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TW200916447A - Sirtuin inhibitors - Google Patents

Sirtuin inhibitors Download PDF

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Publication number
TW200916447A
TW200916447A TW097133327A TW97133327A TW200916447A TW 200916447 A TW200916447 A TW 200916447A TW 097133327 A TW097133327 A TW 097133327A TW 97133327 A TW97133327 A TW 97133327A TW 200916447 A TW200916447 A TW 200916447A
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Taiwan
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alkyl
group
aryl
heteroaryl
heterocyclyl
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TW097133327A
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Chinese (zh)
Inventor
Robert Deziel
Jubrail Rahil
Amal Wahhab
Martin Allan
Natalie Nguyen
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Methylgene Inc
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Publication of TW200916447A publication Critical patent/TW200916447A/en

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Abstract

This invention relates to compounds and methods for the inhibition of sirtuin enzymatic activity. More particularly, the invention provides for compounds of formula (I), Y-L-Z-D (I) and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein Y, L, Z and D are as defined in the specification.

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200916447 九、發明說明： 【發明所屬之技術領域】 本發明係關於抑制種類m組織蛋白脫乙醯酶（HDAc)，亦 稱為組織蛋白去乙醯化酶（SIRT)。更特定言之，本發明係關 於抑制組織蛋白去乙醢化酶酵素活性之化合物與方法。 本申請案係主張2007年8月29日提出申請之美國臨時申 請案序號_68,773之權益。上文所引用申請案之全部陳述 内容係併於本文供參考。 【先前技術】 組織蛋白脫乙醯酶係涉及基因表現經過染色質改造之表 現型之改變調節。正如此名稱所意謂，HDAC係使組織蛋白 乙醯基離胺酸脫乙醯基化。但是’蛋白質之調節乙醯化作 用/脫乙醯基作用可影響除了組織蛋白以外之蛋白質。種類 I與II HDAC係藉由水解作用移除乙醯基，然而種類m HDAC，亦稱為組織蛋白去乙醯化酶（SIRT)，係採用獨特nad * .1 »a. » 1仅顆‘丨王；^剌。 哺乳動物SIRT蛋白質包括酵母SIR2 (一種連結新陳代謝 作用與長哥之NAD依賴性脫乙醯酶）之七種同系物之族群。 SIRT蛋白質含有保守咖核心、功能部位，具有不同長度之 N_或C_末端順序。在七種人類SIRT中，SIRT1已被最廣泛地 研究=人類SIRT1為酵母SiR2之最接近同系物，具有在細胞 存活率與新陳代謝作用上之角色。SIRT μ7係被定位至多種 細胞隔室’具有不同酵素活性，以許多組織蛋白與非組織 蛋白受質為標的’因此影響寬廣範圍之細胞功能’包括細 134026-1 200916447 胞存活、·新陳代謝作用及DNA修補（Haigis，M.C.與L. P. Guarente, 2006, 哺乳動物組織蛋白去乙醯化酶-在生理學，老化及熱 量限制上之浮現角色，基因&發展20 : 2913-2921)。 SIRT1為核NAD依賴性蛋白質脫乙醯酶，且SIRT1已被証實 會於活體外與活體内使許多受質脫乙醯基化，包括組織蛋 白（H3, H4)與非組織蛋白蛋白質（p53, PML, hTERT, AR, Ku70, NFkB, BCL6, TAF68, CTIP2, FOXO, PGC-1 a, PCAF/MyoD, HES-1, HEY-2, MEF2D, MyoD, PPAR % p300, AceCSl 及 tat)，對治療疾病與 病症具有潛在連結，例如腫瘤發生（腫瘤學應用）、老化、 肥胖、胰島素抗藥性（第II型糖尿病）、發炎、心臟衰竭、 軸索退化及AIDS (Blander, G.與L. Guarante，2004，蛋白質脫乙酉£ 酶之 Sir2 族群，Annu. Rev. Biochem. 73 : 417-435 ; Dali-Youcef 等人， 2007, 組織蛋白去乙酸化酶：πν^2〃，功能，新陳代 謝及壽命，醫藥年鑑39 : 335-345 ; Jiang，2008,組織蛋白去乙醯 化酶：在藥物發展上關於代謝疾病之新穎標的，Biochemical and Biophysical Research Comm. 373 : 341-344)。 功能性有效確認數據係支持SIRT1作為關於癌症之候選 治療標的。在細胞培養物中，SIRT1 RNAi係在人類上皮癌細 胞（HCT116結腸上皮癌細胞、HTB-126乳房上皮癌細胞）而非 正常人類細胞（ARPE-19正常著色視網膜上皮細胞、HTB-125 正常乳房上皮細胞、正常真皮成纖維細胞）中引致生長遏制 及/或細胞凋零（Ford, J.等人，2005, SIRT1之癌症專一功能使得 人類上皮癌細胞能夠生長與存活，癌症研究（Cancer Research) 65(22): 10457-10463)。於活體内，SIRT 抑制劑坎必諾（cambinol) 134026-1 200916447 會降低BCL6+ Daudi異種移植腫瘤之生長（Heltweg, B.等人， 2006,人類寂靜訊息調節劑2酵素之小分子抑制劑之抗腫瘤 活性，癌症研究（Cancer Research) 66(8) : 4368-4377)。坎必諾 (cambinol)為SIRT 1與2之受質競爭性抑制劑，具有弱功效 (>50uM IC50)。SIRT1 RNAi、顯性負 SIRT1 (SIRT1H363Y)及 SIRT 抑制劑（於驗酿胺與分裂霉素（splitomicin))已各被使用以証實 在MCF-7與MDA-MB-231乳癌細胞中之SIRT抑制會導致腫瘤 抑制劑基因試驗組之再表現，及在内源基因啟動子上經增 加之H4K16與H3K9乙醯化作用（Pruitt, K.等人，2006, SIRT1之抑 制係使寂靜癌症基因再活化，而不會損失啟動子DNA高曱 基化作用，PLoS遺傳學2(3) : 344-352)。 SIRT2為NAD依賴性蛋白質脫乙醯酶，其已被証實會於活 體外與活體内使許多受質（譬如<2-微管蛋白）脫乙醯酶化 (Dali-Youcef等人，2007，組織蛋白去乙醯化酶：’’magnificent semT，功能，新陳代謝及壽命，醫藥年鑑39 : 335-345)。調制 SIRT2表現含量已被証實會影響細胞循環，其中SIRT2過度表 現係延遲有絲分裂，而SIRT2剔除之MEF具有經延長之G1期 與經縮短之S期（Dryden 2003, Vaquero 2006)。SIRT2受質亦包括 組織蛋白 H4K16 (North 2003, Vaquero 2006)。 SIRT3為粒線體NAD依賴性蛋白質脫乙醯酶，其已被証實 會於活體外與活體内使許多受質（譬如PGC-1 α與AceCS2)脫 乙醯酶化，對治療疾病與病症具有潛在連結，例如與適應 生熱作用及乳癌有關聯者（Dali-Youcef等人，2007,組織蛋白去 乙醯化酶："magm/iiceni 功能，新陳代謝及壽命，醫藥年 134026-1 200916447 鑑39 : 335-345)。SIRT3係被表現於褐色脂肪組織中，且過度 表現係增加粒線體呼吸作用。SIRT3係使粒線體乙醯基-CoA-合成酶脫乙醯基化與活化（Schwer 2006)。 SIRT4為粒線體NAD依賴性蛋白質脫乙醯酶，其已被証實 會於活體外與活體内使許多受質（譬如麩胺酸脫氫酶）脫乙 醯酶化，對治療疾病與病症具有潛在連結，例如第I型與第 II型糖尿病（Dali-Youcef等人，2007，組織蛋白去乙酸化酶： ⑼i MveV,功能，新陳代謝及壽命，醫藥年鑑39 : 335-345)。SIRT4具有ADP-核糖基轉移酶活性與脫乙醯酶活性 兩者，且藉由葡萄糖回應而調節胰島素分泌（Argmannc與 Auwerx 細胞 2006)。 SIRT5為粒線體NAD依賴性蛋白質脫乙醯酶，在腦部、睪 丸、脾臟、腎臟、心臟、肝臟、卵巢、肺臟、甲狀腺、子 宮及骨髓中具有高表現含量（Dali-Youcef等人，2007,組織蛋白 去乙醯化酶：⑼，功能，新陳代謝及壽命，醫藥 年鑑39 : 335-345)。SIRT5可使細胞色素C脫乙醯基化，且可 調節氧化性壓力與細胞凋零（Sclicker等人，J Mol Biol 2008)。 SIRT6為非核NAD依賴性蛋白質脫乙酿酶，其已被言正實會 於活體外與活體内使許多受質（譬如DNApoly5)脫乙醯酶化， 對治療疾病與病症具有潛在連結，例如與老化有關聯者（皮 下脂肪之失去、經降低之骨礦物質密度等）（Dali-Youcef等人， 2007,組織蛋白去乙醯化酶：seven〃，功能，新陳代 謝及壽命，醫藥年鑑39 : 335-345)。SIRT6具有ADP-核糖基轉 移酶與脫乙醯酶活性兩者。其可使H3K9脫乙醯基化，以調 134026-1 200916447 制調節計量染色質（Michishita等人，Nature 2008)。 SIRT7為核NAD依賴性蛋白質脫乙醯酶，其已被証實會於 活體外使p53脫乙醯基化。SIRT7缺乏之老鼠已被証實會於 活體内顯示p53在心肌中之高乙醯化作用（Vakhrusheva等人， Circ Res 2008)。SIRT7亦已被証實為RNA聚合酶I轉錄之活化 劑，對治療疾病與病症具有潛在連結，例如曱狀腺癌與乳 癌（Dali-Youcef等人，2007，組織蛋白去乙醢化酶： seven 〃，功能，新陳代謝及壽命，醫藥年鑑39 : 335-345)。SIRT7 係被定位至核仁，在增生組織（肝臟、脾臟、睪丸）中具有 高表現，而在非增生組織（心臟、腦部、肌肉）中具有低表 現。SIRT7係在高含量下被表現於曱狀腺癌瘤中。調制SIRT7 表現會影響rRNA轉錄，且SIRT7 RNAi會在U20S細胞中引致 細胞凋零（Ford等人，同前文出處）。 使SIRT1連結至又頭轉錄因子之FOXO族群（Giannakou 2004) ，有增進中之証據。SIRT1已被証實會使FOXOl、F0X03及 FOX04脫乙醯基化，對此等轉錄因子之定位及/或轉移活化 作用可能性具有不同作用。組織蛋白去乙醯化酶活性會影 響穿梭在核與細胞質間之F0X01，且增加F0X01-所媒介之 轉移活化作用（Frescas 2005)。SIRT1係使F0X03脫乙醯基化， 對F0X03功能具有雙重作用，抑制細胞死亡誘發，但增加 細胞循環遏制與氧化性壓力抵抗性機制（Brunet 2004)。在轉 移感染檢測之背景中，SIRT1已被証實會抑制F0X03a所媒介 之轉移活化作用（Motta 2004)。而且，SIRT1係使F0X04脫乙醯 基化，提高FOX04轉錄與生物學活性（Van der Horst 2004)。在 134026-1 •10· 200916447 移轉FOXO依賴性回應遠離細胞死亡以有利於細胞存活上 之SIRT1功能，係顯然地與癌細胞生物學有關聯。 SIRT1脫乙醯酶活性之目前已知抑制劑包括菸鹼醯胺、坎 必諾（cambinol)、捨亭諾（sirtin〇l)、分裂霉素（spiitomicin)、苯胺 基苯曱醯胺#7及EX527 (Suzuki，T.等人，2006,作為SIRT抑制劑 之 2-苯胺基笨曱醯胺類，ChemMedChem 1: 1059-1062; Napper，A.D. 等人，2005,吲哚作為脫乙醯酶SIRT1之有效與選擇性抑制劑 之發現，醫藥化學期刊48(25) : 8045-8054 ; Huhtiniemi, T.等人， 2006，關於脫乙醯酶SIRT1之比較與藥效基團模式，J. Comput. Aided Mol. Des. 20: 589-599; Heltweg 等人，同前文出處；及 Blander 等人，同前文出處）。除了苯胺基苯甲醯胺#7 (SIRT1 IC50 = 17uM)與 EX527 (SIRT1IC5 Q = 98nM)之外，其他抑制劑係對 SIRT2 為非選擇性，且極弱（SIRT1 IC5〇> 40uM)。 【發明内容】 本發明係提供關於抑制組織蛋白去乙醯化酶酵素活性之 化合物與方法。本發明係提供關於治療細胞增生疾病與症 狀之化合物與方法。 於第一方面，本發明係提供化合物，其可作為組織蛋白 去乙醯化酶之抑制劑使用，且其具有式⑴： Y—L—-Z——D (I) 及其N-氧化物、水合物、溶劑合物、藥學上可接受之鹽、 前體藥物及複合物，以及其外消旋與呈比例混合物、非對 映異構物及對掌異構物，其中Y、L、Z及D均如下文定義。 在此第一方面，本發明係提供式I化合物，其可作為組織蛋 134026-1 • 11 - 200916447 2去乙酿化酶抑制劑使用，因此係為有用研究工且，供研 九組織蛋白去乙醯化酶在正常與疾病狀態兩者中之角色 入nr，本發明係提供包含根據本發明化合物之組 合物。於另一項具體實施例中，此組 種抑制劑。 選#包含另一 本發明係提供一種抑制組織蛋白去 酶活性例如SIRT1之方法，此方 酶，與根據本發明之化合物，或與蛋白去乙酿化 4興根據本發明之組A 觸。組織蛋白去乙醯化酶 σ 中m M PfJ 了在細胞或多細胞生物體 中右在細胞中，則根據本發明此方面之 細胞，與根據本發明之化合物私ά使該 接Μ。— a > 次，、根據本發明之組合物 传勺^ 胞生物體中，職據本發明此方面之方法 '、匕括對该生物體投予根據 明之細人私 β之化°物’或根據本發 物。生物體較佳為哺乳動物，更佳為人類。 二=面’本發明係提供-種治療_蛋白質所媒介 ==法’其包括:對需要治療之病患投 上：效1之根據本發明之化合物或其組合物。 兩文僅只是摘述本發明 欲成；&月之上述方面’而在本性上並不意 欲成為限制。此等方面與 整地描述於下女w a⑯及，、體貫施例’係更完 確立孰过此^ 引用之專利與科學文獻，係 之專利1藝者可取得之知識。於本文中引用之各經頒予 參料申請案及其他公報，均據此以其全文併入供 佔優勢中’本發明揭示内容之陳述内容將 134026-1 -12- 200916447 發明詳述 本發明係提供關於抑制組織蛋白去乙醢化酶酵素活性之 化合物與方法。本發明亦接 、 狀之化合物與方法。"關於>口療細胞增生疾病與症 於一方面，本發明係提供式(I)化合物，及其外消旋盘呈 比例混合物、非對映異構物及對掌異構物： 、 Y—L—z—D (I) 二及其N-氧化物、水合物、溶劑合物、藥學上可接受之鹽、 則體藥物及複合物，其中Y、L、Z及D均如本文定義。 i =二方面，本發明係提供組合物，其包含根據第—方 面或^任何具體實施例之化合物，及藥學上可接受之載劑。 〃於弟三方面’本發明係提供—種抑制組織蛋白去乙酿化 酶活性之方法，此方法包括使組織蛋白去乙酿化酶，或含 2組織蛋白去乙醯化酶活性之細胞，與抑制有效量之根據 發明之化合物’或與抑制有效量之根據本發明之組合物 接觸。組織蛋白去乙醯化酶活性之抑制可在細胞或多細胞 生物體令。若在多細胞生物體中，則根據本發明此方面之 方法係包括對該生物體投予抑制有效量之根據本發明之化 合或抑制有效量之根據本發明之組合物。生物體較佳 為甫子L動物’更佳為人類。於另一項具體實施例中，此方 法進—步包括共同或相繼地使該組織蛋白去乙酿化酶或該 :細胞’與有效量之另一種組織蛋白去乙醯化酶抑制劑接觸， 或若在多細胞生物體中，則共同或相繼地投予抑制有效量 另 種組織蛋白去乙酿化酶抑制齊J。 134026-1 -13- 200916447 對本發明之目的而言’係使用下述定義（除非另有明破地 陳述）。 於本文中指稱”式（I)、式（II)化合物等，，(；或相當地為”根據 第 方面之化合物”或"本發明之化合物'’等），應明瞭係包 括指稱其N-氧化物、水合物、溶劑合物、藥學上可接受之 鹽、前體藥物及複合物，以及其外消旋與呈比例混合物、 非對映異構物、對掌異構物及互變異構物，而除非另有指 出。 