斤之劑量下，作為正對照組。 在0.003微莫耳/公斤至3微莫耳/公斤劑量下皮下投藥後 ，本發明之代表性化合物係在大白鼠中誘發最少30%之陰莖 勃起發生率。 活體外與活體内數據証實本發明化合物為多巴胺D4受體催 動劑，其會在哺乳動物中謗發陰莖勃起。 本發明化合物為多巴胺d4受體催動劑，並可用於治療男性 性功能障礙、女性性功能障礙、注意力不足活動過度病症 、阿耳滋海默氏疾病、藥物濫用、巴金生氏病、焦慮、精 神分裂症、心情病症及抑鬱，如在以下之中所述者：多巴 胺D4受體：一種引起爭論之治療標的，N.J.Hrib，未來藥物，25 :587-611 (2000);多巴胺與性行為，M. Melis 與 A· Argiolas，神經科 學與生物行為回顧19 : 19-38 (1995);及多巴胺受體：從結構 至功能，C. Missale，S.R· Nash，S· Robinson，M· Jabber 及 M. Caron，生理 學回顧 78 ·· 189-225 (1998)。 本發明化合物為多巴胺D4受體催動劑，並可用於心與血管 病症之治療。多巴胺與多巴胺能劑已被報告，會對血壓與 心跳速率施加藥理學上顯著之心與血管作用，並可用於心 與血管病症之治療，如在以下之中所述者：Chen FF與Lin MT， 多巴胺、阿樸嗎啡7-巍丁酸、齒喊啶醇及喊迷清（pimozide)對 於大白鼠中之反射心搏徐緩之作用，藥理學與實驗治療學期 刊（1980) 214 : 427-432 ;且已經報告的是，靈長類動物數據支 持多巴胺受體催動劑在治療心與血管疾病上之潛在臨床利 用性，如在以下之中所述者：Hahn，RA及MacDonald BR，藉由多 85228 -367- 200404539 巴胺受體所媒介之靈長類動物心與血管回應：N，N-二丙基多 巴胺與LY171555之作用，藥理學與實驗治療學期刊（1984) 229 : 132-138 。 本發明化合物為多巴胺D4受體催動劑，並可用於發炎之治 療。多巴胺能劑可施加消炎作用，並可用於治療其中發炎 扮演有害角色之疾病，如在以下之中所述者：Bendele AM, Spaethe SM，Benslay DN及Bryant HU，一種多巴胺受體催動劑伯郭 内酯（pergolide)之消炎活性，在藥理學與實驗治療學之藥理學 期刊（1991) 259 : 169-175中。多巴胺能劑亦可在癌症治療上具 有利用性，如在以下之中所述者：Lissoni P，Mandala M，Giani L， Malugani F，Secondino S，Zonato S，Rocco F，Gardani G，溴麥角環肽在轉 移性乳癌及前列腺癌相關催乳激素過高症之治療上之功效 5 Neuroendocrinology Letters (2000) 21 ' 405-408 ° 於本文中使用之催動劑一詞，係意謂本發明化合物在本文 中所述活體外檢測中顯示30%或較大之功效。 於本文中使用之π藥學上可接受之載劑π —詞，係意謂任何 型式之無毒性惰性固體、半固體或液體填料、稀釋劑、包 膠物質或調配助劑。可充作藥學上可接受載劑之物質，其 一些實例為糖類，譬如乳糖、葡萄糖及蔗糖；澱粉，譬如 玉米澱粉與馬鈴薯澱粉；纖維素及其衍生物，譬如羧甲基 纖維素鈉、乙基纖維素及醋酸纖維素；粉末狀西黃蓍樹膠 ;麥芽；明膠；滑石；賦形劑，譬如可可豆脂與栓劑蠟類 ;油類，譬如花生油、棉籽油、紅花油、芝麻油、橄欖油 、玉米油及大豆油；二醇類，譬如丙二醇；酯類，譬如油 85228 -368- 200404539 酸乙酉旨與月桂酸乙酉旨；瓊脂；緩衝劑，譬如氫氧化錢與氣 氧化鋁；海藻酸；不含熱原水；等滲鹽水；林格氏溶液. 乙醇與磷酸鹽緩衝劑溶液’以及其他無毒性可相容潤滑劑 ，譬如月桂基硫酸鈉與硬脂酸鎂，以及著色劑、離型劑、 塗覆劑，增甜、料及芳香劑，防腐劑與抗氧化劑，亦可 存在於組合物中，根據配方設計師之判斷而定。本發明係 提供醫藥組合物，#包含與—或多種無毒性藥學上；接受 之載劑一起調配之本發明化合物。 供本發明化合物局部投藥之劑量形式，包括粉末、喷霧劑 、軟霄及吸藥。活性化合物係於無菌條件下，與藥學上可 接受i載劑，及任何所必須之防腐劑、緩衝劑，或可能需 要之推進劑混合。眼藥配方、眼用軟膏、粉末及溶液，亦 意欲涵蓋在本發明之範圍内。 當使用於上文或其他治療中時，治療上有效量之本發明化 ^物之一 ’可以純形式採㈤，或在以下形式存在時，係以 藥學上可接受之鹽、S旨、醯胺或前體藥物形式採用。或者 ’化合物可以含有吾人感興趣化合物之醫藥組合物投予， 且併用-或多種藥學上可接受之載劑。本發明化合物之&quot;治 療上有效量”之措辭，係意謂足量之化合物，以治療病症， 在可應用於任何醫療處理之合理利益/風險比之下。對:何 特定病患、之特S治療上有效劑量程度係依多種目素而定， 包括被治療I病症與病症之嚴重性；所採用之 活性：所採用之特定組合物；病患之年齡、雜重疋= 康狀態、性別及飲食；所採用特定化合物之投藥時間、投 85228 -369- 200404539 樂途徑及排泄速率；治療期間；與所採用之特定化合物併 用或同時使用I藥物；及醫學技藝上習知之類似因素。 旦被投予哺乳動物且特別是人類之本發明化合物之總日服劑 ^可涵蓋從約_1至約3〇毫克/公斤/天之範圍。對口服 投藥之目的而言，更佳劑量可在〇〇1至約1〇毫克/公斤/天 、範圍内若而要’可針對投樂目的，將有效日服劑量區 分成多劑量；目此，單—劑量組合物可含有此種量或其約 數，以構成日服劑量。 本發明之醫藥組合物可以口服、直腸、非經腸、腦池内、 陰道内、腹膜腔内、局部(譬如藉由粉末、軟膏或滴劑）、 面頰方式’或作成口腔或鼻噴霧劑’投予人類及其他哺乳 動物。於本文中使用之，，非經腸方式&quot;一詞，係指投藥模式 ’其包括靜脈内、肌内、腹膜腔内、胸骨内、皮下與關節 内注射及灌注。 η 供非經腸注射之本發明醫藥組合物，包括藥學上可接受之 無菌含水或非水性溶液、分散液、懸浮液或乳化液，以及 在即將使用之前，供重配成無菌可注射溶液或分散液之無 菌粉末。適當水性與非水性載劑、稀釋劑、溶劑或媒劑之 實例，包括水、乙醇、多元醇(譬如甘油、丙二醇、聚乙二 醇等）、植物油（譬如橄梗油）、可注射有機酉旨類（譬如油酸乙 酯)及其適當混合物。適當流動性可利用例如塗覆物質，譬 如即磷脂，在分散液之情況中，#由維持所需要之粒子大 小，及利用界面活性劑而保持著。 此等組合物亦可含有佐劑，譬如防腐劑、潤濕劑、乳化劑 -370- 85228 200404539 及分散劑。微生物作用之預防可# 劑確保，例如I ^ A ^ 種杭、、、田囷與抗真菌 。：如對殘基本甲酸酸類、氯丁醇、紛、花楸酸等 τ 7把期望包含等滲劑，例如 、* ^ 醫藥$ 4、 口夂、鼠化鈉等。可注射 _ /式 &lt; 長期吸收，可經由；^入# β 如單硬脂酸銘與明膠。由加入延遲吸收劑而產生’譬 下在二情況中，為延長藥物之作用，-般期望減緩來自皮 ::::注射之藥物之吸收。這可利用具有不良水溶解度 =或非晶質物質之液體懸浮液達成。於是，藥物之 率係依其溶解速率而定，其依次可依晶體大小與結 f 足。或者，以非經腸方式投予之藥物形式之延遲 吸收’係經由使藥物溶解或懸浮於油媒劑中而達成。 可注射積辟形式係經由形成藥物在生物可降解之聚合體邀 如聚内又酯-聚乙交醋中之微膠囊基質而製成。依化合物對 聚合體之比例’及所採用特定聚合體之性質而定，藥物釋 出之速率可加以控制。其他生物可降解聚合體之實例，包 括聚（原酸酿類）與聚（奸類）。積野可注射配方亦藉由捕獲藥 物於可與身體組織相容之微脂粒或微乳化液中而製成。 此—可注射配方可被滅菌，例如經過留住細菌之濾器過濾， 或藉由摻入呈無菌固體組合物形式之滅菌劑，其可在即將 使用之前，料或分散於無菌水或其他無菌可注射媒質中。 供口服投藥之固體劑量形式，包括膠囊、片劑、丸劑、粉 末及顆粒。在此種固體劑量形式中，可將活性化合物與至 少一種惰#藥學上可接受之賦形劑或載劑混合，譬如棒檬 酸鈉或磷酸二約及/或a)填料或增量劑，譬如殿粉、乳糖、Example 33 ID Phenyl farphen-2-yltetrazolium pbiha-1-yl) ethylamine Follow the procedure described in Example 247B to replace 1- (2-cyanopyridine) with the product from Example 331C. Hexahydropyridine, and replacing 247A with 2-chloro-N- (4-fluorophenyl) acetamide (Maybridge) to provide the title compound (23% yield). iHNMR (300 MHz, DMSO_d6) δ 2.14 (m, 1H), 3.20-4.00 (m, 6H), 4.33 (s, 2H), 7.03 (m, 2Η), 7.21 (dd, 2Η, J = 8.8, 8 · 8 Ηζ), 7.46 (dd, 1Η, J = 5.1, 1.0 · Ηζ), 7.61 (m, 2Η), 10.50 (br s5 1Η) 5 10.66 (s? 1Η); MS (DCI / NH3) m / e 305 (M + H) +. In vitro data Functional activity of Da The compounds of the present invention are effective and pharmacologically effective on human D4 receptors using human 04 receptors and chimeric G The protein was determined on HEK-293 cells in a stable cell line 85228-365-200404539. This cell line allows potent calcium signals and can be detected using calcium fluorescent dyes and a fluorescent shadow plate reader (FLIPR) (Coward et al., Anal. Biochem. 270: 242-248, 1999). These cells were covered (20,000 / well) into a 96-well culture medium and cultured for 48 hours. The culture medium was removed, Fluo-4 dye was added, and the cells were incubated at room temperature for 1 hour. Cells were washed with phosphate buffered saline to remove excess dye, the compound to be tested was added to the well, and the signal was measured in FLIPR. The percentage of efficacy is the maximum response produced by the compound and is related to the maximum effect of 10 / ZM dopamine. EC50 is the effective concentration of a compound that will cause 50% of the compound's maximum response. Chimeric G-protein lines allow high-throughput detection of Gi-coupled receptors, P. Coward, S. Chan? H. Wada5 G. Humpries Ά. B. Conklin, Biochemistry 270, 242-248 (1999). Representative compounds of the invention show EC50 in the range of about 0.8 nM to about 5200 nM. In vivo data Rat penile erection mode Wistai rats were used as the main animal model to study penile erection in vivo. All experiments were performed in a test room using diffused red light between 9:00 AM and 3:00 PM. Animals were weighed and allowed to acclimate to the test chamber for 60 minutes before the experiment began. After the drug injection, the rats were individually placed in transparent cages (20x30x30 cm). After the drug was taken, the number of penile erections was recorded by direct observation over 60 minutes, and the number of animals with one or more erections will be displayed, expressed as the incidence (%). (L) -ascorbic acid (1 mg / ml) in saline was used as a vehicle, and apomorphine was used at a dose of 0.1 μ 85228 -366- 200404539 mol / kg as a positive control group. After subcutaneous administration at a dose of 0.003 μmol / kg to 3 μmol / kg, the representative compound of the present invention induces a penile erection rate of at least 30% in rats. In vitro and in vivo data confirm that the compounds of the invention are dopamine D4 receptor activators, which can elicit penile erections in mammals. The compound of the present invention is a dopamine d4 receptor activator, and can be used to treat male sexual dysfunction, female sexual dysfunction, attention deficit hyperactivity disorder, Alzheimer's disease, drug abuse, Parkinson's disease, anxiety , Schizophrenia, mood disorders, and depression, as described in the following: dopamine D4 receptor: a controversial target of treatment, NJ Hrib, future medicine, 25: 587-611 (2000); dopamine and sex, M. Melis and A. Argiolas, Review of Neuroscience and Biological Behavior 19: 19-38 (1995); and Dopamine Receptors: From Structure to Function, C. Missale, SR · Nash, S. Robinson, M. Jabber, and M. Caron, Physiological Review 78 · 189-225 (1998). The compounds of the present invention are dopamine D4 receptor activators and can be used for the treatment of cardiac and vascular disorders. Dopamine and dopaminergic agents have been reported to exert pharmacologically significant cardiac and vascular effects on blood pressure and heart rate, and can be used for the treatment of cardiac and vascular disorders, such as those described in: Chen FF and Lin MT The effects of dopamine, apomorphine 7-butyric acid, dinaprol and pimozide on reflex bradycardia in rats, Journal of Pharmacology and Experimental Therapy (1980) 214: 427-432 And it has been reported that primate data support the potential clinical utility of dopamine receptor activators in the treatment of cardiac and vascular disease, as described in: Hahn, RA and MacDonald BR, by Ti 85228 -367- 200404539 Cardiac and vascular responses of primates mediated by dopamine receptors: The role of N, N-dipropyldopamine and LY171555, Journal of Pharmacology and Experimental Therapy (1984) 229: 132-138 . The compounds of the present invention are dopamine D4 receptor activators and are useful in the treatment of inflammation. Dopaminergic agents can exert anti-inflammatory effects and can be used to treat diseases in which inflammation plays a harmful role, as described in the following: Bendele AM, Spaethe SM, Benslay DN, and Bryant HU, a dopamine receptor activator, Berger The anti-inflammatory activity of lactones (pergolide) is described in the Journal of Pharmacology and Experimental Therapy (1991) 259: 169-175. Dopaminergic agents can also be useful in the treatment of cancer, as described in the following: Lissoni P, Mandala M, Giani L, Malugani F, Secondino S, Zonato S, Rocco F, Gardani G, bromoergine ring The efficacy of peptides in the treatment of metastatic breast cancer and prostate cancer-related hyperprolactinemia 5 Neuroendocrinology Letters (2000) 21 '405-408 ° The term activator as used herein means that the compounds of the present invention are used herein Efficacy shown in 30% or greater in in vitro assays. The term π pharmaceutically acceptable carrier π, as used herein, means any type of non-toxic inert solid, semi-solid or liquid filler, diluent, encapsulating substance or formulation aid. Substances that can be used as pharmaceutically acceptable carriers, some examples are sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, beta Base cellulose and cellulose acetate; powdered cedar gum; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olives Oils, corn oil and soybean oil; glycols, such as propylene glycol; esters, such as oil 85228 -368- 200404539; ethyl acetate and ethyl laurate; agar; buffers, such as sodium hydroxide and alumina; alginic acid Pyrogen-free water; isotonic saline; Ringer's solution. Ethanol and phosphate buffer solutions' and other non-toxic compatible lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as colorants, release Agents, coating agents, sweeteners, flavors and fragrances, preservatives and antioxidants may also be present in the composition, depending on the judgment of the formulator. The present invention provides a pharmaceutical composition, which comprises a compound of the present invention formulated with—or with multiple non-toxic pharmaceutically acceptable carriers. Dosage forms for topical administration of a compound of this invention include powders, sprays, softgels, and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any necessary preservatives, buffers, or propellants that may be required. Ophthalmic formulations, ointments, powders and solutions are also intended to be included within the scope of the present invention. When used in the above or other treatments, a therapeutically effective amount of one of the compounds of the present invention can be collected in pure form, or when present in the following form, it is a pharmaceutically acceptable salt, Amines or prodrugs are used. Alternatively, the compound can be administered in a pharmaceutical composition containing a compound of interest, and used in combination with one or more pharmaceutically acceptable carriers. The term "therapeutic effective amount" of a compound of the present invention means a sufficient amount of a compound to treat a condition at a reasonable benefit / risk ratio that can be applied to any medical treatment. To: any particular patient, the The degree of therapeutically effective dose depends on a variety of factors, including the severity of the disease and condition being treated; the activity used: the specific composition used; the patient's age, mixed weight, health status, Gender and diet; time of administration of specific compounds used, 85228-369- 200404539 and route of excretion; duration of treatment; concurrent use or simultaneous use of I drugs with specific compounds used; and similar factors known in medical technology. The total daily dose of a compound of the present invention administered to mammals, and particularly humans, may range from about -1 to about 30 mg / kg / day. For oral administration purposes, a preferred dose may be 0.001 to about 10 mg / kg / day, within the range, if necessary, the effective daily dose can be divided into multiple doses for the purpose of pleasure; for this reason, single-dose compositions may contain such amounts or The pharmaceutical composition of the present invention can be taken orally, rectally, parenterally, intracranially, intravaginally, intraperitoneally, locally (e.g., by powder, ointment or drops), cheek method 'or Prepared as an oral or nasal spray 'for administration to humans and other mammals. As used herein, the term parenteral &quot; refers to the mode of administration', which includes intravenous, intramuscular, intraperitoneal, and sternum , Subcutaneous and intra-articular injection and perfusion. Η The pharmaceutical composition of the present invention for parenteral injection includes pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, and immediately before use, Sterile powder for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (e.g. glycerol, propylene glycol, polyethylene glycol Etc.), vegetable oils (such as olive oil), injectable organic ingredients (such as ethyl oleate), and appropriate mixtures thereof. Suitable fluidity can be utilized, such as coating materials, such as Namely phospholipids, in the case of dispersions, # are maintained by maintaining the required particle size and using a surfactant. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifiers -370 -85228 200404539 and dispersing agents. Prevention of microbial effects can be ensured by agents such as I ^ A ^ species of Hanging, Tian, Tianyu and antifungal .: such as residual basic formic acids, chlorobutanol, pentamidine, anthocyanic acid, etc. τ 7 is expected to contain isotonic agents, for example, * ^ Medicine $ 4, oral cavity, sodium methionate, etc. Injectable _ / long-term absorption, can be via; ^ 入 # β As monostearate and gelatin It is caused by the addition of a delayed absorption agent, for example, in the second case, in order to prolong the effect of the drug, it is generally expected to slow the absorption of the drug from the skin :::: injection. This can be achieved with liquid suspensions with poor water solubility = or amorphous materials. Therefore, the rate of the drug depends on its dissolution rate, which in turn can depend on the size of the crystal and the size of the knot. Alternatively, the delayed absorption of a pharmaceutical form administered parenterally is achieved by dissolving or suspending the drug in an oil vehicle. The injectable form is made by forming a microcapsule matrix of the drug in a biodegradable polymer such as polylactone-polyglycolide. Depending on the ratio of compound to polymer 'and the nature of the particular polymer used, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (ortho-acids) and poly (rapids). SEKINO injectables are also made by capturing the drug in microlipids or microemulsions that are compatible with body tissues. This—injectable formulations can be sterilized, such as by filtering through a bacteria-retaining filter, or by incorporating a sterilizing agent in the form of a sterile solid composition, which can be prepared or dispersed in sterile water or other sterile In the injection medium. Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such a solid dosage form, the active compound can be mixed with at least one inert #pharmaceutically acceptable excipient or carrier, such as sodium clavulanate or diphosphate and / or a) a filler or extender, Such as Dian Fan, Lactose,

85228 -371- 200404539 蔗糖、葡萄糖、甘露醇、及矽酸；b)黏合劑，譬如羧甲基纖 維素、海藻酸鹽、明膠、聚乙烯基四氫吡咯酮、蔗糖及阿 拉伯膠；c)保濕劑，譬如甘油；d)崩解劑，譬如瓊脂、竣酸 鈣、馬給薯或木薯殿粉、海藻酸、某些矽酸鹽及碳酸鈉；e) 溶解阻滯劑，譬如石壤；f)吸收加速劑，譬如四級銨化合物 ;g)潤濕劑，譬如鯨蠟醇與單硬脂酸甘油酯；h)吸收劑，譬 如咼嶺土與膨土；及i)潤滑劑，譬如滑石、硬脂酸妈、硬脂 酸鎂、固體聚乙二醇、月桂基硫酸鈉及其混合物。在膠囊 、片劑及丸劑之情況中，此劑量形式亦可包含緩衝劑。 類似型式之固體組合物，亦可被採用作為敕與硬充填明膠 膠囊中之填料，使用賦形劑，譬如乳糖或牛奶糖，以及高 分子量聚乙二醇等。 片劑、糖衣錠、膠囊、丸劑及顆粒之固體劑量形式，可被 製成具有塗層與殼層，譬如腸溶性塗層及醫藥調配技藝上 習知之其他塗層。其可視情況含有遮光劑，且亦可為組合 物，以致使其釋出活性成份僅在於或優先在於腸道之某— 部份中，視情況以延遲方式。可使用之包埋組合物之實例 ，包括聚合體物質與蠟類。 活性化合物亦可呈微包覆形式，若適當則使用一或多種如 上述之賦形劑。 包括藥學上可接受之乳化液 。除了活性化合物以外，液 技藝中之惰性稀釋劑，例如 劑，譬如乙醇、異丙醇、碳 供口服投藥之液體劑量形式， 、落液、懸浮液、糖漿及酏劑 體劑量形式可含有常用於此項 水或其他溶劑，促溶劑與乳化 85228 -372- 200404539 酸乙酯、醋酸乙酯、苄醇、苯曱酸芊酯、丙二醇、丨,3-丁二 醇、二甲基甲醯胺、油類(特別是棉籽、落花生、玉米、胚 芽、橄欖、萬麻及芝麻油）、甘油、四氫吱喃甲醇、聚乙二 醇及花楸聚糖之脂肪酸酯類，及其混合物。 除了活性化合物以外，懸浮液可含有懸浮劑，例如乙氧基 化異硬脂基醇類、聚氧化乙缔花楸醇與花楸聚㈣類、微 晶性纖維素、偏氫氧化鋁、膨土、瓊脂、西黃蓍樹膠及其 混合物。 供直腸或陰道投藥用之組合物較佳係為栓劑，其可經由將 本發明化合物與適當無刺激性賦形劑或載劑譬如可可豆脂 、聚乙二醇或栓劑蟻混合而製成’其在室溫下為固體，但 在體溫下為液體，因此熔解於直腸或陰道腔穴中，並釋出 活性化合物。 本發明化合物亦可呈微脂粒形式投予。正如此項技藝中所 已知者，微脂粒通常係衍生自磷脂或其他脂質物質。微脂 粒係藉由被分散在水性媒質中之單_4多層狀水合液晶形成 。可使用能夠形成微脂粒之任何無毒性生理學上可接受及 可生物代謝之脂質。呈微脂粒形式之本發明組合物，除了 本發明化合物以外’可含有安定劑、防腐劑、賦形劑等。 較佳脂質為天然與合成磷脂及磷脂醯膽鹼（卵磷脂），個別 或一起使用。 形成微脂粒之方法係為此項技藝中所已知。參閱，例如 Prescott編著，細胞生物學之方法，第χιν卷，大學出版社 ，New York，Ν_Υ· (1976)，第 33 頁及其後文。 85228 •373 - 200404539 本發明意欲涵蓋醫藥活性化合物，無論是以化學方式合成 ，或藉由活體内生物轉化成式①化合物所形成者。 本發明化合物可以未溶劑化合以及溶劑化合形式存在，包 括水合形式，譬如半水合物。一般而言，具有藥學上可接 受溶劑之溶劑化合形式，其中尤其是譬如水與乙醇，對本 發明之目的而言，係相當於未溶劑化合形式。 於本文中使用之&quot;藥學上可接受之鹽、酯、醯胺及前體藥 物”一詞，係指式（I)化合物之羧酸鹽、胺基酸加成鹽、兩性 離子、酯、醯胺及前體藥物，其係在安全可靠醫療判斷範 圍内，適用於與人類及低等動物之組織接觸而無不當毒性 、刺激、過敏性回應等，伴隨著合理利益/風險比，且對於 其所意欲之用途有效。 本發明化合物可以衍生自無機或有機酸之藥學上可接受鹽 之形式使用。”藥學上可接受之鹽”一詞係意謂在安全可靠 醫療判斷範圍内，適用於與人類及低等動物之組織接觸， 而無不當毒性、刺激性、過敏性回應等，且伴隨著合理利 盈/風險比之鹽。藥學上可接受之鹽係為此項技藝中所習知 。此等鹽可在本發明化合物之最後單離與純化期間當場製 成，或經由使自由態鹼官能基與適當有機酸反應而分離。 代表性酸加成鹽，包括但不限於醋酸鹽、己二酸鹽、海藥 酸鹽、檸檬酸鹽、天冬胺酸鹽、苯甲酸鹽、苯磺酸鹽、$ 性硫酸鹽、丁酸鹽、樟腦酸鹽、樟腦磺酸鹽、二葡=糖酸 鹽、甘油磷酸鹽、半硫酸鹽、庚酸鹽、己酸鹽、反丁烯二 酸鹽、鹽酸鹽、氫溴酸鹽、氫碘酸鹽、2_羥基乙烷磺酸&amp;鹽一( 85228 374- 200404539 么乙酸鹽）、礼酸鹽、順丁婦二酸鹽、甲燒績酸鹽、终驗 酸鹽、2-莕磺酸鹽、草酸鹽、雙羥萘酸鹽、果膠酯酸鹽、過 硫酸鹽、3-苯基丙酸鹽、苦味酸鹽、三甲基醋酸鹽、丙酸鹽 、號轴酸鹽、硫酸鹽、雙（酒石酸鹽）、酒石酸鹽、（L)酒石 酸鹽、雙㈣酒石豸鹽)，)酒石酸鹽、雙((L)酒石酸鹽)、㈣ 酒石酸鹽、雙_酒石酸鹽）、中酒石酸鹽、雙(中酒石酸 鹽）、硫氰酸鹽、磷酸鹽、麩胺酸鹽、 績酸鹽及十-燒酸鹽。可被採用以形成藥學上可接 成鹽&lt;酸類，纟實例包括無機酸類，譬如鹽酸、氫漠酸、 硫酸及磷酸，及有機酸類，譬如順丁埽二酸、反丁缔二酸 、琥珀酸及擰檬酸。 鹼改加成鹽可在本發明化合物之最後單離與純化期間，經 ^使含幾酸之部份基團與適#驗，譬如藥學上可接受金屬 %離子《氳氧化物、碳酸鹽或重碳酸鹽，或與氨或有機— 級、二級或三級胺反應而當場製成。藥學上可接受之鹽， 包括但不限於讀金屬或驗土金屬為基礎之陽離子，譬如 鋰、鈉、鉀、㉟、鎂及鋁鹽等，以及無毒性四級氨與胺陽 離子’包括铵、四甲基銨、四乙基按、甲胺、二甲胺、三 甲胺、三乙胺、二乙胺、乙胺等。其他可料形成驗㈣ ::代表性有機胺類’包括乙二胺、乙醇胺、二乙醇胺、 :氫吡啶、六氳吡畊等。本發明化合物之較佳鹽，包括磷 酸孤一起甲基胺基甲燒（Tris)及醋酸鹽。 :本又中使用之&quot;藥學上可接受之前體藥物&quot;或&quot;前體藥物 一詞表示本發明化合物之前體藥物，其在安全可靠醫療判85228 -371- 200404539 sucrose, glucose, mannitol, and silicic acid; b) binders, such as carboxymethyl cellulose, alginate, gelatin, polyvinyl tetrahydropyrrolidone, sucrose, and acacia; c) moisturizing Agents, such as glycerol; d) disintegrating agents, such as agar, calcium dibasic acid, horsetail or cassava meal, alginic acid, certain silicates, and sodium carbonate; e) dissolution inhibitors, such as rocky soil; f ) Absorption accelerators, such as quaternary ammonium compounds; g) wetting agents, such as cetyl alcohol and glyceryl monostearate; h) absorbents, such as kaolin and bentonite; and i) lubricants, such as talc , Stearic acid, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, this dosage form may also comprise buffering agents. Similar types of solid compositions can also be used as fillers in tincture and hard-filled gelatin capsules, using excipients such as lactose or milk sugar, and high molecular weight polyethylene glycols. Solid dosage forms of tablets, dragees, capsules, pills, and granules can be made with coatings and shells, such as enteric coatings and other coatings known in the pharmaceutical formulation arts. It may optionally contain opacifying agents, and may also be a composition such that it releases the active ingredient only or preferentially in a certain part of the intestine, optionally in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. The active compounds may also be in microencapsulated form, if appropriate using one or more excipients as described above. Includes pharmaceutically acceptable emulsions. In addition to the active compounds, inert diluents in liquid technology, such as agents such as ethanol, isopropanol, carbon, liquid dosage forms for oral administration, liquids, suspensions, syrups, and elixirs can be This water or other solvents, solubilizers and emulsifiers 85228 -372- 200404539 ethyl acetate, ethyl acetate, benzyl alcohol, ethyl benzoate, propylene glycol, 丨, 3-butanediol, dimethylformamide, Oils (especially cottonseed, groundnut, corn, germ, olive, sesame and sesame oil), glycerin, tetrahydromethanol, polyethylene glycol and fatty acid esters of anthocyanin, and mixtures thereof. In addition to the active compounds, suspensions may contain suspending agents, such as ethoxylated isostearyl alcohols, polyoxyethylene scopolamine and calyx polyfluorene, microcrystalline cellulose, aluminum metahydroxide, Soil, agar, tragacanth gum and mixtures thereof. Compositions for rectal or vaginal administration are preferably suppositories, which can be prepared by mixing a compound of the invention with a suitable non-irritating excipient or vehicle such as cocoa butter, polyethylene glycol or suppository ant ' It is solid at room temperature but liquid at body temperature, so it melts in the rectum or vaginal cavity and releases the active compound. The compounds of the present invention may also be administered in the form of liposomes. As is known in the art, liposomes are usually derived from phospholipids or other lipid substances. Microlipids are formed by mono-4 multilayer hydrated liquid crystals dispersed in an aqueous medium. Any non-toxic physiologically acceptable and biometabolizable lipid capable of forming microliposome can be used. The composition of the present invention in the form of microfat particles may contain a stabilizer, a preservative, an excipient, etc. in addition to the compound of the present invention. Preferred lipids are natural and synthetic phospholipids and phospholipids choline (lecithin), used individually or together. The method of forming liposomes is known in the art. See, for example, Prescott, Methods in Cell Biology, Vol. Χιν, University Press, New York, N.J. (1976), p. 33 and later. 85228 • 373-200404539 The present invention is intended to cover pharmaceutically active compounds, whether chemically synthesized or formed by biological conversion into a compound of formula ① in vivo. The compounds of the present invention can exist in unsolvated as well as solvated forms, including hydrated forms such as hemihydrate. In general, there are solvated, pharmaceutically acceptable forms of solvents, especially water and ethanol, for the purposes of the present invention, equivalent to unsolvated forms. The term "pharmaceutically acceptable salts, esters, amidines and prodrugs" as used herein refers to carboxylic acid salts, amino acid addition salts, zwitterions, esters, compounds of formula (I), Phenamine and prodrugs are within the scope of safe and reliable medical judgment, and are suitable for contact with human and lower animal tissues without undue toxicity, irritation, allergic responses, etc., with a reasonable benefit / risk ratio, and for The intended use is effective. The compounds of the present invention can be used in the form of pharmaceutically acceptable salts derived from inorganic or organic acids. The term "pharmaceutically acceptable salts" means within the scope of safe and reliable medical judgment and is applicable to Contact with human and lower animal tissues without undue toxicity, irritation, allergic responses, etc., accompanied by a reasonable profit / risk ratio salt. Pharmaceutically acceptable salts are known in the art These salts can be made on-site during the final isolation and purification of the compounds of the invention, or isolated by reacting a free-state base functional group with a suitable organic acid. Representative acid addition salts include, but are not limited to Acid salt, adipate salt, sea salt, citrate salt, aspartate salt, benzoate salt, benzene sulfonate salt, sodium sulfate, butyrate salt, camphor salt, camphor sulfonate , Diglucose = gluconate, glyceryl phosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodate, 2-hydroxyethane Sulfonic acid & salt one (85228 374- 200404539 acetic acid salt), uric acid salt, maleic acid salt, formic acid salt, final acid salt, 2-hydrazone sulfonate salt, oxalate salt, Hydronaphthoate, pectinate, persulfate, 3-phenylpropionate, picrate, trimethylacetate, propionate, hornate, sulfate, bis (tartrate) , Tartrate, (L) tartrate, bis (tartrate) salt,)) tartrate, bis ((L) tartrate), ㈣ tartrate, bis_tartrate), tartrate, bis (tartrate) ), Thiocyanate, phosphate, glutamate, sodium phosphate, and decanoate. May be used to form pharmaceutically acceptable salts &lt; acids, examples of which include inorganic acids such as hydrochloric acid Hydroxamic acid, sulfuric acid and phosphoric acid, and organic acids such as maleic acid, fumaric acid, succinic acid, and citric acid. The base-addition salt can be used during the final isolation and purification of the compounds of the present invention, Some groups containing a few acids have been tested, such as pharmaceutically acceptable metal% ions, oxides, carbonates, or bicarbonates, or with ammonia or organic-secondary, secondary, or tertiary amines. The reaction is made on the spot. Pharmaceutically acceptable salts include, but are not limited to, cations based on metal or soil test metals, such as lithium, sodium, potassium, rubidium, magnesium, and aluminum salts, and non-toxic quaternary ammonia and Amine cations' include ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, diethylamine, ethylamine, etc. Others are expected to form tests :: Representative organic amines Classes include ethylenediamine, ethanolamine, diethanolamine, hydropyridine, hexamethylpyridine, and the like. Preferred salts of the compounds of the present invention include trimethyl phosphate and methyl acetate. : The term "pharmaceutically acceptable precursor drug" or "prodrug" used in this specification means the precursor drug of the compound of the present invention, which is safe and reliable in medical treatment.