為簡化起見，化學部份基團係在整個本文中主要被定義 與指稱為單價化學部份基團（例如烧基、芳基等）。雖然如 此’在熟諳此藝者所明瞭之適當結構情況下，此種術語亦 用以傳達相應多價部份基團。例如m基”部份基團 一般係指單價基團（例如CH3_CH2·)，但在某些狀況下，二價 連結部份基團可為，，職”，於此種情況中，熟諳此藝者將 =烧基係為二價基團（例如，偶各），其係相當於"次 $ 具中而要一價部份基團，且被敘述 :·、方土之情況中，熟諳此藝者將明瞭”芳基 相應之二價部份基團次芳基）。應明瞭所有原子均里有2 鍵結形成之正常價數(意即，對碳為4， 、’、 及對⑻、4或6,依S之氧化狀態而定)。有時，= 可被定義為例如⑷a_B…其中以〇或j 〇在 刀土團 時，該部份基團為化 。兄中，當 一處揭示之許多部份基重:部份基團為 存在，其全部均意欲被任何特定構形式 134026-1 14 200916447 為簡化起見，對” Cm-C ” JF饮A ，,〇 m % %烷基、Cm_Cn”雜環基、"c ” 雜芳基或"m至η員環，，等之护益总土 Π ^ 寻之扎柄係思謂環烷基、雜環基、 雜芳基或環，具有，，m”至”，，個 個壌形原子，其中"m”與"η”為整 此例如C5-C6-雜核基為5_或6_員環，具有至少—個 :原子，且包括四氫峨略基(c5)與六氫吨條);C6_雜芳 基包括例如吡啶基與嘧啶基。 ”烴基”一詞係指直鏈、分枝狀，或環狀烧基、燦基或块 基，各如本文定義。”c0 ”烴基係用以指共價鍵。因此，”Co _c 經基”包括共價鍵、曱基、乙美 τ丞 乙烯基、乙炔基、丙基、 丙烯基'丙炔基及環丙基。 知知-係意指飽和與不飽和、直鏈或分枝狀煙類。 正如將被一般熟諳此藝者所明瞭的，”脂族”於本文中係意 欲包括但不限於烷基、烯基或炔基部份基團。 〜 烷基與烷術語係意指直鏈或分枝狀烴基，具有1至 20们奴，較佳為1至12個碳原子，或者，1-8個碳原子，及 或者，1-6個碳原子。其他烷基具有2至12個碳原子，或者， 2-8個碳原子，及或者，2_6個碳原子。烷基之實例包括但不 限於甲基、乙基、丙基、異丙基、丁基'異丁基、第二 丁土 第—丁基、戊基、己基、異己基、庚基、4,4-二甲基 戊基、辛基、2,2,4-三甲基戊基、壬基、癸基 '十一基、十 一基，再各種分枝鏈異構物等。”c〇”烷基（譬如在”Co-Cr烷 基”中）係為共價鍵。 烯基一詞係意指不飽和直鏈、分枝狀，環狀或雙環狀 烴基’具有一或多個碳-碳雙鍵，具有2至20碳，或者，2 134026-1 -15- 200916447 至12個碳原子，或者，2-8個碳原子，及或者，2-6個碳原子。 烯基之實例包括但不限於乙烯基、2_丙稀基、3_丁稀基、2_ 丁烯基、4-戊烯基' 3-戊烯基' 2-己烯基、3-己烯基、2-庚烯 基、3-庚烯基、4-庚烯基、3-辛烯基、3-壬烯基及μ環己烯基。 ”烯基”一詞，當於本文中採用時，係因此涵蓋環烯基。 ”炔基"一詞係意指不飽和直鏈、分枝狀，環狀或雙環狀 烴基，具有一或多個碳_碳參鍵，具有2至2〇個碳，或者，2 至12個碳原子，或者，2_8個碳原子，及或者，％個碳原子。 炔基之實例包括但不限於乙炔基、2_丙炔基、2丁炔基、1 丁炔基、4-戊炔基、3_戊炔基、2_己炔基、3_己炔基、孓庚炔 基、3-庚炔基' 4_庚炔基、3_辛炔基、3_壬炔基及^環己炔基。 "烯基”一詞，當於本文中採用時，係因此涵蓋環烯基。 於本文中使用之次烷基、”次烯基，，或，，次炔基"術語， 係意指個別如前文定義之院基、烯基錢基，其係、位在兩 個其他化學基團之間，且係用以連接之。較佳次燒基之實 例包括但不限於亞甲基、次乙基、次丙基及次丁基。較佳 次烯基之實例包括但不限於次乙烯基、次丙烯基及次丁烯 基。較佳次炔基之實例包括但不限於次乙炔基、次丙炔基 及次丁炔基。 、土 裱烷基”一詞係意指飽和、部份不飽和或不飽和單_，雙 三-或多環狀煙基，具有約3至20個碳，或者，3至15個|，’ =者’具有3至12個碳，或者，3至8個碳，或者，3至6個 妷，及或者，5或6個碳。在某些具體實施例中，環烷基係 i稠σ至或多個芳基、雜芳基或雜環族基團（例如1或2 !34〇26-1 -16- 200916447200916447 IX. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to the inhibition of species m tissue protein deacetylase (HDAc), also known as tissue protein deacetylase (SIRT). More specifically, the present invention relates to compounds and methods for inhibiting the activity of tissue protein deacetylase enzymes. This application claims the right to apply for the US Temporary Application No. _68,773 on August 29, 2007. The entire contents of the above-referenced application are incorporated herein by reference. [Prior Art] The tissue protein deacetylase system is involved in the regulation of changes in the expression of the gene through chromatin modification. As the name implies, HDAC is deacetylated from the amino acid of the tissue protein. However, the regulation of protein acetylation/deacetylation can affect proteins other than tissue proteins. Type I and II HDACs remove acetamyl by hydrolysis, whereas the species m HDAC, also known as tissue protein deacetylase (SIRT), uses a unique nad * .1 »a. » 1 only丨王; ^剌. Mammalian SIRT proteins include the population of seven homologs of yeast SIR2, a congener that links metabolism to Naga-dependent deacetylase of Changge. The SIRT protein contains a conserved coffee core, a functional site, and has N_ or C_terminal sequences of different lengths. Among the seven human SIRTs, SIRT1 has been most widely studied = human SIRT1 is the closest homolog of yeast SiR2, with a role in cell survival and metabolism. SIRT μ7 is localized to a variety of cell compartments with different enzyme activities, targeting many tissue proteins and non-tissue protein receptors, thus affecting a wide range of cellular functions, including fine 134026-1 200916447 cell survival, metabolism and DNA repair (Haigis, MC and LP Guarente, 2006, Mammalian tissue protein deacetylase - the emerging role in physiology, aging and caloric restriction, Gene & Development 20: 2913-2921). SIRT1 is a nuclear NAD-dependent protein deacetylase, and SIRT1 has been shown to deacetylate many receptors in vitro and in vivo, including tissue proteins (H3, H4) and non-tissue protein proteins (p53, PML, hTERT, AR, Ku70, NFkB, BCL6, TAF68, CTIP2, FOXO, PGC-1 a, PCAF/MyoD, HES-1, HEY-2, MEF2D, MyoD, PPAR % p300, AceCSl and tat), for treatment Diseases and conditions have potential links, such as oncogenesis (oncology applications), aging, obesity, insulin resistance (type II diabetes), inflammation, heart failure, axonal degeneration and AIDS (Blander, G. and L. Guarante, 2004, the Sir2 group of protein deacetylation enzymes, Annu. Rev. Biochem. 73: 417-435; Dali-Youcef et al., 2007, tissue protein deacetamylase: πν^2〃, function, metabolism and lifespan, medicine Yearbook 39: 335-345; Jiang, 2008, Tissue Protein Deacetylase: A Novel Target for Metabolic Diseases in Drug Development, Biochemical and Biophysical Research Comm. 373: 341-344). Functionally validated validation data supports SIRT1 as a candidate for treatment of cancer. In cell culture, SIRT1 RNAi is expressed in human epithelial cancer cells (HCT116 colonic epithelial cancer cells, HTB-126 breast epithelial cancer cells) rather than normal human cells (ARPE-19 normally stained retinal epithelial cells, HTB-125 normal breast epithelium) Growth inhibition and/or cell dying in cells, normal dermal fibroblasts (Ford, J. et al., 2005, SIRT1's cancer-specific function enables human epithelial cancer cells to grow and survive, Cancer Research 65 ( 22): 10457-10463). In vivo, the SIRT inhibitor cambinol 134026-1 200916447 reduces the growth of BCL6+ Daudi xenograft tumors (Heltweg, B. et al., 2006, Anti-small molecule inhibitors of human silent message regulator 2 enzymes) Tumor activity, Cancer Research 66(8): 4368-4377). Campinol is a competitive inhibitor of SIRT 1 and 2 with weak efficacy (> 50 uM IC50). SIRT1 RNAi, dominant negative SIRT1 (SIRT1H363Y) and SIRT inhibitors (in assayed amines and splitomicin) have been used to confirm SIRT inhibition in MCF-7 and MDA-MB-231 breast cancer cells. This led to the re-expression of the tumor suppressor gene test group and the increased H4K16 and H3K9 acetylation of the endogenous gene promoter (Pruitt, K. et al., 2006, SIRT1 inhibition system reactivates the silent cancer gene, Without loss of promoter DNA sorgification, PLoS Genetics 2 (3): 344-352). SIRT2 is an NAD-dependent protein deacetylase that has been shown to deacetylate many receptors (such as <2-tubulin) in vitro and in vivo (Dali-Youcef et al., 2007, Tissue protein deacetylase: ''magnificent semT, function, metabolism and longevity, Medical Yearbook 39: 335-345). Modulation of SIRT2 expression levels has been shown to affect cell cycle, where SIRT2 overexpression is delayed mitosis, whereas SIRT2 knockout MEF has an extended G1 phase and a shortened S phase (Dryden 2003, Vaquero 2006). SIRT2 receptor also includes tissue protein H4K16 (North 2003, Vaquero 2006). SIRT3 is a mitochondrial NAD-dependent protein deacetylase that has been shown to deacetylate many receptors (such as PGC-1 alpha and AceCS2) in vitro and in vivo, for the treatment of diseases and conditions. Potential links, for example, associated with adaptation to heat production and breast cancer (Dali-Youcef et al., 2007, Tissue Protein Deacetylase: "magm/iiceni Function, Metabolism and Lifespan, Pharmaceutical Year 134026-1 200916447 39 : 335-345). SIRT3 is expressed in brown adipose tissue and excessive expression increases mitochondrial respiration. SIRT3 deacetylates and activates the mitochondrial acetyl-CoA-synthase (Schwer 2006). SIRT4 is a mitochondrial NAD-dependent protein deacetylase that has been shown to deacetylate many receptors (such as glutamate dehydrogenase) in vitro and in vivo, for the treatment of diseases and conditions. Potential links, such as Type I and Type II diabetes (Dali-Youcef et al., 2007, Tissue Protein Deacetalase: (9) i MveV, Function, Metabolism and Lifespan, Medical Yearbook 39: 335-345). SIRT4 has both ADP-ribosyltransferase activity and deacetylase activity, and regulates insulin secretion by glucose response (Argmannc and Auwerx cells 2006). SIRT5 is a mitochondrial NAD-dependent protein deacetylase with high expression in brain, testis, spleen, kidney, heart, liver, ovary, lung, thyroid, uterus and bone marrow (Dali-Youcef et al., 2007 , Tissue protein deacetylase: (9), function, metabolism and longevity, Medical Yearbook 39: 335-345). SIRT5 deacetylates cytochrome C and regulates oxidative stress and cell dying (Sclicker et al., J Mol Biol 2008). SIRT6 is a non-nuclear NAD-dependent protein de-branching enzyme that has been used to deacetylate many receptors (such as DNApoly5) in vitro and in vivo, and has potential links to treat diseases and conditions, such as aging. Associated (loss of subcutaneous fat, reduced bone mineral density, etc.) (Dali-Youcef et al., 2007, tissue protein deacetylase: seven〃, function, metabolism and longevity, Medical Yearbook 39: 335- 345). SIRT6 has both ADP-ribosyltransferase and deacetylase activity. It can deacetylate H3K9 to regulate the measurement of chromatin by 134026-1 200916447 (Michishita et al., Nature 2008). SIRT7 is a nuclear NAD-dependent protein deacetylase that has been shown to deacetylate p53 in vitro. Rats deficient in SIRT7 have been shown to display high levels of p53 in the myocardium in vivo (Vakhrusheva et al., Circ Res 2008). SIRT7 has also been shown to be an activator of RNA polymerase I transcription, potentially linked to the treatment of diseases and conditions, such as squamous cell carcinoma and breast cancer (Dali-Youcef et al., 2007, tissue protein deacetylase: seven 〃 , function, metabolism and longevity, Medical Yearbook 39: 335-345). SIRT7 is localized to the nucleolus and has high performance in proliferating tissues (liver, spleen, and testis) and low expression in non-proliferative tissues (heart, brain, muscle). SIRT7 is expressed in squamous adenocarcinoma at high levels. Modulation of SIRT7 expression affects rRNA transcription, and SIRT7 RNAi causes cell wilting in U20S cells (Ford et al., supra). There is evidence of improvement in linking the SIRT1 to the FOXO population of the transcript factor (Giannakou 2004). SIRT1 has been shown to deacetylate FOXOl, F0X03 and FOX04, and these transcription factors have different roles for localization and/or metastasis activation. Tissue protein deacetylase activity affects F0X01 that shuttles between the nucleus and the cytoplasm and increases the transfer activation of F0X01-mediated (Frescas 2005). SIRT1 deacetylation of F0X03 has a dual role in F0X03 function, inhibiting cell death induction, but increasing cell cycle arrest and oxidative stress resistance mechanisms (Brunet 2004). In the context of transfer infection detection, SIRT1 has been shown to inhibit transfer activation by F0X03a (Motta 2004). Moreover, SIRT1 deacetylated F0X04 and increased FOX04 transcription and biological activity (Van der Horst 2004). The transfer of FOXO-dependent responses away from cell death at 134026-1 •10·200916447 to facilitate SIRT1 function on cell survival is clearly associated with cancer cell biology. Currently known inhibitors of SIRT1 deacetylase activity include nicotinic acid amide, campinol, sirtin sir, spiitomicin, anilinophenamide #7 and EX527 (Suzuki, T. et al., 2006, 2-anilino amidoxime as a SIRT inhibitor, ChemMedChem 1: 1059-1062; Napper, AD et al., 2005, 吲哚 as a deacetylase SIRT1 Discovery of potent and selective inhibitors, Journal of Medicinal Chemistry 48(25): 8045-8054; Huhtiniemi, T. et al., 2006, Comparison of the deacetylase SIRT1 and pharmacophore model, J. Comput. Aided Mol. Des. 20: 589-599; Heltweg et al., supra; and Blander et al., supra). With the exception of anilinobenzamide #7 (SIRT1 IC50 = 17 uM) and EX527 (SIRT1IC5 Q = 98 nM), the other inhibitors were non-selective to SIRT2 and very weak (SIRT1 IC5〇> 40 uM). SUMMARY OF THE INVENTION The present invention provides compounds and methods for inhibiting the activity of tissue protein deacetylase enzymes. The present invention provides compounds and methods for treating cell proliferative diseases and conditions. In a first aspect, the present invention provides a compound which is useful as an inhibitor of tissue protein deacetylase and which has the formula (1): Y-L--Z-D (I) and its N-oxide , hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes, as well as racemic and proportional mixtures thereof, diastereomers and palmomerisomers, of which Y, L, Z and D are as defined below. In this first aspect, the present invention provides a compound of formula I which can be used as a tissue-fermenting enzyme for the production of egg 134026-1 • 11 - 200916447 2 and is therefore useful as a researcher and The role of acetamylase in both normal and disease states is incorporated into nr, and the present invention provides compositions comprising a compound according to the invention. In another specific embodiment, the group of inhibitors. Else includes another method of the present invention which provides a method for inhibiting tissue protein de-enzymatic activity, such as SIRT1, which is in contact with a compound according to the present invention or with a protein. The tissue protein deacetylase σ is m M PfJ in the right cell of the cell or multicellular organism, and the cell according to this aspect of the invention is entangled with the compound according to the invention. - a >, in accordance with the method of the present invention, in the method of the present invention, the method according to the aspect of the present invention, and the method of administering the organism according to the description of the individual Or according to the present invention. The organism is preferably a mammal, more preferably a human. The present invention provides a therapeutic-protein medium == method which comprises: a compound according to the invention or a composition thereof for administration to a patient in need of treatment. The two articles are merely illustrative of the present invention; & the above aspects of the month' and are not intended to be limiting in nature. These aspects are described in the description of the whole woman w a16 and the physical application of the system. The patent and scientific literature cited in this ^ is the knowledge that can be obtained by the patent. Each of the referenced applications and other publications cited herein is hereby incorporated by reference in its entirety in its entirety, the content of the disclosure of the present disclosure. The invention provides methods and methods for inhibiting the activity of tissue protein deacetylase enzymes. The invention also relates to compounds and methods. "About > Oral Therapy Cell Proliferative Diseases and Symptoms In one aspect, the present invention provides a compound of formula (I), and a racemic mixture thereof, a mixture of diastereomers and a palmomerisomer: Y-L-z-D (I) II and its N-oxides, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutically acceptable drugs and