85228 375 - 200404539 斷Ιϋ圍内’適用於與人類及低等動物之組織接觸而盖不各 毒性、刺激性、過敏性回應等，伴隨著合理利益/風險比: 及對於其所意欲之用途有效。本發明化合物之前體藥物， 可於活to内轉.【成本發明化合物，例如經由在血液中水解。 於本文中使用之&quot;藥學上可接受之酿&quot;或&quot;酿&quot;一詞，係指 本發明化合物之㈣’其係於活體内水解，且包括易在^ 類體中分解而留下母體化合物或其鹽者。本發明藥學上可 ，受之無毒性s旨類之實例’包括基賴，及CJC7 ¥燒基酯類，惟q至C4烷基酯類較佳。式①化合物之酯類 ’可根據習用方法製成。 於本文中使用之’’樂學上可接受之醯胺，，或”醯胺&quot;一詞， 係扣衍生自氨、一級(^至仏烷基胺類及二級(^至^二烷基胺 類之本發明無毒性醯胺。在二級胺類之情況中，此胺亦可 主έ有一個氮原子之5-或6_員雜環形式。衍生自氨、q至c3 基級醯胺及ci至Q —燒基二級酿胺之醯胺類，係為較 佳。式（I)化合物之醯胺，可根據習用方法製成。 85228 -376-85228 375-200404539 "Inside ϋIϋ" is suitable for contact with tissues of humans and lower animals, covering various toxicity, irritation, allergic responses, etc., with a reasonable benefit / risk ratio: and effective for the intended use . The prodrug of the compound of the present invention can be transferred in vivo. [Cost of the compound of the present invention, for example, by hydrolysis in blood. The term &quot; pharmaceutically acceptable brew &quot; or &quot; brew &quot; as used herein refers to the compound of the present invention, which is hydrolyzed in vivo and includes residues which are easily decomposed in ^ The parent compound or its salt. Examples of pharmaceutically acceptable and non-toxic compounds of the present invention include bases and CJC7 alkyl esters, but q to C4 alkyl esters are preferred. The esters of the compound of formula ① can be prepared according to conventional methods. As used herein, the term "musically acceptable amidine," or "amidine", is derived from ammonia, primary (^ to alkyl alkylamines, and secondary (^ to ^ dioxane) Non-toxic amidines of the present invention based on amines. In the case of secondary amines, this amine may also have a 5- or 6-membered heterocyclic form with a nitrogen atom. Derived from ammonia, q to c3 radicals Amidoamines and ci to Q-ammonium amines of secondary alcohols which are alkyl radicals are preferred. Amidoamines of the compound of formula (I) can be made according to conventional methods. 85228 -376-

Claims (1)

200404539 拾、申請專利範園： 1. 一種在哺乳動物中治療性功能障礙之方法，其包括對嗦 需要此種治療之哺乳動物投予治療上有效量之式（I)化合物200404539 Patent application park: 1. A method for treating sexual dysfunction in mammals, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (I) (I) 或其樂學上可接受之鹽、酯、醯胺或前體藥物，其中 A係選自包括芳基、芳烷基、環烷基、環烷基烷基、 雜環及雜環烷基； L 係選自包括 _n(R7)C(0)·、_C(0)N(R7)-、_N(R7)C(S)_ 及 _ C(S)N(R7)-，其中該_N(R7)C(0)-、_c(〇)N(R7&gt; …n(R7)c(s)^ C(S)N(R7)-之左端係連接至a，而右端係連接至d ; D係選自包括次烷基、氟次烷基及羥基次烷基； Z係選自包括N、C及CRB ; Ra係選自包括氫與燒基； Rb係選自包括氫、燒基及鹵素； 當Z為C時，…為一個鍵結，而當z為N或CRB時，…為 不存在， B係選自包括(I) or an pharmaceutically acceptable salt, ester, amidine, or prodrug thereof, wherein A is selected from the group consisting of aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocycle, and heterocycle Alkyl; L is selected from the group consisting of _n (R7) C (0) ·, _C (0) N (R7)-, _N (R7) C (S) _, and _C (S) N (R7)-, Where the left end of the _N (R7) C (0)-, _c (〇) N (R7 &gt; ... n (R7) c (s) ^ C (S) N (R7)-is connected to a, and the right end is Connected to d; D is selected from the group consisting of alkylene, fluoroalkylene and hydroxyalkylene; Z is selected from the group consisting of N, C and CRB; Ra is selected from the group consisting of hydrogen and alkyl; Rb is selected from the group consisting of hydrogen , Alkyl and halogen; when Z is C, ... is a bond, and when z is N or CRB, ... is absent, B is selected from the group consisting of 85228 200404539 Ri、R2、R3、R4及R5各獨立選自包括氫、烷氧基、烯 基、烷基、烷基亞磺醯基、烷基磺醯基、烷硫基、炔基 、境氧羰基、烷羰基、烷羰基氧基、羧基、氰基、f醯 基、_素、i烷氧基、自烷基、羥基、羥烷基、巯基、 確基、-NZiZ2、（NZ3Z4)燒基、（NZ3Z4)羰基及(NZ3Z4)績醯基； ζι與Z2各獨立選自包括氫、烷基、烷羰基、烷基磺醯 基、芳基、芳烷基、芳烷基磺醯基、芳基磺醯基及甲醯 基； 4與Z4各獨立選自包括氫、烷基、芳基及芳烷基； X係選自包括N(R6)、〇及S ; Y係選自包括C(R4)與N ; 汉6係選自包括氫與燒基；及 R?係選自包括氫與烷基。 2·根據申請專利範圍第1項之方法，其中 A為芳基； B為85228 200404539 Ri, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, and oxygen Carbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxyl, cyano, fluorenyl, hydrogen, i-alkoxy, alkyl, hydroxy, hydroxyalkyl, thiol, thiol, -NZiZ2, (NZ3Z4) alkyl , (NZ3Z4) carbonyl and (NZ3Z4) mercapto; ζι and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, aralkyl, aralkylsulfonyl, aryl 4 and Z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl and aralkyl; X is selected from the group consisting of N (R6), 0 and S; Y is selected from the group consisting of C ( R4) and N; Han 6 is selected from the group consisting of hydrogen and alkyl; and R? Is selected from the group consisting of hydrogen and alkyl. 2. The method according to item 1 of the scope of patent application, wherein A is aryl; B is z為N ; …為不存在；及 [為 _n(r7)c(o)… 3.根據申請專利範圍第丨項之方法，其中 A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 85228 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、、坑基、fe硫基、卞基、氣基、函素、1¾燒氧基、鹵fe 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;z is N;… is absent; and [is _n (r7) c (o) ... 3. According to the method of the scope of application for patent, wherein A is aryl, wherein aryl is phenyl, and is 1, 2, 3, 4 or 5 85228 200404539 substituents, the substituents are selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, pit, fethio, fluorenyl, fluorenyl, oxon, halo, 1¾ Carbooxy, halo, methylenedioxy, nitro, phenyl and -NZiZ2; I係選自包括氫、烷氧基、烷基、烷硫基、氰基、鹵 素、羥基、硝基、-NZJ2及(NZ3Z4)烷基； R2係選自包括氫、烷氧基、氰基、齒素及羥基； R3係選自包括氫與羥基； R4與R5為氫； Z為N ; …為不存在， D 為-CH2 -，及 L 為-N(R7)C(0)-。 4.根據申請專利範圍第1項之方法，其中 A為芳基； B為I is selected from the group consisting of hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, hydroxy, nitro, -NZJ2 and (NZ3Z4) alkyl; R2 is selected from the group consisting of hydrogen, alkoxy, cyano , Tooth element and hydroxyl group; R3 is selected from the group consisting of hydrogen and hydroxyl group; R4 and R5 are hydrogen; Z is N; ... is absent, D is -CH2-, and L is -N (R7) C (0)-. 4. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z為N ; …為不存在；及 L 為-N(R7)C(0)-。 5.根據申請專利範圍第1項之方法，其中 85228 200404539 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、画素、鹵燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為 ?2 XXR Λ N r4. Ri係選自包括氫、烷基、氰基、li烷基、iS素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； 112與114為氫； r3係選自包括氫與羥基； Z為N ; …為不存在， D 為-CH?-，及 L 為-N(R7)C(0)_。 6.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為2,3-二氫_1Η·茚-5-基； Β為 愈 &amp;係選自包括氫、烷基、氰基、iS烷基、iS素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氮， r3係選自包括氫與羥基； 85228 200404539 Z為N ; —為不存在， D 為-CH2 -;及 L 為-N(R7)C(0)-。 7.根據申請專利範圍第1項之方法，其中 A為芳基；Z is N; ... is absent; and L is -N (R7) C (0)-. 5. The method according to item 1 of the scope of patent application, wherein 85228 200404539 A is an aryl group, wherein the aryl group is a phenyl group and is substituted by 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenes Alkoxy, alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, hexyl, cyano, pixel, halooxy, haloyl, methylenedioxy, nitro, phenyl, and -NZiZ2; B Is? 2 XXR Λ N r4. Ri is selected from the group consisting of hydrogen, alkyl, cyano, lialkyl, iS, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; 112 and 114 are hydrogen; r3 Selected from the group consisting of hydrogen and hydroxyl; Z is N; ... is absent, D is -CH?-, And L is -N (R7) C (0) _. 6. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is 2,3-dihydro_1Η · inden-5-yl; B is a group selected from the group consisting of hydrogen and alkyl , Cyano, iS alkyl, iS element, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen, and r3 is selected from the group consisting of hydrogen and hydroxyl; 85228 200404539 Z is N;-is absent , D is -CH2-; and L is -N (R7) C (0)-. 7. The method according to item 1 of the scope of patent application, wherein A is aryl; Z為N ; —為不存在，及 L 為-N(R7)C(0)-。 8.根據申請專利範圍第1項之方法，其中 A為芳基’其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、iS素、iS烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-ΝΖ! Z2 ; B為Z is N;-is absent, and L is -N (R7) C (0)-. 8. The method according to item 1 of the scope of patent application, wherein A is aryl 'wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, iS element, iS alkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZ! Z2; B is R2、及R4為氫； Z為N ; …為不存在； D 為-CH]-，及 L 為-N(R7)C(0)-。 85228 200404539 9.根據申請專利範圍第1項之方法，其中 A為芳基； B為R2 and R4 are hydrogen; Z is N; ... is absent; D is -CH]-, and L is -N (R7) C (0)-. 85228 200404539 9. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z為N ; —為不存在，及 L 為-N(R7)C(0)-。 10.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、燒硫基、苄基、氰基、lS素、鹵烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-ΝΖΘ2 ;Z is N;-is absent, and L is -N (R7) C (0)-. 10. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, thiothio, benzyl, cyano, 1S element, haloalkoxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZΘ2; R2與R3為氮， X 為 N(R6)、Ο 或 S ; Y為N ; Z為N ; …為不存在； D 為-CH]-，及 L 為-N(R7)C(0)-。 11.根據申請專利範圍第1項之方法，其中 85228 200404539 A為雜環； B為 200404539R2 and R3 are nitrogen, X is N (R6), 0, or S; Y is N; Z is N; ... is absent; D is -CH]-, and L is -N (R7) C (0)- . 11. The method according to item 1 of the scope of patent application, wherein 85228 200404539 A is a heterocyclic ring; B is 200404539 Z為N ; …為不存在；及 L 為-N(R7)C(0)-。 12.根據申請專利範圍第1項之方法，其中 A為雜環’其中雜環係選自包括苯并咪唑基、苯并嘧 峻基、吱喃基、咪嗤基、嘮唑基、吡畊基、吡唑基、 塔喷基、吨淀基、嘧啶基、吡咯基、塞唑基及嘍吩基 ，其中雜％係獨JL被〇、丨、2或3個取代基取代，取代基 選自包括烷氧基、烷氧羰基、烷基、氰基、_素、鹵烷 氧基、S垸基及硝基； B為Z is N; ... is absent; and L is -N (R7) C (0)-. 12. The method according to item 1 of the scope of patent application, wherein A is a heterocyclic ring, wherein the heterocyclic ring system is selected from the group consisting of benzimidazolyl, benzimidyl, succinyl, imidino, oxazolyl, and pyrenyl Group, pyrazolyl, tapentyl, glutamyl, pyrimidinyl, pyrrolyl, sedazolyl, and fluorenyl, in which the hetero% is independently JL substituted with 0, 丨, 2 or 3 substituents. Including alkoxy, alkoxycarbonyl, alkyl, cyano, halogen, haloalkoxy, sulfonyl and nitro; B is …為不存在； D 為-CH2-;及 L 為 _N(R7 )C(〇)- 〇 13·根據申請專利範圍第1項之方法，其中 、丰并口塞 、2或3個 Α為雜環，其中雜環係選自包括料味唆基 嗅基、吡唑基、吡啶基或嘍吩基，獨立被〇」 85228 200404539 取代基取代，取代基選自包括烷氧基、烷氧羰基、燒基 、氰基、iS素、i烷氧基、自烷基及硝基；... is absent; D is -CH2-; and L is _N (R7) C (〇)-〇13. According to the method in the scope of patent application No. 1 wherein, Feng Fengkou plug, 2 or 3 A is miscellaneous Ring, wherein the heterocyclic ring is selected from the group consisting of melamine, pyrazolyl, pyridyl, or phenenyl, and is independently substituted with a substituent of "85228 200404539", and the substituent is selected from the group consisting of Alkyl, cyano, iS element, i alkoxy, self alkyl and nitro; Ri係選自包括氫、燒基、氰基、燒基、卣素、確基 、（nz3z4)烷基及(NZ3Z4)羰基； 與為氫； R3係選自包括氫與輕基； Z為N ; 為不存在， D 為-CH2-;及 L 為-N(R7)C(0)… 14.根據申請專利範圍第1項之方法，其中 A為環烷基； B為Ri is selected from the group consisting of hydrogen, alkynyl, cyano, alkynyl, halogen, sulfanyl, (nz3z4) alkyl and (NZ3Z4) carbonyl; and R is hydrogen; R3 is selected from the group consisting of hydrogen and light group; Is absent, D is -CH2-; and L is -N (R7) C (0) ... 14. The method according to item 1 of the scope of patent application, wherein A is cycloalkyl; B is 15·根據申請專利範圍第1項之方法，其中15. The method according to item 1 of the scope of patent application, wherein A為環烷基，其中環烷基係選自包括 基； 衣己 B為A is a cycloalkyl group, wherein the cycloalkyl group is selected from the group consisting of; 85228 200404539 Ri係選自包括氫、统基、氰基、_燒基、自素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； 112與114為氫； r3係選自包括氫與羥基； Z為N ; …為不存在； D 為 _CH2 -，及 L 為-N(R7)C(0)_。 16·根據申請專利範圍第1項之方法，其中 A為芳烷基； B為85228 200404539 Ri is selected from hydrogen, hydrogen, cyano, alkynyl, autogen, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; 112 and 114 are hydrogen; r3 is selected from hydrogen and hydroxyl Z is N;… is absent; D is _CH2-, and L is -N (R7) C (0) _. 16. The method according to item 1 of the scope of patent application, wherein A is an aralkyl group; B is Z為N ; …為不存在；及 L 為-N(R7)C(0)… 17_根據申請專利範圍第i項之方法，其中 A為芳烷基，其中芳烷基之芳基為苯基，被〇、工、2、 3、4或5個取代基取代，取代基選自包括烯基、烷氧基 ’元乳奴基火元基、燒硫基、爷基、氯基、_素、鹵燒 氧基、鹵烷基、亞甲二氧基、硝基、苯基及-NZJ2 ;Z is N; ... is absent; and L is -N (R7) C (0) ... 17_ The method according to item i of the scope of patent application, wherein A is an aralkyl group, wherein the aryl group of the aralkyl group is benzene Group, which is substituted with 0, i, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, alkoxy'-membered nunuyl, thio, thio, chloro, chloro, Element, haloalkyl, haloalkyl, methylenedioxy, nitro, phenyl and -NZJ2; 85228 200404539 Ri係選自包括氫、燒基、氰基、_燒基、_素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R_4為氮， r3係選自包括氫與羥基； Z為N ; …為不存在； D 為-CH2 -，及 L 為-N(R7)C(0)·。 18. 根據申請專利範圍第1項之方法，其中 A為芳基； B為 ?2 Ά R5 . Ζ 為 CRb ; …為不存在，及 L 為-N(R7)C(0)-。 19. 根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、iS素、iS燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為 85228 -10- 20040453985228 200404539 Ri is selected from the group consisting of hydrogen, alkynyl, cyano, alkynyl, phenylene, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R_4 are nitrogen, and r3 is selected from the group including hydrogen and hydroxyl Z is N;… is absent; D is -CH2-, and L is -N (R7) C (0) ·. 18. The method according to item 1 of the scope of patent application, wherein A is aryl; B is? 2 Ά R5; Z is CRb; ... is absent, and L is -N (R7) C (0)-. 19. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl, alkyl, thio, thio, cyano, iS, iS, oxy, halo, methylenedioxy, nitro, phenyl, and -NZiZ2; B is 85228 -10- 200404539 心係選自包括氫、烷氧基、烷基、烷硫基、氰基、鹵 素、羥基、硝基、-ΝΖΘ2及（NZ3Z4)烷基； R2係選自包括氫、烷氧基、氰基、鹵素及羥基； ^係選自包括氫與羥基； R4與R5為氮， Z 為 CRb， Rb為鼠， —為不存在， D 為-CH2 -，及 L 為-N(R7)C(0)-。 20. 根據申請專利範圍第1項之方法，其中 A為芳基； B為 ?2 j XR r4. Z 為 CRB ; …為不存在；及 L 為-N(R7)C(0)-。 21. 根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 85228 -11 - 200404539 、燒基、燒硫基、爷基、氰基、鹵素、ii燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為The heart system is selected from the group consisting of hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, hydroxyl, nitro, -NZΘ2 and (NZ3Z4) alkyl; the R2 system is selected from including hydrogen, alkoxy, cyano , Halogen and hydroxyl; ^ is selected from the group consisting of hydrogen and hydroxyl; R4 and R5 are nitrogen, Z is CRb, Rb is murine,-is absent, D is -CH2-, and L is -N (R7) C (0 )-. 20. The method according to item 1 of the scope of patent application, wherein A is aryl; B is? 2 j XR r4. Z is CRB; ... is absent; and L is -N (R7) C (0)-. 21. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl 85228 -11-200404539, alkyl, thio, thio, cyano, cyano, halogen, ii, oxy, halo, methylenedioxy, nitro, phenyl, and- NZiZ2; B is Ri係選自包括氫、燒基、氰基、ii燒基、ii素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氫； 113係選自包括氫與羥基； Z 為 CR_b， Rb為氣， —為不存在， D 為-CH2 -，及 L 為-N(R7)C(0)·。 22. 根據申請專利範圍第1項之方法，其中 A為芳基； B為 5 Z 為 CRb， —為不存在，及 L 為-N(R7)C(0)- 〇 23. 根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -12- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、鹵素、鹵燒氧基、鹵院 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Ri is selected from the group consisting of hydrogen, alkyl, cyano, ii, alkyl, nitro, (NZ3Z4) alkyl, and (NZ3Z4) carbonyl; R2 and R4 are hydrogen; 113 is selected from the group consisting of hydrogen and hydroxyl; Z Is CR_b, Rb is gas,-is absent, D is -CH2-, and L is -N (R7) C (0) ·. 22. The method according to item 1 of the scope of patent application, wherein A is aryl; B is 5 Z is CRb,-is absent, and L is -N (R7) C (0)-〇23. According to the scope of patent application The method of item 1, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4, or 5 85228-12-200404539 substituents selected from the group consisting of alkenyl and alkane Oxy, alkoxycarbonyl, alkyl, thio, thio, cyano, halogen, halooxy, haloyl, methylenedioxy, nitro, phenyl, and -NZiZ2; X 為 N(R6)、Ο 或 S ; Y為N ; R2與R3為氮， Z 為 CRg， Rb為氮， …為不存在； D 為-CH2 -，及 L 為-N(R7)C(0)·。 24.根據申請專利範圍第1項之方法，其中 A為芳基； B為X is N (R6), 0 or S; Y is N; R2 and R3 are nitrogen, Z is CRg, Rb is nitrogen, ... is absent; D is -CH2-, and L is -N (R7) C ( 0) ·. 24. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z 為 CRg， …為不存在；及 L 為-N(R7)C(0)-。 25.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -13- 200404539 取代基取代，取代基選自包括婦基、烷氧基、烷氧羰基 、燒基、燒硫基、苄基、氰基、鹵素、燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及_NZi Z2 ; B為Z is CRg, ... is absent; and L is -N (R7) C (0)-. 25. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4, or 5 85228 -13- 200404539 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, alkyl, thio, benzyl, cyano, halogen, alkyl, halogen, methylenedioxy, nitro, phenyl, and _NZi Z2; B is Z 為 CRB ; Rb為氯； —為不存在， L 為-N(R7)C(0)-; D 為-CH2 -，及 R2、R3及化4為氯。 26.根據申請專利範圍第1項之方法，其中 A為芳基； B為Z is CRB; Rb is chlorine;-is absent, L is -N (R7) C (0)-; D is -CH2-, and R2, R3 and CH4 are chlorine. 26. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z 為 CRB ; …為不存在；及 L 為-N(R7)C(0)-。 27.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 85228 -14- 200404539 、燒基、燒硫基、苄基、氰基、鹵素、鹵燒氧基、鹵院 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為Z is CRB;… is absent; and L is -N (R7) C (0)-. 27. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl 85228 -14- 200404539, alkyl, thio, Benzyl, cyano, halogen, halooxy, haloalkyl, methylenedioxy, nitro, phenyl and- NZiZ2; B is Ri、R2、R3 及 R4 為鼠， Z 為 CRg， Rb為氯， —為不存在， D 為-CH2 -，及 L 為-N(R7)C(0)-。 28.根據申請專利範圍第1項之方法，其中 A為環烷基； B為Ri, R2, R3 and R4 are rats, Z is CRg, Rb is chlorine,-is absent, D is -CH2-, and L is -N (R7) C (0)-. 28. The method according to item 1 of the scope of patent application, wherein A is cycloalkyl; B is Z 為 CRb， …為不存在，及 L 為-N(R7)C(0)-。 29.根據申請專利範圍第1項之方法，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 基； B為 85228 -15- 200404539Z is CRb,… is absent, and L is -N (R7) C (0)-. 29. The method according to item 1 of the scope of patent application, wherein A is a cycloalkyl group, wherein the cycloalkyl group is selected from the group consisting of cyclohexyl group and gold steel alkyl group; B is 85228 -15-200404539 Ri係選自包括氫、燒基、氰基、齒燒基、鹵素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氮； r3係選自包括氫與羥基； Z 為 CRg， Rb為氮， …為不存在； D 為-CH2 -，及 L 為-N(R7)C(0)-。 30.根據申請專利範圍第1項之方法，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkyl, cyano, halo, halogen, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z is CRg, Rb is nitrogen, ... is absent; D is -CH2-, and L is -N (R7) C (0)-. 30. The method according to item 1 of the scope of patent application, wherein A is aryl; B is R5 · Z為C ; …為一個键結；及 L 為-N(R7)C(0)-。 31.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、：fe硫基、卞基、氣基、1¾素、鹵燒氧基、鹵燒 85228 -16- 200404539 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為 Rs ? 心係選自包括氫、烷氧基、烷基、烷硫基、氰基、鹵 素、羥基、硝基、-NZiZ2及(NZ3Z4)烷基； R2係選自包括氫、烷氧基、氰基、函素及羥基； R3係選自包括氫與羥基； R4與R5為氯， Z為C ; …為一個鍵結； D為-CH】-，及 L 為-N(R7)C(0)-。 32. 根據申請專利範圍第1項之方法，其中 A為芳基； B為 Ά Λ N R4. Z為C ; …為一個键結；及 L 為-N(R7)C(0)-。 33. 根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -17- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、宇基、氰基、鹵素、鹵燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;R5 · Z is C; ... is a bond; and L is -N (R7) C (0)-. 31. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkynyl: fethio, fluorenyl, carbamoyl, 1¾ element, halooxy, halo 85228 -16- 200404539, methylenedioxy, nitro, phenyl And -NZiZ2; B is Rs? The heart system is selected from the group consisting of hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, hydroxyl, nitro, -NZiZ2 and (NZ3Z4) alkyl; R2 is selected from Hydrogen, alkoxy, cyano, functional element and hydroxyl; R3 is selected from the group consisting of hydrogen and hydroxyl; R4 and R5 are chlorine, Z is C; ... is a bond; D is -CH]-, and L is- N (R7) C (0)-. 32. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Ά Λ N R4. Z is C; ... is a bond; and L is -N (R7) C (0)-. 33. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4 or 5 85228 -17- 200404539 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, uryl, cyano, halogen, halooxy, haloalkyl, methylenedioxy, nitro, phenyl, and- NZiZ2; Ri係選自包括氫、燒基、氰基、燒基、素、硝基 、（NZ3Z4)烷基及(NZ3Z4)羰基； R2與R4為氮； r3係選自包括氫與羥基； Z為C ; …為'^個键結； D 為-CH2-;及 L 為-N(R7)C(0)-。 34.根據申請專利範圍第1項之方法，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkyl, cyano, alkyl, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z is C ... are '^ bonds; D is -CH2-; and L is -N (R7) C (0)-. 34. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z為C ; …為一個键結； L 為-N(R7)C(0)·。 35.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -18- 200404539 取代基取代，取代基選自包括晞基、燒氧基、燒氧羰基 '烷基、烷硫基、苄基、氰基、画素、卣烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-ΝΖι Z〗’ B為 」R2 X 為 N(R6)、Ο 或 s ; Y為 C(R4); R2與r3為氫； R4係選自包括氮、燒*基及氯基； Z為c ; …為一個键結； D 為 _CH2-;及 L 為 _N(R7)C(0)_。 36·根據申請專利範圍第1項之方法，其中 A為壤基， B為 ， Z為C ; …為一個鍵結；及 L 為-N(R7)C(0)_ 〇 37·根據申請專利範圍第1項之方法，其中 A為環烷基’其中環烷基係選自包括環己基與金鋼烷 85228 -19- 200404539 基；Z is C;… is a bond; L is -N (R7) C (0) ·. 35. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4 or 5 85228 -18- 200404539 substituents Including fluorenyl, alkoxy, alkoxycarbonyl'alkyl, alkylthio, benzyl, cyano, pixel, fluorenyloxy, haloalkyl, methylenedioxy, nitro, phenyl, and- ΝZιZ "'B is" R2 X is N (R6), 0 or s; Y is C (R4); R2 and r3 are hydrogen; R4 is selected from the group consisting of nitrogen, alkyl and chloro; Z is c; … Is a bond; D is _CH2-; and L is _N (R7) C (0) _. 36. The method according to item 1 of the scope of patent application, wherein A is soil base, B is, Z is C; ... is a bond; and L is -N (R7) C (0) _ 〇37 · According to the patent application The method of the first item, wherein A is a cycloalkyl group, wherein the cycloalkyl group is selected from the group consisting of cyclohexyl and adamantane 85228-19-200404539; Ri係選自包括氫、燒基、氰基、鹵燒基、li素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氫； R3係選自包括氫與羥基； Z為C ; …為一個键結； D 為-CH2 -，及 L 為-N(R7)C(0)·。 38.根據申請專利範圍第1項之方法，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkynyl, cyano, haloalkyl, lidin, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are hydrogen; R3 is selected from the group consisting of hydrogen and hydroxyl; Z Is C;… is a bond; D is -CH2-, and L is -N (R7) C (0) ·. 38. The method according to item 1 of the claims, wherein A is aryl; B is Z為N ; …為不存在，及 L 為-C(0)N(R7)-〇 39.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 85228 -20- 200404539 、燒基、燒硫基、苄基、氰基、鹵素、ii燒氧基、鹵 基、，亞甲二氧基、硝基、苯基及-NZiZz ;Z is N;… is absent, and L is -C (0) N (R7) -〇39. According to the method in the scope of patent application No. 1, wherein A is aryl, wherein aryl is phenyl, and is 0 , 1, 2, 3, 4 or 5 substituents, the substituent is selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl 85228 -20-200404539, alkyl, thio, Benzyl, cyano, halogen , Ii alkoxy, halo, methylenedioxy, nitro, phenyl and -NZiZz; R5 · 鹵 參 Ri係選自包括氫、燒氧基、燒基、燒硫基、氰基、 素、羥基、硝基、-ΝΖΘ2及(NZ3Z4)烷基； R2係選自包括氫、烷氧基、氰基、鹵素及羥基； R3係選自包括氫與羥基； R4與R5為氯， Z為N ; …為不存在； D 為-CH2 -;及 L 為-C(0)N(R7)-。 40.根據申請專利範圍第1項之方法，其中 A為芳基； B為R5 · Halogen Ri is selected from the group consisting of hydrogen, alkoxy, thio, thio, cyano, cyano, hydroxy, nitro, -NZΘ2 and (NZ3Z4) alkyl; R2 is selected from the group consisting of hydrogen, alkoxy R3 is selected from the group consisting of hydrogen and hydroxyl; R4 and R5 are chlorine, Z is N; ... is absent; D is -CH2-; and L is -C (0) N (R7 )-. 40. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z為N ; …為不存在，及 ls_c(o)n(r7)_。 41.根據申請專利範圍第1項之方法，其中 85228 -21 - 200404539 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、宇基、氰基、_素、齒燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為Z is N;… is absent, and ls_c (o) n (r7) _. 41. The method according to item 1 of the scope of patent application, wherein 85228 -21-200404539 A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4 or 5 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, alkynyl, thiosulfanyl, uryl, cyano, hydrogen, sulfonyl, haloalkyl, methylenedioxy, nitro, phenyl and -NZiZ2; B is &amp;係選自包括氫、烷基、氰基、鹵烷基、iS素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氮， r3係選自包括氫與羥基； Z為N ; …為不存在； D 為-CH2 -，及 1^為_0(0)风117)-。 42.根據申請專利範圍第1項之方法，其中 A為芳基；&amp; is selected from the group consisting of hydrogen, alkyl, cyano, haloalkyl, iS, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen, and r3 is selected from the group consisting of hydrogen and hydroxyl; Z is N;… is absent; D is -CH2-, and 1 ^ is _0 (0) wind 117)-. 42. The method according to item 1 of the scope of patent application, wherein A is aryl; Z為N ; …為不存在；及 L 為-C(0)N(R7)-。 43.根據申請專利範圍第1項之方法，其中 85228 -22- 200404539 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、亨基、氰基、iS素、iS燒氧基、鹵燒* 基、亞甲二氧基、硝基、苯基及-NZi Z2 ;Z is N; ... is absent; and L is -C (0) N (R7)-. 