complexes, wherein Y, L, Z and D are as herein definition. i = two aspects, the invention provides a composition comprising a compound according to the first aspect or any of the specific embodiments, and a pharmaceutically acceptable carrier. In the third aspect of the invention, the present invention provides a method for inhibiting the activity of tissue protein to dehydrogenase, which comprises removing tissue protein into a brewing enzyme, or a cell containing 2 tissue proteins to deacetylase activity. Contact with an inhibitory effective amount of a compound according to the invention or with an inhibitory effective amount of a composition according to the invention. Inhibition of tissue protein deacetylase activity can be achieved in cells or multicellular organisms. If in a multicellular organism, the method according to this aspect of the invention comprises administering to the organism an inhibitory effective amount of a composition according to the invention in a compounding or inhibiting effective amount according to the invention. Preferably, the organism is a scorpion L animal, which is more preferably a human. In another embodiment, the method further comprises: contacting the tissue protein dehydrogenase together or sequentially: the cell 'in contact with an effective amount of another tissue protein deacetylase inhibitor, Or, if in a multicellular organism, the inhibitory effective amount of another tissue protein is administered in combination with or in addition to the inhibition of the enzyme. 134026-1 -13- 200916447 For the purposes of the present invention, the following definitions are used (unless otherwise stated). As used herein to refer to "a compound of formula (I), formula (II), etc., (or equivalently a "compound according to the aspect" or "a compound of the invention", etc.), it is to be understood that - oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes, as well as racemic and proportional mixtures thereof, diastereomers, palmomerisomers and tautomers The structure, unless otherwise indicated. For the sake of simplicity, the chemical moiety is primarily defined throughout the text and is referred to as a monovalent chemical moiety (eg, alkyl, aryl, etc.). This term is also used to convey the corresponding multivalent moiety in the context of the appropriate structure as understood by the artist. For example, a m-based moiety generally refers to a monovalent group (eg, CH3_CH2.), but at a certain In some cases, the divalent linking moiety can be, "," in this case, those skilled in the art will = the base is a divalent group (for example, even), which is equivalent to &quot The second $ has a one-price partial group and is described as: ·, the situation of the square soil , Will be apparent to skilled artisans, "a divalent aromatic group of the corresponding secondary aryl moiety). It should be understood that all atoms have a normal valence of 2 bond formation (ie, for carbon 4, , ', and for (8), 4 or 6, depending on the oxidation state of S). Sometimes, = can be defined as, for example, (4) a_B... where 〇 or j 〇 is in the group, the part is chemistry. In the brothers, when a part of the revealing part of the basis weight: some groups are existent, all of them are intended to be simplified by any particular form of 134026-1 14 200916447, for "Cm-C" JF drink A, , 〇m % % alkyl, Cm_Cn" heterocyclic, "c ”heteroaryl or "m to η 环,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, a heterocyclic group, a heteroaryl group or a ring having, m' to "," a 壌-shaped atom, wherein "m" and "η" are integers such as a C5-C6-heteronucleobase is 5_ or A 6-membered ring having at least one: an atom and including a tetrahydroindenyl group (c5) and a hexahydro ton strip); and a C6-heteroaryl group includes, for example, a pyridyl group and a pyrimidinyl group. The term "hydrocarbyl" refers to a straight chain, a branched, or a cyclic alkyl group, a decyl group or a block group, each as defined herein. The "c0" hydrocarbon group is used to refer to a covalent bond. Therefore, "Co _c thiol" includes a covalent bond, a fluorenyl group, a acetamino group, an ethynyl group, a propyl group, a propylene group 'propynyl group, and a cyclopropyl group. Known - means saturated and unsaturated, linear or branched tobacco. As will be apparent to those skilled in the art, "aliphatic" is intended herein to include, but is not limited to, alkyl, alkenyl or alkynyl moiety. The term "alkyl and alkane" means a straight or branched hydrocarbon group having from 1 to 20, preferably from 1 to 12 carbon atoms, alternatively from 1 to 8 carbon atoms, and or from 1 to 6 carbon atom. Other alkyl groups have from 2 to 12 carbon atoms, alternatively from 2 to 8 carbon atoms, and alternatively, from 2 to 6 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl 'isobutyl, second butadiene, butyl, pentyl, hexyl, isohexyl, heptyl, 4, 4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, indenyl, fluorenyl 'undenyl, eleven, further various branched chain isomers, and the like. The "c" alkyl group (e.g., in the "Co-Cr alkyl group") is a covalent bond. The term alkenyl means an unsaturated straight-chain, branched, cyclic or bicyclic hydrocarbon group having one or more carbon-carbon double bonds, having 2 to 20 carbons, or 2 134026-1 -15- 200916447 to 12 carbon atoms, or 2-8 carbon atoms, and or 2-6 carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, 2-propenyl, 3-butyryl, 2-butenyl, 4-pentenyl '3-pentenyl' 2-hexenyl, 3-hexene Base, 2-heptenyl, 3-heptenyl, 4-heptenyl, 3-octenyl, 3-decenyl and μcyclohexenyl. The term "alkenyl", as used herein, thus encompasses a cycloalkenyl group. The term "alkynyl" means an unsaturated straight-chain, branched, cyclic or bicyclic hydrocarbon group having one or more carbon-carbon bonds, having 2 to 2 carbons, or 2 to 12 carbon atoms, or 2-8 carbon atoms, and or, % carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl, 2-propynyl, 2-butynyl, 1-butynyl, 4-pentyl Alkynyl, 3-pentynyl, 2-hexynyl, 3-hexynyl, anthracenyl, 3-heptynyl-4-heptynyl, 3-octynyl, 3-deynyl and ^cyclohexynyl. The term "alkenyl", as used herein, thus encompasses cycloalkenyl. As used herein, a secondary alkyl, "alkenylene," or ", alkynyl" term refers to an individual, alkenyl, and alkenyl group, as defined above, in two other chemistry. Between the groups, and used to connect. Examples of preferred sub-alkyl groups include, but are not limited to, methylene, hypoethyl, propylene and sec-butyl. Examples of preferred alkenyl groups include, but are not limited to, Examples of the vinylidene group, the propylene group and the benzylidene group. Examples of preferred alkynyl groups include, but are not limited to, the sub-ethynyl group, the cypronyl group and the sec-butynyl group. The term "indolyl" means saturation. , partially unsaturated or unsaturated mono-, double-tri- or polycyclic nicotine, having about 3 to 20 carbons, or, 3 to 15 |, '=' has 3 to 12 carbons, or, 3 to 8 carbons, or 3 to 6 bismuth, and or 5 or 6 carbons. In certain embodiments, the cycloalkyl group i is fused to a plurality of aryl, heteroaryl or heterocyclic groups (eg, 1 or 2 !34〇26-1 -16- 200916447)

)環燒基之實例包括但不限於環六搭^ κ 烯醇、環己-2._、己稀_2姻 '環戊H 知基、壤戊基'環戊稀基、環己基衣丁 甥叁# 衣匕締基、裱庚基、 衣辛基、環癸基及環十二基等。 基：，？二:Γ:飽和或不飽和、直鏈或分枝狀脂族 缸n 0 次夕個呶原子係獨立被選自每 之部份基:置：基、娜，)2 ||芳基”或”芳”術語係意指單_，雙·，三_ 份其囿，，， 乂夕衣狀方麵部 A :團，例如Q-C14芳族部份基團’例如包含一至三個芳 ，環。芳基可視情況包含經稠合至碳環或雜環(譬如芳基方 %烷基、雜芳基或環雜烷基環）之芳族環。 — 」-Ci〇方基，或者為Q芳基。芳基之實例包括但不限於笨基、 奈基（包括1-萘基與2-萘基）、慝基及蕹基。 ”芳烷基”或"芳基烷基”術語係意指包含芳基而以共價 方式連結至烷基之基團。若芳烷基係被描述為，，視情況經取 代"，則所意欲的是，芳基與烷基部份基團之任一個或兩者 可獨立地視情況經取代或未經取代。或者，芳烷基為C匸） 烷（Cs-Q 〇)芳基，包括但不限於苄基 '苯乙基及苯曱基。為 簡化起見，當書寫成，'芳烷基，，時，此術語及其相關之術語 係葸欲指示基團在化合物中之順序為”芳基-烷基”。同樣 地’烧基-芳基”係意欲指示基團在化合物中之順序為"产 基-芳基"。 ’’雜環并，’、"雜環基，，、”雜環族，，或"雜環，，等術語係音指 134026-1 -17· 200916447 —種基團，其係為單雙_ 又次夕％狀結構，具有約3至約20 衣’、子，或者’約3至約14個環s早忐水 名甘+ „ 子或者，3至10個環原 ’/、中環原子包括碳原子盘 ^ ^ . . &原子與一或多個獨立選自包括N、 雜产二原子。環結構可為飽和、不飽和或部份不飽和。此 早衣被連接在會造成產生安定結構之任何雜原子或碳原 上。在某些具體實施财，雜環族基團為非芳族，於此 情財’該基團亦被稱為雜我基。在某些具體實施例 & ’雜壤族基團為經橋接之雜環族基團（例如具有亞甲基、 或人丙基橋基之雙環狀部份基團）。在雙環狀或多環 T結射，一或多個環可為芳族；例如雙環狀雜環之一個 %，或二裱狀雜環之一或兩個環，可為芳族，嬖如在氫茚 與9瓜二氫愚中。雜環基之實例包括但不限於氮丙咬基、 四虱呋喃基、四氫吡咯基、六氫吡啶基、六氫吡畊基、嘧 坐疋基四氫P号唑基、四氫p号唑酮基、酮基六氫吡畊基、 酮基六氫吡啶基、酮基四氫吡咯基、氧一氮七圜烯基、一 \ 氮七園烯S、吡咯基、呋喃基”塞吩基、吡唑基、四氫吡 坐基、咪唑基、二氫咪唑基、四氫咪唑基、吡啶基、吡畊 基' 嘧啶基、嗒畊基、嘮唑基、異哼唑基、異四氫噚唑基、 嗎福啉基、嘧唑基、異噻唑基、噻二唑基' 四氫哌喃基、 ’IL基馬福π林基、硫基嗎福”林基亞颯、硫基嗎福4基颯、号 —°坐基’及其他在Katritzky，A R與以取C w編著综合雜環 化學.雜環族化合物之結構、反應 '合成及用途1984, pergam〇n 出版社，New York, Ν·Υ.;與 Katritzky，A. R” Rees, C. W·, Scriven, E. F. 編著，综合雜環化學H :文獻之回顧1982 1995 1996, Elsevier科 134026-1 •18- 200916447 學公司，Tanytown，Ν.γ·;及其中之參考資料中所述之雜學 某些較佳者巾，雜環職團係_合至芳基、雜^或严 烷基。此種稠合雜環之實例包括但不限於四氯嗜啦盘二二 苯并吱喃。明確地自此術語之範圍排除在外者為其中= 0或S原子係鄰近另—個〇或5原子之化合物。 衣》 在某些具體實施例中，雜環族基團為雜芳基。於本文 使用之"雜芳基I.-詞係意指單、雙.，三_或多環基團， 5至18個環原子’或者，5至14個環原子，或者，$至1〇個 環原子，或者，5、6、9或1〇個環原子·較佳係具有6、叩 或14個;r電？，在環狀陣列中被共用；且除了碳原 具有一或多個間之雜原子，選自包括Ν、〇及s。，,雜芳基i 一詞亦意欲涵蓋含氮雜芳基之N_氧化物衍生物（或n_氧化 物衍生物，若雜芳基含有超過一個氮，則致使超過一種队 氧化物衍生物可被形成）。例如，雜芳基可為嘧啶基、吡啶 基、苯并咪唑基、嘧吩基、苯并嘧唑基、苯并呋喃基及2 氫吲哚基。雜芳基之實例包括但不限於噹吩基、苯并嘍吩 基、呋喃基、苯并呋喃基、二苯并呋喃基、吡咯基、咪唑 基、吡唑基、吡啶基、吡畊基、嘧啶基、吲哚基、喹啉基、 異4啉基、喳喏啉基、四唑基、，号唑基、嘍唑基、異呤唑 基、苯并[b]噻吩基、莕[2,3-b]噻嗯基、咄基、喹啉基、笨并 噻唑基、苯并咪唑基、尽咔啉基及呕啶基。雜芳基之队氧 化物衍生物之說明例包括但不限於吡啶基N_氧化物、峨呼 基N-氧化物、嘴β定基N-氧化物、σ荅畊基N_氧化物、三畊基 N-氧化物、異喳啉基N_氧化物、喹啉基队氧化物，及其他如 134026-1 -19- 200916447 在Katritzky，A.R.與Rees，cw.編著，綜合雜環化學：雜環族化 口物之、°構反應、合成及用途1984, Pergamum出版社，New π ’ N.Y. ’ 與 Katntzky，A. R” Rees，C. w，Scriven，E. F 編著，综合雜 環化學11 :文獻之回顧1982-1995 1996, Elsevier科學公司Examples of cycloalkyl groups include, but are not limited to, cyclohexamethylene ketone enol, cyclohexa-2._, hexahedral 2 valence, cyclopentyl H, beryl, cyclopentyl, cyclohexyl pentyl甥叁# 匕 匕 裱, 裱 基, octyl, fluorenyl and cyclododeyl. base:,? Two: Γ: saturated or unsaturated, linear or branched aliphatic cylinders n 0 夕 呶 a 呶 atomic system is independently selected from each part of the base: set: base, Na,) 2 || aryl" or The term "aromatic" means mono-, di-, tri-, 囿, ,, 乂, 方面, A, 团, for example, Q-C14 aromatic moiety, for example, containing one to three aromatic, ring The aryl group may optionally include an aromatic ring fused to a carbocyclic or heterocyclic ring (such as an aryl-based alkyl, heteroaryl or cycloheteroalkyl ring). - "-Ci", or Q Aryl. Examples of aryl groups include, but are not limited to, stupid, naphthyl (including 1-naphthyl and 2-naphthyl), anthracenyl and anthracenyl. The term "aralkyl" or "arylalkyl" is intended to mean a group containing an aryl group and attached to the alkyl group in a covalent manner. If the aralkyl group is described as being substituted, " It is intended that either or both of the aryl and alkyl moiety may be independently substituted or unsubstituted as appropriate. Alternatively, the aralkyl group may be a C(C)-alkyl group. Bases, including but not limited to benzyl 'phenethyl and phenyl fluorenyl. For the sake of simplicity, when written as 'aralkyl,' the term and its related terms are intended to indicate a group in a compound. The order is "aryl-alkyl". Similarly, 'alkyl-aryl" is intended to indicate that the order of the group in the compound is "base-aryl". ''Heterocyclic,', "heterocyclic,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Double _ and then eve % structure, with about 3 to about 20 clothes ', children, or 'about 3 to about 14 rings s early water name Gan + „ sub or, 3 to 10 ring original ' /, Central The atom includes a carbon atom disk ^ ^ . . . & atom and one or more independently selected from the group consisting of N, a heterogeneous diatomic atom. The ring structure can be saturated, unsaturated or partially unsaturated. This morning coat is attached to any heteroatoms or carbon atoms that will create a stable structure. In some implementations, the heterocyclic group is non-aromatic, and this group is also referred to as a hetero group. In certain embodiments &'' heterotic group is a bridged heterocyclic group (e.g., a bicyclic moiety having a methylene group or a human propyl bridging group). In bicyclic or polycyclic T-junction, one or more of the rings may be aromatic; for example, one % of a bicyclic heterocyclic ring, or one or two rings of a dicyclic heterocyclic ring, which may be aromatic, fluorene Such as in hydroquinone and 9 melon dihydrogen fools. Examples of heterocyclic groups include, but are not limited to, aziridine, tetrahydrofuranyl, tetrahydropyrrolyl, hexahydropyridyl, hexahydropyrrole, pyrimidine, tetrahydro P, oxazolyl, tetrahydrop Azolidinyl, ketohexahydropyrutyl, ketohexahydropyridyl, ketotetrahydropyrrolyl, oxynitridinyl, aziridine, pyrrolyl, furanyl , pyrazolyl, tetrahydropyridyl, imidazolyl, dihydroimidazolyl, tetrahydroimidazolyl, pyridyl, pyridinyl pyrimidinyl, hydrazine, carbazolyl, isoxazolyl, isotetra Hydrocarbazolyl, morpholinyl, pyrazolyl, isothiazolyl, thiadiazolyl tetrahydropyranyl, 'IL kefif π-linyl, thio carbaryl, linoleyl, thiol福福4基飒,号—°坐基' and others in Katritzky, AR and Cw compiled comprehensive heterocyclic chemistry. Structure, reaction 'synthesis and use of heterocyclic compounds 1984, pergam〇n publisher, New York, Ν·Υ.; and Katritzky, A. R” Rees, C. W., Scriven, EF, Compilation of Heterocyclic Chemistry H: Review of the Literature 1982 1995 1996, Elsevier Section 134026-1 •18- 200916447 Division, Tanytown, Ν.γ·; and the reference materials described therein, some of the preferred towels, heterocyclic groups _ to aryl, hetero or sulphur alkyl. Examples of rings include, but are not limited to, tetrachloro-dip dibenzopyrene. It is expressly excluded from the scope of the term that the compound is 0 or the S atom is adjacent to another 〇 or 5 atom. In certain embodiments, the heterocyclic group is a heteroaryl group. As used herein, "heteroaryl I.-" means mono, di., tri- or polycyclic groups, 5 to 18 Ring atoms 'or, 5 to 14 ring atoms, or, $1 to 1 ring atom, or 5, 6, 9 or 1 ring atoms, preferably having 6, 叩 or 14; Is shared in a circular array; and in addition to the carbon atom having one or more heteroatoms selected from the group consisting of ruthenium, osmium and s., the term heteroaryl i is also intended to encompass a nitrogen-containing heteroaryl group. An N-oxide derivative (or an n-oxide derivative, if the heteroaryl contains more than one nitrogen, such that more than one group of oxide derivatives can be formed). For example, the heteroaryl group can be a pyrimidinyl group. Pyridyl, benzimidazolyl, pyrimenyl, benzopyrazole, benzofuranyl and 2-hydroindenyl. Examples of heteroaryl include, but are not limited to, phenyl, benzophenantyl, furyl , benzofuranyl, dibenzofuranyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridinyl, pyrimidinyl, fluorenyl, quinolyl, isotetralinyl, porphyrin Tetrazolyl, oxazolyl, oxazolyl, isoxazolyl, benzo[b]thienyl, anthracene [2,3-b]thiol, fluorenyl, quinolyl, benzothiazolyl, Benzimidazolyl, oxalinyl and vodinyl. Illustrative examples of heteroaryl group oxide derivatives include, but are not limited to, pyridyl N-oxide, oxime N-oxide, mouth β-based N-oxide, σ 荅 基 N_oxide, three tillage Base N-oxides, isoindolyl N-oxides, quinolinyl group oxides, and others such as 134026-1 -19- 200916447 edited by Katritzky, AR and Rees, cw., Integrated Heterocyclic Chemistry: Heterocycle The composition, synthesis, and use of the genus of the mouth, 1984, Pergamum Press, New π 'NY ' and Katntzky, A. R" Rees, C. w, Scriven, E. F, edited, integrated heterocyclic chemistry 11: Review of the literature 1982-1995 1996, Elsevier Science Corporation