43. The method according to item 1 of the scope of patent application, wherein 85228 -22-200404539 A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4 or 5 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, thio, thio, henyl, cyano, iS, iS, oxy, halo *, methylenedioxy, nitro, phenyl And -NZi Z2; R2、R3 及 R4 為·® i， Z為N ; —為不存在， D 為-CH2 -，及 L 為-C(0)N(R7)-。 44.根據申請專利範圍第1項之方法，其中 A為環烷基； B為R2, R3, and R4 are · ® i, Z is N;-is absent, D is -CH2-, and L is -C (0) N (R7)-. 44. The method according to item 1 of the claims, wherein A is cycloalkyl; B is Z為N ; …為不存在，及 L 為-C(0)N(R7)-。 45.根據申請專利範圍第1項之方法，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 基； B為 85228 -23- 200404539 Ri係選自包括氫、燒基、氰基、卣燒基、_素、硝基 、（NZ3Z4)烷基及(NZ3Z4)羰基； R2與R_4為氮； R3係選自包括氫與羥基； Z為N ; …為不存在， D 為-CH2 -，及 L 為-C(0)N(R7)-。 46. 根據申請專利範圍第1項之方法，其中 A為芳基； B為 ?2 r5 . Z 為 CR_b， …為不存在；及 L 為-C(0)N(R7)-。 47. 根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、窄基、氰基、鹵素、ii燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZJ2 ; 85228 -24- 200404539 B為 Ά R5 . &amp;係選自包括氫、烷氧基、烷基、烷硫基、氰基、鹵 素、羥基、硝基、-NZiZ2及(NZ3Z4)烷基； r2係選自包括氫、烷氧基、氰基、鹵素及羥基； r3係選自包括氫與羥基； R4與R5為氫； Z 為 CRg， Rb為氮， —為不存在， D 為-CH2-;及 L 為-C(0)N(R7)-。 48.根據申請專利範圍第1項之方法，其中 A為芳基； B為Z is N;… is absent, and L is -C (0) N (R7)-. 45. The method according to item 1 of the application, wherein A is a cycloalkyl group, wherein the cycloalkyl group is selected from the group consisting of cyclohexyl and gold steel alkyl groups; B is 85228 -23- 200404539 Ri is selected from the group consisting of hydrogen, R2 and R_4 are nitrogen; R3 is selected from the group consisting of hydrogen and hydroxyl; Z is N;… is absent, ，, ，, 卣, _, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; D is -CH2-, and L is -C (0) N (R7)-. 46. The method according to item 1 of the scope of patent application, wherein A is aryl; B is? 2 r5; Z is CR_b, ... is absent; and L is -C (0) N (R7)-. 47. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, thio, narrow, cyano, halogen, ii, oxy, halo, methylenedioxy, nitro, phenyl, and -NZJ2; 85228 -24 -200404539 B is Ά R5. &Amp; is selected from the group consisting of hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, hydroxy, nitro, -NZiZ2 and (NZ3Z4) alkyl; r2 is selected from the group consisting of Hydrogen, alkoxy, cyano, halogen and hydroxyl; r3 is selected from the group consisting of hydrogen and hydroxyl; R4 and R5 are hydrogen; Z is CRg, Rb is nitrogen,-is absent, D is -CH2-; and L is -C (0) N (R7)-. 48. The method according to item 1 of the claims, wherein A is aryl; B is ZCRb ； …為不存在；及 L 為-C(0)N(R7)-。 49.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -25- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、节基、氰基、南素、鹵燒*氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;ZCRb; ... is absent; and L is -C (0) N (R7)-. 49. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4 or 5 85228 -25- 200404539 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, alkynyl, thiosulfanyl, benzyl, cyano, sulfanil, halogenated * oxy, halogenated, methylenedioxy, nitro, phenyl And -NZiZ2; Ri係選自包括氫、烷基、氰基、齒烷基、iS素、硝基 、（NZ3Z4)烷基及(NZ3Z4)羰基； 112與114為氫； r3係選自包括氫與羥基； Z 為 CRB ; Rb為氮， …為不存在； D 為-CH2-;及 L 為-C(0)N(R7)-。 50.根據申請專利範圍第1項之方法，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkyl, cyano, haloalkyl, iS, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; 112 and 114 are hydrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z Is CRB; Rb is nitrogen, ... is absent; D is -CH2-; and L is -C (0) N (R7)-. 50. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z 為 CRg， 為不存在；及 L 為-C(0)N(R7)·。 51.根據申請專利範圍第1項之方法，其中 85228 -26- 200404539 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、节基、氰基、iS素、it燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-ΝΖΘ2 ;Z is CRg, is absent; and L is -C (0) N (R7). 51. The method according to item 1 of the scope of patent application, wherein 85228 -26- 200404539 A is an aryl group, wherein the aryl group is a phenyl group, and is substituted by 0, 1, 2, 3, 4 or 5 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, alkynyl, thiosulfanyl, benzyl, cyano, iS element, ityloxy, haloalkyl, methylenedioxy, nitro, phenyl, and -ΝZOΘ2; R2、R3及R4為鼠， Z 為 CRb， Rb為氯； —為不存在， D為-CH〗-，及 L 為-C(0)N(R7)-。 52.根據申請專利範圍第1項之方法，其中 A為芳基； B為R2, R3 and R4 are rats, Z is CRb, Rb is chlorine;-is absent, D is -CH?-, And L is -C (0) N (R7)-. 52. The method according to item 1 of the claims, wherein A is aryl; Z 為 CRB ; …為不存在；及 L 為-C(0)N(R7)-。 53.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -27- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、鹵素、ii烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZ! z2 ;Z is CRB; ... is absent; and L is -C (0) N (R7)-. 53. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4, or 5 85228 -27- 200404539 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halogen, iialkoxy, haloalkyl, methylenedioxy, nitro, phenyl, and- NZ! Z2; Ri、R2、R3 及 R4 為鼠， Z 為 CRB ; Rb為氮， —為不存在， D 為-CH2-;及 L 為-C(0)N(R7)-。 54.根據申請專利範圍第1項之方法，其中 A為環烷基； B為Ri, R2, R3 and R4 are rats, Z is CRB; Rb is nitrogen,-is absent, D is -CH2-; and L is -C (0) N (R7)-. 54. The method according to item 1 of the scope of patent application, wherein A is cycloalkyl; B is Z 為 CRg， …為不存在；及 L 為-C(0)N(R7)-。 55.根據申請專利範圍第1項之方法，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 基； 85228 -28- 200404539 B為Z is CRg, ... is absent; and L is -C (0) N (R7)-. 55. The method according to item 1 of the scope of patent application, wherein A is a cycloalkyl group, wherein the cycloalkyl system is selected from the group consisting of cyclohexyl and auranyl; 85228 -28- 200404539 B is V^N^R4. 5 Ri係選自包括氫、燒基、氰基、卣燒基、ii素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氮； r3係選自包括氫與羥基； Z 為 CRg， Rb為鼠， …為不存在， D 為-CH2-;及 L 為-C(0)N(R7)-。 56.根據申請專利範圍第1項之方法，其中 A為芳基； B為V ^ N ^ R4. 5 Ri is selected from the group consisting of hydrogen, alkynyl, cyano, sulfanyl, sulfanyl, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen; Including hydrogen and hydroxyl; Z is CRg, Rb is murine, ... is absent, D is -CH2-; and L is -C (0) N (R7)-. 56. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z為C ; —為· 個键結，及 L 為-C(0)N(R7)-。 57.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 85228 -29- 200404539 、烷基、烷硫基、苄基、氰基、鹵素、ii烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZi Z2 ; B為 r2Z is C; — is · bonds, and L is -C (0) N (R7)-. 57. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl 85228 -29- 200404539, alkyl, alkylthio, benzyl, cyano, halogen, iialkoxy, haloalkyl, methylenedioxy, nitro, phenyl and- NZi Z2; B is r2 Ri } R4 Ri係選自包括氫、烷氧基、烷基、烷硫基、氰基、鹵 素、羥基、硝基、-NZJ2及(NZ3Z4)烷基； R2係選自包括氫、烷氧基、氰基、ii素及羥基； R*3係選自包括氫與藉基； 114與115為氫； Z為C ; —為 個键結， D 為-CH2-;及 L 為-C(0)N(R7)-。 58.根據申請專利範圍第1項之方法，其中 A為芳基； B為Ri} R4 Ri is selected from the group consisting of hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, hydroxyl, nitro, -NZJ2 and (NZ3Z4) alkyl; R2 is selected from the group consisting of hydrogen, alkoxy , Cyano, ii, and hydroxyl; R * 3 is selected from the group consisting of hydrogen and a boring group; 114 and 115 are hydrogen; Z is C;-is a bond, D is -CH2-; and L is -C (0 ) N (R7)-. 58. The method according to item 1 of the claims, wherein A is aryl; B is Z為C ; 為一個键結；及 L 為-C(0)N(R7)-。 59.根據申請專利範圍第1項之方法，其中 85228 -30- 20040^539 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、麵基、fe硫基、卞基、氣基、由素、氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Z is C; is a bond; and L is -C (0) N (R7)-. 59. The method according to item 1 of the scope of patent application, wherein 85228 -30- 20040 ^ 539 A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents. The group is selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, sulfanyl, fethio, fluorenyl, oxo, sulfonyl, oxy, halo, methylenedioxy, nitro, phenyl, and -NZiZ2; &amp;係選自包括氫、烷基、氰基、鹵烷基、齒素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氫； r3係選自包括氫與羥基； Z為C ; …為'^個键結； D 為-CH2 -，及 L 為-C(0)N(R7)-。 60.根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為莕基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、燒硫基、苄基、氰基、iS素、i烷氧基、鹵烷 基、亞甲二氧基、硝基苯基及-NZiZ2 ;&amp; is selected from the group consisting of hydrogen, alkyl, cyano, haloalkyl, halide, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are hydrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z is C; ... is' ^ bonds; D is -CH2-, and L is -C (0) N (R7)-. 60. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a fluorenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, thiothio, benzyl, cyano, iS element, i alkoxy, haloalkyl, methylenedioxy, nitrophenyl and -NZiZ2; &amp;係選自包括氫、烷基、氰基、鹵烷基、鹵素、硝基 85228 -31 - 200404539 、（NZ3Z4)烷基及(NZ3Z4)羰基； R_2與R4為氮； r3係選自包括氳與羥基； Z為C ; …為一個键結； D 為-CH]-，及 L 為-C(0)N(R7)-。 61. 根據申請專利範圍第1項之方法，其中 A為芳基； B為 Z為C ; …為一個键結；及 L 為-C(0)N(R7)-。 62. 根據申請專利範圍第1項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、院硫基、爷基、氰基、鹵素、鹵燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為&amp; is selected from the group consisting of hydrogen, alkyl, cyano, haloalkyl, halogen, nitro 85228-31-200404539, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R_2 and R4 are nitrogen; r3 is selected from the group consisting of And hydroxyl; Z is C; ... is a bond; D is -CH]-, and L is -C (0) N (R7)-. 61. The method according to item 1 of the scope of patent application, wherein A is aryl; B is Z is C; ... is a bond; and L is -C (0) N (R7)-. 62. The method according to item 1 of the scope of patent application, wherein A is an aryl group, wherein the aryl group is a phenyl group, and is substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, thio, thio, cyano, halogen, halooxy, halo, methylenedioxy, nitro, phenyl, and -NZiZ2; B is R2與R3為氮， 85228 32- 200404539 X 為 N(R6)、0 或 s ; Y為N ; Z為c ; …為一個鍵結； D 為-CH2-;及 L 為-C(0)N(R7)-。 63·根據申請專利範圍第1項之方法，其中 A為環燒基； B為R2 and R3 are nitrogen, 85228 32- 200404539 X is N (R6), 0 or s; Y is N; Z is c; ... is a bond; D is -CH2-; and L is -C (0) N (R7)-. 63. The method according to item 1 of the scope of patent application, wherein A is cycloalkyl; B is …為一個鍵結；及 L 為-C(0)N(R7)· 〇 64·根據申請專利範圍第1項之方法，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 鲁 基；… Is a bond; and L is -C (0) N (R7) · 〇64 · The method according to item 1 of the scope of patent application, wherein A is cycloalkyl, wherein cycloalkyl is selected from the group consisting of Adamantine Ri係選自包括氫、烷基、氰基、_烷基、_素、硝基 、（NZJ4)燒基及(NZ3Z4)羰基； 心與I為氫； I係選自包括氫與羥基； 85228 -33- 200404539 …為一個鍵結； D 為-CH2 -;及 L 為-C(0)N(R7)-。 65·根據申請專利範圍第1項之方法’其中式（I)化合物係選自 包括 2-[4-(2-甲氧苯基）小六氫吡畊基]-N-(3-甲基苯基）乙醯胺； 2-[4-(2-氰基苯基）-1-ττ氮峨呼基]-N-(3-甲基苯基）乙酿胺； N-(3-甲基苯基）-2-[4-(2-痛淀基）-1-六氫峨喷基]乙酸胺； N-(3-甲基苯基）-2-[4-(2^比淀基）小六氫p比呼基]乙酸胺； 2·[4-(3•氰基-2-P比淀基）-1-六氫外1： p井基]甲基苯基）乙醯 胺； Ν-(3-甲基苯基）-2-[4-(2-甲基苯基）小六氫p比ρ井基]乙酸胺； Ν-(3-甲基苯基）-2-[4-(2-硝基苯基）-1-六氫吡畊基]乙醯胺； 2_[4-(3•氣基-2-p比淀基）-1-ττ戴^比呼基]-N-(3-确基苯基）乙酸 胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡啡基]-N-|&gt;(三氟甲基）苯 基]乙醯胺； N-(3-甲基苯基）-2-(4-苯基-1-六氫吡畊基）乙醯胺； N-(3-氣基苯基）-2-[4-(3-氣基-2-ρ比淀基）-1-ττ氮峨p井基]乙酉蠢 胺‘； N-(4-溴基-3-甲基苯基&gt;2-[4-(2-氰基苯基）-1-六氫吡畊基]乙 醯胺； 2-[4-(2-氰基苯基）小六氫吡畊基]-N-苯基乙醯胺； -34- S47 85228 200404539 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-苯基乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(4-氟苯基）乙醯胺； 2-[4_(3_氰基I吡啶基）小六氫吡啡基]-N-(3,5_二甲基苯基） 乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(2,3-二甲基苯基） 乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡啡基]-N-(2-甲基苯基）乙醯 胺； · 2-[4-(3-氰基-2-吡啶基）小六氫吡p井基]-N-(2,5-二甲基苯基） 乙醯胺； N-(3-氯苯基）-2-[4-(3-氰基-2-吡啶基&gt;1—六氫吡畊基]乙醯胺； N-(3-氯基-4-氟苯基）-2-[4-(3-氣基-2-峨淀基）-ΐ·六氫峨p井基] 乙醯胺； 2-[4-(3·氰基-2·吡啶基）-1-六氫吡畊基]-N-(3,4,5-三甲氧基苯 基）乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-[4-氟基-3-(三氟甲 _ 基）苯基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡呼基]-Ν-[3-氟基-5-(三氟甲 基）苯基]乙醯胺； 2-[4_(3-氰基_2_吡啶基）小六氫吡畊基]_N-[2-氟基-5-(三氟甲 基）苯基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-[2-氟基各(三氟甲 基）苯基]乙醯胺； 2-[4-(3-氰基-2-p比淀基）小六氫吡畊基]-N-(4-氟基各甲基苯 85228 -35- 200404539 基）乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-(2-氟苯基）乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-(2-甲氧苯基）乙醯 胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-(2-硝基苯基）乙醯 胺； 2·[4-(3-氯基-2-ρ比淀基）小六氮p比喷基]-Ν-[2-(二氟甲基）苯 基]乙醯胺； Ν-苯基-2-[4-(2-吡啶基）小六氫吡畊基]乙醯胺； Ν·(3·甲基苯基）-2-[4-(1，3-ρ塞吐-2-基氯被ρ井基]乙驗胺； 2-[4-(3-夜基-2-P比淀基）-1·ά氮说p井基]-N-(4-甲基苯基）乙酸 胺； 2-[4-(2-甲氧苯基）小六氫吡啶基]-N-(3-甲基苯基）乙醯胺； N-(3-甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； 2-[4-(2-氟苯基）小六氫吡啶基]-N-(3-甲基苯基）乙醯胺； N-(3-甲基苯基）-2-[4-(2_甲基苯基）小六氫吡啶基]乙醯胺； 2-[4-(3-氟苯基）-1-六氫吡啶基]-N-(3-甲基苯基）乙醯胺； N-(3_甲基苯基）-2-[4-(6-酮基-1(6H)-嗒畊基）小六氫吡啶基] 乙醯胺； &gt; N-(2,6-二甲基苯基）-2-[4-(2-p塞吩基）-1-ττ氯外1：淀基]乙醒胺； Ν-(2,5-&gt;一甲基苯基）-2-[4-(2-ρ塞吩基）-1-ττ氫ρ比淀基]乙酸胺； Ν-(2-甲基苯基）-2-[4-(2-遠吩基）小六氫吡啶基]乙醯胺； Ν-(3-氯基-4-氟苯基）-2-[4-(2-ρ塞吩基）-1-六氫p比淀基]乙酸胺； N-(4-溴苯基）-2-[4-(24啶基&gt;1-六氫吡啶基]乙醯胺； 85228 -36- 200404539 N-(2,6-二甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2-硝基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(3-硝基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； N-(2,4-二氟苯基）-2-[4-(2-吡啶基）-1-六氫吡碇基]乙醯胺； N-(2,5-二甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2-甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(4-甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡啶基]-N-[3-(三氟甲基）苯基]乙醯 _ 胺； 4-({[4-(2-吡啶基)-1-六氫吡啶基]乙醯基}胺基）苯甲酸乙酯； N-(3-氯基-4-甲基苯基&gt;2-[4-(2-吡啶基&gt;1-六氫吡啶基]乙醯 胺； N-(2-氰基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； N-(3-氯苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； 2_[4-(3-氰基-2-吡啶基）-1-六氫吡啶基]-N-(3-甲基苯基）乙醯 胺； · Ν-(3·甲基苯基）-2-(4-苯基-3,6-二氫-1(2H)-吡啶基）乙醯胺； 2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）-N-(3-甲基苯基）乙醯胺； 2-(3’，6f-二氫 _2,4’-聯吡啶-Γ(2Ή)-基）-N-(2,6-二甲基苯基）乙醯 胺； 2-(3f二氫-2,4’-聯吡啶-1’(2Ή)-基）-N-(2-硝基苯基）乙醯胺； 2-(3’，6f-二氫-2,4’-聯吡啶-1’(2Ή)-基）-N-(3-硝基苯基）乙醯胺； 2_(3’，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基）-N-(4-氟苯基）乙醯胺； N-(2,4-二氟苯基)-2-(3’，6’_二氫-2,4’-聯吡啶-1’(2Ή)·基）乙醯胺； 85228 -37- 200404539 二-⑺万-二氫-2,4’·聯吡啶-Γ(2Ή)_基）-Ν-(2,5·二甲基苯基）乙醯 胺； 2-(3’，6’-二氫-2,4’_聯吡啶-Γ(2Ή)-基）-N-(2-甲基苯基）乙醯胺； N-環己基-2-(3’，6，-二氫·2,4，_聯吡啶_Γ(2Ή)_基）乙醯胺； 2-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）_Ν-(4-甲基苯基）乙醯胺； 2-(3f，6’_二氫-2,4’_聯吡啶_1’(2Ή)_基）_Ν-[3-(三氟甲基）苯基]乙 醯胺； 4-[(3’，6f-二氫-2,4f-聯吡啶-1’(2Ή)-基乙醯基）胺基]苯甲酸乙 · 酯； Ν_[2-氯基-5-(三氟甲基）苯基]-2-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)- 基）乙醯胺； Ν_(3_氯基-4_甲基苯基）-2-(3f，6’-二氩-2,4，-聯吡啶-Γ(2Ή)-基）乙 醯胺； Ν-(2-氰基苯基）·2-(3\6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； Ν-(3-氯苯基）-2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)·基）乙醯胺； Ν-(3-氯基冰氟苯基）-2-(3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯 籲 胺； 2_(3f，6’_二氫·2,4’·聯吡啶·Γ(2Ή)_基）-Ν-[4-(三氟甲氧基）苯基] 乙醯胺； 2-(3’，6’_二氫-2,聯吡啶-1’(2Ή)_基）-Ν_[2-(三氟甲基）苯基]乙 疏胺； Ν-(4-氯苯基）-2-(3’，6’-二氳-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； Ν-(2,3-二氣苯基)-2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）乙醯胺； Ν-(3,5_二氯苯基)-2-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）乙醯胺； 85228 -38- 200404539 2-(3’，6’-二氫Ά聯吡啶_Γ(2Ή)-基）-N-(4_氟基-2-甲基苯基）乙 醯胺； N-(4-氣笨基）-2-[4-(2-ρ比淀基）-1-六鼠峨淀基]乙驗胺； Ν-(3,5-二氯苯基）-2_[4-(2-ρ比淀基）-1-ττ氯卩比淀基]乙醒胺； Ν-(2,3-二氯苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； 2-[4-(2-吡啶基）小六氫吡啶基]-N-[2-(三氟甲基）苯基]乙醯 胺； N-(3-氯基-4-氣苯基)-2-[4-(2-p比淀基）-1-ττ氣ρ比淀基]乙酿胺； 2- [4-(2-吡啶基）-1-六氫吡啶基]-Ν-[4-(三氟甲氧基）苯基]乙 醯胺； Ν-環己基-2-(3’，4’，5’，6’-四氫-2Ή-[2,4’]聯吡啶基-1’-基）乙醯胺； Ν-{[4-(2-氰基苯基）小六氫吡畊基]甲基}-3-甲基苯甲醯胺； 3- 甲基-Ν-{[4-(2·ρ密淀基）-1-ττ氮ρ比啡基]甲基}苯甲酸胺； 3-甲基-Ν-{[4-(2-吡啶基）_1_六氫吡畊基]甲基}苯甲醯胺； 3-甲基-Ν-[(4-苯基-1·六氫吡畊基）甲基]苯甲醯胺； Ν-{[4-(2-甲氧苯基）-1-六氫吡畊基]甲基}-3-甲基苯甲醯胺；_ N-{[4-(2-氰基苯基）小六氫吡畊基]甲基}-2-甲基苯甲醯胺； N-{[4-(2-氣基苯基）-1-ττ氮吨p井基]甲基}-4-甲基苯甲酸胺； N-{[4-(3-氰基-2-吡啶基）小六氫吡畊基]甲基}-3-甲基苯甲 醯胺； N_{[4-(3-氣基苯基氫外I：啡基]甲基}-3-甲基苯甲酸胺； N-{[4-(3-氣基苯基氯批p井基]甲基}-2-甲基苯甲酿胺； N-{[4-(3-氣基-2-ρ比淀基氣井基]甲基}苯甲酿胺； N-{[4-(3-氣基-2-p比淀基）-1-ττ氮p比喷基]甲基}-4-甲基苯甲 85228 -39- 200404539 醯胺； N-{[4-(3-氯基-2-p比淀基氯峨p井基]甲基}-2-甲基苯甲 醯胺； N-{[4-(2-吡啶基&gt;1-六氫吡畊基]甲基}苯甲醯胺； N-{[4-(2-氯苯基）-1-六氬吡畊基]甲基}苯甲醯胺； 3- 氯-N-{[4-(2-氰基苯基）-1-六氫吡畊基]甲基}苯甲醯胺； 4- 氯-N-{[4-(2-甲氧苯基）-1-六氫吡啡基]甲基}苯甲醯胺； 2- 氣-N-{[4-(3-氰基-2-吡啶基）小六氫吡畊基]甲基}苯甲醯 鲁 胺； N-{[4-(3-氰基-2-吡啶基）-1-六氫吡畊基]甲基卜2-(三氟甲基） 苯甲醯胺； N-{[4-(2-氰基苯基）小六氫吡畊基]甲基}苯甲醯胺； Ν-{[4-(2-甲氧苯基）小六氮吡啶基]甲基}-3-甲基苯甲醯胺； 3- 甲基-Ν-{[4-(2-吡啶基）-1-六氫吡啶基]甲基}苯甲醯胺； 3-甲基-N-[(4-苯基-3,6-二氫-1(2H)-吡啶基）甲基]苯甲醯胺； N-(3’，6f-二氫-2,聯吡啶·1’(2Ή)_基甲基）各甲基苯甲醯胺； ® Ν-(3’，6’·二氫-2,4，·聯吡啶-Γ(2Ή)-基甲基）-3-甲氧基苯甲醯胺； N-(3f，6f-二氫-2,4’-聯吡啶-ΙβΉ)·基甲基）-3•氟基苯甲醯胺； Ν-(3’，6’-二氫_2,4’_聯吡啶-Γ(2Ή)-基甲基）-3,5-二氟苯甲醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-3-吡啶基乙醯胺； 2-(1-{2-[(3_甲基苯基）胺基]_2_酮基乙基}六氫吡啶-4-基）吡 4足Ν-氧化物； Ν-2-金鋼燒基-2-[4-(3•氰基-2-外1:淀基）_1_六氫峨啡基]乙酿 胺； SSJ 85228 -40- 200404539 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]環己基乙醯胺； 2-[4-(3-氰基-2-吡啶基&gt;1-六氫吡畊基]-N-5,6,7,8-四氫-1-莕基 乙醯胺； 2- (3’，6’-二氫-2,4’-聯吡啶_1’(2Ή)-基）-N-(4-氟基-2-甲基苯基）乙 醯胺； N-{[4-(2-峨淀基）-1-六氫p比淀基]甲基}-3-(三氟甲基）苯甲酸 胺； 3,5-二甲氧基-N-{[4-(2-p比咬基）-1-六氫P比淀基]甲基}苯甲酿 ❿ 胺； N-{[4-(2-峨淀基）-1-六氫p比淀基]甲基}環己燒叛醯胺； 3,4-二氟-N-{[4-(2^比啶基）小六氫吡啶基]甲基}苯甲醯胺； 3- 鼠-Ν-{[4-(2-ρ比淀基）-1_六氮p比咬基]甲基}苯〒S盈胺； 2,3_二甲基-Ν-{[4-(2-ρ比淀基)小六氫外井基]甲基}苯甲酸胺； N-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）-3-(三氟甲基）苯甲 醯胺； 3-氯-N-(3’，6，_二氫-2,4，-聯吡啶-1，(2Ή)-基甲基）苯T醯胺； _ Ν-(3’，6’-二氫-2,聯吡啶·1’(2Ή)_基甲基）環己烷羧醯胺； Ν_(3’，6’-二氫_2,4f-聯吡啶-1’(2Ή)_基甲基）-3,4-二氟苯甲醯胺； N_(3f，6f-二氫-2,4’·聯吡啶-1’(2Ή)-基甲基）-3,5-二甲氧基苯甲 醯胺； Ν-(3·甲基苯基）-2-(4-苯基-1-六氫υ比淀基）乙酿胺； 2-(3\6’-二氫-2,聯吡啶-i’(2，H)-基）-N-(3-硝基苯基）乙醯胺； N-1-金鋼烷基-2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]乙醯 胺； 85228 -41- 200404539 3-甲基-N-{[2-甲基-4-(2-p比淀基）-1-六氫？比p井基]甲基}苯甲 醯胺； N-(3-甲基苯基）-2-[2-甲基_4-(2·^比淀基）-1-六氫p比呼基]乙醯 胺； 3,5_二甲基-N-{[4-(2-峨淀基）小六氫外1：淀基]甲基}苯甲酸胺； N-(3’，6f-二氫-2,4’-聯吡啶-1’(2Ή)_基甲基）-3,5-二甲基苯甲醯 胺； 3-甲基-Ν-[(3-甲基-3f，6f·二氫-2,4’-聯吡啶-1’(2Ή)_基）甲基]苯 φ 甲醯胺； Ν-[(3-氰基-3’，6f-二氫-2,4，-聯吡啶_1，(2Ή)_基）甲基]-3-甲基苯 甲醯胺； Ν-(2?6--一 甲基冬基）_2-(3-甲基-3’，6’-二氮·2,4’_聯 口比淀-l’(2’H)_ 基）乙醯胺； N-(4-氟苯基)-2-(3_甲基·3’，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯 胺； Ν-(2,4·二氟苯基）_2_(3·甲基 _3，，6’-二氫 _2,4’-聯吡啶·ΐ’(2，Η)_基）籲 乙醯胺； 2-(3-甲基-3^6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）-Ν-(2-甲基苯基）乙 醯胺； 2-(3-甲基二氫-2,聯吡啶-1’(2Ή)_基）-Ν-[3-(三氟甲基） 苯基]乙醯胺； Ν-(3-氯基-4-氟苯基）-2-(3-甲基 _3，，6，_二氫-2,4，-聯吡啶-1，(2Ή)- 基）乙醯胺； 2-(3-甲基-3f，6’-二氫-2,4’-聯吡啶_Γ(2Ή)_基）-Ν_[4·(三氟甲氧基） 85228 -42- 200404539 苯基]乙醯胺； 2-(3-甲基 _3’，6’-二氳 _2,4，_聯吡啶]，(2Ή)·基）_N-[2_(三氟甲基） 苯基]乙醯胺； N-(2,3-二氯苯基 &gt;2_(3-甲基-3’，6，-二氫-2,4，-聯吡啶-Γ(2Ή)-基） 乙醯胺； 2-(3-曱基_3’，6匕二氫_2,4，·聯吡啶-1，(2Ή)-基）-Ν·[4-(三氟甲基） 苯基]乙醯胺； 2-[4-(3-氰基-2-嘧吩基）-3,6-二氫-1(2Η)-吡啶基]-Ν-(3-甲基苯 _ 基）乙醯胺； 2-(3-氰基-3’，6’-二氫-2,4f-聯吡啶-Γ(2Ή)-基）-Ν-(2,6-二甲基苯 基）乙醯胺； 2_(3_氯基-3’，6’-二氨_2,4’_聯ρ比淀-1’(2Ή)-基）-Ν-(4_氣苯基）乙酿 胺； 2-(3-氰基-3’，6’-二氫-2,4f-聯吡啶-1’(2Ή)-基）-Ν-(2,4-二氟苯基） 乙醯胺； 2-(3•氰基_3’，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-(2_甲基苯基）乙 ® 醯胺； 2-(3-氰基-3’，6’-二氫-2,4’-聯吡啶-1’(2坶-基：^-[3-(三氟甲基） 苯基]乙醯胺； 2-(3-氰基-3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-[4-(三氟甲氧基） 苯基]乙醯胺； 2-(3-氰基-3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-[2-(三氟甲基） 苯基]乙醯胺； 2-(3-氰基-3’，6’-二氫-2,4f-聯吡啶-1’(2Ή)-基）-Ν-(2,3-二氯苯基） 85228 -43- 200404539 乙醯胺； 3-甲基-N-{[4-(6-酮基-1(6H)-塔畊基）-1-六氫吡啶基]甲基}苯 甲醯胺； N-(3’，6f-二氫_2,聯吡啶-Γ(2Ή)-基甲基）-1-金剛烷羧醯胺； 3-甲基_Ν-{[4-(1，3-噻唑-2-基）·3,6-二氫-1(2H)4啶基]甲基}苯 甲醯胺； 2-[4-(3-氰基-2-吡啶基）-1-六氫吡畊基]-N-l，2,3,4-四氫-l-莕基 乙醯胺； 2-[4-(3-氰基-2_吡啶基）小六氫吡畊基]-N-[(1S)-1，2,3,4-四氫_1_ 蓁基]乙醯:胺； 2-[4-(3-氰基_2-p比淀基）小六氫p比呼基]_N-[(1R)-1，2,3,4-四氫小 萘基]乙驢胺； N-(2,6-二乙基苯基）-2-[4-(2-ρ比淀基）-1-六氫p比淀基]乙醯胺； 2-[4-(2^比淀基）-1-ττ氮π比淀基]-N-(2,4,6-三氟^苯基）乙酿胺； N-(4-氯基-2,6-二甲基苯基）-2-[4-(2-外1：淀基）-1-六氫p比淀基] 乙驢胺； 鲁 2-[4-(2-p比喊基）-1-ττ氮？比淀基]-N-(2,4,6-三氯苯基）乙酸胺； N-(2,6-二乙基苯基）-2-(3’，6’-二氫-2，^聯吡啶-Γ(2Ή)·基）乙醯 胺； 2_(3*，6匕二氫-2,4’·聯外1:淀-Γ(2Ή)-基）-Ν·(2,4,6·三氟苯基）乙醯 胺； Ν-(4-氯基-2,6-二甲基苯基）_2-(3’，6’-二氫-2,4’-聯吡啶 _1’(2Ή)_ 基）乙醯胺； 2-(3’，6’-二氫-2,4’_聯吡啶-Γ(2Ή)-基）-Ν-(2,4,6·三氯苯基）乙醯 85228 -44- 200404539 胺； N-{[4-(2-外(：啶基）小六氫吡畊基]甲基}各(三氟甲基）笨甲醯 胺； 3,5-二甲氧基-N-{[4-(24啶基）小六氫吡畊基]甲基}苯甲醯 胺； N-{[4-(2-峨啶基）-1-六氫吡畊基]甲基}環己烷羧醯胺； Ν-(2,6·二甲基苯基）-2-[4-(2-吡啶基H-六氫吡畊基]乙醯胺； Ν-(4-氟苯基）-2-[4-(2-吡啶基）小六氫吡畊基]乙醯胺； Ν-(2,4-二氟苯基）-2-[4-(2-外1：淀基）-1_六氫外t畊基]乙醯胺； N-(2-甲基苯基）-2-[4-(2巧比淀基）小六氫外t畊基]乙醯胺； 2-[4-(2-吡啶基）小六氫吡畊基]-N-[3-(三氟甲基）苯基]乙醯 胺； N-(3-氯苯基）-2-[4-(2-ρ比淀基鼠批p井基]乙酸胺； N-卞基·2-[4·(2-ρ比淀基鼠卩比p井基]乙i盈胺； 2-[4-(2-吡啶基）-1-六氫吡畊基]-Ν-[4-(三氟甲氧基）苯基]乙 醯胺； 2-[4-(2-吡啶基）小六氫吡畊基]-Ν-[2-(三氟甲基）苯基]乙醯 胺； Ν-(4-氣苯基）-2-[4-(2·ρ比淀基）-1-六氮ρ比啡基]乙醒胺； Ν-(2,3-二氯苯基）_2-[4-(2-吡啶基）-1·六氫ρ比啡基]乙醯胺； Ν-(3,4-二氯苯基）-2_[4_(2-卩比淀基）-1-ττ氮卩比啡基]乙酸胺； 2- [4-(2-吡啶基）小六氫吡畊基]-Ν-[4-(三氟甲基）苯基]乙醯 胺； 3- 氯-Ν-{[4-(2-吡啶基）小六氫吡畊基]甲基}苯甲醯胺；Ri is selected from the group consisting of hydrogen, alkyl, cyano, alkyl, nitro, (NZJ4) alkyl and (NZ3Z4) carbonyl; heart and I are hydrogen; I is selected from the group consisting of hydrogen and hydroxyl; 85228 -33- 200404539… is a bond; D is -CH2-; and L is -C (0) N (R7)-. 65. The method according to item 1 of the scope of the patent application, wherein the compound of formula (I) is selected from the group consisting of 2- [4- (2-methoxyphenyl) hexahydropyridyl] -N- (3-methyl Phenyl) acetamidamine; 2- [4- (2-cyanophenyl) -1-ττazetidinyl] -N- (3-methylphenyl) ethynamine; N- (3-methyl Phenyl) -2- [4- (2-Anodonyl) -1-hexahydroepentyl] amine; N- (3-methylphenyl) -2- [4- (2 ^ ) Small hexahydro p-pyridyl] amine acetate; 2 · [4- (3 • cyano-2-P-pyridyl) -1-hexahydroex 1: p-pyridyl] methylphenyl) acetamidine Amine; Ν- (3-methylphenyl) -2- [4- (2-methylphenyl) small hexahydro p ratio ρ sylyl] amine acetate; Ν- (3-methylphenyl) -2 -[4- (2-nitrophenyl) -1-hexahydropyridyl] acetamidine; 2_ [4- (3 • amino-2-p than yodoyl) -1-ττDa ^ bihu Group] -N- (3-Cerylphenyl) acetamide; 2- [4- (3-cyano-2-pyridyl) small hexahydropyridinyl] -N- | &gt; (trifluoromethyl ) Phenyl] acetamidine; N- (3-methylphenyl) -2- (4-phenyl-1-hexahydropyridyl) acetamidine; N- (3-aminophenyl)- 2- [4- (3-Gasyl-2-p ratio ytyl) -1-ττnitropyridyl] acetamidine '; N- (4-bromo-3-methylbenzene &Gt; 2- [4- (2-cyanophenyl) -1-hexahydropyridyl] ethenylamine; 2- [4- (2-cyanophenyl) pyrohexapyridyl]- N-phenylacetamidamine; -34- S47 85228 200404539 2- [4- (3-cyano-2-pyridyl) pyrhotyl] -N-phenylacetamidamine; 2- [4 -(3-cyano-2-pyridyl) pyrihydropyridyl] -N- (4-fluorophenyl) acetamidamine; 2- [4_ (3_cyanoIpyridyl) pyrohexapy Phynyl] -N- (3,5-dimethylphenyl) acetamidamine; 2- [4- (3-cyano-2-pyridyl) hexahydropyridyl] -N- (2, 3-dimethylphenyl) acetamidine; 2- [4- (3-cyano-2-pyridyl) pyrhexahydropyridinyl] -N- (2-methylphenyl) acetamidine; · 2- [4- (3-cyano-2-pyridyl) hexahydropyridyl] -N- (2,5-dimethylphenyl) acetamidine; N- (3-chlorobenzene ) -2- [4- (3-cyano-2-pyridyl) &gt; 1-hexahydropyridyl] acetamidine; N- (3-chloro-4-fluorophenyl) -2- [ 4- (3-Gasyl-2-gadolide) -pyridine · hexahydropyridyl] acetamidine; 2- [4- (3 · cyano-2 · pyridyl) -1-hexahydropyridine [Ploughyl] -N- (3,4,5-trimethoxyphenyl) acetamidamine; 2- [4- (3-cyano-2-pyridyl) pyrrolidine] -N- [ 4-fluoro-3- ( Trifluoromethyl-phenyl) phenyl] ethanamine; 2- [4- (3-cyano-2-pyridyl) microhexahydropyridyl] -N- [3-fluoroyl-5- (trifluoro Methyl) phenyl] acetamidamine; 2- [4_ (3-cyano_2_pyridyl) small hexahydropyridyl] _N- [2-fluoroyl-5- (trifluoromethyl) phenyl ] Acetylamine; 2- [4- (3-cyano-2-pyridyl) pyrihydropyridyl] -N- [2-fluoroyl (trifluoromethyl) phenyl] acetamidamine; 2- [4- (3-cyano-2-p than yodoyl) hexahydropyridyl] -N- (4-fluoromethylmethylbenzene 85228 -35- 200404539 group) acetamide; 2- [4- (3-cyano-2-pyridyl) pyrihydropyridyl] -N- (2-fluorophenyl) acetamidinyl; 2- [4- (3-cyano-2-pyridyl) ) Hexahydropyridyl] -N- (2-methoxyphenyl) acetamidamine; 2- [4- (3-cyano-2-pyridyl) pyrohexanyl] -N- ( 2-nitrophenyl) acetamide; 2 · [4- (3-chloroyl-2-ρ is less than ydoyl) hexanitro p-pyridyl] -N- [2- (difluoromethyl) benzene Propyl] ethenylamine; Ν-phenyl-2- [4- (2-pyridyl) pyroxypyridyl] ethenylamine; Ν · (3 · methylphenyl) -2- [4- ( 1,3-ρceto-2-yl chloride is ρ well-based] ethyl test amine; 2- [4- (3-night-based 2-P than Yodo-based) -1 · nitrogen said p-well-based ] -N- (4-methylphenyl) amine; 2- [4- (2-methoxyphenyl) hexahexapyridyl] -N- (3-methylphenyl) acetamide; N -(3-methylphenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; 2- [4- (2-fluorophenyl) petit hexahydropyridyl ] -N- (3-methylphenyl) acetamidamine; N- (3-methylphenyl) -2- [4- (2-methylphenyl) small hexahydropyridyl] acetamidamine; 2- [4- (3-fluorophenyl) -1-hexahydropyridyl] -N- (3-methylphenyl) acetamide; N- (3-methylphenyl) -2- [4 -(6-keto-1 (6H) -dalophenyl) pyrhexahydropyridyl] acetamidine; &gt; N- (2,6-dimethylphenyl) -2- [4- (2- p-Cephenyl) -1-ττchloroex1: ytyl] ethoxyamine; N- (2,5- &gt; monomethylphenyl) -2- [4- (2-p-cephenyl)- 1-ττ hydrogen ρ than yodoyl] acetic acid; Ν- (2-methylphenyl) -2- [4- (2-telephenyl) small hexahydropyridyl] acetamidine; Ν- (3- Chloro-4-fluorophenyl) -2- [4- (2-ρ sephenyl) -1-hexahydro p-pyridyl] amine; N- (4-bromophenyl) -2- [4 -(24pyridyl &gt; 1-hexahydropyridyl] acetamidine; 85228 -36- 200404539 N- (2,6-dimethylphenyl) -2- [4- (2-pyridyl) -1 -Hexahydropyridyl] acetamidine ; N- (2-nitrophenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; N- (3-nitrophenyl) -2- [4 -(2-pyridyl) small hexahydropyridyl] acetamidine; N- (2,4-difluorophenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] Acetylamine; N- (2,5-dimethylphenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidamine; N- (2-methylphenyl ) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidinium; N- (4-methylphenyl) -2- [4- (2-pyridyl) minor hexahydro Pyridyl] acetamidine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- [3- (trifluoromethyl) phenyl] ethyridamine; 4-({ [4- (2-Pyridyl) -1-hexahydropyridyl] ethylfluorenyl} amino) benzoic acid ethyl ester; N- (3-chloro-4-methylphenyl) &gt; 2- [4- (2-Pyridyl) &gt; 1-hexahydropyridyl] acetamidine; N- (2-cyanophenyl) -2- [4- (2-pyridyl) small hexahydropyridyl] acetamidamine; N- (3-chlorophenyl) -2- [4- (2-pyridyl) small hexahydropyridyl] ethanamine; 2_ [4- (3-cyano-2-pyridyl) -1-hexa Hydropyridyl] -N- (3-methylphenyl) acetamidine; · Ν- (3 · methylphenyl) -2- (4-phenyl-3,6-dihydro-1 (2H) -Pyridyl Acetamide; 2- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -yl) -N- (3-methylphenyl) acetamide; 2- ( 3 ', 6f-dihydro_2,4'-bipyridine-Γ (2Ή) -yl) -N- (2,6-dimethylphenyl) acetamide; 2- (3f dihydro-2, 4'-bipyridine-1 '(2Ή) -yl) -N- (2-nitrophenyl) acetamidamine; 2- (3', 6f-dihydro-2,4'-bipyridine-1 ' (2Ή) -yl) -N- (3-nitrophenyl) acetamidamine; 2- (3 ', 6'_dihydro-2,4'-bipyridyl-Γ (2Ή) -yl) -N- (4-fluorophenyl) acetamide; N- (2,4-difluorophenyl) -2- (3 ', 6'_dihydro-2,4'-bipyridine-1' (2Ή) · Group) Ethylamine; 85228 -37- 200404539 Di-fluorene-dihydro-2,4 '· bipyridine-Γ (2Ή) -yl) -N- (2,5 · dimethylphenyl) acetone Amine; 2- (3 ', 6'-dihydro-2,4'_bipyridine-Γ (2Ή) -yl) -N- (2-methylphenyl) acetamidine; N-cyclohexyl-2 -(3 ', 6, -dihydro · 2,4, _bipyridine_Γ (2Ή) _yl) acetamide; 2- (3', 6'-dihydro-2,4'-bipyridine- Γ (2Ή) -yl) _N- (4-methylphenyl) acetamide; 2- (3f, 6'_dihydro-2,4'_bipyridine_1 '(2Ή) _yl) _Ν- [3- (trifluoromethyl) phenyl] Amidoamine; 4-[(3 ', 6f-dihydro-2,4f-bipyridine-1' (2Ή) -ylacetamido) amino] benzoic acid ethyl ester; Ν_ [2-chloro-5 -(Trifluoromethyl) phenyl] -2- (3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; Ν_ (3_chloro-4 _Methylphenyl) -2- (3f, 6'-diargon-2,4, -bipyridine-Γ (2Ή) -yl) acetamide; Ν- (2-cyanophenyl) · 2- (3 \ 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; Ν- (3-chlorophenyl) -2- (3 ', 6'-dihydro- 2,4'-bipyridine-1 '(2Ή) · yl) acetamide; Ν- (3-chlorobenzylfluorophenyl) -2- (3f, 6'-dihydro-2,4'-linked Pyridine-Γ (2Ή) -yl) ethoxyamine; 2_ (3f, 6'_dihydro · 2,4 '· bipyridine · Γ (2Ή) _yl) -N- [4- (trifluoromethoxy (Phenyl) phenyl] acetamidinium; 2- (3 ', 6'_dihydro-2, bipyridine-1' (2Ή) _yl) -N_ [2- (trifluoromethyl) phenyl] ethene Amine; N- (4-chlorophenyl) -2- (3 ', 6'-difluorene-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; Ν- (2,3- Diphenylphenyl) -2- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -yl) acetamide; Ν- (3,5-dichlorophenyl) -2- (3 ', 6'- Hydrogen-2,4'-bipyridine-1 '(2Ή) -yl) acetamidinium; 85228 -38- 200404539 2- (3', 6'-dihydrobipyridine_Γ (2Ή) -yl)- N- (4-fluoro-2-methylphenyl) acetamidamine; N- (4-aminobenzyl) -2- [4- (2-ρ 比基基) -1-hexamidine ] Ethylamine; Ν- (3,5-dichlorophenyl) -2_ [4- (2-ρbidianyl) -1-ττchloropyridyl] ethylamine; Ν- (2,3 -Dichlorophenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) small hexahydropyridyl] -N- [2- (trifluoromethyl) phenyl] acetamidamine; N- (3-chloro-4-phenylphenyl) -2- [4- (2-p than yodoyl) -1-ττ gasρ Biyenyl] ethylamine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- [4- (trifluoromethoxy) phenyl] acetamidine; NR-ring Hexyl-2- (3 ', 4', 5 ', 6'-tetrahydro-2'-[2,4 '] bipyridyl-1'-yl) acetamide; NH-{[4- (2- Cyanophenyl) hexahydropyridyl] methyl} -3-methylbenzylamine; 3-methyl-N-{[4- (2 · ρ dense lake) -1-ττ nitrogenρ Biffinyl] methyl} benzoic acid amine; 3-methyl-N-{[4- (2-pyridyl) _1_hexahydropyridyl] methyl} benzamide; 3-methyl-N -[( 4-phenyl-1 · hexahydropyridyl) methyl] benzylamine; Ν-{[4- (2-methoxyphenyl) -1-hexahydropyridyl] methyl} -3- Methylbenzylamine; _ N-{[4- (2-cyanophenyl) pyralinyl] methyl} -2-methylbenzylamine; N-{[4- (2 -Gasylphenyl) -1-ττnitrogen p-wellyl] methyl} -4-methylbenzoic acid amine; N-{[4- (3-cyano-2-pyridyl) pyrrolidine Methyl] methyl} -3-methylbenzylamine; N _ {[4- (3-aminophenylhydrogen I: morphinyl] methyl} -3-methylbenzoate; N-{[ 4- (3-Gasylphenyl chloride, p-wellyl] methyl} -2-methylbenzylamine; N-{[4- (3-Gasyl-2-ρ than Yodo-based gas well-based] methyl Methyl} benzylamine; N-{[4- (3-Gas-2-yl than p-yl) -1-ττ nitrogen p-pyridyl] methyl} -4-methylbenzyl 85228 -39- 200404539 fluorenamine; N-{[4- (3-chloro- 2-p-pyridyl chloro-pyridyl] methyl} -2-methylbenzamide; N-{[4- (2- Pyridyl &gt; 1-hexahydropyridyl] methyl} benzylamine; N-{[4- (2-chlorophenyl) -1-hexahydropyridyl] methyl} benzylamine; 3-chloro-N-{[4- (2-cyanophenyl) -1-hexahydropyridyl] methyl} benzamide; 4-chloro-N-{[4- (2-methoxy Phenyl) -1-hexahydropyridine [Methyl] methyl} benzimidamine; 2-Ga-N-{[4- (3-cyano-2-pyridyl) small hexahydropyridyl] methyl} benziridamine; N- { [4- (3-Cyano-2-pyridyl) -1-hexahydropyridyl] methylbutan-2- (trifluoromethyl) benzamidine; N-{[4- (2-cyano Phenyl) hexahydropyridyl] methyl} benzylamine; Ν-{[4- (2-methoxyphenyl) hexahexapyridyl] methyl} -3-methylbenzylamine ; 3-methyl-N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzamide; 3-methyl-N-[(4-phenyl-3, 6-dihydro-1 (2H) -pyridyl) methyl] benzidine; N- (3 ', 6f-dihydro-2, bipyridine · 1' (2Ή) -ylmethyl) methyl Benzamidine; ® Ν- (3 ', 6' · dihydro-2,4, · bipyridine-Γ (2Ή) -ylmethyl) -3-methoxybenzamide; N- (3f , 6f-dihydro-2,4'-bipyridine-1βΉ) · methylmethyl) -3 • fluorobenzylamine; Ν- (3 ', 6'-dihydro_2,4'_bipyridine -Γ (2Ή) -ylmethyl) -3,5-difluorobenzylamine; 2- [4- (3-cyano-2-pyridyl) pyrrolidine] -N-3- Pyridylacetamide; 2- (1- {2-[(3-methylphenyl) amino] _2_ketoethyl} hexahydropyridin-4-yl) pyridine 4-foot Ν-oxide; Ν-2- 金钢 烧 基 -2- [4- (3 • cyano-2-exo 1: Yodo) _1_hexahydroerphyl] ethyl amine; SSJ 85228- 40- 200404539 2- [4- (3-cyano-2-pyridyl) pyrhexahydropyridyl] cyclohexylacetamidamine; 2- [4- (3-cyano-2-pyridyl) &gt; 1 -Hexahydropyridyl] -N-5,6,7,8-tetrahydro-1-fluorenylacetamidamine; 2- (3 ', 6'-dihydro-2,4'-bipyridine_1 '(2Ή) -yl) -N- (4-fluoro-2-methylphenyl) acetamidamine; N-{[4- (2-Eodoyl) -1-hexahydro p-pyridyl] Methyl} -3- (trifluoromethyl) benzoic acid amine; 3,5-dimethoxy-N-{[4- (2-p specific phenyl) -1-hexahydro P specific phenyl] methyl Methyl} benzylpyridine amine; N-{[4- (2-Edianyl) -1-hexahydro p-pyridyl] methyl} cyclohexyl benzylamine; 3,4-difluoro-N- {[4- (2 ^ bipyridyl) small hexahydropyridyl] methyl} benzamide; 3-rat-N-{[4- (2-ρ 比基基) -1_hexaaza p ratio Benzyl] methyl} phenylsulfonium amine; 2,3_dimethyl-N-{[4- (2-ρ smaller than ydoyl) hexahydroouteryl] methyl} benzoate; N- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -ylmethyl) -3- (trifluoromethyl) benzamide; 3-chloro-N- (3 ', 6, _dihydro-2,4 -Bipyridine-1, (2Ή) -ylmethyl) phenyl Tamidine; Ν- (3 ', 6'-dihydro-2, bipyridine · 1' (2Ή) _ylmethyl) cyclohexane Carboxamidine; Ν_ (3 ', 6'-dihydro_2,4f-bipyridine-1' (2Ή) _ylmethyl) -3,4-difluorobenzamide; N_ (3f, 6f- Dihydro-2,4 '· bipyridine-1' (2Ή) -ylmethyl) -3,5-dimethoxybenzamide; Ν- (3 · methylphenyl) -2- (4 -Phenyl-1-hexahydrov-pyridyl) ethyl amine; 2- (3 \ 6'-dihydro-2, bipyridine-i '(2, H) -yl) -N- (3-nitro Phenyl) acetamidine; N-1-gold steel alkyl-2- [4- (3-cyano-2-pyridyl) pyrhexahydropyridyl] acetamidine; 85228 -41- 200404539 3 -Methyl-N-{[2-methyl-4- (2-p than ydoyl) -1-hexahydro? P-pyl [methyl] benzamidine; N- (3-methylphenyl) -2- [2-methyl_4- (2 · ^ pyridyl) -1-hexahydro p-pyhexyl [Methyl] acetamidine; 3,5_dimethyl-N-{[4- (2-etherediyl) minor hexahydroex 1: 1: yl] methyl} benzoic acid amine; N- (3 ', 6f -Dihydro-2,4'-bipyridine-1 '(2Ή) -ylmethyl) -3,5-dimethylbenzamide; 3-methyl-N-[(3-methyl-3f , 6f · dihydro-2,4'-bipyridine-1 '(2Ή) _yl) methyl] benzene formamidine; Ν-[(3-cyano-3', 6f-dihydro-2, 4, -bipyridine_1, (2Ή) _yl) methyl] -3-methylbenzylamine; Ν- (2? 6--monomethyldongyl) _2- (3-methyl-3 ', 6'-Diazine · 2,4'_Coupledo-l' (2'H) _yl) acetamide; N- (4-fluorophenyl) -2- (3-methyl · 3 ', 6'_dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; Ν- (2,4 · difluorophenyl) _2_ (3 · methyl_3 ,, 6'-dihydro_2,4'-bipyridine · '' (2, fluorene) -yl) oxetamine; 2- (3-methyl-3 ^ 6'-dihydro-2,4'- Bipyridine-1 '(2Ή) -yl) -N- (2-methylphenyl) acetamide; 2- (3-methyldihydro-2, bipyridine-1' (2Ή) _yl)- Ν- [3- (trifluoromethyl) phenyl] ethyl Amine; N- (3-chloro-4-fluorophenyl) -2- (3-methyl-3,, 6, -dihydro-2,4, -bipyridine-1, (2Ή) -yl) Acetylamine; 2- (3-methyl-3f, 6'-dihydro-2,4'-bipyridine_Γ (2Ή) _yl) -N_ [4 · (trifluoromethoxy) 85228 -42 -200404539 phenyl] acetamidamine; 2- (3-methyl-3 ', 6'-difluorene_2,4, _bipyridine], (2Ή) · yl) _N- [2_ (trifluoromethyl ) Phenyl] acetamide; N- (2,3-dichlorophenyl)> 2- (3-methyl-3 ', 6, -dihydro-2,4, -bipyridine-Γ (2Ή)- Group) Ethylamine; 2- (3-fluorenyl-3 ', 6 dihydro-2,4, · bipyridine-1, (2Ή) -yl) -N · [4- (trifluoromethyl) Phenyl] acetamidine; 2- [4- (3-cyano-2-pyrimyl) -3,6-dihydro-1 (2Η) -pyridyl] -N- (3-methylbenzene_ Acetylam); 2- (3-cyano-3 ', 6'-dihydro-2,4f-bipyridine-Γ (2Ή) -yl) -N- (2,6-dimethylphenyl ) Ethylamine; 2_ (3_chloro-3 ', 6'-diamino_2,4'_bi-pyridine-1' (2Ή) -yl) -N- (4-fluorophenyl) ethyl Styramine; 2- (3-cyano-3 ', 6'-dihydro-2,4f-bipyridine-1' (2Ή) -yl) -N- (2,4-difluorophenyl) acetamidine Amine; 2- (3 • cyano_3 ', 6'_dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N- (2-methylphenyl) ethyl®amidamine; 2- (3-cyano-3 ', 6' -Dihydro-2,4'-bipyridine-1 '(2fluorenyl-yl: ^-[3- (trifluoromethyl) phenyl] acetamidamine; 2- (3-cyano-3f, 6' -Dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N- [4- (trifluoromethoxy) phenyl] ethanamine; 2- (3-cyano-3f, 6 '-Dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N- [2- (trifluoromethyl) phenyl] ethanamine; 2- (3-cyano-3', 6'-dihydro-2,4f-bipyridine-1 '(2Ή) -yl) -N- (2,3-dichlorophenyl) 85228 -43- 200404539 acetamide; 3-methyl-N- {[4- (6-Keto-1 (6H) -Talkenyl) -1-hexahydropyridyl] methyl} benzidine; N- (3 ', 6f-dihydro_2, bipyridine -Γ (2Ή) -ylmethyl) -1-adamantanecarboxamide; 3-methyl_N-{[4- (1,3-thiazol-2-yl) · 3,6-dihydro-1 (2H) 4pyridyl] methyl} benzamide; 2- [4- (3-cyano-2-pyridyl) -1-hexahydropyridyl] -Nl, 2,3,4-tetra Hydrogen-l-fluorenylacetamidine; 2- [4- (3-cyano-2_pyridyl) pyrhexahydropyridyl] -N-[(1S) -1,2,3,4-tetrakis Hydrogen_1_fluorenyl] acetamidine: amine; 2- [4- (3-cyano_2-p (Yendyl) p-Hydroxy hexahydro] -N-[(1R) -1,2,3,4-tetrahydro-naphthyl] ethyldonylamine; N- (2,6-diethylphenyl)- 2- [4- (2-ρ 比比基基) -1-hexahydro p-pyridyl] acetamidoamine; 2- [4- (2 ^ bipyridyl) -1-ττnitroπpyridyl]- N- (2,4,6-trifluoro ^ phenyl) ethanamine; N- (4-chloro-2,6-dimethylphenyl) -2- [4- (2-out 1: lake Phenyl) -1-hexahydro p-pyridyl] ethynylamine; 2- [4- (2-p-pyridyl) -1-ττ nitrogen? Biyodo] -N- (2,4,6-trichlorophenyl) amine; N- (2,6-diethylphenyl) -2- (3 ', 6'-dihydro-2, ^ Bipyridine-Γ (2Ή) · yl) acetamide; 2_ (3 *, 6 dihydro-2,4 '· Lianwai 1: Yodo-Γ (2Ή) -yl) -N · (2,4 , 6 · trifluorophenyl) acetamidine; Ν- (4-chloro-2,6-dimethylphenyl) _2- (3 ', 6'-dihydro-2,4'-bipyridine_ 1 '(2Ή) _yl) acetamide; 2- (3', 6'-dihydro-2,4'_bipyridine-Γ (2Ή) -yl) -N- (2,4,6 · tri Chlorophenyl) acetam 85228 -44- 200404539 amines; N-{[4- (2-exo (: pyridinyl) hexylpyridyl] methyl} (trifluoromethyl) benzidine; 3,5-dimethoxy-N-{[4- (24pyridinyl) pyralinyl] methyl} benzamide; N-{[4- (2-eridinyl) -1 -Hexahydropyridyl] methyl} cyclohexanecarboxamide; Ν- (2,6 · dimethylphenyl) -2- [4- (2-pyridylH-hexahydropyridyl] ethyl Amidoamine; Ν- (4-fluorophenyl) -2- [4- (2-pyridyl) pyrihydropyridyl] acetamide; Ν- (2,4-difluorophenyl) -2- [4- (2-Ex1: Yodo) -1_Hexahydroexocyl] Acetylamine; N- (2-methylphenyl) -2- [4- (2 is smaller than Yodo) Hexahydrogenyl] acetamidine ; 2- [4- (2-pyridyl) pyrhydropyridyl] -N- [3- (trifluoromethyl) phenyl] ethanamine; N- (3-chlorophenyl) -2- [4- (2-ρ ratio yodolide p-well-based] amine acetate; N-fluorenyl · 2- [4 · (2-ρ ratio yodolide-row-based p-well-based) ethylamine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- [4- (trifluoromethoxy) phenyl] acetamidamine; 2- [4- (2-pyridyl) small Hexahydropyridyl] -N- [2- (trifluoromethyl) phenyl] acetamidine; Ν- (4-phenyl) -2- [4- (2 · ρ 比 淀 基) -1 -Hexaline p-biffinyl] acetamide; Ν- (2,3-dichlorophenyl) _2- [4- (2-pyridyl) -1 · hexahydrop-biffinyl] acetamide; Ν -(3,4-dichlorophenyl) -2_ [4- (2-pyridyl) -1-ττazepine-pyridyl] acetamide; 2- [4- (2-pyridyl) small hexahydro Pyridyl] -N- [4- (trifluoromethyl) phenyl] acetamidinium; 3-chloro-N-{[4- (2-pyridyl) small hexahydropyridyl] methyl} benzene Formamidine Γ Γ ί 85228 -45- 200404539 4-氟基-3-甲基-N-{[4-(2-吡啶基）小六氫吡畊基]甲基}苯甲 醯胺； N-(3’，6’-二氫-2,4’-聯吡啶_Γ(2Ή)_基甲基）-4-氟基各甲基苯甲 醯胺； 3-甲基-Ν-{[4-(1，3-噚唑-2_基）-3,6-二氫-1(2H)-吡啶基]甲基}苯 甲醯胺； 2-甲基-N-[(3-甲基-3W-二氫_2,4’_聯吡啶_Γ(2Ή)_基）甲基]苯 甲醯胺； φ 2-[4-(3-氰基-2-吡啶基）小六氫吡啶基]-Ν-(2,6-二甲基苯基） 乙醯胺； Ν-(3-甲基苯基）-2_[4-(3-甲基-2-吡啶基）小六氫吡畊基]乙醯 胺； 2-[4-(3-裹基-2-ρ比淀基）-1-六氫峨啡基]-Ν-[4-(三氟甲基）苯 基]乙酸胺； Ν-(2-乙基-6-甲基苯基）-2-[4·(2-吡啶基）小六氳吡啶基]乙醯 胺； 參 Ν-(2-異丙基-6-甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙 醯胺； Ν-(2-氯基-6-甲基苯基&gt;2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯 胺； N-(2-甲氧基-6-甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙 醯胺； 2-(3’，6f-二氫-2,4f-聯吡啶-1’(2Ή)-基）-N-(2_乙基-6-甲基苯基）乙 醯胺； 85228 -46- 200404539 2-(3f，6’_二氫-2,4’-聯吡啶-1，(2Ή)-基）-N-(2-異丙基-6_甲基苯基） 乙醯胺； N-(2-氯基-6_甲基苯基）-2-(3，，6，-二氫-2,4，-聯吡啶-1，(2Ή)·基）乙 醯胺； 2- (3’，6’-二氫_2,4’-聯吡啶_；Τ(2Ή)-基）-Ν-(2-甲氧基-6-甲基苯基） 乙醯胺； 3- 氯_Ν-[(3-甲基彳方-二氫-2,4f-聯吡啶-Γ(2Ή)-基）甲基]苯甲 驢胺； 籲 3-氟-Ν-[(3_甲基-3f，6f-二氫_2,聯吡啶-Γ(2Ή)-基）甲基]苯甲 醯胺； 3-甲基-N_{[(2S)-2-甲基-4-(2-吡啶基）小六氫吡畊基]甲基}苯 甲酸胺； N_(3_甲基苯基）-2-[(2S)-2-甲基冰(2-吡啶基）_1_六氫吡畊基] 乙醯胺； 3_甲基-N_{[(2R)-2-甲基冬(2-吡啶基）小六氫吡畊基]甲基} 苯甲醯胺； _ N_(3_甲基苯基）-2-[(2R)-2-甲基-4-(2-吡啶基）·1-六氫吡畊基] 乙醯胺； 3- 甲氧基-Ν-[(3-甲基义心二氫-2,4’-聯吡啶-1’(2Ή)-基）甲基] 苯甲醒胺； 4- 氟-Ν-[(3-甲基_3’，6’_二氫-2,4’-聯吡啶-1’(2Ή)-基）甲基]苯甲 醯胺； 2-(3-氯基-3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-(2,6-二甲基笨 基）乙驗胺； 85228 -47- 200404539 2- (3-氯基-3’，6’-二氫_2,4’-聯吡啶-ΐ，(2Ή)-基）-N-(2-甲基苯基）乙 醯胺； N-(3#二氫-2,4f-聯吡啶-r(2，H)-基甲基）-1_萘甲醯胺； Ν-{[4-(3-氰基-2-吡啶基）-1_六氫吡畊基]甲基卜3_氟基苯甲 醯胺； 3- 甲基-Ν-{[4-(1，3-噻唑冬基）小六氫吡啶基]甲基}苯甲醯胺； 2-(1-{2-[(4-氟基-2-甲基苯基）胺基]-2-酮基乙基}_4-六氫吡 啶基）吡錠N-氧化物； 2-(1-{2-[(4-氟基-3-甲基苯基）胺基]-2-酮基乙基}-4-六氫外匕 啶基）吡錠N·氧化物； 2-(1-{2-[(3-敦苯基）胺基]-2-酮基乙基}-4-六氫p比淀基 &gt;比錠 N-氧化物； 2-(1-{2-[(2-氟基-5-甲基苯基）胺基]-2-酮基乙基}-4-六氫吡 啶基&gt;比錠N-氧化物； 2-(1-{1-甲基冬[(3-甲基苯基）胺基]-2-酮基乙基}-4-六氫吡 淀基 &gt;比錠N-氧化物； 2-(1-{2-[(4-氟苯基）胺基]-2-酮基乙基}-4-六氫吡啶基）吡錠 N-氧化物； 2-(1-{2-[(2-氟苯基）胺基]-2-S同基乙基}-4-六氫吡啶基）吡錠 N-氧化物； N-(3-甲基苯基）_2_{4-[3-(三氣甲基）-2-峨淀基]鼠峨17井 基}乙醯胺； N-(3-甲基苯基）-2-[4-(1，3_嘧唑-2-基）-3,6-二氫吡啶-1(2H)-基] 乙醯胺； 85228 -48- 200404539 N-(3-甲基苯基）-2-(4-噻吩-2-基-3,6-二氫吡啶·1(2Η)_基）乙醯 胺； 3-甲基-Ν-[(4-嘧吩-2-基·3,6-二氫吡啶_1(2Η)_基）甲基]苯甲醯 胺； 2-(1-{2-[(3-氯苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡錠 Ν-氧化物； 2-[4-(1_ 甲基-1Η-咪唑-2-基）-3,6-二氫吡啶-1(2Η)-基]-Ν-(3-甲 基苯基）乙醯胺； _ Ν-(3-甲基苯基）-2-[4-(3-硝基吡啶-2-基）六氫吡啡-1-基]乙醯 胺； 2-[4-(3-氯基吡啶-2-基）六氳吡畊小基]-Ν-(3-甲基苯基）乙醯 胺； 2-(1-{2-酮基-2_[(2,4,6-三溴基-3-甲基苯基）胺基]乙基}六氫 吡啶-4_基）吡錠Ν-氧化物； 2-{4-[3-(胺基甲基）吡啶-2-基]六氫吡啡小基}-Ν-(3-甲基苯 基）乙酸胺； @ 2-[4-(2-異丙氧基苯基）六氫吡畊小基]-Ν-(3-甲基苯基）乙醯 胺； 2-(4-{2-[(3-甲基苯基）胺基]-2-酮基乙基}六氫吡畊-μ基）於 鹼醯胺； Ν-(3_甲基苯基）_2-[(2S)-2-甲基冰吡啶-2-基六氫吡畊小基] 乙烷硫醯胺； 2-(1-{[(4-溴基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶冰基） 吡錠N-氧化物； 85228 -49- 200404539 2-[4-(3-氰基吡啶-2-基）六氫吡畊_丨_基]_Ν_[3-(甲硫基）苯基] 乙醯胺； Ν·(3_第三丁基苯基）-2-[4-(3•氰基吡啶_2_基）六氫吡畊小基] 乙醯胺； 2-[4-(2-起苯基）六氫吡畊小基]甲基苯基）乙醯胺； 2-[4-(3-羥苯基）六氫吡畊小基]-队(3_甲基苯基）乙醯胺； 2-[4-(4_輕苯基）六氫吡畊小基]界(3_甲基苯基）乙醯胺； 2-[4-(2-乙氧苯基）六氫吡畊小基;|_义(3_甲基苯基）乙醯胺；籲 N-(3-甲基苯基）-2-{4_[2-(甲硫基）苯基]六氫吡畊小基丨乙醯 胺； 2-[4-(2-氟苯基）六氫吡畊_1_基]-N-(3-甲基苯基）乙醯胺； 2-[4-(3·氰基吡啶-2-基）六氫吡畊-l-基 氟苯基）乙醯胺； N-(3-溴苯基)-2-[4_(3-氰基峨淀-2-基）六氫咐^井-1-基]乙醯胺； N-(3-甲基苯基）-2-(4_?比淀-2-基六氫17比呼小基）乙燒硫酿胺； 2-[4-(2-胺基苯基）六氫吡畊-1-基]-N-(3-甲基苯基）乙醯胺； N-(3-硝基苯基）-2-(4-0比淀-2-基六氫p比p井小基）乙酸胺； · 2-[4-(2-氰基苯基）ττ氫吨味-1-基]-N-(3-硝基苯基）乙酿胺； N-(3-氰基苯基）-2-(扣比淀-2-基六氫p比呼·ΐ-基）乙酸胺； N-(3-氰基苯基)-2-[4-(2-氰基苯基）六氫p比畊小基]乙縫胺； 2-[4-(3-散基p比淀-2-基氮峨呼-1-基]-N-(五氣苯基）乙酉盛 胺； 2-[4-(3-氰基吡啶-2-基）六氫吡畊小基]·Ν-(1，3-二甲基_1Η-吡 唑-5-基）乙醯胺； Ν-(3-苄基苯基）-2-[4-(3•氰基吡啶-2-基）六氫吡畊_1_基]乙醯Γ Γ ί 85228 -45- 200404539 4-fluoro-3-methyl-N-{[4- (2-pyridyl) pyrhydropyridyl] methyl} benzamide; N- (3 ' , 6'-dihydro-2,4'-bipyridine_Γ (2Ή) _ylmethyl) -4-fluoromethylmethylbenzamide; 3-methyl-N-{[4- (1 , 3-oxazol-2-yl) -3,6-dihydro-1 (2H) -pyridyl] methyl} benzamide; 2-methyl-N-[(3-methyl-3W- Dihydro_2,4'_bipyridine_Γ (2Ή) _yl) methyl] benzidine; φ 2- [4- (3-cyano-2-pyridyl) small hexahydropyridyl]- Ν- (2,6-dimethylphenyl) acetamidine; Ν- (3-methylphenyl) -2_ [4- (3-methyl-2-pyridyl) pyrrolidine] Acetylamine; 2- [4- (3-Wrapped-2-rpyridyl) -1-hexahydroerphinyl] -N- [4- (trifluoromethyl) phenyl] acetamide; Ν -(2-ethyl-6-methylphenyl) -2- [4 · (2-pyridyl) small hexamethylpyridyl] acetamidamine; see N- (2-isopropyl-6-methyl Phenyl) -2- [4- (2-pyridyl) small hexahydropyridyl] acetamidamine; N- (2-chloro-6-methylphenyl) &gt; 2- [4- (2-pyridine Group) -1-hexahydropyridyl] acetamidine; N- (2-methoxy-6-methylphenyl) -2- [4- (2-pyridyl) small hexahydropyridyl] Acetamide; 2- (3 ', 6f-dihydro-2,4f-bipyridine-1' (2fluoren) -yl) -N- (2-ethyl-6-methylphenyl) acetamidine; 85228 -46- 200404539 2- (3f, 6'_dihydro-2,4'-bipyridine-1, (2Ή) -yl) -N- (2-isopropyl-6-methylphenyl) ethyl Fluorenamine; N- (2-chloro-6-methylphenyl) -2- (3,, 6, -dihydro-2,4, -bipyridine-1, (2fluorenyl) ethanil) ; 2- (3 ', 6'-dihydro_2,4'-bipyridine_; T (2Ή) -yl) -N- (2-methoxy-6-methylphenyl) acetamide; 3-chloro-N-[(3-methylpyrene-dihydro-2,4f-bipyridine-Γ (2Ή) -yl) methyl] benzyl donutylamine; 3-fluoro-N-[(3 _Methyl-3f, 6f-dihydro_2, bipyridine-Γ (2Ή) -yl) methyl] benzidine; 3-methyl-N _ {[(2S) -2-methyl-4- (2-Pyridinyl) hexahydropyridyl] methyl} benzoic acid amine; N_ (3-methylphenyl) -2-[(2S) -2-methylice (2-pyridyl) _1_ Hexahydropyridyl] Ethylamine; 3-methyl-N _ {[((2R) -2-methyldong (2-pyridyl) small hexahydropyridyl] methyl} benzamidine; _ N_ (3-Methylphenyl) -2-[(2R) -2-methyl-4- (2-pyridyl) · 1-hexahydropyridyl] acetamidine; 3-methoxy- Ν-[(3-methylsense dihydro-2,4'-bipyridine-1 '(2Ή) -yl) methyl] benzylamine; 4-fluoro-N-[(3-methyl_ 3 ', 6'_dihydro-2,4'-bipyridine-1' (2Ή) -yl) methyl] benzidine; 2- (3-chloro-3 ', 6'-dihydro- 2,4'-bipyridyl-Γ (2Ή) -yl) -N- (2,6-dimethylbenzyl) ethoxyamine; 85228 -47- 200404539 2- (3-chloro-3 ', 6 '-Dihydro_2,4'-bipyridine-fluorene, (2Ή) -yl) -N- (2-methylphenyl) acetamide; N- (3 # dihydro-2,4f-bipyridine -r (2, H) -ylmethyl) -l-naphthylamidine; Ν-{[4- (3-cyano-2-pyridyl) -1_hexahydropyridyl] methyl trimethyl 3 _Fluorobenzamide; 3-methyl-N-{[4- (1,3-thiazolyl) ylhexahydropyridyl] methyl} benzamide; 2- (1- {2- [(4-Fluoro-2-methylphenyl) amino] -2-ketoethyl} _4-hexahydropyridyl) pyridine N-oxide; 2- (1- {2-[(4 -Fluoro-3-methylphenyl) amino] -2-ketoethyl} -4-hexahydroexordinyl) pyridine N · oxide; 2- (1- {2-[(3 -Dentyl) amino] -2-ketoethyl} -4-hexahydrop-pyridyl> Pyridium N-oxide; 2- (1- {2-[(2-fluoro-5 -Methylphenyl) amino] -2- Ketoethyl} -4-hexahydropyridyl &gt; Bismuth N-oxide; 2- (1- {1-methyl winter [(3-methylphenyl) amino] -2-ketoethyl } -4-Hexahydropyridyl &gt; Titanium N-oxide; 2- (1- {2-[(4-fluorophenyl) amino] -2-ketoethyl} -4-hexa Hydropyridyl) pyridine N-oxide; 2- (1- {2-[(2-fluorophenyl) amino] -2-S isopropylethyl} -4-hexahydropyridyl) pyridine N -Oxide; N- (3-methylphenyl) _2_ {4- [3- (trigasmethyl) -2-eodoyl] romo 17 wellyl} acetamidine; N- (3-formyl Phenyl) -2- [4- (1,3-pyrimazol-2-yl) -3,6-dihydropyridine-1 (2H) -yl] acetamide; 85228 -48- 200404539 N- ( 3-methylphenyl) -2- (4-thien-2-yl-3,6-dihydropyridine · 1 (2Η) -yl) acetamide; 3-methyl-N-[(4-pyrimidine Phen-2-yl · 3,6-dihydropyridine_1 (2Η) _yl) methyl] benzamide; 2- (1- {2-[(3-chlorophenyl) amino] -2 -Ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- [4- (1-methyl-1 -imidazol-2-yl) -3,6-dihydropyridine-1 ( 2Η) -yl] -N- (3-methylphenyl) acetamide; _N- (3-methylphenyl) -2- [4- (3-nitropyridin-2-yl) hexahydro Pyridin-1-yl] acetamide; 2 -[4- (3-chloropyridin-2-yl) hexamethylpyridyl] -N- (3-methylphenyl) acetamidamine; 2- (1- {2-keto-2_ [ (2,4,6-tribromo-3-methylphenyl) amino] ethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- {4- [3- (amino Methyl) pyridin-2-yl] hexahydropyridinyl} -N- (3-methylphenyl) amine; @ 2- [4- (2-isopropoxyphenyl) hexahydropyridine Small group] -N- (3-methylphenyl) acetamidamine; 2- (4- {2-[(3-methylphenyl) amino] -2-ketoethyl} hexahydropyridine -μ group) in amidoamine; Ν- (3-methylphenyl) _2-[(2S) -2-methylpyridin-2-ylhexahydropyridine] ethanethioamide; 2 -(1-{[(4-Bromo-3-methylbenzylidene) amino] methyl} hexahydropyridineicelyl) pyridinium N-oxide; 85228 -49- 200404539 2- [4- (3-Cyanopyridin-2-yl) hexahydropyridine_ 丨 _yl] _N_ [3- (methylthio) phenyl] acetamide; Ν · (3-third-butylphenyl) -2 -[4- (3 • cyanopyridine_2_yl) hexahydropyridine] acetamidine; 2- [4- (2-phenyl) hexahydropyridine] methylphenyl) Acetylamine; 2- [4- (3-hydroxyphenyl) hexahydropyridine] -Team (3-methylphenyl) Amidoamine; 2- [4- (4- light phenyl) hexahydropyridyl] imine (3-methylphenyl) acetamide; 2- [4- (2-ethoxyphenyl) hexahydro Pycnogenol; | _sense (3-methylphenyl) acetamide; N- (3-methylphenyl) -2- {4_ [2- (methylthio) phenyl] hexahydropyridine Phenyl group 丨 Acetylamine; 2- [4- (2-fluorophenyl) hexahydropyridine_1-yl] -N- (3-methylphenyl) acetamidin; 2- [4- ( 3 · Cyanopyridin-2-yl) hexahydropyridine-l-ylfluorophenyl) acetamidamine; N- (3-bromophenyl) -2- [4_ (3-cyanoethyl) -2- Hexahydrocarbyl-1-yl] acetamidine; N- (3-methylphenyl) -2- (4-? Hyodo-2-ylhexahydro 17-Hydro) Amine; 2- [4- (2-Aminophenyl) hexahydropyrine-1-yl] -N- (3-methylphenyl) acetamide; N- (3-nitrophenyl)- 2- (4-0 Biyodo-2-ylhexahydrop-p-p-well small group) amine acetate; · 2- [4- (2-cyanophenyl) ττ hydrogen ton-1-yl] -N- (3-Nitrophenyl) ethyl amine; N- (3-cyanophenyl) -2- (Kabiyodo-2-ylhexahydrop-bihu · ΐ-yl) amine; N- (3 -Cyanophenyl) -2- [4- (2-cyanophenyl) hexahydro-p-pyridyl] ethanoylamine; 2- [4- (3-scyl-p-pyridine-2-yl nitrogen Ehu-1-yl] -N- (5 Phenyl) acetamidine; 2- [4- (3-cyanopyridine-2-yl) hexahydropyridine] · N- (1,3-dimethyl_1Η-pyrazol-5-yl ) Ethylamine; Ν- (3-benzylphenyl) -2- [4- (3 • cyanopyridine-2-yl) hexahydropyrimyl_1-yl] acetamidine 85228 -50- 200404539 胺； 2-[4-(2-氯苯基）六氫吡畊-1_基]-N_(3-甲基苯基）乙醯胺； 2-[4-(3-氰基吡畊-2-基）六氫吡畊-i_基]_N_(&gt;甲基苯基）乙醯 胺； 2-(4-吡啶基六氫吡畊小基）-N-(2-{[(4-吡啶-2-基六氫吡畊 •1-基）乙醒基]胺基}苯基）乙醒胺； N-(3-甲基苯基）-2-(4-吡啶-2-基六氫吡啶-1-基）乙烷硫醯胺； 2-[4-(1-甲基-1H-咪嗤-2-基）六氫峨咬_1_基]-N-(3-甲基苯基）_ 乙醯胺； N-(3-甲基苯基）-2-[4-(1，3-隹唑-2_基）六氫吡啶小基]乙醯胺； N-(4-硪基-3-甲基苯基）-2-(4-峨淀-2-基六氫p比症-1-基）乙醯 胺； 2-(4-氟基-4_苯基六氫吡啶-1-基&gt;Ν-(3·甲基苯基）乙醯胺； 2-[4-(5-羥基吡啶-2-基）六氫吡啶-1-基]-Ν-(3-甲基苯基）乙醯 胺； Ν-(5_氣基-I，3·苯并ρ塞口圭_2_基）_2_[4_(3_甲氧苯基）六氫ρ比啡- 1- 基]乙驗胺； 2-[4-(2-甲氧苯基）六氫吡畊小基]_N-(1-甲基-1H-苯并咪唑- 2- 基）乙酿胺； N-(3-甲基苯基）-2-[4-(3-甲基嘧吩-2-基）-3,6_二氫吡啶-1(2H)-基]乙醯胺； 2-(1-{2-[(3,5-二氯苯基）胺基]-2-酮基乙基}六氫ρ比淀-4-基） 吡鍵N-氧化物； 2-(1-{2-[(2,3二氯苯基）胺基]-2-酮基乙基}六氫吡啶-4-基） 85228 -51 - 200404539 吡錠N-氧化物； 2-(l-{2-[(2-甲氧基-6-甲基苯基）胺基]-2-酮基乙基}六氫吡 啶-4-基）吡錠N-氧化物； 2-{1-[2-(1，Γ-聯苯-3-基胺基）_2•酮基乙基]六氫吡啶冰基}外匕 錠Ν-氧化物； 2·(1-{2-[(3-乙基苯基）胺基]_2_酮基乙基}六氫吡啶-4-基 &gt;比 錠Ν-氧化物； 2-{1-[2-(2?3-—氣-1Η-印-5_基胺基）-2-ί同基乙基]穴A 比淀-4- 基比键N-氧化物； 酮基_2-(5,6,7,8-四氫莕-1-基胺基）乙基]六氫吡啶-4-基}说錠N-氧化物； 2-(1-{2-[(3-異丙氧基苯基）胺基]酮基乙基}六氫吡啶-4-基）峨錠N-氧化物； 2-(1_{2_[(3,5-二甲基苯基）胺基]_2_酮基乙基}六氫吡啶_4_基） 外匕錠N-氧化物； 2-(1-{2-[(4-溴基-2-甲基苯基）胺基&gt;2-酮基乙基}六氫吡啶-籲 4-基）p比鍵N-氧化物； 2_[1_(2_酮基-2-{[3-(三氟甲氧基）苯基]胺基}乙基）六氫吡啶 _4_基风錠N-氧化物； 2-(1-{2-[(5-甲基-2-硝基苯基）胺基]_2_酮基乙基}六氫吡啶_ 4-基）吡錠N-氧化物； 2-(1-{2-[(2,6-二甲基苯基）胺基]_2項同基乙基}六氫吡啶冰基） 外匕錠N-氧化物； 2-(1-{2-[(2,6-二氯-3_甲基苯基）胺基]_2項同基乙基}六氫吡啶 85228 -52- 200404539 -4-基）峨鍵N-氧化物； 2-{1-[2-(1，3-苯并二氧伍圜烯-5-基胺基）-2-酮基乙基]六氫 吡啶-4-基}吡錠N-氧化物； 2-[1-(2-{[3-(甲硫基）苯基]胺基卜2-酮基乙基）六氫吡啶-4-基] 外匕錠N-氧化物； 2-(1-{2-[(5-氣基-2-甲基苯基）胺基]-2-銅基乙基}：^鼠^1比淀_ 4_基）峨鍵N-氧化物； 2-(1-{2-[(2,5-二甲氧基苯基）胺基]-2-酮基乙基}六氫吡啶_4_ _ 基 &gt;比錠N-氧化物； 2-(1-{2-[(3,5-二甲氧基苯基）胺基]—2-酮基乙基}六氫吡啶-4-基）峨錠N-氧化物； 2-[1-(2-{〇(二甲胺基）苯基]胺基}-2-酮基乙基）六氫吡啶-4-基]峨錠N-氧化物； 2-(1-{2-[(3_異丙基苯基）胺基]_2_酮基乙基}六氫吡啶-4-基） 吡錠N-氧化物； 2- (1-{2-[(3·氯基-2_甲基苯基）胺基]-2-酮基乙基}六氫吡啶_ _ 4-基）ρ比鍵N-氧化物； 3- 甲基-N-[2-(4-峨啶-2-基六氫吡畊-1-基）乙基]苯甲醯胺； 2-(1-{[(2,3-二溴基-5-甲基苯甲醯基）胺基]甲基}六氫吡啶- 4-基）吡錠N-氧化物； 2-{1-[(苯甲醯胺基）甲基]六氫吡啶冰基}吡錠N_氧化物； 2-(1-{[(4-氯基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶-4-基） 吡錠N-氧化物； 2-(1-{[(4_氟基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶4-基） 85228 -53- 200404539 叶匕錠N-氧化物； 2-[l-({[3-氯基-4-(三氟甲氧基）苯甲醯基]胺基}甲基）六氳 吡啶-4-基]吡錠N-氧化物； 2-(1-{[(3-乙氧基苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠 N-氧化物； 2-(1-{[(3,5-二氯苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠 N-氧化物； 2-[1-({[4-甲基-3-(三氟甲基）苯甲醯基]胺基}甲基）六氫吡 _ 啶-4-基]吡錠N-氧化物； 2-(1-{[(3,4-二甲苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠 N-氧化物； 2-(1-{[(3·氯基-4-氟苯甲醯基）胺基]甲基}六氫吡啶冰基）吡 錠N-氧化物； 2·(1·{[(口比淀-2-基談基）月安基]甲基}六氯外匕淀-4-基）口比鍵N-氧 化物； 2-(1-{[(3,5-二甲苯甲縫基）胺基]甲基}τ^氫峨淀-4-基）ρ比鍵 Ν-氧化物； 2-(1-{[(3-乙烯基苯甲醯基）胺基]甲基}六氫吡啶斗基）吡錠 Ν-氧化物； 2-(1-{[(4-溴基-3-甲基苯甲醯基）胺基]甲基}-1，2,3,6-四氫吡 啶-4-基）吡錠Ν-氧化物； 2-{1-[(2-萘甲醯基胺基）甲基]六氫吡啶-4-基}吡錠Ν-氧化 物； 2-(1-{[〇塞吩-2-基羰基）胺基]甲基}六氫吡啶冬基风錠队氧 85228 -54- 200404539 化物； 2-[H{[(6-氯基吡啶-3-基）羰基]胺基}甲基）六氫吡啶-4-基] 外匕錠N-氧化物； 2-(H[(3-氰基苯甲酸基）胺基]甲基}六氫被淀_4_基风鉸N-氧化物； 2-(M[(2,3-二溴基-5-甲基苯甲醯基）胺基]甲基}-1，2,3,6-四氫 吡啶冰基）吡錠N-氧化物； 2-(1-{[(4-溴基苯甲酸基）胺基]，甲基}六氫12比淀_4-基 &gt;比錠⑩ 氧化物； 2-(M[(3-氯基-4-甲基苯甲醯基）胺基]甲基}六氫吡啶基） 外匕錠N-氧化物； 2-(1-{[甲基（3·甲基苯甲醯基）胺基]甲基}六氫吡啶_4_基 &gt;比 錠N-氧化物； 2-(1-{[(3-硝基苯甲醯基）胺基]甲基}六氫吡啶_4_基）吡錠N-氧化物； 2-(1-{[(2-氯基-5-甲基苯甲醯基）胺基]甲基}六氫吡啶-4-基）_ 吡錠N-氧化物； 2-(1-{[(3-甲氧基-2-甲基苯甲醯基）胺基]甲基}六氫吡啶冰 基Η錠N-氧化物； 2-(1-{[(4-氯基各甲氧苯甲醯基）胺基]甲基}六氫吡啶-4-基） 吡鉸Ν-氧化物； Ν-(3-甲基苯基）-2-(3•吡啶-2-基六氫吡啶-1-基）乙醯胺； N-(3-甲基苯基）-2-(3-吡啶-2-基四氫吡咯-1-基）乙醯胺； N-(l-甲基-1H-苯并咪唑-2-基）_2-[3-(1，3-嘧唑-2-基）六氫吡啶-85228 -50- 200404539 amine; 2- [4- (2-chlorophenyl) hexahydropyrine-1_yl] -N_ (3-methylphenyl) acetamide; 2- [4- (3- Cyanopyridin-2-yl) hexahydropyridine-i_yl] _N _ (&gt; methylphenyl) acetamide; 2- (4-pyridylhexahydropyridine) -N- (2 -{[(4-pyridin-2-ylhexahydropyridine • 1-yl) ethoxy] amino} phenyl) ethoxyamine; N- (3-methylphenyl) -2- (4- Pyridin-2-ylhexahydropyridin-1-yl) ethanethiocarbamide; 2- [4- (1-methyl-1H-imid-2-yl) hexahydroepi-1-yl] -N -(3-methylphenyl) _acetamidine; N- (3-methylphenyl) -2- [4- (1,3-oxazole-2_yl) hexahydropyridine small group] acetamidine Amine; N- (4-fluorenyl-3-methylphenyl) -2- (4-amido-2-ylhexahydrop-pyridin-1-yl) acetamide; 2- (4-fluoro group -4-Phenylhexahydropyridin-1-yl &gt; N- (3 · methylphenyl) acetamidamine; 2- [4- (5-hydroxypyridin-2-yl) hexahydropyridin-1-yl ] -Ν- (3-methylphenyl) acetamide; Ν- (5_amino-I, 3 · benzoρ Secuyl_2_yl) _2_ [4_ (3_methoxyphenyl) Hexahydrop-biffin-1-yl] ethoxyamine; 2- [4- (2-methoxyphenyl) hexahydropyracyl] _N- (1-methyl-1H-benzimidazole-2 base Ethylamine; N- (3-methylphenyl) -2- [4- (3-methylpyridin-2-yl) -3,6-dihydropyridine-1 (2H) -yl] acetamidine Amines; 2- (1- {2-[(3,5-dichlorophenyl) amino] -2-ketoethyl} hexahydroρ biden-4-yl) pyridine bond N-oxide; 2 -(1- {2-[(2,3dichlorophenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) 85228 -51-200404539 pyridinium N-oxide; 2- (l- {2-[(2-methoxy-6-methylphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- { 1- [2- (1, Γ-biphenyl-3-ylamino) _2 • ketoethyl] hexahydropyridylicel} outer N-oxide; 2 · (1- {2-[( 3-ethylphenyl) amino] _2_ketoethyl} hexahydropyridin-4-yl> ratio N-oxide; 2- {1- [2- (2? 3-—Ga-1Η -Indo-5_ylamino) -2-Homoethyl] hole A Biyodo-4-yl ratio N-oxide; keto_2- (5,6,7,8-tetrahydrofluorene -1-ylamino) ethyl] hexahydropyridin-4-yl}, N-oxide; 2- (1- {2-[(3-isopropoxyphenyl) amino] ketoethyl Group} hexahydropyridin-4-yl) eolide N-oxide; 2- (1_ {2 _ [(3,5-dimethylphenyl) amino] _2_ketoethyl} hexahydropyridine_4 _ Base) outside Ingot N-oxide; 2- (1- {2-[(4-bromo-2-methylphenyl) amino group> 2-ketoethyl} hexahydropyridine- 4-yl) p ratio Bond N-oxide; 2_ [1_ (2_keto-2-{[3- (trifluoromethoxy) phenyl] amino} ethyl) hexahydropyridine_4_ylwind ingot N-oxide ; 2- (1- {2-[(5-methyl-2-nitrophenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1- {2-[(2,6-Dimethylphenyl) amino] -2 isopropylethyl} hexahydropyridylicelyl) N-oxide; 2- (1- {2- [(2,6-dichloro-3_methylphenyl) amino] -2 isopropylethyl} hexahydropyridine 85228 -52- 200404539 -4-yl) -E bond N-oxide; 2- {1 -[2- (1,3-benzodioxin-5-ylamino) -2-ketoethyl] hexahydropyridin-4-yl} pyridine N-oxide; 2- [1 -(2-{[3- (methylthio) phenyl] amino-2-ketoethyl) hexahydropyridin-4-yl] outer N-oxide; 2- (1- {2- [(5-Gas-2-methylphenyl) amino] -2-copperethyl}: ^^^ 1 Biyodo_ 4-yl) E bond N-oxide; 2- (1- { 2-[(2,5-dimethoxyphenyl) amino] -2-ketoethyl} hexahydropyridine_4__ group> ratio N-oxide; 2- (1- {2-[(3,5-dimethoxyphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) eolide N-oxide; 2- [ 1- (2- {〇 (dimethylamino) phenyl] amino} -2-ketoethyl) hexahydropyridin-4-yl] eolide N-oxide; 2- (1- {2- [(3_Isopropylphenyl) amino] _2_ketoethyl} hexahydropyridin-4-yl) pyridinium N-oxide; 2- (1- {2-[(3 · chloro- 2-methylphenyl) amino] -2-ketoethyl} hexahydropyridine_-4-yl) ρ ratio N-oxide; 3-methyl-N- [2- (4-eridine 2-ylhexahydropyridin-1-yl) ethyl] benzylamine; 2- (1-{[((2,3-dibromo-5-methylbenzyl) amino) amino] methyl Yl} hexahydropyridine- 4-yl) pyridine N-oxide; 2- {1-[(benzylideneamino) methyl] hexahydropyridinyl} pyridine N_oxide; 2- (1 -{[(4-chloro-3-methylbenzylidene) amino] methyl} hexahydropyridin-4-yl) pyridinium N-oxide; 2- (1-{[(4_fluoro Methyl-3-methylbenzyl) amino] methyl} hexahydropyridine 4-yl) 85228 -53- 200404539 leaf dagger N-oxide; 2- [l-({[3-chloro- 4- (trifluoromethoxy) benzylidene] amino} methyl) hexamidinepyridin-4-yl] pyridine N-oxide; 2- ( 1-{[(3-ethoxybenzyl) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1-{[((3,5-dichloro Benzamidine) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- [1-({[4-methyl-3- (trifluoromethyl) benzidine [Amino] amino} methyl) hexahydropyridin-4-yl] pyridine N-oxide; 2- (1-{[((3,4-Xylylmethyl) amino) amino] methyl} hexa Hydropyridin-4-yl) pyridine N-oxide; 2- (1-{[((3 · chloro-4-fluorobenzylidene) amino) methyl] hexahydropyridinyl) pyridine N -Oxide; 2 · (1 · {[((Kyobido-2-yl) yl) Yueanji] methyl} hexachloroexo-4-yl) N-oxide; 2- ( 1-{[(3,5-Xylenylmethylamino) amino] methyl} τ ^ hydroeide-4-yl) ρ ratio bond N-oxide; 2- (1-{[(3-ethylene Benzamidine) amino] methyl} hexahydropyridyl) pyridine N-oxide; 2- (1-{[(4-bromo-3-methylbenzyl) amino] Methyl} -1,2,3,6-tetrahydropyridin-4-yl) pyridine N-oxide; 2- {1-[(2-naphthyridinylamino) methyl] hexahydropyridine- 4-yl} pyridine N-oxide; 2- (1-{[〇thiophen-2-ylcarbonyl) amino] methyl} Hydropyridine winter based ingots oxygen 85228 -54- 200404539 compounds; 2- [H {[(6-chloropyridin-3-yl) carbonyl] amino} methyl) hexahydropyridin-4-yl] Ingot N-oxide; 2- (H [(3-cyanobenzoate) amino] methyl} hexahydrogenated N-oxide; 4- (M [(2,3 -Dibromo-5-methylbenzylidene) amino] methyl} -1,2,3,6-tetrahydropyridinyl) pyridine N-oxide; 2- (1-{[( 4-bromobenzoate) amino], methyl} hexahydro 12-Hydro 4-yl >> Hydroxybenzyl oxide; 2- (M [(3-Chloro-4-methylbenzidine (Amino) amino] methyl} hexahydropyridyl) N-oxide; 2- (1-{[methyl (3 · methylbenzyl) amino] methyl} hexahydropyridine 4-groups> specific N-oxides; 2- (1-{[(3-nitrobenzylidene) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxides; 2- (1-{[(2-chloro-5-methylbenzylidene) amino] methyl} hexahydropyridin-4-yl) _pyridine N-oxide; 2- (1- { [(3-methoxy-2-methylbenzylidene) amino] methyl} hexahydropyridine ice-based sulfonium N-oxide; 2- (1-{[(4-chloroyl methoxy Benzamidine) amino] methyl} hexahydro Pyridin-4-yl) pyrimidine N-oxide; N- (3-methylphenyl) -2- (3 • pyridin-2-ylhexahydropyridin-1-yl) acetamidine; N- (3 -Methylphenyl) -2- (3-pyridin-2-yltetrahydropyrrole-1-yl) acetamidamine; N- (l-methyl-1H-benzimidazol-2-yl) _2- [ 3- (1,3-pyrazol-2-yl) hexahydropyridine- 85228 -55- 200404539 1-基]乙醯胺； 一 N-(l-甲基-1H-苯并咪唑1基）-2_[3_(1，3^塞唑冬基）四氫吡咯_ 1-基]乙醯胺； 2-(2-爷基四氫吡咯-1-基）1(3_氟苯基）乙醯胺；及 N-(4-氟苯基）-2-(3-噻吩-2-基四氫吡咯-1-基）乙醯胺。 66.根據申請專利範圍第！項之方法，其中式①化合物為孓屮 {[(3-甲基苯甲醯基)胺基；|甲基}冰六氫吡啶基)吡錠诈氧化物。 67· —種在哺乳動物中治療性功能障礙之方法，其包括對該籲 哺乳動物投予治療上有效量之式（I)化合物，或其藥學上 可接受之鹽、酯、醯胺或前體藥物，且併用藥學上可接 受之載劑。 68·根據申請專利範圍第67項之方法，其中式①化合物為 {[(3-甲基苯甲醯基)胺基]甲基丨冰六氫吡啶基)吡錠化氧化物。 69· —種在哺乳動物中治療性功能障礙之方法，其包括對該 哺乳動物投予治療上有效量之式①化合物，或其藥學上 可接文之鹽、酯、醯胺或前體藥物，且併用磷酸二酯酶5 φ 抑制劑。 7〇·根據申請專利範圍第69項之方法，其中式①化合物為以μ {[(3甲基表甲驢基)胺基]甲基丨冰六氫峨淀基)ρ比錠化氧化物。 71. —種在哺乳動物中治療性功能障礙之方法，其包括對該 哺乳動物投予治療上有效量之式①化合物，或其藥學上 可接文之鹽、醋、醯胺或前體藥物，且併用腎上腺素能 雙體结抗劑。 72. 根據申請專利範圍第Ή項之方法，其中式①化合物為^卜85228 -55- 200404539 1-yl] acetamidamine; mono-N- (l-methyl-1H-benzimidazole 1yl) -2_ [3_ (1,3 ^ setazolyl) tetrahydropyrrole_ 1- Yl] acetamidinium; 2- (2-decyltetrahydropyrrole-1-yl) 1 (3-fluorophenyl) acetamidinium; and N- (4-fluorophenyl) -2- (3-thiophene 2-yltetrahydropyrrole-1-yl) acetamidamine. 66. According to the scope of patent application! The method according to item 1, wherein the compound of formula ① is {{((3-methylbenzylidene)) amino group; | methyl} benzylhydropyridyl) pyridine oxide. 67. A method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof. And a pharmaceutically acceptable carrier. 68. The method according to item 67 of the application, wherein the compound of formula (1) is {[(3-methylbenzyl) amino] methyl 丨 hexylpyridyl) pyridinized oxide. 69 · —A method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof , And combined with phosphodiesterase 5 φ inhibitor. 70. The method according to item 69 of the scope of the patent application, wherein the compound of formula (1) is an ingot oxide with a μ ([(3methylepidonyl) amino] methyl 丨 hexylhydrogenide) ratio. . 71. A method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable salt, vinegar, amidine, or prodrug thereof , And combined with adrenaline-resistant diploid agent. 72. The method according to item 范围 of the scope of patent application, wherein the compound of formula ① is ^ bu 85228 -56- 200404539 {[(3-甲基苯甲醯基)胺基]甲基卜4-六氫吡啶基风錠n-氣化物。 73.—種在哺乳動物中治療性功能障礙之方法，其包括對該 哺乳動物投予治療上有效量之式①化合物，或其藥學上 可接受之鹽、酯、醯胺或前體藥物，且併用多巴胺催動 劑。 74·根據申請專利範圍第73項之方法，其中式①化合物為2-(μ {[(3-甲基苯甲酸基)胺基]甲基丨冰六氫吡啶基)吡錠队氧化物。 75·—種在哺乳動物中治療男性勃起功能障礙之方法，其包 _ 括對孩需要此種治療之哺乳動物投予治療上有效量之式① 化合物’或其藥學上可接受之鹽、酯、醯胺或前體藥物。 76·根據申請專利範圍第75項之方法，其中式①化合物為2-(μ {[(3-甲基苯甲酿基)胺基]甲基卜4-六氫吡啶基)吡錠怵氧化物。 77· —種在哺乳動物中治療女性性功能障礙之方法，其包括 對孩需要此種治療之哺乳動物投予治療上有效量之式① 化合物，或其藥學上可接受之鹽、酯、醯胺或前體藥物。 78·根據中請專利範圍第77項之方法，其中式①化合物為2·(μ _ {[Ο甲基苯甲酿基)胺基]甲基卜4_六氫吡啶基)吡錠n-氣化物。 79· —種在哺乳動物中治療病症之方法，該病症係選自包括 〜與血f病症、炎性病症、注意力不足活動過度病症、 阿耳滋海默氏疾病、藥物濫用、巴金生氏病、精神分裂 症、焦慮、心情病症及抑營，其包括對該需要此種治療 &lt;哺乳動物投予治療上有效量之式（I)化合物，或其藥學 上可接文之鹽、酯、醯胺或前體藥物。 8〇·根據申請專利範圍第79項之方法，其中式①化合物為冲 遠 85228 -57- 200404539 {[(3_甲基苯甲醯基)胺基]甲基卜4-六氫吡啶基比錠队氧化物。 81·—種式（Π)化合物85228 -56- 200404539 {[(3-methylbenzylidene) amino] methylbull 4-hexahydropyridyl wind ingot n-gas. 73. A method for treating sexual dysfunction in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof, And dopamine activator was used in combination. 74. The method according to item 73 of the scope of patent application, wherein the compound of formula ① is 2- (μ {[(3-methylbenzoate) amino] methyl 丨 hexylpyridyl) pyridine oxide. 75 · —A method for treating male erectile dysfunction in mammals, which includes administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula ① or a pharmaceutically acceptable salt or ester thereof , Amidine, or prodrugs. 76. The method according to item 75 of the patent application, wherein the compound of formula ① is 2- (μ {[((3-methylbenzyl) amino] methyl] 4-hexahydropyridyl) pyridine) oxidized Thing. 77 · —A method for treating female sexual dysfunction in a mammal, which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula ①, or a pharmaceutically acceptable salt, ester, or hydrazone Amine or prodrug. 78. The method according to item 77 of the patent application, wherein the compound of formula ① is 2 · (μ _ {[0methylbenzyl) amino] methylbull 4-hexahydropyridyl) pyridine n- Gasification. 79 · —A method for treating a condition in a mammal, the condition being selected from the group consisting of a blood condition, an inflammatory condition, a hyperactivity disorder, Alzheimer's disease, drug abuse, and Buckingson's Diseases, schizophrenia, anxiety, mood disorders, and depression, which include administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof , Amidine, or prodrugs. 80. The method according to item 79 of the scope of patent application, wherein the compound of formula ① is Chongyuan 85228 -57- 200404539 {[((3-methylbenzyl) amino) methyl] 4-hexahydropyridyl ratio Ingot team oxide. 81 · —Species (Π) compounds 或其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 A係選自包括芳基、芳烷基、環烷基及環烷基烷基； L 係選自包括-N(R7)C(0)-、-C(0)N(R7)_、-N(R7)C(S)-及 _ C(S)N(R7)-其中-N(R7)C(0)-、-C(0)N(R7)-、-N(R7)C(S)·及-C(S)N(R7)-之左端係連接至A，而右端係連接至D ; D係選自包括次烷基、氟次烷基及羥基次烷基； Z係選自包括N、C及CRB ; RA係選自包括氫與烷基； RB係選自包括氫、烷基及鹵素； 當Z為C時’…為一個鍵結，而當Z為N或CRB時，…為 不存在； B係選自包括Or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof, wherein A is selected from the group consisting of aryl, aralkyl, cycloalkyl, and cycloalkylalkyl; L is selected from the group consisting of -N (R7 ) C (0)-, -C (0) N (R7) _, -N (R7) C (S)-, and C (S) N (R7) -where -N (R7) C (0)- The left end of -C (0) N (R7)-, -N (R7) C (S), and -C (S) N (R7)-is connected to A, and the right end is connected to D; D is selected From the group consisting of alkylene, fluoroalkylene and hydroxyalkylene; Z is selected from the group consisting of N, C and CRB; RA is selected from the group consisting of hydrogen and alkyl; RB is selected from the group consisting of hydrogen, alkyl and halogen; When Z is C '... is a bond, and when Z is N or CRB, ... is absent; B is selected from the group consisting of &amp;、&amp;、R3及R4各獨立選自包括氫、烷氧基、烯基、 烷基、烷基亞磺醯基、烷基磺醯基、烷硫基、炔基、烷 85228 -58- 200404539 氧羰基、烷羰基、烷羰基氧基、羧基、氰基、甲醯基、 i素、i燒氧基、_燒基、輕基、輕烷基、疏基、硝基 、-NZiZ2、（NZSZ4)燒基、（NZ3Z4)羧基及(NZ3Z4)續醯基； Z!與Z2各獨立選自包括氫、烷基、烷羰基、烷基磺醯 基、芳基、芳烷基、芳烷基磺醯基、芳基磺醯基及甲醯 基； Z3與Z4各獨立選自包括氫、燒基、芳基及芳燒基； X係選自包括n(r6 )、〇及s ; Y係選自包括C(R4)與N ; R6係選自包括氫與燒基；及 R7係選自包括氫與燒基。 82·根據申請專利範圍第81項之化合物，其中 A為芳基； B為&amp;, &amp;, R3 and R4 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkanes 85228 -58 -200404539 oxycarbonyl, alkoxycarbonyl, alkoxycarbonyl, carboxyl, cyano, methyl, thiol, thiol, thiol, thiol, light, light alkyl, thiol, nitro, -NZiZ2, (NZSZ4) alkyl, (NZ3Z4) carboxyl and (NZ3Z4) continyl; Z! And Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, aralkyl, and arane Sulfosulfanyl, arylsulfonyl, and methylfluorenyl; Z3 and Z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and aryl; X is selected from the group consisting of n (r6), 0, and s; Is selected from the group consisting of C (R4) and N; R6 is selected from the group consisting of hydrogen and alkyl; and R7 is selected from the group consisting of hydrogen and alkyl. 82. The compound according to the scope of application for patent item 81, wherein A is aryl; B is Z為N ; …為不存在；及 L 為-N(R7)C(0)… 83·根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、_素、_燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZi Z2 ; 85228 -59- 200404539Z is N; ... is absent; and L is -N (R7) C (0) ... 83. Compound according to item 81 of the scope of patent application, where A is aryl, where aryl is phenyl, and is 1, 2, 3, 4 or 5 substituent substitutions, the substituents are selected from the group consisting of fluorenyl, alkoxy, alkoxycarbonyl, alkynyl, thiol, hexyl, cyano, , Haloalkyl, methylenedioxy, nitro, phenyl, and -NZi Z2; 85228 -59- 200404539 Ri係選自包括氫、燒基、氰基、鹵燒基、li素、硝基 、（nz3z4)烷基及（NZ3Z4)羰基； R2與R4為氮， r3係選自包括氫與羥基； Z為N ; …為不存在； D 為-CH2-;及 L 為-N(R7)C(0)-。 84.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基係選自包括四氫莕基與2,3-二氫-1H-Ri is selected from the group consisting of hydrogen, alkyl, cyano, haloalkyl, lidin, nitro, (nz3z4) alkyl, and (NZ3Z4) carbonyl; R2 and R4 are nitrogen, and r3 is selected from the group consisting of hydrogen and hydroxyl; Z Is N;… is absent; D is -CH2-; and L is -N (R7) C (0)-. 84. The compound according to item 81 of the application, wherein A is aryl, and the aryl group is selected from the group consisting of tetrahydrofluorenyl and 2,3-dihydro-1H- 心係選自包括氫、烷基、氰基、画烷基、画素、硝基(NZ3Z4) 烷基及(NZ3Z4)羰基； R_2與R4為氮， r3係選自包括氫與羥基； Z為N ; —為不存在， D 為-CH2 -;及 85228 -60- 200404539 L 為-N(R7)C(0)-。 85.根據申請專利範圍第81項之化合物，其中 A為芳基； B為The heart system is selected from the group consisting of hydrogen, alkyl, cyano, alkyl, pixel, nitro (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R_2 and R4 are nitrogen, and r3 is selected from hydrogen and hydroxyl; Z is N ; Is absent, D is -CH2-; and 85228 -60- 200404539 L is -N (R7) C (0)-. 85. The compound according to the scope of application for patent item 81, wherein A is aryl; B is Z為N ; —為不存在，及 L 為-N(R7)C(0)… 86.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、鹵素、1¾燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Z is N;-is absent, and L is -N (R7) C (0) ... 86. The compound according to item 81 of the application, wherein A is aryl, wherein aryl is phenyl, 1, 2, 3, 4 or 5 substituents, the substituents are selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, thio, phenyl, cyano, halogen, halogen Haloalkyl, methylenedioxy, nitro, phenyl and -NZiZ2; R_2、R3及R4為氮， Z為N ; —為不存在， D 為-CH2-;及 L 為-N(R7)C(0)-。 87.根據申請專利範圍第81項之化合物，其中 A為芳基； 85228 -61 - 200404539 B為 Ζ為Ν ; —為不存在，及 L 為-N(R7)C(0)-。 88.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 鲁 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、鹵素、ii燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZi Z2 ; B為R_2, R3 and R4 are nitrogen, Z is N;-is absent, D is -CH2-; and L is -N (R7) C (0)-. 87. The compound according to item 81 of the application, wherein A is aryl; 85228 -61-200404539 B is Z is N;-is absent, and L is -N (R7) C (0)-. 88. The compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituent is selected from the group consisting of alkenyl , Alkoxy, alkoxycarbonyl, alkyl, thio, thio, cyano, halogen, ii, oxy, halo, methylenedioxy, nitro, phenyl, and -NZi Z2; B for R2與R3為氯； X 為 N(R6)、Ο 或 S ; Y為N ; Z為N ; …為不存在， D 為-CH2-;及 L 為-N(R7)C(0)-。 89.根據申請專利範圍第81項之化合物，其中 A為環烷基； B為 85228 -62- 200404539R2 and R3 are chlorine; X is N (R6), O or S; Y is N; Z is N; ... is absent, D is -CH2-; and L is -N (R7) C (0)-. 89. The compound according to item 81 of the patent application, wherein A is cycloalkyl; B is 85228 -62- 200404539 Z為N ; …為不存在；及 L 為-N(R7)C(0)-。 90.根據申請專利範圍第81項之化合物，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 基；Z is N; ... is absent; and L is -N (R7) C (0)-. 90. The compound according to item 81 of the scope of application, wherein A is a cycloalkyl group, wherein the cycloalkyl group is selected from the group consisting of cyclohexyl and gold steel alkyl; Ri係選自包括氮、燒基、氰基、iS燒基、素、硝基 、（nz3z4)烷基及（NZ3Z4)羰基； R2與R4為氮， r3係選自包括氫與羥基； Z為N ; —為不存在， D 為-CH]-，及 L 為-N(R7)C(0)- 〇 91.根據申請專利範圍第81項之化合物，其中 A為芳、)見基； B為Ri is selected from the group consisting of nitrogen, alkyl, cyano, iS, alkyl, nitro, (nz3z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen, and r3 is selected from the group consisting of hydrogen and hydroxyl; N;-is absent, D is -CH]-, and L is -N (R7) C (0)-〇91. According to the scope of application of the patent application No. 81 compound, wherein A is aromatic,) see group; B for 85228 -63- 200404539 Z為N ; …為不存在；及 i^_n(r7)c(o)_。 92.根據申請專利範圍第81項之化合物，其中 A為芳烷基，其中芳烷基之芳基為苯基，被〇、丨、2、 3、4或5個取代基取代，取代基選自包括婦基、烷氧基 ’元氧叛基、燒基、燒硫基、爷基、氯基、_素、齒燒 氣基、鹵燒基、亞甲二氧基、硝基、苯基及-ΝΖ! Z2 ;85228 -63- 200404539 Z is N;… is absent; and i ^ _n (r7) c (o) _. 92. The compound according to item 81 of the scope of patent application, wherein A is an aralkyl group, wherein the aryl group of the aralkyl group is a phenyl group, and is substituted by 0, 丨, 2, 3, 4, or 5 substituents. Including alkenyl, alkoxy, alkoxy, alkoxy, thio, thio, chloro, chloro, halogen, halogen, halyl, methylenedioxy, nitro, phenyl And -NZ! Z2; Ri係選自包括氫、烷基、氰基、_烷基、i素、硝基 、（nz3z4)烷基及(NZ3Z4)羰基； 與心為氫； R3係選自包括氫與羥基； Z為N ; …為不存在； D 為-CH2 -;及 L 為-N(R7)C(0)-。 93.根據申請專利範圍第81項之化合物，其中 A為芳基；Ri is selected from the group consisting of hydrogen, alkyl, cyano, alkyl, i-nitro, nitro, (nz3z4) alkyl, and (NZ3Z4) carbonyl; R is selected from the group consisting of hydrogen and hydroxyl; Z is N;… is absent; D is -CH2-; and L is -N (R7) C (0)-. 93. The compound according to the scope of application for patent item 81, wherein A is aryl; 85228 200404539 Z 為 CRb， —為不存在，及 L 為-N(R7)C(0)-。 94.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、齒素、lS烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZiZ?;85228 200404539 Z is CRb, —is absent, and L is -N (R7) C (0)-. 94. The compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, halide, 1S alkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZiZ ?; &amp;係選自包括氫、烷基、氰基、i烷基、||素、硝基 、（NZ3Z4)烷基及(NZ3Z4)羰基； R2與R4為氯， r3係選自包括氫與羥基； Z 為 CRb， Rb為氮， …為不存在， D 為-CH2-;及 L 為-N(R7)C(0)-。 95.根據申請專利範圍第81項之化合物，其中 A為芳基； B為&amp; is selected from the group consisting of hydrogen, alkyl, cyano, i-alkyl, || Z is CRb, Rb is nitrogen, ... is absent, D is -CH2-; and L is -N (R7) C (0)-. 95. The compound according to the 81st patent application range, wherein A is aryl; B is 85228 -65- 200404539 Z 為 CRb， —為不存在， L 為 _N(R7)C(0)-。 96.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、lS素、函烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZ! Z2 ;85228 -65- 200404539 Z is CRb, — is absent, L is _N (R7) C (0)-. 96. The compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, 1S element, alkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZ! Z2; X 為 N(R6)、Ο 或 S ; Y為N ; R2與R3為鼠， Z 為 CRb， Rb為氮， …為不存在， D 為-CH2-;及 L 為-N(R7)C(0)-。 97.根據申請專利範圍第81項之化合物，其中 A為芳基； B為X is N (R6), 0 or S; Y is N; R2 and R3 are mice, Z is CRb, Rb is nitrogen, ... is absent, D is -CH2-; and L is -N (R7) C ( 0)-. 97. The compound according to item 81 of the patent application, wherein A is aryl; B is C 85228 -66- 200404539 Z 為 CRb， …為不存在；及 L 為-N(R7)C(0)-。 98.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、iS素、卣烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZi Z2 ;C 85228 -66- 200404539 Z is CRb,… is absent; and L is -N (R7) C (0)-. 98. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is phenyl, and is substituted by 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, iS element, fluorenylalkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZi Z2; Z 為 CRB ; Rb為氮， …為不存在； L 為-N(R7)C(0&gt; ; D 為-CH2-;及 R2、R3及R4為氫。 99.根據申請專利範圍第81項之化合物，其中 A為芳基；Z is CRB; Rb is nitrogen, ... is absent; L is -N (R7) C (0 &gt;; D is -CH2-; and R2, R3 and R4 are hydrogen. 99. According to the 81st item Compounds, wherein A is aryl; Z 為 CRB ; 85228 -67- 200404539 —為不存在，及 L 為-N(R7)C(0)-。 100.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、函素、S烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Z is CRB; 85228 -67- 200404539 — is absent, and L is -N (R7) C (0)-. 100. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, functional group, S alkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZiZ2; Ri、R2、R3 及 R4 為風i， Z 為 CRg， Rb為氮， —為不存在， D 為-CH2-;及 L 為-N(R7)C(0)·。 101.根據申請專利範圍第81項之化合物，其中 A為環烷基； B為Ri, R2, R3 and R4 are wind i, Z is CRg, Rb is nitrogen,-is absent, D is -CH2-; and L is -N (R7) C (0) ·. 101. The compound according to item 81 of the patent application, wherein A is cycloalkyl; B is Z 為 CRB ; 為不存在；及 85228 -68- 200404539 L 為-N(R7 )C(0)- 〇 l〇2·根據申請專利範圍第81項之化合物，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 基； B為Z is CRB; is absent; and 85228 -68- 200404539 L is -N (R7) C (0)-〇 102. Compound according to item 81 of the scope of patent application, wherein A is cycloalkyl and The alkyl group is selected from the group consisting of cyclohexyl and gold steel alkyl; B is Ri係選自包括氫、燒基、氰基、鹵燒基、_素、硝基讲&amp; z4) 烷基及(NZ3Z4)羰基； 尺2與114為氫； R3係選自包括氫與羥基； Z CRb， Rb為氫； —為不存在； D 為-CH2 _，及 L 為-N(R7)C(0)… 103·根據申請專利範圍第81項之化合物，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkynyl, cyano, haloalkyl, nitro, nitro, z4) alkyl and (NZ3Z4) carbonyl; R 2 and 114 are hydrogen; R 3 is selected from including hydrogen and hydroxyl Z CRb, Rb is hydrogen; — is absent; D is —CH 2 —, and L is —N (R7) C (0)… 103. The compound according to item 81 of the scope of application, wherein A is aryl; B is Z為C ; 為一個键結；及 L 為-N(R7)C(0)… 85228 -69- 200404539 104.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、素、齒燒氧基、鹵院 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Z is C; is a bond; and L is -N (R7) C (0) ... 85228 -69- 200404539 104. The compound according to item 81 of the scope of patent application, wherein A is aryl and aryl is benzene Group, substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents are selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, hexyl, cyano, sulfone, Dentyloxy, haloyl, methylenedioxy, nitro, phenyl and -NZiZ2; Ri係選自包括氫、烷基、氰基、商烷基、函素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氮， R3係選自包括氫與羥基； Z為C ; …為'^個键結， D 為-CH2 -，及 L 為-N(R7)C(0)-〇 105.根據申請專利範圍第81項之化合物，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkyl, cyano, succinyl, halo, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen, and R3 is selected from the group consisting of hydrogen and hydroxyl; Z Is C;… is' ^ bonding, D is -CH2-, and L is -N (R7) C (0) -〇105. A compound according to item 81 of the scope of patent application, wherein A is aryl; B for Z為C ; 為一個鍵結；及 L 為-N(R7)C(0)-。 85228 -70- 200404539 1〇6·根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被〇、1、2、3、 4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧襞基 、烷基、烷硫基、苄基、氰基、鹵素、画烷氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZi Z2 ; B為Z is C; is a bond; and L is -N (R7) C (0)-. 85228 -70- 200404539 1〇6. The compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl, substituted with 0, 1, 2, 3, 4 or 5 substituents. The group is selected from the group consisting of fluorenyl, alkoxy, alkoxyfluorenyl, alkyl, alkylthio, benzyl, cyano, halogen, alkoxy, haloalkyl, methylenedioxy, nitro, benzene Base and -NZi Z2; B is X 為 N(R6)、0 或 S ; Y為 C(R4); R2與R3為氫； 係選自包括氫、烷基及氰基； Z為c ; …為一個键結； D 為-CH2-;及 L 為-N(R7)C(0)-。 