Tarrytown，N.Y.;及 ΐφ 夕会上 ，丨丄 ’ 汉具〒之參考資料中所述之雜芳基。 ”次環烷基"、’，次芳基”、”次雜芳基，丨及”次雜環基”術古五 係意指個別如前文定義之環絲、芳基、雜芳基或雜環基， 其係位在兩個其他化學基團之間，且係用以連接之。Tarrytown, N.Y.; and 杂 φ 夕 夕 , , 丨丄 汉 汉 汉 汉 汉 汉 杂 杂 杂 杂 杂 杂 杂 杂 杂 杂"Subcycloalkyl", ", aryryl", "heteroaryl", hydrazine, and "heteroheterocyclyl" are meant to be individually cyclized, aryl, heteroaryl or as defined above. A heterocyclic group which is between two other chemical groups and which is attached.

雜脂環族基®係特別指料㈣環基。雜脂環族可含有 不飽和性’但並非芳族。 雜環純基係指其”環基係經由线基、亞燒基或低 烧基之一連接至母結構之殘基。實例包括（4_甲基六氯吨畊 -1-基）甲基、（嗎福K基）甲基基）甲基L坐琳 -2-基）乙基、4_(4_甲基六氫峨吨*基财烯基等。若雜環基 炫基係被描述V，視情況經取代"，則其係指雜環基院基之 雜環基及其相應之找基、亞烧基或低烧基部份兩者0視 情況經取代。”低碳雜環基縣，，係指雜環㈣基，其中此 基團之"烷基”部份具有一至六個碳。 雜脂環基貌基係特別指雜環基烧基，其中此基團之雜環 基部份為非芳族。 雜環基與雜芳基之實例包括但不限於—氮七圜烯基、一 氮四隸、'/丫。定基、ϋ烯基、苯并心基、苯并味 唑基、苯并呋喃基、苯并呋咕基'苯并呋喃基、苯并硫代 吱喃基 '苯并硫苯基、苯并㈣基、笨并❹基、苯并違 134026-1 •20- 200916447 吩基、苯并三録、苯并四録、苯并異㈣基、苯并異 嗜唾基、料㈣4基、料⑼基、苯并$二嗤基、苯 并旅喃基“卡唾基、4aH+坐基、味料、咬基、咬焊基、 和林基、香^、十氫如林基、二苯并吱味基、u_二氧伍 圜、2H，6H-1,5,2-二㈣基、二氫吱喃并[2,3_b]四氫咬喃、二氯 異吲哚基、二氫喹唑啉基（譬如3,4_二氫斗酮基-喳唑啉基）' 呋喃基、呋喃并吡啶基（譬如呋喃并[2,3_c风啶基、呋喃并 [3,2七风啶基或呋喃并[2,3_b]吡啶基）、呋喃基、呋咕基、六 氫二氮七圜烯基、四氫咪唑基、二氫咪唑基、咪唑基 '吲 唑基、1H-峋唑基、吲哚烯基、二氫吲哚基、峋畊基、啕哚 基、3H-^ 木基、異苯并呋喃基、異咬基、異峭唑基、異吲 哚啉基、異峭哚基 '異喹啉基、異喳啉基、異噻唑啶基、 異嘧唑基、異二氫哼唑基、異咩唑基、亞甲二氧基苯基、 嗎福P林基、峰α定基、八氫異p奎琳基、吟二σ坐基、1，2,3-吟二 。坐基、1,2,4-11号一。坐基、1，2,5』号二。坐基、1，3,4』号二嗤基、四氫 号。坐基、呤唑基、四氫哼唑基、環氧丙烷基、2_氧一氮七 圜烯基、2-酮基六氫吡畊基、2_酮基六氫吡啶基、2_酮基四 鼠？比°各基、。密咬基、啡咬基、非琳基、_ P井基、_遠P井基、 笨氧硫陸圜烯基、啡0号喷基、吹P井基、六氫?比P井基、六氫 峨啶基、六氫吡啶酮基、4-六氫吡啶酮基、向日葵基、喋 σ定基、嘌呤基、'^底喃基、咐畊基、四氫P比哇基、二氫P比唾 基、Ρ比唾基、塔Ρ井基、Ρ比咬g π坐、Ρ比咬并味嗤、吨咬ρ塞嗤、 叶匕σ定基、p比咬基、嘴咬基、四氫Ρ比略基、二氫ρ比略基、叶匕 11各并吡啶基、2Η-吡咯基、吡咯基、咬峻琳基、4 ρ林基、0奎 134026-1 21· 200916447 啉基、4H-喹畊基、喳喏啉基、嗝啶基、四氫4，丨-二酮基嘧 为基、四氫呋喃基、四氫呋喃基、四氫異喹啉基、四氫喳 啉基、四氫哌喃基、四唑基 '噻唑啶基、6H_U，5-嘧二畊基、 噻二唑基（例如1，2,3-噻二唑基、u，4_p塞二唑基、u,5_嘍二唑 基、1，3’4-喧二唑基）、硫基嗎福啉基、硫基嗎福啉基亞颯、 硫基嗎福啉基颯、噻嗯基、嘧唑基、嘧吩基、噻吩噻唑基、 嘧吩噚唑基、嘧吩咪唑基、硫苯基、三畊基、三畊基一氮 七圜烯基、三唑基（例如唑基、u，4_三唑基、丨，2,5-三 唑基、1,3,4-三唑基）及咄基。 ”鹵基烴基”，當於本文中採用時，係為烴基部份基團， 其中從一個至全部氫已被獨立經選擇之鹵基置換。 當於本文中採用時’且除非另有述及，否則當部份基團 (例如烧基、雜烧基、壞烧基、芳基、雜芳基、雜環基等） 係被描述為”視情況經取代"時，其係指該基團視情況具有 至四個，或者，一至二個，或者，一或兩個獨立經選擇 之非氫取代基。適當取代基包括但不限於！|基、羥基、酮 基（例如’被酮基取代之環形-CH為-C(O)-)、硝基、_基烴 基、烴基、烷基、環烷基、雜環基、芳基、雜芳基、芳烧 基、炫》氧基、芳氧基、胺基、酿基胺基、烧基胺甲隨基、 务基胺甲醯基、胺基烧基、醯基、缓基、經炫基、烧續醯 基、芳環磺醯基、烷磺醯胺基、芳環磺醯胺基、芳燒基續 酿胺基、烷羰基、醢氧基、氰基及脲基。取代基，其本身 未進一步被取代（除非另有明確地陳述），其實例為： ⑻鹵基、羥基、氰基、酮基、羧基、甲醯基、頌基、 134026-1 -22- 200916447 胺基、甲脒基、胍基， (b) q -C5烷基或烯基或芳烷基亞胺基、胺甲醯基、疊氮 基、羧醯胺基、毓基、羥基、羥烷基、烷基芳基、 芳烷基、CVC8烷基、CVC8烯基、q-Cg烷氧基、q-Cg 烷基胺基、（^-(：8烷氧羰基、芳氧基羰基、c2-c8醯基、 -C(0)-N(R3°)-烷基-環烷基、-C(0)-N(R30)-烷基-雜環基、 -C(0)-N(R30)-烷基-芳基、-C(0)-N(R30)-烷基-雜芳基、 -C(O)-環烷基、-C(O)-雜環基' -C(O)-芳基、-C(O)-雜芳基、 C：2 -C：8醯基胺基、Ci -C：8烷硫基、芳烷基硫基、芳基硫 基、q-C：8烷基亞磺醯基、芳烷基亞磺醯基、芳基亞 磺醯基、q-C8烷基磺醯基、芳烷基磺醯基、芳基磺 醯基、CVqN-烷基胺甲醯基、c：2_Cl5N，N_二烷基胺甲 醯基、q-C7環烷基、芳醯基、芳氧基、芳烷基醚、 芳基，經稠合至環院基或雜環或另一個芳基環之芳 基，C：3 -C：7雜環、c：5 -C】5雜芳基或任何此等環經稠人 或螺-稠合至環㈣、雜環基或芳基，其中各前述係 進一步視情況被一或多個列示於上文⑻中之部份義 團取代；及 77 土 (C) -(CR32R33)s.NR3〇R3i , 氮係直接結合至經取代The heteroalicyclic group is specifically referred to as a (iv) ring group. The heteroalicyclic group may contain unsaturation but is not aromatic. A heterocyclic ring is a residue in which the "ring group" is attached to the parent structure via one of a linear group, a pyridinyl group or a low alkyl group. Examples include (4-methylhexachloroxanthene-1-yl)methyl, (Mofic K-based) methyl) methyl L-based 2-yl) ethyl, 4-(4-methylhexahydroindole*-based alkenyl, etc.. And, as the case may be substituted, it means that the heterocyclic group of the heterocyclic group and its corresponding radical, alkylene or lower alkyl group are optionally substituted. "Low carbon heterocyclic group a county, which means a heterocyclic (tetra) group in which the "alkyl" moiety of the group has from one to six carbons. The heteroalicyclic radical system particularly refers to a heterocyclic group, wherein the heterocyclic group of the group The base moiety is non-aromatic. Examples of heterocyclic and heteroaryl groups include, but are not limited to, nitrogen heptaenyl, mononitrogen, '/丫, decyl, nonenyl, benzo, benzo Oxazolyl, benzofuranyl, benzofurazyl 'benzofuranyl, benzothiofuranyl 'benzothiophenyl, benzo(tetra)yl, stupidinyl, benzoin 134026-1 •20- 200916447 phenyl, benzotriz, benzotetraz Benzoiso(tetra)yl, benzoiso-indanyl, (4) 4-yl, (9)-based, benzo-bi-indenyl, benzoxanyl "carboyl, 4aH+ siting, flavoring, biting, bite welding Base, and forest base, fragrant ^, decahydro, such as forest, dibenzoxanthene, u_dioxoanthene, 2H, 6H-1,5,2-di(tetra)yl, dihydrofuran[2] , 3_b] tetrahydroanion, dichloroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydroindolyl-oxazolinyl)' furanyl, furopyridinyl (such as furan [2,3_c oxaridinyl, furo[3,2-heptazinyl or furo[2,3_b]pyridyl), furyl, furazyl, hexahydrodiazepines, tetrahydroimidazolyl , dihydroimidazolyl, imidazolyl 'carbazolyl, 1H-carbazolyl, decenyl, indanyl, hydrazine, fluorenyl, 3H-^, benzofuranyl, Iso-bite, isotazolyl, isoindolyl, iso-thyl-isoquinolyl, isoindolyl, isothiazolidinyl, isopyrazolyl, iso-dihydrocarbazolyl, isoxazole Base, methylenedioxyphenyl, phenanthrene P-based, peak α-based, octahydroiso-p-quine-based, quinone sigma, 1,2,3-anthracene Sit-base, 1, 2, 4-11 No. 1. Sit-base, 1, 2, 5 y 2. Sit-base, 1, 3, 4 y, diterpene, tetrahydrogen. Sedentary, carbazolyl , tetrahydrocarbazolyl, propylene oxide, 2-nitro-nitrosopentenyl, 2-ketohexahydropyrrole, 2-ketohexahydropyridyl, 2-keto-tetra-rat ratio Each base, dense bite base, brown bite base, non-line base, _ P well base, _ far P well base, oxysulfide thioenyl, morphine 0 spray base, blow P well base, hexahydro? P-well, hexahydropyridinyl, hexahydropyridinyl, 4-hexahydropyridinone, sunflower, 喋σ-decyl, fluorenyl, thiol, hydrazine, tetrahydro-P-butyl , Dihydrogen P is more than salivation, sputum than sulphate, sputum, sputum, squat, g π, Ρ bite and miso, ton bite, 匕 定 定, p than bite, mouth bite , tetrahydroindolyl, dihydropyrrolidyl, acaroid 11 pyridyl, 2Η-pyrrolyl, pyrrolyl, sulphide, 4 ρ lin, 0 134 026 026 026 026 026 026 026 026 026 026 026 026 026 026 026 026 026 026 Alkyl group, 4H-quinoline, porphyrin group, acridinyl group, tetrahydro 4, fluorenyl-dione sulfonyl group, tetrahydrofuranyl group, tetrahydrofuranyl group, tetrahydroisoquinolyl group , tetrahydroporphyrinyl, tetrahydropyranyl, tetrazolyl 'thiazolidinyl, 6H_U, 5-pyrimidine, thiadiazolyl (eg 1,2,3-thiadiazolyl, u, 4_p Satroxazolyl, u,5-oxadiazolyl, 1,3'4-oxadiazolyl, thiophyllinolyl, thiophyllinolinyl hydrazide, thionorfosyl hydrazine, Thiamine, pyrazolyl, pyrimenyl, thiophenothiazole, pyrimenoxazolyl, pyrimidazolyl, thiophenyl, tri-cultivation, tri-n-nitros-7-nonyl, triazolyl (eg Azyl, u, 4-triazolyl, anthracene, 2,5-triazolyl, 1,3,4-triazolyl) and anthracenyl. "Halohydrocarbyl", as employed herein, is a hydrocarbyl moiety wherein one to all hydrogens have been replaced by an independently selected halo group. As used herein, and unless otherwise stated, when a moiety (eg, alkyl, heteroalkyl, decyl, aryl, heteroaryl, heterocyclyl, etc.) is described as "" When substituted " as appropriate, it means that the group optionally has up to four, or