1G7·根據申請專利範圍第81項之化合物，其中 A為環烷基； B為X is N (R6), 0 or S; Y is C (R4); R2 and R3 are hydrogen; selected from the group consisting of hydrogen, alkyl and cyano; Z is c;… is a bond; D is -CH2 -; And L is -N (R7) C (0)-. 1G7. The compound according to item 81 of the scope of patent application, wherein A is cycloalkyl; B is Z為C ; 〜為一個键結；及 L 為-N(R7)C(0)-。 85228 -71- 200404539 1〇8·根據申請專利範圍第81項之化合物，其中 A為環烷基，其中環烷基係選自包括 衣己基與金鋼烷 暴， B為 ?2 丄 R4. Ri係選自包括氫、燒基、氰基、函燒基、_素、確爲 、（NZA)燒基及(NZ3Z4)羰基； R2與R4為氫； &amp;係選自包括氫與羥基； Z為C ; …為一個鍵結； D 為-CH2-;及 L 為-N(R7 )C(0)- 〇 1〇9·根據申請專利範圍第81項之化合物，其中 A為芳基； B為 Z為N ; 為不存在，及 L 為-C(0)N(R7)_ 〇 110·根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被〇、1、2、3、 斗或5個 85228 -72- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、齒素、卣燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-ΝΖ! Z2 ;Z is C; ~ is a bond; and L is -N (R7) C (0)-. 85228 -71- 200404539 1〇8 · According to the scope of application of the patent No. 81 compound, wherein A is a cycloalkyl, wherein the cycloalkyl system is selected from the group consisting of hexyl and adamantane, B is? 2 丄 R4. It is selected from the group consisting of hydrogen, alkynyl, cyano, succinyl, sulfonium, indeed, (NZA) alkyl and (NZ3Z4) carbonyl; R2 and R4 are hydrogen; &amp; Is C;... Is a bond; D is -CH2-; and L is -N (R7) C (0)-〇09. · A compound according to item 81 of the scope of patent application, wherein A is aryl; B Z is N; is absent, and L is -C (0) N (R7) _ 〇110 · A compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl, and is , 1, 2, 3, or 5 85228 -72- 200404539 substituents, the substituents are selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkynyl, thiosulfanyl, hexyl, cyano, dentate Element, fluorenyloxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZ! Z2; Ri係選自包括氫、燒基、氰基、ώ燒基、鹵素、硝基 、（ΝΖ3Ζ4)烷基及（ΝΖ3Ζ4)羰基； 112與114為氫； r3係選自包括氫與羥基； Z為N ; …為不存在； D 為-CH2 -;及 L 為-C(0)N(R7)-。 111.根據申請專利範圍第81項之化合物，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkynyl, cyano, thiol, halogen, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; 112 and 114 are hydrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z is N;… are absent; D is -CH2-; and L is -C (0) N (R7)-. 111. The compound according to the scope of application for patent item 81, wherein A is aryl; B is Z為N ; …為不存在；及 L 為-C(0)N(R7)-。 112.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -73- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、ii素、ii燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Z is N; ... is absent; and L is -C (0) N (R7)-. 112. The compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl, substituted by 0, 1, 2, 3, 4, or 5 85228 -73- 200404539 substituents, and the substituents are selected Including alkenyl, alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, hexyl, cyano, sulfonium, sulfonyl, halo, methylenedioxy, nitro, phenyl, -NZiZ2; R2、R3及R4為鼠 Z為N ; —為不存在， D 為-CH2-;及 L 為-C(0)N(R7)-。 113.根據申請專利範圍第81項之化合物，其中 A為環烷基； B為R2, R3 and R4 are rats; Z is N;-is absent, D is -CH2-; and L is -C (0) N (R7)-. 113. The compound according to the scope of application for patent item 81, wherein A is cycloalkyl; B is Z為N ; —為不存在，及 L 為-C(0)N(R7)-。 114.根據申請專利範圍第81項之化合物，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷Z is N;-is absent, and L is -C (0) N (R7)-. 114. The compound according to item 81 of the application, wherein A is cycloalkyl, and the cycloalkyl is selected from the group consisting of cyclohexyl and adamantane 200404539 Rl係遠自包括氫、烷基、氰基、_烷基、_素、石“ 、（NZ3Z4)烷基及(NZ3Z4)羰基； 肖基 R2與為氫； R3係選自包括氫與羥基； Z為N ; …為不存在； D 為-CH2-;及 L 為-C(0)N(R7)—200404539 R1 is far from including hydrogen, alkyl, cyano, _alkyl, _ element, stone ", (NZ3Z4) alkyl and (NZ3Z4) carbonyl; Rho is R2 and is hydrogen; R3 is selected from including hydrogen and hydroxyl Z is N;… is absent; D is -CH2-; and L is -C (0) N (R7) — 115.根據申請專利範圍第μ項之化合物，其中 A為芳基； B為 aXR Λ N r4. z 為 crb ; 為不存在，及 L 為-C(0)N(R7)-。 116·根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被〇、1、2、 、 4或5個 取代基取代’取代基選自包括晞基、燒氧基、燒氧羰其 、烷基、烷硫基、苄基、氰基、i素、ii烷氧基、鹵燒 基、亞曱二氧基、硝基、苯基及-ΝΖ! Z2 ; B為 ?2 RinA^R3 ί0^4· 85228 -75- 200404539 Ri係選自包括氫、燒基、氰基、鹵燒基、_素、硝基 、（NZ3Z4)烷基及(NZ3Z4)羰基； R2與民4為氮； r3係選自包括氫與羥基； Z 為 CRB ; Rb為氮； …為不存在， D為-CH2-;及 籲 L 為-C(0)N(R7)-。 117.根據申請專利範圍第81項之化合物，其中 A為芳基； B為115. The compound according to item μ of the application, wherein A is aryl; B is aXR Λ N r4. Z is crb; is absent, and L is -C (0) N (R7)-. 116. The compound according to item 81 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 4, or 5 substituents. The substituent is selected from the group consisting of fluorenyl, Oxy, oxocarbonyl, alkyl, alkylthio, benzyl, cyano, i-prime, ii-alkoxy, haloalkyl, fluorenyldioxy, nitro, phenyl, and -NZ! Z2; B is? 2 RinA ^ R3 00228 · 75-200404539 Ri is selected from the group consisting of hydrogen, alkynyl, cyano, haloalkyl, sulfonium, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 are nitrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z is CRB; Rb is nitrogen; ... is absent, D is -CH2-; and L is -C (0) N (R7)-. 117. The compound according to the scope of application for patent item 81, wherein A is aryl; B is Z 為 CRb， —為不存在，及 L 為·0(0)Ν(Ι17)-。 118.根據申請專利範圍第81項之化合物，其中 Α為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 、说基、硫基、卞基、氣基、齒素、氧基、 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Z is CRb,-is absent, and L is · 0 (0) N (I17)-. 118. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is phenyl, and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl, hydrocarbyl, thio, fluorenyl, carbamoyl, halide, oxy, methyl, methylenedioxy, nitro, phenyl, and -NZiZ2; 85228 -76- 200404539 R_2、R3及R4為氯； Z 為 CRg， Rb為氯； …為不存在； D 為-CH2 -，及 L 為 _C(0)N(R7)_。 119.根據申請專利範圍第81項之化合物，其中 A為芳基； _85228 -76- 200404539 R_2, R3 and R4 are chlorine; Z is CRg, Rb is chlorine; ... is absent; D is -CH2-, and L is _C (0) N (R7) _. 119. The compound according to the scope of application for patent item 81, wherein A is aryl; Z 為 CRB ; —為不存在，及 L 為-C(0)N(R7)-。 120.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、芊基、氰基、卣素、i烷氧基、鹵烷 基、亞曱二氧基、硝基、苯基及-NZiZ2 ;Z is CRB;-is absent, and L is -C (0) N (R7)-. 120. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, fluorenyl, cyano, halogen, i-alkoxy, haloalkyl, fluorenyldioxy, nitro, phenyl, and -NZiZ2; 85228 77- 200404539 Rl、R】、R3及民4為鼠， Z 為 CRb， Rb為氮， —為不存在， D 為-CH2 -;及 L 為-C(0)N(R7)-。 121.根據申請專利範圍第81項之化合物，其中 A為環烷基； B為85228 77- 200404539 R1, R], R3 and R4 are rats, Z is CRb, Rb is nitrogen,-is absent, D is -CH2-; and L is -C (0) N (R7)-. 121. The compound according to the scope of application for patent item 81, wherein A is cycloalkyl; B is Z 為 CRB ; —為不存在，及 L 為-C(0)N(R7)-。 122.根據申請專利範圍第81項之化合物，其中 A為環烷基，其中環烷基係選自包括環己基與金鋼烷 基； B為Z is CRB;-is absent, and L is -C (0) N (R7)-. 122. The compound according to item 81 of the patent application, wherein A is cycloalkyl, wherein the cycloalkyl system is selected from the group consisting of cyclohexyl and gold steel alkyl; B is Ri係選自包括氫、燒基、氰基、iS燒基、iS素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與R4為氮， r3係選自包括氫與羥基； 85228 -78- 200404539 Z 為 CRg， Rb為氯； …為不存在； D 為-CH]-，及 L 為-C(0)N(R7)-。 123.根據申請專利範圍第81項之化合物，其中 A為芳基； B為Ri is selected from the group consisting of hydrogen, alkyl, cyano, iS, alkyl, iS, nitro, (NZ3Z4) alkyl, and (NZ3Z4) carbonyl; R2 and R4 are nitrogen, and r3 is selected from hydrogen and hydroxyl; 85228 -78- 200404539 Z is CRg, Rb is chlorine; ... is absent; D is -CH]-, and L is -C (0) N (R7)-. 123. The compound according to the scope of application for patent item 81, wherein A is aryl; B is Z為C ; …為一個键結；及 L 為-C(0)N(R7)-。 124.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、姨硫基、卞基、氣基、1¾素、1¾燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZJ2 ;Z is C; ... is a bond; and L is -C (0) N (R7)-. 124. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, thio, fluorenyl, alkyl, 1¾, 12¾, haloxy, methylenedioxy, nitro, phenyl and -NZJ2 Ri係選自包括氫、燒基、氰基、1¾燒基、自素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； 112與114為氫； 85228 -79- 200404539 R3係選自包括氫與羥基； Z為C ; …為一個键結； D 為-CH2 _，及 L 為-C(0)N(R7)·。 125.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為莕基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、节基、氰基、素、卣燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Ri is selected from the group consisting of hydrogen, alkynyl, cyano, 12-alkyl, sulfonium, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; 112 and 114 are hydrogen; 85228 -79- 200404539 Hydrogen and hydroxyl; Z is C;… is a bond; D is -CH2 _, and L is -C (0) N (R7) ·. 125. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is fluorenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, benzyl, cyano, sulfonyl, pyrenyloxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZiZ2; Ri係選自包括氫、燒基、氰基、自燒基、鹵素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； 112與114為氫； R3係選自包括氫與羥基； Z為C ; …為一個鍵結； D 為-CH2-;及 L 為-C(0)N(R7)-。 126.根據申請專利範圍第81項之化合物，其中 A為芳基； B為 85228 -80- 200404539Ri is selected from the group consisting of hydrogen, alkyl, cyano, self-baking, halogen, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; 112 and 114 are hydrogen; R3 is selected from the group consisting of hydrogen and hydroxyl; Z is C; ... is a bond; D is -CH2-; and L is -C (0) N (R7)-. 126. The compound according to item 81 of the patent application, wherein A is aryl; B is 85228 -80- 200404539 z為c ; …為一個键結；及 L 為-C(0)N(R7)-。 127.根據申請專利範圍第81項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、素、1¾燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZJ2 ; B為z is c; ... is a bond; and L is -C (0) N (R7)-. 127. The compound according to item 81 of the patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, hexyl, cyano, phenyl, 1¾ alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZJ2; B is 與R3為氯， X 為 N(R6)、Ο 或 S ; Y為N ; Z為C ; …為一個鍵結； D 為-CH2-;及 L 為-C(0)N(R7)-。 128.根據申請專利範圍第81項之化合物，其中 A為環燒基； B為And R3 is chlorine, X is N (R6), 0 or S; Y is N; Z is C; ... is a bond; D is -CH2-; and L is -C (0) N (R7)-. 128. The compound according to the scope of application for patent item 81, wherein A is cycloalkyl; B is R3 r4· 85228 -81 - 200404539 z為c ; …為一個鍵結；及 L 為-C(0)N(R7)-〇 I29·根據申請專利範圍第81項之化合物，其中 A為環燒基’其中環燒基係選自包括環己基與金鋼貌 基； B為R3 r4 · 85228 -81-200404539 z is c;… is a bond; and L is -C (0) N (R7) -〇I29. The compound according to item 81 of the scope of patent application, wherein A is cycloalkyl 'Wherein the cycloalkyl group is selected from the group consisting of cyclohexyl and gold steel base; B is Ri係選自包括氫、烷基、氰基、_烷基、_素、硝基 、（NZJ4)院基及(NZ3Z4)羰基； 與R4為氫； r3係選自包括氫與羥基； Z為c ; …為一個鍵結； D 為-CH2-;及 L 為-C(0)N(R7)-〇 l3〇.根據申請專利範圍第81項之化合物，其係選自包括 N-(3-甲基苯基）-2-[4-(2-嘧啶基）小六氳吡畊基]乙醯胺； 曱基苯基）-2-[4-(2-p比淀基）-1-六氫外1：畊基]乙醯胺； 2-[4-(3-氰基-2-外I：淀基）-1-六氫峨p井基]-N-(3-甲基苯基）乙龜 胺； 2-[4-(3-氰基-2-P比淀基）-1-六氫ρ比啡基]-N-(3-硝基苯基）乙釅 85228 -82- 200404539 2-[4-(3-氰基-2-吡啶基&gt;1-六氫吡畊基]-N-[3-(三氟甲基）苯 基]乙醯胺； N-(3-氰基苯基）-2-[4-(3-氰基-2-吡啶基&gt;1-六氫吡畊基]乙醯 胺； 2-[4-(3-氰基-2-吡啶基&gt;1-六氫吡畊基]-N-苯基乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(4-氟苯基）乙醯胺； 2-[4-(3-氰基-2-吡啶基）-1-六氫吡畊基]-N-(3,5-二甲基苯基） 乙醯胺； 2-[4·(3_氰基-2-吡啶基）小六氫吡畊基]-N-(2,3-二甲基苯基） 乙醯胺； 2-[4-(3-戴基-2-ϊ1比淀基）_1·ττ氮p比呼基]-N-(2-甲基苯基）乙酿 胺； 2-[4-(3-氣基-2-p比淀基）-1-穴鼠峨啡基]-N-(2,5-二甲基苯基） 乙醯胺； N-(3-氯苯基）-2·[4-(3·氰基-2-τ7比淀基）-1-六氫p比p井基]乙酸胺； N-(3-氯基-4-氟苯基）-2-[4-(3-來基-2〜比淀基）_1 •六氫p比π井基] 乙醯胺； 2-[4-(3-氣基-2-外b違基）-1_κ鼠说井基]-N-(3,4,5-三甲氧基苯 基）乙驗胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-[4-氟基各(三氟甲 基）苯基]乙醯胺； 2-[4-(3-氰基-2-吡啶基)小六氫吡畊基]-Ν-[3-氟基-5-(三氟甲 基）苯基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-[2-氟基-5_(三氟甲 85228 -83- 200404539 基）苯基]乙酸胺； 2-[4-(3-氰基-2-p比淀基）-1-ά氣批u井基]-N-[2-氟基_3-(三氟甲 基）苯基]乙醯胺； 2-[4-(3-氰基-2-p比淀基）-1-ττ氫p比井基]_N-(4-氟基-3-甲基苯 基）乙醯胺； 2-[4-(3-氰基-2-ρ比淀基）-1-六氫外b 0井基]-N-(2-氟苯基）乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(2-甲氧苯基）乙醯 胺； 2-[4-(3-散基-2-ρ比淀基）-1-ττ氣外b u井基]-N-(2-硝基苯基）乙酿 胺； 2-[4-(3-孰基-2-ρ比淀基）-1-ττ氯说p井基]-N-[2-(三氟甲基）苯 基]乙醯胺； N-苯基-2-[4_(2·ρ比淀基氯卩比呼基]乙酿胺； Ν-(3-甲基苯基）-2-[4-(1，3-嘧唑-2-基）-1-六氫吡畊基]乙醯胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-(4-甲基苯基）乙醯 胺； N-(3-甲基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(3-甲基苯基）-2-[4-(6-酮基-1(6H)-嗒畊基）小六氫吡啶基] 乙醯胺； N-(2,6-二甲基苯基)-2-[4-(2-嘧吩基）小六氫吡啶基]乙醯胺； N-(2,5-二甲基苯基)-2-[4-(2-嘧吩基）-1-六氫吡啶基]乙醯胺； N-(2-甲基苯基）-2-[4-(2-噻吩基）-1-六氫吡啶基]乙醯胺； N-(3-氣基-4-氣苯基）-2-[4-(2-p塞吩基）_1-ττ氮p比淀基]乙胺， N-(4_溴苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； 85228 -84- 200404539 Ν-(2,6·二〒基苯基）-2-[4-(2-p比淀基）-1_六氯外b淀基]乙酿胺， N-(2-硝基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； N-(3-硝基苯基）-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2,4-二氟苯基）-2_[4-(2_吡啶基）-1-六氫吡啶基]乙醯胺； N_(2,5-二甲基苯基)-2-[4-(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2-甲基苯基）-2_[4-(2-p比淀基）-1·ή A ?比淀基]乙酿胺， N-(4-甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； 2-[4-(2-吡啶基）小六氫吡啶基]-N-[3-(三氟甲基）苯基]乙醯 鲁 胺； 4-({[4-(2-吡啶基）-1-六氫吡啶基]乙醯基}胺基）苯甲酸乙酯； N-(3-氣基-4-甲基苯基）_2-[4-(2-吡啶基）小六氫吡啶基]乙醯 胺； N-(2-氣基苯基）-2-[4·(2-卩比淀基）-1-ττ氮卩比淀基]乙酿胺， N-(3-氯苯基）-2-[4-(2-ρ比淀基）-1-ττ鼠峨淀基]乙酿胺， 2-[4-(3-氰基-2-吡啶基）小六氫吡啶基]-N-(3-甲基苯基）乙醯 胺； · 2-(3’，6’-二氫-2,4’-聯吡啶-r(2’H)_基）-N-(3-甲基苯基）乙醯胺； 2-(3’,6’-二氫_2,聯吡啶-Γ(2Ή)_基）-N-(2,6_二甲基苯基）乙醯 胺； 2-(3’，6f-二氫-2,4’_聯吡啶-Γ(2Ή)·基）_N-(2-硝基苯基）乙醯胺； 2_(3*，6f-二氯-2,4*-聯p比淀-Γ(2Ή)-基）-N-(3-硝基苯基）乙驗胺； 2-(3'6’_二氮-2,4’-聯p比淀-1’(2Ή)-基)-N-(4-氣苯基）乙酸胺； N-(2,4-二氟苯基)-2_(3\6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； 2-(3’，心二氫-2,聯吡啶_1’(2Ή)·基）-Ν-(2,5-二甲基苯基）乙醯 85228 -85- 200404539 胺； 2-(3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-N-(2-甲基苯基）乙醯胺； N_環己基-2-(3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； 2-(3’，6’-二氫聯吡啶-1’(2Ή)·基）-Ν-(4-甲基苯基）乙醯胺； 2-(3’，6匕二氫_2,4’-聯吡啶_1’(2Ή)·基）·Ν_[3-(三氟甲基）苯基]乙 醯胺； 4-[(3’，6’-二氫-2,4f-聯吡啶-Γ(2Ή)-基乙醯基）胺基]苯甲酸乙 酯； Ν-[2-氯基-5-(三氟甲基）苯基]-2-(3f，6’-二氫-2,4’-聯吡啶_Γ(2Ή)_ 基）乙醯胺； Ν-(3_氯基-4-甲基苯基）-2-(3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙 醯胺； Ν-(2·氰基苯基)-2-(3’，6’_二氫-2,4’-聯吡啶_1’(2’11)_基）乙醯胺； Ν-(3_氯苯基）-2-(3’，6f-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯胺； Ν-(3-氯基-4-氟苯基)-2-(3’，6’·二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯 胺； 2·(3’，6’·二氫_2,-聯吡啶·Γ(2Ή)-基）-Ν-[4-(三氟甲氧基）苯基] 乙醯胺； 2-(3f，6’-二氫-2,4’-聯吡啶·Γ(2Ή)_基）-Ν-[2-(三氟甲基）苯基]乙 醯胺； Ν_(4-氯苯基)-2-(3’，6f-二氫-2,4f-聯吡啶-Γ(2Ή)·基）乙醯胺； Ν-(2,3-二氯苯基)-2-(3f，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）乙醯胺； 乂(3,5-二氯苯基)-2-(3’乂二氫-2,4’-聯吡啶-1’(2’11)-基）乙醯胺； 2-(3f，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基）-Ν-(4-氟基-2-甲基苯基）乙 85228 -86- 200404539 醯胺； N-(4-氟苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； N-(3,5-二氯苯基）-2-[4“(2-吡啶基）-1-六氫吡啶基]乙醯胺； N-(2,3-二氯苯基）-2-[4-(2·吡啶基）_1_六氫吡啶基]乙醯胺； 2- [4-(2-吡啶基）-1-六氫吡啶基]-Ν-[2-(三氟甲基）苯基]乙醯 胺； Ν-(3-氯基-4-氟苯基&gt;2-[4-(2-吡啶基）小六氫吡啶基]乙醯胺； 2·[4-(2-吡啶基）-1-六氫吡啶基]-Ν-[4-(三氟甲氧基）苯基]乙 _ 醯胺； Ν-環己基-2-(3'4’，5'6’_四氫-2Ή-[2,4’]聯吡啶基·Γ-基）乙醯胺； 3- 甲基-Ν-{[4-(2-嘧啶基）-1-六氫吡畊基]甲基}苯甲醯胺； 3-甲基-N-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲醯胺； N-{[4-(3-氰基-2-吡啶基）-1-六氫吡畊基]甲基}-3-甲基苯甲 醯胺； Ν·{[4-(3-氰基-2-吡啶基）小六氫吡畊基]甲基}苯甲醯胺； Ν-{[4-(3_氰基-2-吡啶基）小六氫吡呼基]甲基}-4-甲基苯甲 鲁 醯胺； Ν-{[4-(3-氰基-2-吡啶基）小六氫吡畊基]甲基}-2-甲基苯甲 醯胺； Ν-{[4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲醯胺； 2-氯_N_{[4-(3-氣基-2-p比淀基）_1-ττ氯P比1(1井基]甲基}苯甲酿 胺； Ν-{[4·(3-氰基-2-吡啶基）小六氫吡畊基]甲基}-2-(三氟甲基） 苯甲醯胺； 85228 -87- 200404539 N-(3’，6’-二氫-2,聯吡啶-1’(2Ή)_基甲基）各甲基苯甲醯胺； Ν-(3’，6^二氫-2,聯吡啶-Γ(2Ή)-基甲基）-3-甲氧基苯甲醯胺； N-(3f，6’-二氫-2,聯吡啶-Γ(2Ή)-基甲基）各氟基苯甲醯胺； Ν·(3’，6·-二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基）-3,5-二氟苯甲醯胺； Ν-2-金鋼燒基-2-[4-(3-氣基-2-ρ比淀基）-1-六氫ρ比呼基]乙酿 胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-環己基乙醯胺； 2-[4-(3-氰基-2_吡啶基）小六氫吡畊基]-Ν-5,6,7,8-四氫小莕基 鲁 乙醯胺； 2- (3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-(4-氟基-2-甲基苯基）乙 醯胺； Ν-{[4-(2-吡啶基）-1-六氫吡啶基]甲基卜3-(三氟甲基）苯甲醯 胺； 3,5-«—甲氧基-Ν-{[4-(2-ρ比淀基）-1-ττ氯ρ比淀基]甲基}苯甲驗 胺； N-{[4-(2-峨咬基）-1-六氫说淀基]甲基}環己燒叛驗胺； 馨 3,4-二氟_N_{[4-(2-吡啶基）小六氫吡啶基]甲基}苯甲醯胺； 3- 氯-N-{[4-(2-吡啶基）-1-六氫吡啶基]甲基}苯甲醯胺； 2,3-二甲基-N-{[4-(2-吡啶基)-1_六氫吡畊基]甲基}苯甲醯胺； N-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）各(三氟甲基）苯甲 醯胺； 3-氯-Ν_(3’，6’-二氫·2,4’_聯吡啶_Γ(2Ή)_基甲基）苯甲醯胺； Ν-(3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基）環己烷羧醯胺； Ν-(3’，6’-二氫_2,4’_聯吡啶_Γ(2Ή&gt;基甲基）-3,4-二氟苯甲醯胺； 85228 -88- 200404539 N_(3，，6’_二氫-2,4’-聯吡啶-Γ(2Ή)_基甲基）·3,5_二甲氧基苯甲 醯胺； 2- (3\6f-二氫-2,4’-聯吡啶_Γ(2Ή)_基）_Ν-(3-硝基苯基）乙醯胺； Ν-1-金鋼燒基-2-[4-(3-氰基-2-外t淀基）小六氫外t呼基]乙醯 胺； 3- 甲基-N-{[2-甲基-4-(2-吡啶基）-1-六氫吡畊基]甲基}苯甲 醯胺； N-(3-甲基苯基）_2-[2-甲基冰(2-吡啶基）小六氫吡畊基]乙醯 春 胺； 3,5-二甲基-N-{[4-(2-吡啶基)小六氫吡啶基]甲基}苯甲醯胺； N-(3’，6’_二氫-2,4’-聯吡啶·1’(2Ή)_基甲基）-3,5_二甲基苯甲醯 胺； 3-甲基_Ν-[(3-甲基-3’，6’_二氫_2,4’_聯吡啶-Γ(2Ή)-基）甲基]苯 甲醯胺； Ν-[(3-氰基4,6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基）甲基]_3_甲基苯 甲驢胺； 春 Ν-(2,6-二甲基苯基）-2-(3-甲基-3’，6’-二氫 _2,4’_聯吡啶-1，(2Ή)-基）乙醯胺； Ν-(4-氟苯基）-2-(3-甲基-3，，6，-二氫-2,4，-聯吡啶 _1’(2，11)_基）乙醯 胺； Ν_(2,4_二氟苯基）冬(3•甲基-3’，6，·二氫-2,4，-聯吡啶·1’(2Ή)_ 基） 乙醯胺； 2-(3-甲基-3f，6’·二氫-2,4，-聯吡啶-1，(2Ή)-基）-Ν-(2-甲基苯基）乙 醯胺； 85228 -89- 200404539 2-(3-f 基 _3、6f_二氫 _2,4’_聯吡啶-1’(2Ή)·基）-Ν·[3-(三氟甲基） 苯基]乙醯胺； Ν-(3-氣基-4-氟苯基）_2-(3-甲基-3，，6’-二氫-2,4，-聯吡啶-Γ(2Ή)-基）乙醯胺； 2-(3-甲基-3f，6f-二氫-2,4’-聯吡啶-1’(2Ή)-基）-Ν-[4-(三氟甲氧基） 苯基]乙醯胺； 2-(3-甲基二氫-2,4，-聯吡啶-1，(2Ή)-基）-Ν-[2-(三氟甲基） 苯基]乙醯胺； Ν-(2,3-二氯苯基）-2-(3-甲基-3，，6，-二氫-2,4，-聯吡啶 _1，(2Ή)_基） 乙醯胺； 2·(3_ 甲基-3’，6f-二氫 _2,4，_聯吡啶-1，(2Ή)-基）_Ν-[4-(三氟甲基） 苯基]乙醯胺； 2-[4-(3-氰基-2-嘧吩基）-3,6-二氫-1(2Η)_吡啶基]_Ν_(3_甲基苯 基）乙醯胺； 2-(3-氰基-3f，6f-二氫 _2,4，_聯吡啶-1，(2Ή)-基）-Ν-(2,6-二甲基苯 基）乙醯胺； 2·(3-氰基-3f，6f_二氫-2,4，-聯吡啶-1，(2Ή)-基）-Ν-(4-氟苯基）乙醯 胺； 2-(3-氰基 _3’，6’-二氫 _2,4’_聯吡啶-1，(2Ή)-基）-Ν-(2,4-二氟苯基） 乙醯胺； 2-(3-氰基-3f，6f•二氫_2,4’·聯吡啶-1’(2Ή)-基）-Ν-(2-甲基苯基）乙 醯胺； 2-(3-氰基-3\6’-二氫-2,仁聯吡啶-1，(2Ή)-基）三氟甲基） 苯基]乙醯胺； 85228 -90- 200404539 2-(3-氰基_3’，6，_二氫_2,4f•聯吡啶_Γ(2Ή)·基）-N_[4-(三氟甲氧基） 苯基]乙醯胺； 2-(3-氰基 _3’，6’_二氫-2,4’-聯吡啶-1’(2Ή)-基）-N_[2-(三氟甲基） 苯基]乙醯胺； 2- (3-氰基-3’，6’-二氫-2,4’-聯吡啶 _Γ(2Ή)_基）_乂(2,3_二氯苯基） 乙醯胺； 3- 甲基-Ν-{[4-(6-酮基-1(611)_塔畊基）小六氫批淀基]甲基}苯 甲醯胺； φ Ν-(3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)-基甲基）小金剛烷羧醯胺； 3-甲基-N-{[4-(l，3-嘧唑-2-基）-3,6-二氫-1(2Η)-吡啶基]甲基}苯 甲醒胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-Ν-1，2,3,4-四氫-1-莕基 乙si胺； 2-[4-(3-氰基-2-吡啶基）小六氫吡畊基]-N-[(1S)-1，2,3,4-四氫-1- 萘基]乙醯胺； 2-[4-(3_氰基-2-吡啶基）小六氫吡畊基]-N-[(1R)-1，2,3,4-四氫-1- · 萘基]乙醯胺； N-(2,6-二乙基苯基)-2-[4-(2-吡啶基）-1_六氫吡啶基]乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡啶基]-N-(2,4,6-三氟苯基）乙醯胺； N-(4-氯基-2,6-二甲基苯基&gt;2-[4-(2-吡啶基）小六氫吡啶基] 乙醯胺； 2-[4-(2-吡啶基）-1-六氫吡啶基]-N-(2,4,6-三氯苯基）乙醯胺； N-(2,6-二乙基苯基）-2-(3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）乙醯 胺； 1&gt;〇4 85228 -91 - 200404539 2_(3f，6’_二氫-2,4’-聯吡啶-1’(2Ή)-基）-Ν-(2,4,6·三氟苯基）乙醯 胺； Ν-(4-氯基-2,6-二甲基苯基）-2-(3*，6L二氫-2,4*_聯峨淀 基）乙醯胺； 2-(3\6’_二氫-2,4’-聯吡啶_1’(2贤)_基）-Ν-(2,4,6-三氯苯基）乙醯 胺； Ν-{[4-(2-吡啶基）小六氫吡畊基]甲基卜3-(三氟甲基）苯甲醯 胺； · 3,5-二甲氧基-Ν-{[4-(2-外b淀基）-1-ττ氮ρ比p井基]甲基}苯甲酸 胺； N-{[4-(2-吡啶基）小六氫吡畊基]甲基}環己烷羧醯胺； N-(2,6_二甲基苯基)-2-[4-(2-外b淀基）·1-ττ氯外b p井基]乙酿胺； Ν-(4·氟苯基）-2-[4-(2-吡啶基）小六氫吡畊基]乙醯胺； Ν·(2,4-二氟苯基）-2-[4-(2-吡啶基）-1-六氫吡畊基]乙醯胺； N-(2-甲基苯基）-2-[4-(2-ρ比淀基氣吨p井基]乙酸胺； 2-[4-(2-吡啶基）小六氫吡畊基]-N-[3-(三氟甲基）苯基]乙醯 _ 胺；. N-(3-氯苯基）-2-[4-(2-吡啶基）小六氫吡畊基]乙醯胺； N·卞基-2-[4-(2-ρ比淀基）_1-ττ鼠p比卩井基]乙醒胺； 2-[4-(2-吡啶基）小六氫外t畊基]-Ν-[4-(三氟甲氧基）苯基]乙 醯胺； 2-[4-(2-吡啶基）-1-六氫吡畊基]-Ν-[2-(三氟甲基）苯基]乙醯 胺； Ν-(4-氯苯基）-2·[4-(2-ρ比淀基）-1-ή氮ρ比哨基]乙酸胺， 85228 -92- 200404539 N-(2,3_二氯苯基）-2-[4-(2-p比淀泰）小六氯吨p井基]乙酿胺； N-(3,4-二氯苯基）-2-[4-(2-p比淀基）-1-：γτ氫？比p井基]乙酸胺； 2- [4-(2-吡啶基&gt;1-六氫吡畊基]-N_[4-(三氟甲基）苯基]乙酸 胺； 3- 氯-N-{[4-(2-吡啶基）小六氫吡畊基]甲基}苯甲醯胺； 4- 氟基-3-甲基-N-{[4-(2-吡啶基）小六氫吡畊基]甲基}苯甲 醯胺； N-(3’，6’-二氫-2,4f-聯吡啶·1’(2Ή)_基甲基）-4-氟基-3-甲基苯甲 · 醯胺； 3-甲基-Ν-{[4·(1，3-噚唑-2-基）-3,6-二氫-1(2H)-吡啶基]甲基}苯 甲醯胺； 2-甲基-N-[(3-甲基-3’，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）甲基]苯 甲醯胺； 2-[4-(3-氰基-2-吡啶基）-1-六氫吡啶基]-Ν-(2,6-二甲基苯基） 乙醯胺； Ν-(3-甲基苯基）·2·[4-(3-甲基-2-ρ比淀基）·1-ττ氣口比ρ井基]乙酸 胺； 2-[4-(3-氰基-2·吡啶基）小六氫吡畊基]-Ν-[4-(三氟甲基）苯 基]乙醯胺； Ν-(2-乙基-6-甲基苯基）-2_[4-(2-ρ比淀基）-1-穴氮p比矣基]乙酉盈 胺； Ν-(2-異丙基_6_甲基苯基）-2-[4-(2-吡啶基）小六氫吡啶基]乙 醯胺； Ν-(2-氯基-6-甲基苯基）-2-[4-(2-吡啶基&gt;1-六氫吡啶基]乙醯 85228 -93- 200404539 胺； N-(2-甲氧基-6-甲基秦基）_2-[4-(2-ρ比症基）-1-ττ氯π比淀基]乙 醯胺； 2-(3f，6f-二氫-2,4f_聯吡啶-1’(2Ή)-基）-N-(2-乙基-6-甲基苯基）乙 醯胺； 2-(3’，仏二氫_2,4f-聯吡啶_1’(2Ή)_基）_N_(2-異丙基_6_甲基苯基） 乙醯胺； N_(2_氯基-6_甲基苯基）_2-(3，，6，-二氫-2,4，-聯吡啶-1，(2Ή)_基）乙 φ 醯胺； 2- (3’方-二氫-2,聯吡啶_1’(2Ή)·基）_Ν-(2-甲氧基各甲基苯基） 乙醯胺； 3- 氯-Ν-[(3-甲基·3’，6’-二氫-2,4’-聯吡啶-1’(2Ή)·基）甲基]苯甲 醯胺； 3_氟-Ν-[(3-甲基-3’，6·-二氫-2,4’-聯吡啶-1’(2Ή)-基）甲基]苯甲 醯胺； 3-甲基-N-{[(2S)-2-甲基-4-(2-吡啶基）-1-六氫吡畊基]甲基}苯 _ 甲醯胺； N-(3-甲基苯基）-2-[(2S)-2-甲基-4-(2-吡啶基）小六氫吡畊基] 乙醯胺； 3-甲基-N-{[(2R)-2_甲基-4-(2-吡啶基）小六氫吡啡基]甲基} 苯甲醯胺； N-(3-甲基苯基）-2-[(2R)-2-甲基-4-(2-吡啶基）小六氫吡呼基] 乙醯胺； 3-甲氧基-N-[(3_甲基-3f，6’-二氫-2,4’-聯吡啶-Γ(2Ή)-基）甲基] 85228 -94- 200404539 苯甲醯胺； 4-氟-N-[(3-甲基_3’，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基）甲基]苯甲 醯胺； 2-(3-氯基-3’，6·-二氫-2,4’-聯吡啶-Γ(2Ή)-基）-Ν-(2,6-二甲基苯 基）乙醯胺； 2- (3-氯基_3’，6f-二氫-2,4’_聯吡啶_1’(2况)_基）_Ν-(2-甲基苯基）乙 醯胺； Ν-(3’，6’_二氫-2,4’-聯吡啶-Γ(2Ή)-基甲基）-1•莕甲醯胺； φ Ν-{[4_(3-氰基-2-吡啶基）-1-六氫吡畊基]甲基}各氟基苯甲 醯胺； 3- 甲基-Ν-{[4-(1，3&lt;塞峻-2-基）-1•六氫ρ比淀基]甲基}苯甲酿胺； Ν-(3-甲基苯基）-2-{4-[3-(三氣甲基比淀基]-1-六氫峨_ 基}乙醯胺； Ν-(3-甲基苯基）_2-[4-(1，3-嘧唑-2-基）-3,6-二氫吡啶·1(2Η)-基] 乙醯胺； Ν-(3-甲基本基）-2-(4-隹吩-2-基-3,6-二氯ρ比淀-1(2Η)-基）乙驢 胺； 3-甲基·Ν-[(4-噻吩-2-基-3,6-二氫吡啶-1(2Η)-基）甲基]苯甲醯 胺； 2-[4-(1-甲基-1Η-咪唑冬基）-3,6-二氫吡啶·1(2Η)_基]_Ν-(3-甲 基苯基）乙醯胺； N-(3-甲基苯基）-2-[4-(3-硝基吡啶_2_基）六氫吡畊小基]乙醯 胺； 2_[4-(3-氯基吡啶_2_基）六氫吡畊-1-基]-N-(3-甲基苯基）乙醯 85228 -95- 200404539 胺； 2-{4-[3-(胺基甲基）峨咬-2-基]六氫外卜井-i_基卜n-(3-甲基苯 基）乙醯胺； 2-[4-(2-異丙氧基苯基）六氫吡畊-1-基]_n_(3-甲基苯基）乙酿 胺； 2-(4-{2-[(3-甲基苯基）胺基]-2-酮基乙基}六氫峨啡-1_基）於 鹼醯胺； N-(3-甲基苯基）_2-[(2S)-2-甲基-4-外1：淀-2-基六氫p比p井小基]_ 乙烷硫醯胺； 2-[4-(3-氰基p比淀-2-基）六氫被_ _1_基]-N-[3_(甲硫基）苯基] 乙醯胺； N-(3-第三-丁基苯基)-2-[4·(3-氰基吡啶-2-基）六氫吡啡-μ基] 乙醯胺； 2-[4-(3-氣基17比淀-2-基）ττ氫?比_ -1-基]·Ν-(3_氟苯基）乙醯胺； Ν-(3-溴苯基）-2-[4-(3-氰基ρ比淀-2-基）六氫ρ比畊-1-基]乙醯胺； Ν-(3-甲基苯基）-2-(4-ρ比淀-2-基7Τ氫峨呼_1_基）乙燒硫酸胺； Ν，(3-硝基苯基）-2_(4-^比症-2-基ΤΤ氮ρ比呼-1-基）乙酿胺； Ν-(3-氰基苯基）-2-(4-峨淀-2-基六氫吡畊-1_基）乙醯胺； 2_[4-(3-氰基吡啶-2-基）六氫吡畊-1-基](五氟苯基）乙醯 胺； 2-[4-(3-氰基吡啶-2_基）六氫吡畊小基]-N_(l，3-二甲基-1H-吡 唑-5-基）乙醯胺； N-(3-苄基苯基）-2-[4-(3-氰基吡啶_2_基）六氫吡畊-1-基]乙醯 胺； 85228 -96- 200404539 2-[4-(3-氰基吡畊-2-基）六氫吡畊小基]_N_(3_甲基苯基）乙醯 胺； 2-(4-ϋ比淀-2-基六氫批_ -1-基）-N-(2-{[(4-p比淀-2-基六氫U比_ -1-基）乙醯基]胺基}苯基）乙醯胺； Ν-(3·甲基苯基)_2_(4_吡啶-2_基六氫吡啶小基）乙烷硫醯胺； 2-[4-(1-甲基-1Η-咪唑-2-基）六氫吡啶-1-基]-Ν-(3·甲基苯基） 乙醯胺； Ν-(3-甲基苯基）-2-[4-(1,3-嘧唑-2-基）六氫吡啶小基]乙醯胺； Ν-(4-破基-3-甲基苯基）-2-(4-外1：淀-2_基六氫π比淀小基）乙酉盡 胺； 2- [4-(5-輕基ρ比淀-2-基）ττ氫p比淀-1-基]-N-(3_甲基苯基）乙酸 胺； N-(3-甲基苯基）-2-[4-(3-甲基噻吩-2-基）-3,6-二氫吡啶-1(2H)- 基]乙醯胺； 3- 甲基-N-[2-(4-峨啶-2-基六氫吡畊-1-基）乙基]苯甲醯胺； N-(3-甲基苯基）-2-(3-p比淀_2_基六氫u比淀-1-基）乙龜胺； N-(3-甲基苯基）-2-(3-p比淀-2-基四氫u比咯_1_基）乙酿胺； N-(l-甲基-1H-苯并咪咬-2-基）-2-[3-(1，3·口塞口坐-2-基）六氫p比咬· 1-基]乙醯胺； N-(l-甲基-1H-苯并味口坐_2，基）-2-[3_(1，3-口塞口坐-2-基）四氫口比洛_ 1-基]乙醯胺； 2-(2-苄基四氫p比略-1-基）-N-(3_氟苯基）乙酿胺；及 N_(4-氟苯基）-2-(3-屬吩_2_基四氫峨洛基）乙酸胺。 1M.根據申請專利範圍第81項之化合物，其係選自包括 85228 -97- 200404539 2-(l-{2-[(3-甲基苯基）胺基]-2-酮基乙基}六氫外1：啶-4-基）p比 錠N-氧化物； 2-(1-{2-[(4-氟基-2-甲基苯基）胺基]-2-酮基乙基}冬六氫吡 啶基）吡錠N-氧化物； 2_(1-{2-[(4-氟基-3-甲基苯基）胺基]-2-酮基乙基}-4_六氫吡 淀基 &gt;比錠N_氧化物； 2-(1-{2-[(3-氟苯基）胺基]-2-酮基乙基}-4-六氫说症基 &gt;比錠 N-氧化物； φ 2-(1-{2-[(2-氟-5-甲基苯基）胺基]-2-酮基乙基}冰六氬吡啶 基）吡錠N-氧化物； 2·(1-{1-甲基-2_[(3-甲基苯基）胺基]-2-酮基乙基}-4-六氫吡 啶基Η錠N-氧化物； 2-(1-{2-[(4·氟苯基）胺基]-2-酮基乙基}-4-六氫吡啶基）吡錠 Ν-氧化物； 2-(1-{2-[(2-氟苯基）胺基]-2-酮基乙基}-4-六氫说淀基 &gt;比錠 Ν-氧化物； _ 2-(1-{2-[(3-氯苯基）胺基]-2-酮基乙基}六氫说淀-4-基 &gt;比錠 N-氧化物； 2-(1·{2-酮基-2-[(2,4,6-三溴基-3-甲基苯基）胺基]乙基}六氫 吡啶-4-基）吡錠Ν-氧化物； 2-(1-{[(4-溴基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶-4•基） 外匕鉸Ν-氧化物； 2-(1-{2-[(3,5-二氯苯基）胺基]-2-酮基乙基}六氫吡啶I基） 此鍵Ν-氧化物； 85228 -98- 200404539 2-(l-{2-[(2,3-二氯苯基）胺基]-2-酮基乙基}六氫吡啶·4-基） 外匕鍵Ν-氧化物； 2-(1-{2_[(2-甲氧基-6-甲基苯基）胺基]-2-酮基乙基}六氫吡 淀-4-基 &gt;比錠Ν-氧化物； 2-{1_[2-(1，Γ-聯苯各基胺基）_2_酮基乙基]六氫吡啶·4-基Η匕 錠Ν-氧化物； 2-(1-{2-[(3-乙基苯基）胺基]-2-酮基乙基}六氫外匕淀-4·基）外匕 錠Ν_氧化物； 鲁 2-{1-[2-(2,3-二氫_1Η-茚-5-基胺基）-2-酮基乙基]六氫吡啶-4- 基}吡錠N-氧化物； 2-{1-[2_酮基-2_(5,6,7,8-四氫莕-1-基胺基）乙基]六氫吡啶冰 基}被錠N-氧化物； 2-(1-{2_[(3-異丙乳基苯基）胺基]-2-銅基乙基}六氣ρ比淀-4_ 基）外b錠:N-氧化物； 2_(1-{2-[(3,5-二甲基苯基）胺基]-2-酮基乙基}六氫吡啶冬基） 吡錠N-氧化物； _ 2-(1-{2-[(4-溴基-2-甲基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡錠N-氧化物； 2_[1·(2_酮基-2-{[3-(三氣甲氧基）苯基]胺基}乙基）六氫吡啶 -4-基]ρ比鍵Ν_氧化物； 2-(1-{2-[(5-甲基-2·硝基苯基）胺基]-2-酮基乙基}六氫吡啶· 4-基&gt;比錠诈氧化物； 2-(1-{2-[(2,6-二甲基苯基）胺基]-2-酬基乙基}六氫比淀-4-基） 吡錠Ν-氧化物； 85228 -99- 200404539 2-(l-{2-[(2,6-二氯-3-甲基苯基）胺基]_2_酮基乙基}六氫外I:淀 斗基）吡錠N-氧化物； 2-{1-[2-(1，3-苯并二氧伍圜稀-5-基胺基）-2-酮基乙基]六氫 吡啶-4-基}吡錠N-氧化物； 2-[1-(2-{[3-(甲硫基）苯基]胺基卜2-酮基乙基）六氫吡啶-4-基] 吡錠N-氧化物； 2-(1·{2-[(5-氯基基苯基）胺基]-2-酮基乙基}六氫p比淀-4-基 &gt;比錠Ν·氧化物； φ 2-(1_{2_[(2,5-二甲氧基苯基）胺基]-2-S同基乙基}六氫吡啶_4-基）吡錠Ν-氧化物； 2-(1-{2_[(3,5_二甲氧基苯基）胺基]_2_酮基乙基}六氫吡啶-4-基）吡錠N-氧化物； 2-[1-(2-{|&gt;(二甲胺基）苯基]胺基卜2-酮基乙基）六氫吡啶-4· 基]吡錠Ν-氧化物； 2-(1-{2-[(3-異丙基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基） 吡錠Ν_氧化物； _ 2-(1_{2-[(3-氯基-2-Τ基苯基）胺基]-2-酮基乙基}六氫吡啶-4-基）吡錠Ν-氧化物； 2-(1-{[(2,3-二溴基-5-甲基苯甲醯基）胺基]甲基}六氫吡啶-4_基）吡錠Ν-氧化物； 2-{1-[(苯甲g龜胺基）甲基]六氫外b淀-4-基比錠Ν-氧化物； 2-(1-{[(4-氯基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶-4_基） 峨錠Ν-氧化物； 2-(1-{[(4-氟基-3-甲基苯甲醯基）胺基]甲基}六氫吡啶_4_基） 85228 -100- 200404539 吡錠N-氧化物； 2-[1-({|&gt;氯基-4-(三氟甲氧基）苯甲醯基]胺基}甲基）六氫 吡啶-4_基]吡錠N-氧化物； 2_(1-{[(3-乙氧基苯甲醯基）胺基]甲基}六氫吡啶_4-基）吡錠 N-氧化物； 2-(1-{[(3,5-二氯苯甲醯基）胺基]甲基}六氫吡啶_4_基）吡錠 N-氧化物； 2-[1-({[4-甲基-3-(三氟甲基）苯甲醯基]胺基}甲基）六氫吡 · 啶斗基]吡錠N-氧化物； 2-(1-{[(3,4-二甲苯甲醯基）胺基]甲基}六氫吡啶冬基）吡錠 N-氧化物； 2-(1-{[(3-氯基-4-氟苯甲醯基）胺基]甲基}六氫吡啶冰基）吡 錠N-氧化物； 2-(1-{[(吡啶-2-基羰基）胺基]甲基}六氫吡啶_4_基）吡錠N-氧 化物； 2_(1_{[(3,5_二甲苯甲醯基）胺基]甲基}六氫吡啶基Η錠 參 N-氧化物； 2_(1-{[(3-乙烯基苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠 Ν-氧化物； 2-(1-{[(4-溴基-3-甲基苯甲醯基）胺基]甲基}-1，2,3,6-四氫吡 淀-4-基）ρ比艘Ν-乳化物， 2-{1-[(2-莕甲醯基胺基）甲基]六氫吡啶冰基}吡錠Ν-氧化 物； 2-(1-{[〇塞吩-2-基羰基）胺基]甲基}六氫吡啶-4-基Η錠Ν-氧 -101- &amp;14 85228 200404539 化物； 2-[l-({[(6-氯基π比咬-3_基）窥基]胺基}甲基）六氫p比喊_4-基] 吡錠N-氧化物； 2-(1-{[(3-氰基苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡錠N-氧化物； 2-(1-{[(2,3-二溴基甲基苯甲醯基）胺基]甲基H，2,3,6-四氫 吡啶-4-基）吡錠N-氧化物； 2-(1-{[(4-溴基苯甲醯基）胺基]甲基}六氫吡啶冰基）吡錠N-氧化物； 2-(1-{[(3-氯基-4-甲基苯甲醯基）胺基]甲基}六氫吡啶冬基） 吡錠N-氧化物； [甲基（3-甲基苯甲醯基）胺基]甲基}六氫吡啶-4-基）吡 錠N-氧化物； 2_(1-{[(3-硝基苯甲醯基）胺基]甲基}六氫吡啶-4_基Η錠N-氧化物； 2-(1-{[(2-氯基-5-甲基苯甲醯基）胺基]甲基}六氫吡啶冰基） 吡錠Ν-氧化物； 2-(1-{[(3-甲氧基-2-甲基苯甲醯基）胺基]甲基}六氫吡啶冰 基）吡錠Ν-氧化物；及 2-(1-{[(4-氯基-3-甲氧苯甲驢基）胺基]甲基}六氫外1：淀-4-基） 吡錠Ν-氧化物。 I32·根據申請專利範圍第81項之化合物，其係為2-(1-{[(3-甲基 苯甲醯基）胺基]甲基}-4-六氫吡啶基 &gt;比錠Ν-氧化物。 133.—種式（III)化合物 85228 -102- 200404539 A/URi is selected from the group consisting of hydrogen, alkyl, cyano, alkyl, nitro, (NZJ4), and (NZ3Z4) carbonyl; and R4 is hydrogen; r3 is selected from the group consisting of hydrogen and hydroxyl; Z is c;… is a bond; D is -CH2-; and L is -C (0) N (R7) -013. The compound according to item 81 of the scope of patent application is selected from the group consisting of N- (3 -Methylphenyl) -2- [4- (2-pyrimidinyl) pyraloxapyryl] ethenylamine; fluorenylphenyl) -2- [4- (2-p than yridyl) -1 -Hexahydro-1: plowyl] acetamidine; 2- [4- (3-cyano-2-exo I: yodo) -1-hexahydroepyl] -N- (3-methyl Phenyl) ethenylamine; 2- [4- (3-cyano-2-Ppyridyl) -1-hexahydroρ-pyridinyl] -N- (3-nitrophenyl) acetamidine 85228- 82- 200404539 2- [4- (3-cyano-2-pyridyl) &gt; 1-hexahydropyridyl] -N- [3- (trifluoromethyl) phenyl] acetamidinium; N- ( 3-cyanophenyl) -2- [4- (3-cyano-2-pyridyl) &gt; 1-hexahydropyridyl] acetamidamine; 2- [4- (3-cyano-2- Pyridyl &gt; 1-hexahydropyridyl] -N-phenylacetamidinyl; 2- [4- (3-cyano-2-pyridyl) petit hexahydropyridyl] -N- (4- Fluorophenyl) acetamide; 2- [4- (3-cyano-2-pyridyl) -1-hexahydropyridine Group] -N- (3,5-dimethylphenyl) acetamidamine; 2- [4 · (3_cyano-2-pyridyl) pyrrolidine] -N- (2,3 -Dimethylphenyl) Ethylamine; 2- [4- (3-Dynyl-2-fluorenyl-1pyridyl) _1 · ττnitro ppyridyl] -N- (2-methylphenyl) ethyl Fermented amine; 2- [4- (3-Gasyl-2-p than yodoyl) -1-hamster erphyl] -N- (2,5-dimethylphenyl) acetamidine; N- (3-Chlorophenyl) -2 · [4- (3 · Cyano-2-τ7bitoyl) -1-hexahydro p-p-pyridyl] amine; N- (3-chloro-4- Fluorophenyl) -2- [4- (3-Lycyl-2 ~ BiYenyl) _1 • Hexahydro p-ratio π-Wellyl] Ethylamine; 2- [4- (3-Gasyl-2-exo b-imyl group) -1_κRatyl] -N- (3,4,5-trimethoxyphenyl) ethoxyamine; 2- [4- (3-cyano-2-pyridyl) hexahydro Pyridyl] -N- [4-fluoroyl (trifluoromethyl) phenyl] acetamidamine; 2- [4- (3-cyano-2-pyridyl) pyrhexahydropyridyl]- Ν- [3-Fluoro-5- (trifluoromethyl) phenyl] ethanamine; 2- [4- (3-cyano-2-pyridyl) pyrhydropyridyl] -N- [ 2-Fluoro-5_ (trifluoromethyl 85228 -83- 200404539) phenyl] amine; 2- [4- (3-cyano-2-p than yodoyl) -1-phenyl ] -N- [2-Fluoro_3- (trifluoromethyl ) Phenyl] acetamidine; 2- [4- (3-cyano-2-p ratio yl) -1-ττ hydrogen p ratio yl] _N- (4-fluoro-3-methylphenyl ) Acetylamine; 2- [4- (3-cyano-2-ρ biphenylyl) -1-hexahydrob 0 wells] -N- (2-fluorophenyl) acetamidine; 2- [4- (3-cyano-2-pyridyl) pyrihydropyridyl] -N- (2-methoxyphenyl) acetamidamine; 2- [4- (3-Sanyl-2-ρ Biyodoyl) -1-ττ out-of-air bujingyl] -N- (2-nitrophenyl) ethyl amine; 2- [4- (3-fluorenyl-2-ρ biydyl) -1- ττchloro said p-well-based] -N- [2- (trifluoromethyl) phenyl] ethanamine; N-phenyl-2- [4_ (2 · ρ Amine; Ν- (3-methylphenyl) -2- [4- (1,3-pyrazol-2-yl) -1-hexahydropyridyl] acetamidine; 2- [4- (3 -Cyano-2-pyridyl) pyrihydropyridyl] -N- (4-methylphenyl) acetamidine; N- (3-methylphenyl) -2- [4- (2- Pyridyl) -1-hexahydropyridyl] acetamidinium; N- (3-methylphenyl) -2- [4- (6-keto-1 (6H) -dacrotyl) small hexahydropyridine Group] Ethylamine; N- (2,6-dimethylphenyl) -2- [4- (2-pyriminyl) small hexahydropyridyl] ethanamine; N- (2,5-di Methylphenyl) -2- [4- (2-pyridinyl) -1-hexahydropyridyl] Fluorenylamine; N- (2-methylphenyl) -2- [4- (2-thienyl) -1-hexahydropyridyl] acetamidinylamine; N- (3-amino-4-aminophenyl ) -2- [4- (2-p sephenyl) _1-ττ nitrogen p is less than yodoyl] ethylamine, N- (4-bromophenyl) -2- [4- (2-pyridyl) small six Hydropyridyl] acetamidine; 85228 -84- 200404539 Ν- (2,6 · Difluorenylphenyl) -2- [4- (2-p than ytyl) -1_hexachloroexo-b-yl] Ethylamine, N- (2-nitrophenyl) -2- [4- (2-pyridyl) small hexahydropyridyl] acetamidine; N- (3-nitrophenyl) -2- [ 4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; N- (2,4-difluorophenyl) -2_ [4- (2_pyridyl) -1-hexahydropyridyl ] Acetylamine; N_ (2,5-dimethylphenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidine; N- (2-methylphenyl ) -2_ [4- (2-pbiydyl) -1 · Price A-biydyl] ethylamine, N- (4-methylphenyl) -2- [4- (2-pyridyl) Hexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) pyrhexahydropyridyl] -N- [3- (trifluoromethyl) phenyl] ethamidine; 4- ( {[4- (2-Pyridyl) -1-hexahydropyridyl] ethenyl} amino) benzoate ethyl ester; N- (3-amino-4-methylphenyl) _2- [4- (2-pyridine Group) hexahydropyridyl] acetamidine; N- (2-aminophenyl) -2- [4 · (2-fluorenylpyridyl) -1-ττazepinepyridyl] ethynamine, N- (3-Chlorophenyl) -2- [4- (2-ρ Biydyl) -1-ττmuramine yl] ethylamine, 2- [4- (3-cyano-2-pyridine) Phenyl) hexahydropyridyl] -N- (3-methylphenyl) acetamidamine; 2- (3 ', 6'-dihydro-2,4'-bipyridine-r (2'H) _Yl) -N- (3-methylphenyl) acetamide; 2- (3 ', 6'-dihydro_2, bipyridine-Γ (2Ή) _yl) -N- (2,6_ Dimethylphenyl) acetamide; 2- (3 ', 6f-dihydro-2,4'_bipyridine-Γ (2Ή) · yl) _N- (2-nitrophenyl) acetamide; 2_ (3 *, 6f-dichloro-2,4 * -bi-p ratio lake-Γ (2Ή) -yl) -N- (3-nitrophenyl) ethoxyamine; 2- (3'6'_ Diazo-2,4'-bi-p-pyridian-1 '(2Ή) -yl) -N- (4-Gaphenyl) acetamide; N- (2,4-difluorophenyl) -2_ (3 \ 6'-Dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; 2- (3 ', cardiodihydro-2, bipyridine_1' (2Ή) · yl)- Ν- (2,5-dimethylphenyl) acetamidine 85228 -85- 200404539 amine; 2- (3f, 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) -N -(2-methylphenyl) acetamide; N_ ring Hexyl-2- (3f, 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; 2- (3 ', 6'-dihydrobipyridine-1' (2Ή ) ·))-N- (4-methylphenyl) acetamidamine; 2- (3 ', 6 dihydro-2,4'-bipyridine_1' (2 () · yl) · N_ [3 -(Trifluoromethyl) phenyl] acetamidamine; 4-[(3 ', 6'-dihydro-2,4f-bipyridine-Γ (2Ή) -ylethylfluorenyl) amino] ethyl benzoate Ester; Ν- [2-chloro-5- (trifluoromethyl) phenyl] -2- (3f, 6'-dihydro-2,4'-bipyridine_Γ (2Ή) _yl) acetamidine Amine; N- (3-chloro-4-methylphenyl) -2- (3f, 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; Ν- (2 · Cyanophenyl) -2- (3 ', 6'_dihydro-2,4'-bipyridine_1' (2'11) _yl) acetamide; Ν- (3-chlorobenzene Yl) -2- (3 ', 6f-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamidinium; Ν- (3-chloro-4-fluorophenyl) -2- (3 ', 6' · dihydro-2,4'-bipyridine-Γ (2Ή) -yl) acetamide; 2 · (3 ', 6' · dihydro_2, -bipyridine · Γ (2Ή ) -Yl) -N- [4- (trifluoromethoxy) phenyl] acetamidinium; 2- (3f, 6'-dihydro-2,4'-bipyridine · Γ (2Ή) _yl) -N- [2- (trifluoromethyl) phenyl ] Acetylamine; Ν_ (4-chlorophenyl) -2- (3 ', 6f-dihydro-2,4f-bipyridine-Γ (2Ή) · yl) acetamide; Ν- (2,3- Dichlorophenyl) -2- (3f, 6'-dihydro-2,4'-bipyridine-1 '(2Ή) -yl) acetamide; 乂 (3,5-dichlorophenyl) -2 -(3'fluorenedihydro-2,4'-bipyridine-1 '(2'11) -yl) acetamide; 2- (3f, 6'-dihydro-2,4'-bipyridine-1 '(2Ή) -yl) -N- (4-fluoro-2-methylphenyl) ethyl 85228 -86- 200404539 hydrazine; N- (4-fluorophenyl) -2- [4- (2- Pyridyl) Hexahydropyridyl] acetamidine; N- (3,5-dichlorophenyl) -2- [4 "(2-pyridyl) -1-hexahydropyridyl] acetamidine; N -(2,3-dichlorophenyl) -2- [4- (2 · pyridyl) _1_hexahydropyridyl] acetamidamine; 2- [4- (2-pyridyl) -1-hexahydro Pyridyl] -N- [2- (trifluoromethyl) phenyl] acetamidine; Ν- (3-chloro-4-fluorophenyl &gt; 2- [4- (2-pyridyl) minimal six Hydropyridyl] acetamidine; 2. [4- (2-pyridyl) -1-hexahydropyridyl] -N- [4- (trifluoromethoxy) phenyl] ethamidine; Ν- Cyclohexyl-2- (3'4 ', 5'6'_tetrahydro-2'-[2,4 '] bipyridyl · Γ-yl) acetamidamine; 3-methyl-N-{[4- (2-pyrimidinyl)- 1-hexahydropyridyl] methyl} benzylamine; 3-methyl-N-{[4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzylamine; N-{[4- (3-cyano-2-pyridyl) -1-hexahydropyridyl] methyl} -3-methylbenzylamine; Ν · {[4- (3-cyano -2-pyridyl) Hexahydropyridyl] methyl} benzylamine; Ν-{[4- (3- (cyano-2-pyridyl) small hexahydropyridyl] methyl} -4 -Methylbenzaloxamine; Ν-{[4- (3-cyano-2-pyridyl) pyroxypyridyl] methyl} -2-methylbenzamide; Ν-{[ 4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzylamidine; 2-chloro_N _ {[4- (3-amino-2-p ratio yl) _1-ττ Chlorine P is more than 1 (1 well group) methyl} benzylamine; Ν-{[4 · (3-cyano-2-pyridyl) small hexahydropyridyl] methyl} -2- (trifluoro (Methyl) benzamidine; 85228 -87- 200404539 N- (3 ', 6'-dihydro-2, bipyridine-1' (2Ή) _ylmethyl) each methyl benzamidine; Ν- (3 ', 6 ^ dihydro-2, bipyridine-Γ (2Ή) -ylmethyl) -3-methoxybenzamide; N- (3f, 6'-dihydro-2, bipyridine- Γ (2Ή) -ylmethyl) each fluorobenzylamine; Ν · (3 ', 6 · -dihydro-2,4'-bipyridine-Γ (2 Ii) -Methyl) -3,5-difluorobenzylamine; N-2-Au-steel-2- [4- (3-Gas-2-p ratio) -l-6 Hydrogen ρ is higher than that of ethoxy] ethylamine; 2- [4- (3-cyano-2-pyridyl) hexahydropyridyl] -N-cyclohexylacetamide; 2- [4- (3- Cyano-2_pyridyl) hexahydropyridinyl] -N-5,6,7,8-tetrahydroberberylluosylamine; 2- (3 ', 6'-dihydro-2, 4'-bipyridine-Γ (2Ή) -yl) -N- (4-fluoro-2-methylphenyl) acetamide; Ν-{[4- (2-pyridyl) -1-hexahydro Pyridyl] methyl 3- (trifluoromethyl) benzamidine; 3,5-«-methoxy-N-{[4- (2-ρ than yl) -1-ττchloroρ ratio Yodoyl] methyl} benzidine; N-{[4- (2-eryl) -1-hexahydropyridyl] methyl} cyclohexylamine; xin 3,4-difluoro _N _ {[4- (2-pyridyl) small hexahydropyridyl] methyl} benzamide; 3-chloro-N-{[4- (2-pyridyl) -1-hexahydropyridyl] Methyl} benzamide; 2,3-dimethyl-N-{[4- (2-pyridyl) -1_hexahydropyridyl] methyl} benzamide; N- (3 ' , 6'-dihydro-2,4'-bipyridine-1 '(2Ή) -ylmethyl) (trifluoromethyl) benzidine; 3-chloro-N_ (3', 6'-di Hydrogen2, 4'_bipyridine_Γ (2Ή) _ylmethyl) benzidine; N- (3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -ylmethyl) ring Hexylcarboxamide; Ν- (3 ', 6'-dihydro_2,4'_bipyridine_Γ (2Ή &gt; ylmethyl) -3,4-difluorobenzamide; 85228 -88- 200404539 N_ (3,, 6'_dihydro-2,4'-bipyridine-Γ (2Ή) _ylmethyl) · 3,5_dimethoxybenzamide; 2- (3 \ 6f- Dihydro-2,4'-bipyridine_Γ (2Ή) _yl) _N- (3-nitrophenyl) acetamidine; Ν-1- 金钢 烧 基 -2- [4- (3-cyano Yl-2-exoyl) small hexahydroexoyl] ethenylamine; 3-methyl-N-{[2-methyl-4- (2-pyridyl) -1-hexahydropyridine [Methyl] methyl} benzamide; N- (3-methylphenyl) _2- [2-methylbenzyl (2-pyridyl) pyroxypyridyl] ethosamine; 3,5- Dimethyl-N-{[4- (2-pyridyl) small hexahydropyridyl] methyl} benzidine; N- (3 ', 6'_dihydro-2,4'-bipyridine · 1 '(2Ή) _ylmethyl) -3,5_dimethylbenzamide; 3-methyl_N-[(3-methyl-3', 6'_dihydro_2,4 ' _Bipyridine-Γ (2Ή) -yl) methyl] benzidine; Ν-[(3-cyano4,6'_dihydro-2,4'-bipyridine-Γ (2 ) -Methyl) methyl] -3_methylbenzyl donutylamine; p-N- (2,6-dimethylphenyl) -2- (3-methyl-3 ', 6'-dihydro_2, 4'-bipyridine-1, (2Ή) -yl) acetamide; N- (4-fluorophenyl) -2- (3-methyl-3,6, -dihydro-2,4,- Bipyridine_1 '(2,11) _yl) acetamide; Ν_ (2,4_difluorophenyl) dong (3 • methyl-3', 6, · dihydro-2,4, -bi Pyridine · 1 ′ (2Ή) _ group) Ethylamine; 2- (3-methyl-3f, 6 ′ · dihydro-2,4, -bipyridine-1, (2Ή)-group) -N- ( 2-methylphenyl) acetamide; 85228 -89- 200404539 2- (3-f group_3, 6f_dihydro_2,4'_bipyridin-1 '(2Ή) · yl) -N · [3- (trifluoromethyl) phenyl] acetamidine; Ν- (3-amino-4-fluorophenyl) _2- (3-methyl-3,, 6'-dihydro-2,4 , -Bipyridine-Γ (2Ή) -yl) acetamide; 2- (3-methyl-3f, 6f-dihydro-2,4'-bipyridine-1 '(2Ή) -yl) -N- [4- (trifluoromethoxy) phenyl] acetamidine; 2- (3-methyldihydro-2,4, -bipyridine-1, (2Ή) -yl) -N- [2- ( Trifluoromethyl) phenyl] acetamidine; N- (2,3-dichlorophenyl) -2- (3-methyl-3,6, -dihydro-2,4, -bipyridine 1, (2Ή) _base) Hydrazine; 2 · (3-methyl-3 ', 6f-dihydro_2,4, _bipyridine-1, (2Ή) -yl) _N- [4- (trifluoromethyl) phenyl] acetamidine Amine; 2- [4- (3-cyano-2-pyrimyl) -3,6-dihydro-1 (2Η) _pyridyl] _N_ (3-methylphenyl) acetamide; 2- (3-cyano-3f, 6f-dihydro_2,4, _bipyridine-1, (2Ή) -yl) -N- (2,6-dimethylphenyl) acetamide; 2 · ( 3-cyano-3f, 6f_dihydro-2,4, -bipyridine-1, (2Ή) -yl) -N- (4-fluorophenyl) acetamide; 2- (3-cyano_ 3 ', 6'-dihydro_2,4'_bipyridine-1, (2Ή) -yl) -N- (2,4-difluorophenyl) acetamide; 2- (3-cyano- 3f, 6f • dihydro_2,4 ′ · bipyridine-1 ′ (2Ή) -yl) -N- (2-methylphenyl) acetamide; 2- (3-cyano-3 \ 6 ' -Dihydro-2, renbipyridine-1, (2Ή) -yl) trifluoromethyl) phenyl] acetamidin; 85228 -90- 200404539 2- (3-cyano_3 ', 6, _di Hydrogen_2,4f • bipyridine_Γ (2Ή) · yl) -N_ [4- (trifluoromethoxy) phenyl] ethanamine; 2- (3-cyano_3 ', 6'_di Hydrogen-2,4'-bipyridine-1 '(2Ή) -yl) -N_ [2- (trifluoromethyl) phenyl] ethanamine; 2- (3-cyano-3', 6'- Dihydro-2,4'- Bipyridine_Γ (2Ή) _yl) _ 乂 (2,3_dichlorophenyl) acetamide; 3-methyl-N-{[4- (6-keto-1 (611) _tago Phenyl) hexahydropyridyl] methyl} benzamidine; φ Ν- (3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) -ylmethyl) adamantine Alkylcarboxamide; 3-methyl-N-{[4- (l, 3-pyrazol-2-yl) -3,6-dihydro-1 (2Η) -pyridyl] methyl} benzidine Amines; 2- [4- (3-cyano-2-pyridyl) pyrrolidine] -N-1,2,3,4-tetrahydro-1-fluorenylethyl siamine; 2- [ 4- (3-cyano-2-pyridyl) pyrhexahydropyridyl] -N-[(1S) -1,2,3,4-tetrahydro-1-naphthyl] ethenylamine; 2- [4- (3-Cyano-2-pyridyl) microhexahydropyridyl] -N-[(1R) -1,2,3,4-tetrahydro-1- · naphthyl] acetamidinium; N- (2,6-diethylphenyl) -2- [4- (2-pyridyl) -1_hexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) -1 -Hexahydropyridyl] -N- (2,4,6-trifluorophenyl) acetamide; N- (4-chloro-2,6-dimethylphenyl) &gt; 2- [4- ( 2-Pyridyl) small hexahydropyridyl] acetamidine; 2- [4- (2-pyridyl) -1-hexahydropyridyl] -N- (2,4,6-trichlorophenyl) ethyl Amidine; N- (2,6-diethylphenyl) -2- (3f, 6'-dihydro -2,4'-bipyridine-Γ (2Ή) -yl) acetamide; 1 &gt; 〇4 85228 -91-200404539 2_ (3f, 6'_dihydro-2,4'-bipyridine-1 '( 2Ή) -yl) -N- (2,4,6 · trifluorophenyl) acetamide; Ν- (4-chloro-2,6-dimethylphenyl) -2- (3 *, 6L Dihydro-2,4 * _Lianedianyl) acetamide; 2- (3 \ 6'_dihydro-2,4'-bipyridine_1 '(2xian) _yl) -N- (2 , 4,6-trichlorophenyl) acetamide; Ν-{[4- (2-pyridyl) pyropyryl] methylbu 3- (trifluoromethyl) benzamide; · 3,5-dimethoxy-N-{[4- (2-outer-b-yl) -1-ττ-nitrogen ratio p-well] methyl} benzoate amine; N-{[4- (2- Pyridyl) Hydroxypyridyl] methyl} cyclohexanecarboxamide; N- (2,6_dimethylphenyl) -2- [4- (2-outeryl) · 1- ττ-Chloro-bp bpyl] Ethylamine; Ν- (4 · fluorophenyl) -2- [4- (2-pyridyl) pyrhydropyridyl] acetamidine; Ν · (2,4- Difluorophenyl) -2- [4- (2-pyridyl) -1-hexahydropyridyl] acetamidinium; N- (2-methylphenyl) -2- [4- (2-ρ Pyridyl] acetamide than 2-D-based gas; 2- [4- (2-pyridyl) small hexahydropyridyl] -N- [3- (trifluoromethyl) phenyl] acetamidine; . N- (3- Phenyl) -2- [4- (2-pyridyl) microhexahydropyridyl] ethanamine; N · fluorenyl-2- [4- (2-ρ than ydoyl) _1-ττ rat p ratio Sakaiki] Ethylamine; 2- [4- (2-pyridyl) pyrohexyl] -N- [4- (trifluoromethoxy) phenyl] ethanamine; 2- [ 4- (2-pyridyl) -1-hexahydropyridyl] -N- [2- (trifluoromethyl) phenyl] acetamidine; Ν- (4-chlorophenyl) -2 · [4 -(2-ρ BiYodo) -1-valent nitrogen ρ Bisyl] amine acetate, 85228 -92- 200404539 N- (2,3-dichlorophenyl) -2- [4- (2-p ratio Diantai) Hexachlorot-p-pyl] Ethylamine; N- (3,4-dichlorophenyl) -2- [4- (2-p than Dynyl) -1-: γτ hydrogen? Specific p-well-based] amine acetate; 2- [4- (2-pyridyl)> 1-hexahydropyridyl] -N_ [4- (trifluoromethyl) phenyl] acetate; 3-chloro-N -{[4- (2-Pyridyl) Petylhexamethyl] methyl} benzamide; 4-fluoro-3-methyl-N-{[4- (2-pyridyl) Petyl-6 Hydropyridyl] methyl} benzimidamine; N- (3 ', 6'-dihydro-2,4f-bipyridine · 1' (2Ή) -ylmethyl) -4-fluoroyl-3- Methyl benzylamine; 3-methyl-N-{[4 · (1,3-oxazol-2-yl) -3,6-dihydro-1 (2H) -pyridyl] methyl} Benzamidine; 2-methyl-N-[(3-methyl-3 ', 6'-dihydro-2,4'-bipyridine-Γ (2Ή) -yl) methyl] benzidine ; 2- [4- (3-cyano-2-pyridyl) -1-hexahydropyridyl] -N- (2,6-dimethylphenyl) acetamide; Ν- (3-methyl Phenyl) · 2 · [4- (3-methyl-2-ρ ratio yl) · 1-ττ Gas port ratio ρ yl] acetamide; 2- [4- (3-cyano-2 · pyridyl ) Hexahydropyridyl] -N- [4- (trifluoromethyl) phenyl] acetamidinium; Ν- (2-ethyl-6-methylphenyl) -2_ [4- (2- ρ than ydenyl) -1-hole nitrogen, p than fluorenyl] acetamidine; N- (2-isopropyl-6-methylphenyl) -2- [4- (2-pyridyl) hexahydro Pyridyl] Acetylamine; Ν- (2-chloro-6-methylphenyl) -2- [4- (2-pyridyl &gt; 1-hexahydropyridyl] acetamyl 85228 -93- 200404539 amine; N- (2-Methoxy-6-methylpentyl) _2- [4- (2-ρ Bisynyl) -1-ττchloroπbipyridyl] acetamide; 2- (3f, 6f-dihydro -2,4f_bipyridine-1 '(2Ή) -yl) -N- (2-ethyl-6-methylphenyl) acetamide; 2- (3', fluorene dihydro_2,4f- Bipyridine_1 '(2Ή) _yl) _N_ (2-isopropyl-6_methylphenyl) acetamidamine; N_ (2-chloro-6-methylphenyl) _2- (3 ,, 6, -dihydro-2,4, -bipyridine-1, (2Ή) _yl) ethyl φ fluorenamine; 2- (3'square-dihydro-2, bipyridine_1 '(2Ή) · yl) _N- (2-methoxy each methylphenyl) acetamide; 3-chloro-N-[(3-methyl · 3 ', 6'-dihydro-2,4'-bipyridine-1' (2Ή) · Methyl] benzidine; 3-fluoro-N-[(3-methyl-3 ', 6 · -dihydro-2,4'-bipyridine-1' (2Ή)- ) Methyl] benzamide; 3-methyl-N-{[((2S) -2-methyl-4- (2-pyridyl) -1-hexahydropyridyl] methyl} benzene_ Formamidine; N- (3-methylphenyl) -2-[(2S) -2-methyl-4- (2-pyridyl) pyrrolidine] Acetylamine; 3-methyl -N-{[((2R) -2_methyl-4- (2-pyridyl) microhexahydropyridinyl] methyl} benzamidine; N- (3-methylphenyl) -2- [(2R) -2-methyl-4- (2-pyridyl) microhexahydropyridyl] acetamidine; 3-methoxy-N-[(3-methyl-3f, 6'-di Hydrogen-2,4'-bipyridine-Γ (2Ή) -yl) methyl] 85228 -94- 200404539 benzamidine; 4-fluoro-N-[(3-methyl_3 ', 6'_di Hydrogen-2,4'-bipyridine-Γ (2Ή) -yl) methyl] benzidine; 2- (3-chloro-3 ', 6 · -dihydro-2,4'-bipyridine- Γ (2Ή) -yl) -N- (2,6-dimethylphenyl) acetamide; 2- (3-chloro_3 ', 6f-dihydro-2,4'_bipyridine_1 '(2case) _yl) _N- (2-methylphenyl) acetamide; Ν- (3', 6'_dihydro-2,4'-bipyridine-Γ (2 ()-ylmethyl ) -1 • Metrazidine; φ Ν-{[4_ (3-cyano-2-pyridyl) -1-hexahydropyridyl] methyl} each fluorobenzylamine; 3-methyl -N-{[4- (1,3 &lt; Sejun-2-yl) -1 • Hexahydropyridyl] methyl} benzamide; Ν- (3-methylphenyl) -2- {4- [3- (tris-methyl-pyridyl] -1-hexahydroethanyl} ethyl} amine; Ν- (3-methylphenyl) _2- [4- (1,3-pyrimazole -2-yl) -3,6-dihydro Pyridine · 1 (2-)-yl] acetamide; Ν- (3-methylbenzyl) -2- (4-methylphen-2-yl-3,6-dichlororpyridine-1 (2Η)- Yl) ethynylamine; 3-methyl · N-[(4-thien-2-yl-3,6-dihydropyridine-1 (2Η) -yl) methyl] benzidine; 2- [4 -(1-methyl-1fluoren-imidazolyl) -3,6-dihydropyridine · 1 (2fluoren) _yl] _N- (3-methylphenyl) acetamide; N- (3-methyl Phenyl) -2- [4- (3-nitropyridin_2_yl) hexahydropyridine] ethenamide; 2_ [4- (3-chloropyridin_2_yl) hexahydropyridine -1-yl] -N- (3-methylphenyl) acetamidine 85228 -95- 200404539 amines; 2- {4- [3- (aminomethyl) erb-2-yl] hexahydrocarbazole Well-i_kib n- (3-methylphenyl) acetamidamine; 2- [4- (2-isopropoxyphenyl) hexahydropyrine-1-yl] _n_ (3-methyl Phenyl) ethylamine; 2- (4- {2-[(3-methylphenyl) amino] -2-ketoethyl} hexahydroerphin-1-yl) in amidine; N -(3-methylphenyl) _2-[(2S) -2-methyl-4-out 1: yodo-2-ylhexahydro p ratio p well small group] _ ethanethioamide; 2- [ 4- (3-cyano-p-pyridin-2-yl) hexahydro is __1_yl] -N- [3_ (methylthio) phenyl] acetamidinium; N- (3-third-butyl Phenyl) -2- [4 · (3-cyano Pyridin-2-yl) hexahydropyridine-μyl] acetamidamine; 2- [4- (3-Gas 17-Hydrogenyl-2-yl) ττHydroxy-1 -yl] · N- ( 3-fluorophenyl) acetamidine; Ν- (3-bromophenyl) -2- [4- (3-cyanoρbidian-2-yl) hexahydroρbigen-1-yl] acetamidine Amine; Ν- (3-methylphenyl) -2- (4-ρBiYodo-2-yl 7T hydrogen ehu_1-yl) ethynyl sulfate; Ν, (3-nitrophenyl)- 2_ (4- ^ Bizhen-2-yl TT nitrogen ρ bihu-1-yl) ethyl amine; Ν- (3-cyanophenyl) -2- (4-agido-2-ylhexahydropyridine Phen-1_yl) acetamide; 2_ [4- (3-cyanopyridine-2-yl) hexahydropyrine-1-yl] (pentafluorophenyl) acetamide; 2- [4- ( 3-cyanopyridine-2_yl) hexahydropyridine] -N_ (l, 3-dimethyl-1H-pyrazol-5-yl) acetamidinium; N- (3-benzylphenyl ) -2- [4- (3-cyanopyridine_2_yl) hexahydropyridin-1-yl] acetamidin; 85228 -96- 200404539 2- [4- (3-cyanopyridine-2 -Yl) hexahydropyridine] _N_ (3-methylphenyl) acetamidamine; 2- (4-pyridyl-2-ylhexahydropyridin-1-yl) -N- (2- {[(4-p 比比 -2-ylhexahydroU than -1-yl) ethylfluorenyl] amino} phenyl) acetamidine; Ν- (3 · methylphenyl) _2_ (4_ Pyridin-2-ylhexahydropyridine Pyridyl) ethanethiocarbamide; 2- [4- (1-methyl-1Η-imidazol-2-yl) hexahydropyridin-1-yl] -N- (3 · methylphenyl) acetamidine Amine; Ν- (3-methylphenyl) -2- [4- (1,3-pyrazol-2-yl) hexahydropyridine small group] acetamidinium; Ν- (4-alkyl-3- Methylphenyl) -2- (4-Exo-1: Yodo-2_ylhexahydropi than Yado small group) Acetylamine; 2- [4- (5-Light radical ρBiYodo-2-yl) ττ Hydrogen p ratio lake-1-yl] -N- (3-methylphenyl) amine; N- (3-methylphenyl) -2- [4- (3-methylthiophen-2-yl) -3,6-dihydropyridine-1 (2H) -yl] ethanamine; 3-methyl-N- [2- (4-eridin-2-ylhexahydropyridine-1-yl) ethyl ] Benzamidine; N- (3-methylphenyl) -2- (3-p-Hydro_2-ylhexahydrou-Hydro-1-yl) ethanamide; N- (3-methyl Phenyl) -2- (3-p-Hydrogen-2-yltetrahydrou-pyrrole_1-yl) ethynamine; N- (l-methyl-1H-benzimidyl-2-yl)- 2- [3- (1,3 · mouth plug mouth sitting 2-yl) hexahydro p ratio bite · 1-yl] acetamidine; N- (l-methyl-1H-benzo flavor mouth sitting_2 , Yl) -2- [3_ (1,3-mouth stopper-2-yl) tetrahydropyrrolidine-1-yl] acetamide; 2- (2-benzyltetrahydrop ratio slightly -1 -Yl) -N- (3-fluorophenyl) ethyl amine; and N_ (4-fluorobenzene Phenyl) -2- (3-genus phen-2-yltetrahydroerloyl) amine. 1M. The compound according to item 81 of the scope of patent application, which is selected from the group consisting of 85228 -97- 200404539 2- (l- {2-[(3-methylphenyl) amino] -2-ketoethyl} Hexahydro-1: pyridin-4-yl) p ratio N-oxide; 2- (1- {2-[(4-fluoro-2-methylphenyl) amino] -2-ketoethyl } Winter hexahydropyridyl) pyridinium N-oxide; 2- (1- {2-[(4-fluoro-3-methylphenyl) amino] -2-ketoethyl} -4_ Hexahydropyridyl &gt; Titanium N-oxide; 2- (1- {2-[(3-fluorophenyl) amino] -2-ketoethyl} -4-hexahydrobenzyl &gt;; Ingot N-oxide; φ 2- (1- {2-[(2-fluoro-5-methylphenyl) amino] -2-ketoethyl} pyridinium) pyridine N -Oxides; 2 · (1- {1-methyl-2 _ [(3-methylphenyl) amino] -2-ketoethyl} -4-hexahydropyridylfluorene N-oxide; 2- (1- {2-[(4 · fluorophenyl) amino] -2-ketoethyl} -4-hexahydropyridyl) pyridine N-oxide; 2- (1- {2- [(2-Fluorophenyl) amino] -2-ketoethyl} -4-hexahydroanhydroxyl >> Indium N-oxide; _ 2- (1- {2-[(3-chloro Phenyl) amino] -2-ketoethyl} Hexahydro-4-yl &gt; Specific N-oxide; 2- (1 · {2-keto-2-[( 2,4,6-tribromo-3-methylphenyl) amino] ethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1-{[(4-bromo -3-methylbenzyl) amino] methyl] hexahydropyridine-4 • yl) N-oxide; 2- (1- {2-[(3,5-dichlorophenyl) ) Amino] -2-ketoethyl} hexahydropyridine I-yl) This bond is an N-oxide; 85228 -98- 200404539 2- (l- {2-[(2,3-dichlorophenyl) amine [Yl] -2-ketoethyl} hexahydropyridine · 4-yl) outer bond N-oxide; 2- (1- {2 _ [(2-methoxy-6-methylphenyl) amino ] -2-ketoethyl} hexahydropyridin-4-yl &gt; ratio N-oxide; 2- {1_ [2- (1, Γ-biphenylylamino) _2_ketoethyl [Yl] hexahydropyridine · 4-ylpyridine N-oxide; 2- (1- {2-[(3-ethylphenyl) amino] -2-ketoethyl} hexahydroide -4 · yl) outer N-oxide; Lu 2- {1- [2- (2,3-dihydro_1Η-inden-5-ylamino) -2-ketoethyl] hexahydro Pyridin-4-yl} pyridine N-oxide; 2- {1- [2_keto-2_ (5,6,7,8-tetrahydrofluoren-1-ylamino) ethyl] hexahydropyridine Ice-based} ingot N-oxide; 2- (1- {2 _ [(3-isopropyllactylphenyl) amino] -2-copperethyl} hexaki -4_yl) Outer b ingot: N-oxide; 2_ (1- {2-[(3,5-dimethylphenyl) amino] -2-ketoethyl} hexahydropyridyl) pyridine N-oxide; _ 2- (1- {2-[(4-Bromo-2-methylphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2_ [1 · (2_keto-2-{[3- (trifluoromethoxy) phenyl] amino} ethyl) hexahydropyridin-4-yl] ρ ratio bond N_ Oxide; 2- (1- {2-[(5-methyl-2 · nitrophenyl) amino] -2-ketoethyl} hexahydropyridine · 4-yl ; 2- (1- {2-[(2,6-dimethylphenyl) amino] -2-alanylethyl} hexahydropyridine-4-yl) pyridinium N-oxide; 85228- 99- 200404539 2- (l- {2-[(2,6-dichloro-3-methylphenyl) amino] _2_ketoethyl} hexahydroide I: Yodolide) pyridine N- Oxides; 2- {1- [2- (1,3-benzodioxol-5-ylamino) -2-ketoethyl] hexahydropyridin-4-yl} pyridine N- Oxides; 2- [1- (2-{[3- (methylthio) phenyl] aminob-2-ketoethyl) hexahydropyridin-4-yl] pyridine N-oxide; 2- (1 · {2-[(5-Chlorophenyl) amino] -2-ketoethyl} hexahydrop-bito-4-yl &gt; ratio indium N · oxide; φ 2- (1_ {2 _ [(2,5-dimethoxyphenyl) amino] -2-S isopropylethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1 -{2 _ [(3,5_dimethoxyphenyl) amino] _2_ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- [1- (2- { | &gt; (Dimethylamino) phenyl] amino group 2-ketoethyl) hexahydropyridine-4 · yl] pyridine N-oxide; 2- (1- {2-[(3-iso Propylphenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridinium N_oxide; _ 2- (1_ {2-[(3-chloroyl-2-Tyl Phenyl) amino] -2-ketoethyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1-{[(2,3-dibromo-5-methylbenzene Formamyl) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- {1-[(benzylgamido) methyl] hexahydrooutside Base than ingot N-oxide; 2- (1-{[((4-chloro-3-methylbenzyl) amino) methyl] hexahydropyridin-4-yl) eodonium N-oxide ; 2- (1-{[(4-Fluoro-3-methylbenzylidene) amino] methyl} hexahydropyridin-4-yl) 85228 -100- 200404539 pyridinium N-oxide; 2 -[1-({| &gt; chloro-4- (trifluoromethoxy) benzylidene] amino} methyl) hexahydropyridine- 4-yl] pyridine N-oxide; 2- (1-{[((3-ethoxybenzyl) amino) methyl] hexahydropyridin-4-yl) pyridine N-oxide; 2 -(1-{[((3,5-Dichlorobenzyl) amino) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- [1-({[4- 甲3- (trifluoromethyl) benzylidene] amino} methyl) hexahydropyridinyl] pyridine N-oxide; 2- (1-{[(3,4-xylene Formamyl) amino] methyl} hexahydropyridyl) pyridine N-oxide; 2- (1-{[((3-chloro-4-fluorobenzyl) amino) amino] methyl} Hexahydropyridyl) pyridinium N-oxide; 2- (1-{[(pyridin-2-ylcarbonyl) amino] methyl} hexahydropyridin-4-yl) pyridinium N-oxide; 2_ (1 _ {[(3,5_Xylenylmethylamino) amino] methyl} hexahydropyridylpyridinium N-oxide; 2_ (1-{[(3-vinylbenzylmethyl) amine Group] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1-{[((4-bromo-3-methylbenzyl) amino) amino] methyl} -1 , 2,3,6-tetrahydropyridine-4-yl) p ratio N-emulsions, 2- {1-[(2-methylformamidinylamino) methyl] hexahydropyridylicel} pyridine Ingot N-oxide; 2- (1-{[thiophen-2-ylcarbonyl) amine [Methyl] methyl} hexahydropyridin-4-ylsulfonium N-oxyl-101- &amp; 14 85228 200404539 compound; 2- [l-({[((6-chloro group ] Amine} methyl) hexahydro p ratio_4-yl] pyridinium N-oxide; 2- (1-{[((3-cyanobenzyl) amino) methyl] hexahydropyridine -4-yl) pyridine N-oxide; 2- (1-{[((2,3-dibromomethylbenzyl) amino) methyl] methyl H, 2,3,6-tetrahydropyridine -4-yl) pyridine N-oxide; 2- (1-{[((4-bromobenzyl) amino) methyl] hexahydropyridinyl) pyridine N-oxide; 2- (1-{[(3-chloro-4-methylbenzylidene) amino] methyl} hexahydropyridyl) pyridine N-oxide; [methyl (3-methylbenzidine (Amino) amino] methyl} hexahydropyridin-4-yl) pyridine N-oxide; 2- (1-{[((3-nitrobenzyl) amino) methyl] hexahydropyridine-4 _Base sulfonium N-oxide; 2- (1-{[((2-chloro-5-methylbenzyl) amino) methyl] hexahydropyridinyl)) pyridinium N-oxide; 2- (1-{[((3-methoxy-2-methylbenzyl) amino) amino] methyl} hexahydropyridinyl) pyridine N-oxide; and 2- (1-{[ (4-chloro-3-methoxybenzyl) amino] methyl Outer} hexahydro-1: Lake-yl) pyrazol ingot Ν- oxide. I32. The compound according to item 81 of the scope of application for a patent, which is 2- (1-{[(3-methylbenzylidene) amino] methyl} -4-hexahydropyridyl &gt; -Oxide. 