one to two, or one or two independently selected non-hydrogen substituents. Suitable substituents include, but are not limited to! a hydroxy group, a keto group (eg, a ring-CH substituted with a keto group is -C(O)-), a nitro group, a hydryl group, a hydrocarbon group, an alkyl group, a cycloalkyl group, a heterocyclic group, an aryl group, Heteroaryl, arylalkyl, oxime oxy, aryloxy, amine, arylamino, alkylamine, sulfhydryl, amide, sulfhydryl, sulfhydryl, By thiol, calcined fluorenyl, arylcyclosulfonyl, alkanesulfonylamino, arylcyclosulfonylamino, arylalkylamine, alkylcarbonyl, decyloxy, cyano and ureido. The base, which is not further substituted by itself (unless otherwise explicitly stated), is exemplified by: (8) halo, hydroxy, cyano, keto, carboxy, decyl, fluorenyl, 134026-1 -22- 200916 447 Amino, methionyl, fluorenyl, (b) q-C5 alkyl or alkenyl or aralkylimine, amidyl, azide, carboxyamino, thiol, hydroxy, hydroxy Alkyl, alkylaryl, aralkyl, CVC8 alkyl, CVC8 alkenyl, q-Cg alkoxy, q-Cg alkylamino, (^-(:8 alkoxycarbonyl, aryloxycarbonyl, C2-c8 fluorenyl, -C(0)-N(R3°)-alkyl-cycloalkyl, -C(0)-N(R30)-alkyl-heterocyclyl, -C(0)-N (R30)-alkyl-aryl, -C(0)-N(R30)-alkyl-heteroaryl, -C(O)-cycloalkyl, -C(O)-heterocyclyl'-C (O)-aryl, -C(O)-heteroaryl, C:2 -C:8-decylamino, Ci-C:8 alkylthio, aralkylthio, arylthio, qC : 8 alkylsulfinyl, aralkyl sulfinylene, arylsulfinyl, q-C8 alkylsulfonyl, aralkylsulfonyl, arylsulfonyl, CVqN-alkyl Aminomethyl, c:2_Cl5N, N-dialkylamine, benzyl, aryloxy, arylalkyl, aryl, fused to a ring An aryl group of a heterocyclic ring or another aryl ring, a C:3-C:7 heterocyclic ring, a c:5-C]5 heteroaryl group or any such ring via a thick or snail-fused to a ring (tetra), a heterocyclic group or an aryl group, wherein each of the foregoing systems is further substituted by one or more of the groups represented by the above (8); and 77 (C) -(CR32R33)s.NR3〇 R3i , nitrogen is directly bonded to substituted

其中s為〇 (於此種情況中， 部份基團）至6， R32與R33各獨立為氫、 R30與R31各獨立為氫、 基、q-C8雜烷基、Ci_Cs烯基、羧醯胺基、q七 134026-1 -23- 200916447 燒基-羧醯胺基、羧醯胺基-c3烷基、甲脒基、 (Vc：8經炫基、CrC3烷基芳基、芳基_Cl_c3烷基、 q -C3烷基雜芳基、雜芳基_Ci _c3烷基、Ci _c3烷基 雜環基、雜環基-Cl_C3烷基Cl_C3烷基環烷基、環 烷基-CVC3烷基、c2_c8烷氧基、C2_c8烷氧基_Ci_c4 烷基、q-C8烷氧羰基、芳氧基羰基、芳基_Ci_c3 烷氧羰基、雜芳基氧基羰基、雜芳基_Ci_c3烷氧羰 Γ 基、Cl_C8醯基、C〇-C8烷基-幾基、芳基-C〇-C8烷基 -幾基、雜芳基-C0-C8烷基-缓基、環烷基_C〇_c8烷基 -羰基、雜環基-Cq-C8烷基-幾基、CVC8烷基-NH-羰 基、芳基-C〇 -C：8烷基-NH-裁基、雜芳基_c〇 -C8烷基 -NH-羰基' 環烷基_C()_C8烷基_NH_幾基、雜環基 -C〇 -Cs烧基-NH-截基、環烷基-S(〇)2 -、雜環基_s(〇)2 _ 、芳基-s(o)2-、雜芳基_s(0)2-、c〇_C8烷基_〇_羰基、 芳基-C〇-C8烧基-〇-羰基、雜芳基_c〇_c8烧基_〇幾 I， 基、環院基-〇) -Cs烧基-Ο-幾基、雜環基—Cq _c8烧基 -Ο-幾基、Q-C：8烷基磺醯基、芳烷基磺醯基、芳基 磺酿基、雜芳烷基磺醯基、雜芳基磺醯基、Cl_C8 烧基-NH-磺醯基、芳烷基_NH-續醯基、芳基_nh_確 fe基、雜务统基_NH-績醢基、雜芳基_nH-續醯基芳 醯基、芳基、環烷基、雜環基、雜芳基、芳基_Ci _c3 烧基-、環烷基-CVC3烷基-、雜環基-Cl_C3烷基_、 雜芳基-C3烧基-或保護基，其中各前述係進一 步視情況被一或多個列示於上文⑻中之部份基 134026-1 •24- 200916447 團取代；或 R30與R31和彼等所連接之N 一起採用，形成雜環基或 雜芳基，其每一個係視情況被1至3個選自包括上 文⑻、保護基及（X3〇-Y31 -)之取代基取代，其中該 雜環基亦可經橋接（形成具有亞曱基、次乙基戍次 丙基橋基之雙環狀部份基團）；其中 X30係選自包括Η、Cl_c8烷基、C2_C8烯基…C2_C8炔 基-、-CQ -C3烧基-C2 -C8烯基-C〇 -C3烧基、cQ -C3烧基 -c2-c8 快基-C〇-C3 烷基、CG-C3 烷基-0-CVC3 烷基 _、 HO-C〇-C3 院基-、C〇-C4 烧基-N(R3°)-Cq-C3 院基 _、 N(R3 0 )(R3 1 )—C〇 _c3 烷基-、N(R3 o )(R3 i )_c〇 _c3 稀基 _、 n(r3°)(r31kvc3 炔基-、（n(r3〇)(r31))2_c=n_、c。^ 烧基-S(0)Q. 2-C〇-C3 燒基-、CF3-C〇-C3 炫基-、q-c8 雜烷基、芳基、環烷基、雜環基、雜芳基、芳基 _Ci -C3烧基-、壤烧基-C! -C3烧基-、雜環基-C3 烷基-、雜芳基-Ci-C：3烷基-、N(R30)(RU)_雜環基 -C! -C：3烧基-’其中芳基、環烧基、雜芳基及雜環 基係視情況被1至3個得自⑻之取代基取代；且 Y31係選自包括直接鍵結、-0-、-N(R30)-、-c(0)-、 -O-C(O)-、-C(0)-0-、-N(R30)-C(O)-、-C(0)-N(R30)-、 -N(R3G)-C(S)-、-C(S)-N(R30)-、-N(R3G )-C(0)-N(R3i )-、 -N(R30)-C(NR30)-N(R31)-、-N(R30)-C(NR31)-、-C(NR31)-N(R30)-、-N(R30)-C ⑸-N(R31)-、-N(R30)-C(O)-O-、 -0-C(0)-N(R31)-、-N(R30)-C(S)-O-、-〇-C(S)-N(R31)-、 134026-1 -25- 200916447 3 1 -S(〇)〇.2- so2n(r3Wherein s is 〇 (in this case, a part of the group) to 6, R32 and R33 are each independently hydrogen, and R30 and R31 are each independently hydrogen, a group, a q-C8 heteroalkyl group, a Ci_Cs alkenyl group, a carboxy group. Amino group, q seven 134026-1 -23- 200916447 alkyl-carboxyamino group, carboxylamido-c3 alkyl group, formyl group, (Vc: 8 thiol group, CrC3 alkyl aryl group, aryl group _ Cl_c3 alkyl, q-C3 alkylheteroaryl, heteroaryl-Ci_c3 alkyl, Ci_c3 alkylheterocyclyl, heterocyclyl-Cl_C3 alkyl Cl_C3 alkylcycloalkyl, cycloalkyl-CVC3 alkane Base, c2_c8 alkoxy, C2_c8 alkoxy_Ci_c4 alkyl, q-C8 alkoxycarbonyl, aryloxycarbonyl, aryl_Ci_c3 alkoxycarbonyl, heteroaryloxycarbonyl, heteroaryl_Ci_c3 alkoxy Carbonyl fluorenyl, Cl_C8 fluorenyl, C〇-C8 alkyl-aryl, aryl-C〇-C8 alkyl-aryl, heteroaryl-C0-C8 alkyl-slowyl, cycloalkyl-C〇 _c8 alkyl-carbonyl, heterocyclic-Cq-C8 alkyl-yl, CVC8 alkyl-NH-carbonyl, aryl-C〇-C:8-alkyl-NH-based, heteroaryl-c 〇-C8 alkyl-NH-carbonyl 'cycloalkyl-C()-C8 alkyl_NH-alkyl, heterocyclyl-C〇-Cs alkyl-NH-trending, cycloalkyl-S(〇) 2 -, heterocyclic group _s(〇)2 _, aryl-s(o)2-, heteroaryl_s(0)2-, c〇_C8 alkyl_〇_carbonyl, aryl-C〇-C8 alkyl-hydrazine-carbonyl, heteroaryl Base_c〇_c8 alkyl group 〇 I I, group, ring-based group - 〇) -Cs alkyl group - fluorenyl group, heterocyclic group - Cq _c8 alkyl group - fluorene group, QC: 8 alkyl group Sulfonyl, aralkylsulfonyl, arylsulfonic acid, heteroarylalkylsulfonyl, heteroarylsulfonyl, Cl_C8 alkyl-NH-sulfonyl, aralkyl_NH-continuation , aryl, aryl, aryl, aryl, aryl, aryl, cycloalkyl, heteroaryl, heteroaryl, Aryl-Ci_c3 alkyl-, cycloalkyl-CVC3 alkyl-, heterocyclyl-Cl_C3 alkyl-, heteroaryl-C3 alkyl- or protecting group, wherein each of the foregoing is further one or more Part of the group listed in (8) above is 134026-1 •24-200916447; or R30 is used together with R31 and the N to which they are attached to form a heterocyclic or heteroaryl group, each of which is lined up The case is substituted by 1 to 3 substituents selected from the group consisting of (8) above, a protecting group and (X3〇-Y31 -), wherein the heterocyclic group may also be bridged (formed with an anthracene group, a bicyclic partial group based on a propylidene group; wherein X30 is selected from the group consisting of hydrazine, Cl_c8 alkyl, C2_C8 alkenyl...C2_C8 alkynyl-, -CQ-C3 alkyl-C2-C8 alkenyl -C〇-C3 alkyl, cQ-C3 alkyl-c2-c8 fast-C〇-C3 alkyl, CG-C3 alkyl-0-CVC3 alkyl_, HO-C〇-C3 C〇-C4 alkyl-N(R3°)-Cq-C3 院,_(R3 0 )(R3 1 )—C〇_c3 alkyl-, N(R3 o )(R3 i )_c〇_ C3 dilute base _, n (r3°) (r31kvc3 alkynyl-, (n(r3〇)(r31))) 2_c=n_, c. ^alkyl-S(0)Q. 2-C〇-C3 alkyl-, CF3-C〇-C3 炫-, q-c8 heteroalkyl, aryl, cycloalkyl, heterocyclic, heteroaryl , aryl-Ci-C3 alkyl-, calcyl-C!-C3 alkyl-, heterocyclic-C3 alkyl-, heteroaryl-Ci-C: 3 alkyl-, N (R30) (RU)_heterocyclyl-C!-C:3alkyl-' wherein aryl, cycloalkyl, heteroaryl and heterocyclyl are optionally substituted by 1 to 3 substituents derived from (8); Y31 is selected from the group consisting of direct bonding, -0-, -N(R30)-, -c(0)-, -OC(O)-, -C(0)-0-, -N(R30)-C (O)-, -C(0)-N(R30)-, -N(R3G)-C(S)-, -C(S)-N(R30)-, -N(R3G)-C(0 )-N(R3i )-, -N(R30)-C(NR30)-N(R31)-, -N(R30)-C(NR31)-, -C(NR31)-N(R30)-,- N(R30)-C (5)-N(R31)-, -N(R30)-C(O)-O-, -0-C(0)-N(R31)-, -N(R30)-C( S)-O-, -〇-C(S)-N(R31)-, 134026-1 -25- 200916447 3 1 -S(〇)〇.2- so2n(r3