133.-compound of formula (III) 85228 -102- 200404539 A / U (ΠΙ) 或其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 Χι係選自包括一^固键結與CRg ， X2係述自包括*^個键結與CRj) Re， 其條件是，當Xi為一個键結時，則x2為crdre ; 進一步條件是，當X2為鍵結時，則Xi為CRBRc ; A係選自包括芳基、芳烷基、環烷基及環烷基烷基； h 係選自包括 _N(R7)C(0)-、_C(0)N(R7)_、-N(R7)C(S)-及-C(S)N(R7)-，其中-N(R7)C(〇&gt;、-c(o)n(r7)-、-N(R7)C(S)-及 C(S)N(Ry)-之左端係連接至a，而右端係連接至d ; L2係選自包括一個鍵結與次烷基； D係選自包括次烷基、氟次烷基及羥基次烷基； RA、RB、Rc、RD及RE係獨立選自包括氫與燒基； B係選自包括(II) or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, wherein X1 is selected from the group consisting of a solid bond and CRg, X2 is described from a group consisting of a bond and CRj) Re, The condition is that when Xi is a bond, then x2 is crdre; further, when X2 is a bond, Xi is CRBRc; A is selected from the group consisting of aryl, aralkyl, cycloalkyl, and ring Alkylalkyl; h is selected from the group consisting of _N (R7) C (0)-, _C (0) N (R7) _, -N (R7) C (S)-, and -C (S) N (R7 )-, Where the left ends of -N (R7) C (〇 &gt;, -c (o) n (r7)-, -N (R7) C (S)-, and C (S) N (Ry)-are connected To a, and the right end is connected to d; L2 is selected from the group consisting of a bond and an alkylene group; D is selected from the group consisting of an alkylene group, a fluoroalkylene group, and a hydroxyalkylene group; RA, RB, Rc, RD, and RE is independently selected from the group consisting of hydrogen and alkyl; B is selected from the group consisting of Ri、R2、R3及R4各獨立選自包括氫、燒氧基、烯基、 烷基、烷基亞磺醯基、烷基磺醯基、烷硫基、炔基、烷 85228 -103. 200404539 氧羰基、烷羰基、烷羰基氧基、羧基、氰基、甲醯基、 鹵素、1¾烷氧基、_烷基、羥基、羥烷基、巯基、硝基 、-NZ；^、（NZ3Z4)烷基、（NZ3Z4)羰基及(NZ3Z4)磺醯基； Zi與z2各獨立選自包括氫、烷基、烷羰基、烷基磺醯 基、芳基、芳烷基、芳烷基磺醯基、芳基磺醯基及甲醯 基； 4與z4各獨立選自包括氫、烷基、芳基及芳烷基； X係選自包括N(R^)、Ο及S ; γ係選自包括C(R4)與N; ^6係選自包括氫與烷基；及 R7係選自包括氫與烷基。 I34·根據申請專利範圍第133項之化合物，其中 A為芳基；Ri, R2, R3 and R4 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkanes 85228-103. 200404539 Oxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxyl, cyano, methylamino, halogen, 1¾alkoxy, _alkyl, hydroxy, hydroxyalkyl, mercapto, nitro, -NZ; ^, (NZ3Z4) Alkyl, (NZ3Z4) carbonyl and (NZ3Z4) sulfonyl; Zi and z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, aralkyl, aralkylsulfonyl , Arylsulfonyl and formamyl; 4 and z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl; X is selected from the group consisting of N (R ^), 0, and S; γ is selected from Including C (R4) and N; ^ 6 is selected from the group consisting of hydrogen and alkyl; and R7 is selected from the group consisting of hydrogen and alkyl. I34. The compound according to the scope of application for item 133, wherein A is aryl; Xig CRBRc ; X2 為 CRd Re，及 L 為-N(R7)C(0)_。 I35·根據申請專利範圍第133項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括浠基、烷氧基、烷氧羰基 、燒基、燒硫基、罕基、氰基、1¾素、鹵燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-ΝΖαζ ; 85228 -104- 200404539 B為 &quot;A： N κ4. &amp;係選自包括氫、烷基、氰基、函烷基、鹵素、硝基 、（ΝΖ3Ζ4)烷基及（ΝΖ3Ζ4)羰基； R2與R4為氮， r3係選自包括氫與羥基； X!為 CRb Rc， X2 為 CRD RE ; D 為-CH2_ ; L2為一個鍵結；及 L 為-N(R7)C(0)-。 136.根據申請專利範圍第133項之化合物，其中 A為雜環； B為Xig CRBRc; X2 is CRd Re, and L is -N (R7) C (0) _. I35. The compound according to the scope of application for patent No. 133, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl, alkyl, thio, alkynyl, cyano, 1¾, halooxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZαζ; 85228- 104- 200404539 B is &quot; A: N κ4. &Amp; is selected from the group consisting of hydrogen, alkyl, cyano, alkynyl, halogen, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 and R4 Nitrogen, r3 is selected from the group consisting of hydrogen and hydroxyl; X! Is CRb Rc, X2 is CRD RE; D is -CH2_; L2 is a bond; and L is -N (R7) C (0)-. 136. The compound according to the scope of application for item 133, wherein A is a heterocyclic ring; B is Χι 為 CRb Re， X2 為 CR_d Re，及 L 為 _N(R7)C(0)_。 137.根據申請專利範圍第133項之化合物，其中 A為雜環，其中雜環係選自包括苯并咪唑基、苯并噻 峻基、吱喃基、咪11坐基、1，3-崎嗤基、p比啡基、p比嗤基、 塔p井基、p比淀基、痛淀基、p比洛基、1，3-隹嗤基及隹吩基 85228 -105- 200404539 ，其中雜環係被0、1、2或3個取代基取代，取代基獨立 選自包括烷氧基、烷氧羰基、烷基、氰基、画素、鹵烷 氧基、iS烷基及硝基； B為X i is CRb Re, X2 is CR_d Re, and L is _N (R7) C (0) _. 137. The compound according to item 133 of the application, wherein A is a heterocyclic ring, wherein the heterocyclic ring system is selected from the group consisting of benzimidazolyl, benzothiazyl, succinyl, imidyl 11 Fluorenyl, p-pyrrolyl, p-pyridyl, p-pyridyl, p-pyridyl, acetonyl, p-pyroxy, 1,3-fluorenyl and fluorenyl 85228 -105- 200404539 The heterocyclic system is substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from the group consisting of alkoxy, alkoxycarbonyl, alkyl, cyano, pixel, haloalkoxy, iS alkyl, and nitro; B is R2與R3為氮； 义!為 CRBRc ; X2 為 CRd Re， X 為 N(R6)、Ο 或 s ; Y為N ; D 為-CH2-; L2為一個键結；及 L 為-N(R7)C(0)-。 138.根據申請專利範圍第133項之化合物，其中 A為芳基；R2 and R3 are nitrogen; meaning! Is CRBRc; X2 is CRd Re, X is N (R6), 0 or s; Y is N; D is -CH2-; L2 is a bond; and L is -N (R7 ) C (0)-. 138. The compound according to the scope of application for item 133, wherein A is aryl; Χι為一個键結； X〗為CRd Re，及 L 為-N(R7)C(0)-。 139.根據申請專利範圍第133項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 85228 -106- 200404539 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、燒硫基、芊基、氰基、画素、鹵燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZi Z2 ;X is a bond; X is CRd Re, and L is -N (R7) C (0)-. 139. The compound according to item 133 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl, and is substituted by 0, 1, 2, 3, 4 or 5 85228 -106- 200404539 substituents. Including alkenyl, alkoxy, alkoxycarbonyl, thio, thio, fluorenyl, cyano, pixel, halooxy, halo, methylenedioxy, nitro, phenyl, and- NZi Z2; Ri係選自包括氫、燒基、氰基、iS燒基、素、硝基 、（NZ3Z4)烷基及（NZ3Z4)羰基； φ 112與1^為氫； r3係選自包括氫與羥基； Xl為一個键結； X〗為 CRd Re ; D 為-CH2-; l2為一個鍵結；及 L 為-N(R7)C(0)-。 140.根據申請專利範圍第133項之化合物，其中 籲 A為雜環； B為Ri is selected from the group consisting of hydrogen, alkyl, cyano, iS, alkyl, nitro, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; φ 112 and 1 ^ are hydrogen; r3 is selected from hydrogen and hydroxyl; X1 is a bond; X is CRd Re; D is -CH2-; l2 is a bond; and L is -N (R7) C (0)-. 140. The compound according to the scope of application for patent 133, wherein A is heterocyclic; B is Xl為一個键結； X〗為CRd Rg，及 L 為-N(R7)C(0)-。 141.根據申請專利範圍第133項之化合物，其中 85228 -107- 200404539 A為雜環，其中雜環係選自包括苯并咪唑基、苯并嘧 峻基、吱喃基、咪吐基、1，3-4嗤基、说畊基、p比峻基、 塔呼基、p比淀基、喃違基、被哈基、1，3-隹峻基及遠吩基 ，其中雜環係被0、1、2或3個取代基取代，取代基獨立 選自燒氧基、燒氧黢基、燒基、氰基、ώ素、_燒氧基 、鹵燒基及硝基；X1 is a bond; X is CRd Rg, and L is -N (R7) C (0)-. 141. The compound according to item 133 of the scope of patent application, wherein 85228-107-200404539 A is a heterocyclic ring, wherein the heterocyclic ring system is selected from the group consisting of benzimidazolyl, benzopyrimyl, syl, imidyl, 1 , 3-4 fluorenyl, said pengji, pbijunki, tahuki, pbidian, sulfanyl, hakyl, 1,3-pyridyl and farphenyl, in which the heterocyclic system is 0, 1, 2 or 3 substituents, each of which is independently selected from alkoxy, alkoxy, alkoxy, cyano, gluten, alkoxy, halo and nitro; R2與R3為氮， Xl為一個键結； X〗為 CRd Re， X 為 N(R6)、Ο 或 s ; Y為N ; D 為-CH2-;R2 and R3 are nitrogen, Xl is a bond; X〗 is CRd Re, X is N (R6), 0 or s; Y is N; D is -CH2-; L2為'^固键結；及 L 為-N(R7)C(0)-。 142.根據申請專利範圍第133項之化合物，其中 A為芳基； B為L2 is a '^ solid bond; and L is -N (R7) C (0)-. 142. The compound according to the scope of application for item 133, wherein A is aryl; B is Χι為一個键結； X〗為CRd ，及X is a bond; X is CRd, and 85228 -108- 200404539 L 為-N(R7)C(0)-。 143.根據申請專利範圍第133項之化合物，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、IS素、IS烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZ! Z2 ; B為85228 -108- 200404539 L is -N (R7) C (0)-. 143. The compound according to item 133 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, IS element, IS alkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZ! Z2; B is R2與R3為氯； Xi為一個鍵結； X〗為 CR_d Re， X 為 N(R6)、Ο 或 s ; Y 為 C(R4); R4係選自包括氫、烷基及氰基； D 為-CH2-; L2為一個键結；及 L 為-N(R7)C(0)-。 144.根據申請專利範圍第133項之化合物，其中 A為芳基； B為R2 and R3 are chlorine; Xi is a bond; X is CR_d Re, X is N (R6), 0 or s; Y is C (R4); R4 is selected from the group consisting of hydrogen, alkyl and cyano; D Is -CH2-; L2 is a bond; and L is -N (R7) C (0)-. 144. The compound according to the scope of application for item 133, wherein A is aryl; B is Rs 85228 -109- 200404539 Χι 為 CRg ; x2為一個鍵結；及 L 為-N(R7)C(0)- 〇 I45·根據申請專利範圍第133項之化合物，其中 A為芳基，其中芳基為苯基，被〇、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、燒氧談基 、烷基、烷硫基、苄基、氰基、自素、_烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-ΝΖιζ2 ; B為Rs 85228 -109- 200404539 χ is CRg; x2 is a bond; and L is -N (R7) C (0)-〇45. A compound according to item 133 of the scope of patent application, wherein A is aryl and aryl Is a phenyl group and is substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkenyl, alkoxy, alkoxy, alkyl, alkylthio, benzyl, cyano Group, autogen, alkoxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZιζ2; B is Ri、R2、R3、R4 及 r5 為氫 CRbI^ ; X2為一個鍵結； D 為-CH2_ ; L2為-CH〗-;及 L 為-N(R7 )C(0)- 〇 礙之方法，其包括對該 上有效量之式(IV)化合物 I46· —種在哺乳動物中治療性功能障 需要此種治療之哺乳動物投予治療 A〆Ri, R2, R3, R4 and r5 are hydrogen CRbI ^; X2 is a bond; D is -CH2_; L2 is -CH〗-; and L is -N (R7) C (0)-〇 hinder the method, It includes administering to a therapeutically effective amount of a compound of formula (IV) I46 ·, a mammal in need of such treatment for the treatment of sexual dysfunction. (IV) 85228 -110- 200404539 或其藥學上可接受之鹽、酯、醯胺或前體藥物，其中 Χι係選自包括〆個鍵結與CRBRc ; X2係選自包括〆個鍵結與CRDRE ; 其條件是，當Χι為一個鍵結時，則X2為CRDRE ; 進一步條件是，當X2為鍵結時，則Χι為CRB Rc ; A係選自包括芳基、芳烷基、環烷基及環烷基烷基； q 係選自包括-N(R7)C(0)_、-C(0)N(R7)-、-N(R7)C(S)-及-c(s)n(r7)…其中-N(R7)c(o)-、-C(0)N(R7)-、-N(R7)C(S)-及-φ C(S)N(R7)-之左端係連接至a，而右端係連接至D ; L2係選自包括一個鍵結與次烷基； D係選自包括次烷基、氟次烷基及羥基次烷基； Ra、Rb、Rc、rd及RE係獨立選自包括氫與烷基； B係選自包括(IV) 85228 -110- 200404539 or a pharmaceutically acceptable salt, ester, amidine or prodrug thereof, wherein X is selected from the group consisting of two bonds and CRBRc; X2 is selected from the group consisting of two bonds and CRDRE The condition is that when Xι is a bond, then X2 is CRDRE; further condition is that when X2 is a bond, then X2 is CRB Rc; A is selected from the group consisting of aryl, aralkyl, and cycloalkyl And cycloalkylalkyl; q is selected from the group consisting of -N (R7) C (0) _, -C (0) N (R7)-, -N (R7) C (S)-, and -c (s) n (r7) ... where -N (R7) c (o)-, -C (0) N (R7)-, -N (R7) C (S)-, and -φ C (S) N (R7)- The left end is connected to a, and the right end is connected to D; L2 is selected from a group including a bond and an alkylene group; D is selected from a group including an alkylene group, a fluoroalkylene group, and a hydroxyalkylene group; Ra, Rb, Rc, rd and RE are independently selected from the group consisting of hydrogen and alkyl; B is selected from the group consisting of Ri、R2、R3及R4各獨立選自包括氫、燒氧基、烯基、 ^元基、彡元基亞續8^基、fe基續酸基、燒硫基、決基、 氧羰基、烷羰基、烷羰基氧基、羧基、氰基、甲醯基、 鹵素、_烷氧基、iS烷基、羥基、羥烷基、巯基、硝基 、-NZA、（NZ3Z4)燒基、（NZ3Z4)羰基及(NZ3Z4)續醯基； Zi與z2各獨立選自包括氫、烷基、烷羰基、烷基磺醯 85228 -111- 200404539 基、芳基、芳基、芳燒基績醒基、芳基績s盈基及甲醒 基； z3與z4各獨立選自包括氫、烷基、芳基及芳烷基； X係選自包括N(R6)、Ο及S ; Y係選自包括C(R4)與N ; r6係選自包括氫與烷基；及 r7係選自包括氩與烷基。 147.根據申請專利範圍第146項之方法，其中 A為芳基；Ri, R2, R3, and R4 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, fluorenyl, fluorenyl, sulfonyl, sulfonyl, sulfanyl, carbyl, oxycarbonyl, Alkylcarbonyl, alkylcarbonyloxy, carboxyl, cyano, methylamino, halogen, alkoxy, iS alkyl, hydroxy, hydroxyalkyl, mercapto, nitro, -NZA, (NZ3Z4) alkyl, (NZ3Z4 ) Carbonyl and (NZ3Z4) continyl; Zi and z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl 85228 -111- 200404539, aryl, aryl, aryl, and aryl, The aryl group is syl and methyl; z3 and z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl; X is selected from the group including N (R6), 0, and S; Y is selected from the group including C (R4) and N; r6 is selected from the group consisting of hydrogen and alkyl; and r7 is selected from the group consisting of argon and alkyl. 147. The method according to the scope of application for patent 146, wherein A is aryl; Χι 為 CRb ， X2 為 CRd Re，及 L 為-N(R7)C(0)-。 148.根據申請專利範圍第146項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、烷基、燒硫基、苄基、氰基、ii素、ii烷氧基、鹵烷 基、亞甲二氧基、硝基、苯基及-NZiZ2 ;Xm is CRb, X2 is CRd Re, and L is -N (R7) C (0)-. 148. The method according to the scope of application for patent 146, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of alkenyl Alkoxy, alkoxycarbonyl, alkyl, sulfanyl, benzyl, cyano, ii prime, ii alkoxy, haloalkyl, methylenedioxy, nitro, phenyl and -NZiZ2; Ri係選自包括氫、燒基、氰基、1¾燒基、1¾素、硝基 85228 112- 200404539 、（NZ3Z4)烷基及（NZ3Z4)羰基； R2與為氫； r3係選自包括氫與羥基； Χι 為 CRb Rc， X2 為 CRd Re， D 為-CH2-; l2為一個鍵結；及 L 為-N(R7)C(0)-〇 I49·根據申請專利範圍第146項之方法，其中 A為雜環； B為Ri is selected from the group consisting of hydrogen, alkynyl, cyano, 12-alkyl, 12-nitro, nitro 85228 112-200404539, (NZ3Z4) alkyl and (NZ3Z4) carbonyl; R2 is hydrogen; r3 is selected from Hydroxyl group; Xb is CRb Rc, X2 is CRd Re, D is -CH2-; l2 is a bond; and L is -N (R7) C (0) -〇I49. According to the method of the scope of application for patent 146, Where A is a heterocyclic ring; B is X!為 CRg Rc， X2 為 CRd Re ;及 L 為-N(R7)C(0)-〇 15〇·根據申請專利範圍第146項之方法，其中 Α為雜環，其中雜環係選自包括苯并咪唑基、苯并隹 唑基、呋喃基、咪唑基、1，3-嘮唑基、吡畊基、吡峻基、 嗒畊基、吡啶基、嘧啶基、吡咯基、1，3-噻唑基及噻吩基 ，其中雜環係被0、1、2或3個取代基取代，取代基獨立 選自烷氧基、烷氧羰基、烷基、氰基、齒素、自烷氧基 、鹵烷基及硝基； B為X! Is CRg Rc, X2 is CRd Re; and L is -N (R7) C (0)-015. According to the method of the scope of application for patent No. 146, wherein A is a heterocyclic ring, wherein the heterocyclic ring is selected from Including benzimidazolyl, benzimidazolyl, furyl, imidazolyl, 1,3-oxazolyl, pyridyl, pyridyl, daphnyl, pyridyl, pyrimidinyl, pyrrolyl, 1,3 -Thiazolyl and thienyl, wherein the heterocyclic system is substituted with 0, 1, 2 or 3 substituents, and the substituents are independently selected from alkoxy, alkoxycarbonyl, alkyl, cyano, halide, and alkoxy , Haloalkyl and nitro; B is 85228 -113· 200404539 泰. 5 R2與R3為風， Xi 為 CRb Re， X2 為 CRD RE ; X 為 N(R6)、o 或 s ; Y為N ; D 為-CH2-; L2為一個键結；及 L 為-N(R7)C(0)-。 151. 根據申請專利範圍第146項之方法，其中 A為芳基； B係選自包括 XXR Λ N R4. Xl為一個键結； X〗為CRd Re，及 L 為-N(R7)C(0)-。 152. 根據申請專利範圍第146項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括烯基、烷氧基、烷氧羰基 、燒基、虎硫基、爷基、氰基、iS素、ii燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZi Z2 ; B為 85228 -114- 20040453985228 -113 · 200404539 Thai. 5 R2 and R3 are wind, Xi is CRb Re, X2 is CRD RE; X is N (R6), o or s; Y is N; D is -CH2-; L2 is a bond ; And L is -N (R7) C (0)-. 151. The method according to item 146 of the patent application, wherein A is aryl; B is selected from the group consisting of XCR Λ N R4. X1 is a bond; X is CRd Re, and L is -N (R7) C ( 0)-. 152. The method according to item 146 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkenyl, Alkoxy, alkoxycarbonyl, alkyl, thio, thio, cyano, iS, ii, oxy, halo, methylenedioxy, nitro, phenyl, and -NZi Z2; B For 85228 -114- 200404539 、（NZ3Z4)燒基及(NZ3Z4)羧基； R2與R4為氫； R3係選自包括氫與經基； Xi為一個鍵結； X:為 CRd Rg， D 為-CH2-; L2為*個鍵結，及 L 為-N(R7)C(0)… 1«·根據申請專利範圍第146項之方法，其中 A為雜環； B為, (NZ3Z4) alkyl and (NZ3Z4) carboxyl; R2 and R4 are hydrogen; R3 is selected from the group consisting of hydrogen and meridian; Xi is a bond; X: CRd Rg, D is -CH2-; Bonding, and L is -N (R7) C (0) ... 1 «· According to the method of the scope of application for patent No. 146, wherein A is a heterocyclic ring; B is X!為一個鍵結； X2 為 CRd Re ;及 L 為-N(R7)C(0)-〇 I54·根據申請專利範圍第146項之方法，其中 A為雜環，其中雜環係為苯并咪唑基、苯并嘧唑基、 呋喃基、咪唑基、1，3_呤唑基、吡啡基、吡唑基、嗒畊基 、吡啶基、嘧啶基、吡咯基、L3—嘧唑基及嘧吩基； 85228 -115- 200404539X! Is a bond; X2 is CRd Re; and L is -N (R7) C (0) -〇I54. According to the method of the 146th application, wherein A is a heterocyclic ring, wherein the heterocyclic ring is benzene Benzimidazolyl, benzopyrazolyl, furyl, imidazolyl, 1,3-pyrazolyl, pyridyl, pyrazolyl, dacrotyl, pyridyl, pyrimidinyl, pyrrolyl, L3-pyrazolyl And pyrenyl; 85228 -115- 200404539 r2與R3為氯； Xl為'一個键結； X:為 CR_d Re， X 為 N(R6)、Ο 或 s ; Y為N ; D 為-CH2-; l2為一個鍵結；及 L 為-N(R7)C(0)-。 155.根據申請專利範圍第146項之方法，其中 A為芳基； B為r2 and R3 are chlorine; Xl is' a bond; X: is CR_d Re, X is N (R6), 0 or s; Y is N; D is -CH2-; l2 is a bond; and L is- N (R7) C (0)-. 155. The method according to the scope of application for patent 146, wherein A is aryl; B is Xi為一^固键結； X2 為 CRd Re，及 L 為-N(R7)C(0)-。 156.根據申請專利範圍第146項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 、燒基、燒硫基、爷基、氰基、_素、卣燒氧基、鹵燒 基、亞甲二氧基、硝基、苯基及-NZiZ2 ; B為 85228 -116- 200404539 恭3. 5 112與113為氫； Xl為一個鍵結； X〗為 CRd Re， X 為 N(R6)、Ο 或 s ; Y 為 C(R4); r4係選自包括氫、烷基及氰基； D 為-CH2-; L2為一個鍵結；及 L 為-N(R7)C(0)-。 157. 根據申請專利範圍第146項之方法，其中 A為芳基； B為 ?2 Ά R5 · X!為 CRb Re， x2為一個键結；及 L 為-N(R7)C(0)-。 158. 根據申請專利範圍第146項之方法，其中 A為芳基，其中芳基為苯基，被0、1、2、3、4或5個 取代基取代，取代基選自包括晞基、烷氧基、烷氧羰基 、烷基、烷硫基、苄基、氰基、||素、li烷氧基、鹵烷 85228 -117- 200404539 基、亞甲二氧基、硝基苯基及_NZiz2 ; B為 R5 . ， R1、R2、R3、R4 及 r5 為氫； X!為 CRb Rc ; X2為一個鍵結； D 為-CH2-; L2 為-CH2 -;及 L 為-N(R7 )C(〇)- 〇 159t種在哺乳動物中治療性功能障礙之方法，其包括對該 哺礼動物投予治療上有效量之式（IV)化合物，或其藥學上 可接受I鹽、g旨、醯胺或前體藥物，且併用藥學上可接 受之載劑。 · 一種在哺礼動物中治療性功能障礙之方法，其包括對該 哺礼動物投丁治療上有效量之式①^化合物，或其藥學上 可接受（鹽、酯、醯胺或前體藥物，且併用磷酸二酯酶5 抑制劑。 種在甫乳動物中治療性功能障礙之方法，其包括對該 哺乳動物投予治療上有效量之式(lv)化合物，或其藥學上 可接又（鹽、酯、醯胺或前體藥物，且併用腎上腺素能 受體拮抗劑。 μ 162·-種在哺乳動物中治療性功能障礙之方法，其包括對該 85228 -118- 200404539 哺乳動物投予治療上有效量之式（ιν)化合物，或其藥學上 可接受之鹽、酯、醯胺或前體藥物，且併用多巴胺催動 劑。 163. —種在哺乳動物中治療男性勃起功能障礙之方法，其包 括對該需要此種治療之哺乳動物投予治療上有效量之式 (IV)化合物，或其藥學上可接受之鹽、酯、醯胺或前體藥 物。 164. —種在哺乳動物中治療女性性功能障礙之方法，其包括 對該需要此種治療之哺乳動物投予治療上有效量之式（IV) 化合物，或其藥學上可接受之鹽、酯、醯胺或前體藥物。 165. —種在哺乳動物中治療病症之方法，該病症選自包括心 與血管病症、炎性病症、注意力不足活動過度病症、阿 耳滋海默氏疾病、藥物溢用、巴金生氏病、精神分裂症 、焦慮、心情病症及抑鬱，其包括對該需要此種治療之 哺乳動物投予治療上有效量之式（IV)化合物，或其藥學上 可接受之鹽、酯、醯胺或前體藥物。 85228 119- 200404539 柒、指定代表圖： (一) 本案指定代表圖為：第（ ）圖。 (二) 本代表圖之元件代表符號簡單說明： 捌、本案若有化學式時，請揭示最能顯示發明特徵的化學式:Xi is a solid bond; X2 is CRd Re, and L is -N (R7) C (0)-. 156. The method according to item 146 of the scope of patent application, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, the substituents being selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl, alkynyl, sulfanyl, hexyl, cyano, hydrogen, sulfanyloxy, haloalkyl, methylenedioxy, nitro, phenyl, and -NZiZ2; B is 85228 -116- 200404539 Christine 3. 5 112 and 113 are hydrogen; X1 is a bond; X is CRd Re, X is N (R6), 0 or s; Y is C (R4); r4 is selected from the group consisting of Hydrogen, alkyl, and cyano; D is -CH2-; L2 is a bond; and L is -N (R7) C (0)-. 157. The method according to item 146 of the scope of patent application, wherein A is aryl; B is? 2 Ά R5 · X! Is CRb Re, x2 is a bond; and L is -N (R7) C (0)- . 158. The method according to the scope of application for patent 146, wherein A is aryl, wherein aryl is phenyl and substituted with 0, 1, 2, 3, 4 or 5 substituents, and the substituents are selected from the group consisting of fluorenyl, Alkoxy, alkoxycarbonyl, alkyl, alkylthio, benzyl, cyano, || prime, li alkoxy, haloalkane 85228 -117- 200404539, methylenedioxy, nitrophenyl and _NZiz2; B is R5., R1, R2, R3, R4 and r5 are hydrogen; X! Is CRb Rc; X2 is a bond; D is -CH2-; L2 is -CH2-; and L is -N ( R7) C (〇)-〇159t A method for treating sexual dysfunction in mammals, which comprises administering to the mammal an effective amount of a compound of formula (IV), or a pharmaceutically acceptable I salt thereof, g, amidine or prodrug, and use a pharmaceutically acceptable carrier. · A method for treating sexual dysfunction in a mammal, comprising administering to the mammal an effective amount of a compound of the formula ① ^, or a pharmaceutically acceptable (salt, ester, amidine or prodrug thereof) And a phosphodiesterase 5 inhibitor. A method for treating sexual dysfunction in a mammalian animal, which comprises administering to the mammal a therapeutically effective amount of a compound of formula (lv), or a pharmaceutically acceptable compound thereof (Salts, esters, amines, or prodrugs, and adrenergic receptor antagonists are used in combination. Μ 162 · -A method for treating sexual dysfunction in mammals, which includes administering the 85228-118- 200404539 mammal A therapeutically effective amount of a compound of formula (ιν), or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof, is administered in combination with a dopamine activator. 163. A method for treating male erectile dysfunction in mammals A method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable salt, ester, amidine, or prodrug thereof. Breastfeeding A method for treating female sexual dysfunction in a body, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable salt, ester, amidine or precursor thereof 165. A method for treating a condition in mammals, the condition being selected from the group consisting of heart and vascular disorders, inflammatory disorders, hyperattention disorders, Alzheimer's disease, drug overdose, buckingson 'S disease, schizophrenia, anxiety, mood disorders, and depression, which include administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV), or a pharmaceutically acceptable salt, ester, hydrazone Amine or prodrug. 85228 119- 200404539 柒. Designated representative map: (1) The designated representative map in this case is: (). (II) The representative symbols of the representative map are simply explained: 捌, if there is a chemical formula in this case Please reveal the chemical formula that best characterizes the invention: (I)， 85228(I), 85228
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ZA825719B (en) * 1981-09-03 1983-06-29 Recordati Chem Pharm Alkanoylanilides
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FR2573075B1 (en) * 1984-09-14 1987-03-20 Innothera Lab Sa NEWS (PYRIDYL-2) -1 PIPERAZINES, THEIR PREPARATION PROCESS AND THEIR APPLICATION IN THERAPEUTICS
IL90279A (en) * 1988-05-24 1995-03-30 American Home Prod Piperazinyl carboxamide derivatives, their preparation and pharmaceutical com¦ositions containing them
US5395835A (en) * 1994-03-24 1995-03-07 Warner-Lambert Company Naphthalamides as central nervous system agents
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