-S02N(R N(R31)-S02-及-N(r3〇)- 經取代之部份基團係為其中_或多個（或者，一至四個， 或者’一至三個， 、 4有’一或兩個）氫已獨立被另一個化學 取基置換者。作為非限制性實例，經取代之苯基係包括 2_既苯基、3’4·二氯笨基、3-氯基-4-氟苯基、2-氟基各丙基笨 基。作為另一個非限制性實例，經取代之正-辛基係包括2’4_ 土乙基辛基與3·環戊基-辛基。被包含在此定義内者 為亞甲基（CH2-) ’被氧取代，以形成獄基。 —田有兩個選用取代基結合至環結構之相鄰原子時，例如 苯基、硫苯基或咐α定基，此等取代基和彼等所結合之原子 一起視情況形成5-或6_員環烧基或雜環，具有卜2或3個環 形雜原子。 在某些具體實施例中’基團譬如烴基、㈣基、雜環族 及/或方基係為未經取代。 在其他具體實施例中，基團譬如烴基、雜烧基、雜環族 及/或芳基係被！至4個（或者，一至三個，或者，—或兩個） 獨立經選擇之取代基取代。 在烷基上之取代基實例包括但不限於羥基、鹵素（例如單 一齒素取代基或多重齒基取代基；於後述情況中為基團嬖 如-eh或帶有％之烷基）、酮基、氰基、硝基、烷基、環烷 基、烯基、環稀基、块基、雜環、芳基、芳氧基、芳基 基）或二芳基、芳烷基、芳烷基氧基、環烷基烷基、環烷基 烷氧基、羥烷基、醯基、烷醯基、雜芳基、雜芳基氧基、 134026-1 •26· 200916447 環雜烷基、芳基雜芳基、芳基烷氧羰基、雜芳烷基、雜芳 基烧氧基、方乳基烧基、方氧基芳基、燒基酿胺基、院酿 胺基、芳基羰基胺基、硫醇、i烷基、三_烷基、烷硫基、 -ORa、-SRa、-S(=0)Re、-S(=〇)2Re、_p(=〇)2Re、_s(=〇)2〇Re -P(=0)20Re、-NRbRe、-NRbS(=0)2Re、-NRbp(=〇)2Re、_s(=〇)2NRbRC 、-P(=0)2NRbRc、-C(=0)ORe、-C(=0)Ra、-C(=〇)NRbRc、-〇C(=〇)Ra、 -0C(=0)NRbRc、-NRbC(=0)0Re、-NRdC(=0)NRbRc、-NRdS(=0)2- 、_NRdp(=〇)2NRbRe、NRbc(=〇)R^ NRbp㈤^Re，其中 Ra為氫、烷基、環烷基、烯基、環烯基、炔基、雜環或芳 基；Rb、Rc及Rd係獨立為氫、烷基、環烷基、雜環或芳基， 或該Rb與RC和彼等所結合起視情況形成雜環；且Re 為烷基、環烷基、烯基、環烯基、炔基、雜環或芳基。在 前述舉例之取代基中，基團譬如烷基、環烷基、烯基、炔 基、環烯基、雜環及芳基可本身視情況經取代。 、在烯基與炔基上之取代基實例包括但不限於烷基或經取 代之烷基，以及被敘述為烷基取代基之實例之基團。 在％烷基上之取代基實例包括但不限於硝基、氰基、烷 基或、、二取代之烷基，以及關於被敘述為烷基取代基之實例 :基團。取代基之其他實例包括但不限於經螺連接或經稠 «之衣狀取代基，例如螺連接之環烷基、螺連接之環烯基、 累連接之雜ί衣（排除雜芳基）、稠合之環烷基、稠合之環烯 稠合之雜環或稠合之芳基，其中前文所提及之環院基、 =基、雜環及芳基取代基可本身視情況經取代。於另一 、體實鼽例中，當環烷基係被兩個6烷基取代時，該 134026-1 •27- 200916447 兩個烷基可結合在—起而形成次烷基鏈，例如Ci—3次烷基 鏈。具有此父聯結構之環烷基包括雙環并[2 2 2]辛烷基與正 捐烷基。 ~ 在環烯基上之取代基實例包括但不限於硝基、氰基、烷 基或經取代之烷基，以及被敘述為烷基取代基之實例之基 團取代基之其他貫例包括但不限於經螺連接或經稠合之 環狀取代基，尤其是螺連接之環烷基、螺連接之環烯基、 螺連接之雜環（排除雜芳基）、稠合之環烷基 '稠合之環烯 基、稠合之雜環或稠合之芳基，其中前文所提及之環烷基、 環烯基、雜環及芳基取代基可本身視情況經取代。於另一 項具體實施例中，當環烯基係被兩個C16烷基取代時，該 兩個烷基可結合在一起而形成次烷基鏈，例如c13次烷基 鏈。 在芳基上之取代基實例包括但不限於硝基、環烷基或經 取代之環烷基、環烯基或經取代之環烯基、氰基、烷基或 經取代之烷基’以及上文被敘述為烷基取代基之實例之基 團。取代基之其他實例包括但不限於稠合之環狀基團，尤 其是稠合之環烷基、稠合之環烯基、稠合之雜環或稠合之 芳基’其中前文所提及之環烷基、環烯基、雜環及芳基取 代基可本身視情況經取代。在芳基（苯基，作為非限制性實 例）上之又其他取代基實例’包括但不限於鹵院基及被敘述 為烧基取代基之實例之基團。於另一項具體實施例中，當 芳基係被兩個q—6烷基取代時，該兩個烷基可結合在一起 而形成次烧基鏈，例如C! - 3次烧基鏈。 134026-1 -28- 200916447 在雜環族基團上之取代基實例包括但不限於環烷基、經 取代之環烷基、環烯基、經取代之環烯基、硝基、酮基（意 即=〇)、氰基、院基、經取代之炫基，以及被敘述為院基取 代基之實例之基團。㈣環族基團上之其他取代基實例包 括但不限於經螺連接或經稠合之環狀取代基，在任何可取 用之點或連接點上，例如螺連接之環烷基、螺連接之環烯 基螺連接之雜環（排除雜芳基）、稠合之環烷基、稠合之 環稀基、稠合之雜環及稠合之芳基，以前文所提及之環 烧基、環烯基、雜環及芳基取代基可本身視情況經取代。 於另-項具體實施射，當雜環料被兩個Ci 6烧基取代 時，該兩個烷基可結合在一起而形成次烷基鏈，例如 次烧基鍵。 在某些具體實施例中’ #環族&團係在一 3戈多個位置處 之碳、氮及/或硫上經取代。在碳上之取代基實例包括被敘 述為烷基取代基之實例之基團。在氮上之取代基實例包括 但不限於烧基、芳基、芳烧基、烧幾基、炫基項醯基、芳 基幾基、芳基續醯基、烧氧徵基或芳燒氧基祕。在硫上 之取代基實例包括但不限於酮基與Ci_6烷基。在某些具體 實施例中，氮與硫雜原子可獨立地視情況經氧化，且氮雜 原子可獨立地視情況經四級化。 在壞基團譬如芳基、雜芳基、環烷基及雜環基上之舉例 取代基’係包括_素、烷氧基及烷基。 在烧基上之舉例取代基包括_素與經基。 在芳族多裱包括但不限於莕基與喳啉上之取代基實例包 134026-1 -29- 200916447 括CVQ烧基、環烧基烧基（例如環丙基曱基）、氧基烧基、 i基 '確基、胺基、烷胺基、胺基烷基、烷基酮類、腈、 緩基烧基、烧基石黃醯基、芳基石黃酿基、胺基績醯基及，， 譬如烧氧基，其中Raa係選自包括H、Cl-C6烧基、c4_c9環炫 基、㈣雜環烧基、芳基、雜芳基、芳烧基、雜芳烧基及 -(CH2)Q.6ZaRbb，其中Za係選自包括〇、nr“、5及柳），且 -係選自包括H、Cl_C^基、C4m院基、％雜環院 ζ基、Μ雜環編基、芳基、混合之芳基與非芳基多環、 •雜m烧基（例如爷基）及雜芳垸基（例如峨咬基甲 基）m系選自包括η、Cl_c旧基、Μ環烧基、Μ 雜環貌基、芳基、雜芳基、芳燒基（例如爷基）、雜芳院基（例 如吡啶基甲基）及胺醯基。 非芳族多環之實例包括但不限於雙環狀與三環狀稠合淨 系統，其中各環可為4-9員，且各環可含有零、^更多個 钱及?'參鍵。非芳族多環之適當實例包括但不限於十氫 U 奈、^虱印、全氫笨并環庚烯及全氫苯并-㈣。此種基祖 係視情況被例如但不限於q-c：9環烷基，譬如環丙基、環丁 基、環戊基、環己基等取代。除非另有指明，否二心 多環包括未經取代之環院基，與被—或多個適當取代基取 代之環烷基兩者，該取代基包括但不限於Ci_C6烷基:卣 基、基、胺基烧基、氧基院基、院胺基及0Raa，譬如2 氧基。關於此種環烷基之取代基實例包括幽基、羥基、= 氧基、氧基烷基、烷胺基及胺基烷基。 混合之芳基與非芳基多帛之實4列包括雙環狀與三環狀稍 134026-1 -30· 200916447 :=2中各環可為4-9[且至少一個環為芳族。混 方基與非芳基多環之適當實例包括亞甲二氧基苯美、 二t基苯基、1，2,3,4-四氫萘、二苯并環庚:::蕙 第此種基團係為未經取代或被硝基取代， 關於非芳㈣輯述。 或如上文 多雜芳基包括雙環狀與三環狀稠合環系統 獨立為5或6員，且含有一或多個雜原子，例如:、、2: 個：原：：選自〇、NW，以致使稠合環系統為芳族：多 雜方基環线之適當實例包括料、異4 #、㈣并十井、 吡'并咐。定”夫鳴并P比咬”㈣、苯并味喃、笨并硫代味 喃、苯并♦果、苯并.坐”比略并峻淋等。除非另有指明， =則多雜芳基係為未經取代’或在碳原子上被一或多個適 田取代基取代’取代基包括但不限於直鏈與分枝狀視情況 經取代之Ci-c6院基、不飽和性（意即有一或多個雙或參c_c 鍵結）、酿基、環烧基、齒基、氧基烧基、院胺基、胺基烧 基、醯基胺基及㈣，例如燒氧基，及式_〇仰舞 之取代基。適當直鏈與分枝狀c「C6院基 取代基之實例包括但不限於^基、乙基、正-丙基、2-丙基、 正-丁基、第二-丁基、第三-丁基等。取代基之實例包括函 基L基、院氧基、氧基烧基、貌胺基及胺基烧基。氣原 子係為未經取代，或例如被RCC取代。在此種氮原子上之取 代基實例包括Η、Cl(4烧基、酿基、胺醯基及續酿基。 非芳族多雜環族之實例包括但不限於雙環狀與三環狀環 系統，其中各環可為4_9員，含有_或多個雜原子，例如i、 134026-1 -31 - 200916447 2、3或4個雜原子，逻白 遲自Ο、N或s，且含有零或一或多個 C-C雙或參鍵。非若旅枣 ^ t雜5衣類之適當實例包括但不限於己 糖西子順式-全虱-環庚并[b>比咬基、十氫-苯并_，聰氮七 園稀基、2,8-二氧雙環并[3 3 〇]辛燒、六氫4吩并[训噻吩、 全氯十各并[3场比Π各、全氫‘定、全氫_1H-二環五[b，e]喊喃。 、卜另有扣Θ $則非芳族多雜環族係為未經取代，或在 碳原子上被-或多個取代基取代，取代基包括但不限於直 鏈與分枝狀視情況經取代之Ci_C6烧基、不飽和性（意即有 -或多個雙或參C-C鍵結）、醯基、環烷基、㈣、氧基烷 基、烷胺基、胺基烷基、醯基胺基及0Raa，例如烷氧基。 L田直鏈與刀枝狀q -C：6燒基取代基之實例包括但不限於 甲基、乙基、正-丙基、2-丙基、正-丁基、第二_ 丁基、第三 -丁基等。取代基之實例包括鹵基、羥基、烷氧基、氧基烷 基、烷胺基及胺基烷基。氮原子係為未經取代，或例如被-S02N(RN(R31)-S02- and -N(r3〇)- Part of the substituted group is _ or more (or, one to four, or 'one to three, four have one' Or both) hydrogen has been independently replaced by another chemical group. As a non-limiting example, the substituted phenyl group includes 2_ylphenyl, 3'4.dichlorophenyl, 3-chloro-4 - Fluorophenyl, 2-fluoropropylpropyl phenyl. As another non-limiting example, the substituted n-octyl group includes 2'4_ ticethyloctyl and 3 pentylpentyl-octyl. Included within this definition is methylene (CH2-) 'substituted by oxygen to form a prison base. - Field has two substituents bonded to adjacent atoms of the ring structure, such as phenyl, thiophenyl Or a 咐α group, such substituents, together with the atoms to which they are attached, form a 5- or 6-membered cycloalkyl or heterocyclic ring, having 2 or 3 ring heteroatoms. In certain embodiments 'Substituents such as hydrocarbyl, (tetra), heterocyclic and/or aryl are unsubstituted. In other embodiments, groups such as hydrocarbyl, heteroalkyl, heterocyclic and/or aryl are! Up to 4 Alternatively, one to three, or, or two, independently substituted substituents. Examples of substituents on the alkyl group include, but are not limited to, hydroxy, halo (eg, a single dentate substituent or a multiple dentate substituent; In the latter case, it is a group such as -eh or an alkyl group having a %), a keto group, a cyano group, a nitro group, an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkyl group, a block group, a heterocyclic ring, and an aromatic group. , aryloxy, aryl) or diaryl, aralkyl, aralkyloxy, cycloalkylalkyl, cycloalkylalkoxy, hydroxyalkyl, decyl, alkanoyl, hetero Aryl, heteroaryloxy, 134026-1 •26· 200916447 cycloheteroalkyl, arylheteroaryl, arylalkoxycarbonyl, heteroaralkyl, heteroaryl alkoxy, galvanyl , aryloxyaryl, alkyl amide, aryl amine, arylcarbonylamino, thiol, i alkyl, tri-alkyl, alkylthio, -ORa, -SRa, -S (= 0) Re, -S(=〇)2Re, _p(=〇)2Re, _s(=〇)2〇Re -P(=0)20Re, -NRbRe, -NRbS(=0)2Re, -NRbp(= 〇) 2Re, _s(=〇)2NRbRC, -P(=0)2NRbRc, -C(=0)ORe, -C(=0)Ra, -C(=〇)NRbRc, -〇C(= )Ra, -0C(=0)NRbRc, -NRbC(=0)0Re, -NRdC(=0)NRbRc, -NRdS(=0)2-, _NRdp(=〇)2NRbRe, NRbc(=〇)R^ NRbp(五)^Re, wherein Ra is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, heterocyclic or aryl; Rb, Rc and Rd are independently hydrogen, alkyl, cycloalkyl, hetero A ring or aryl group, or a combination of Rb and RC and the like, forms a heterocyclic ring; and Re is an alkyl group, a cycloalkyl group, an alkenyl group, a cycloalkenyl group, an alkynyl group, a heterocyclic group or an aryl group. In the above-exemplified substituents, a group such as an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, a cycloalkenyl group, a heterocyclic ring and an aryl group may be optionally substituted by itself. Examples of the substituent on the alkenyl group and the alkynyl group include, but are not limited to, an alkyl group or a substituted alkyl group, and a group described as an example of an alkyl substituent. Examples of the substituent on the % alkyl group include, but are not limited to, a nitro group, a cyano group, an alkyl group or a disubstituted alkyl group, and an example relating to an alkyl group substituent: a group. Other examples of substituents include, but are not limited to, spiro-linked or fused-like substituents such as spiro-linked cycloalkyl, spiro-linked cycloalkenyl, dentately attached (excluding heteroaryl), a fused cycloalkyl group, a fused cycloolefin fused heterocyclic ring or a fused aryl group, wherein the ring-based, =, heterocyclic and aryl substituents mentioned above may themselves be substituted as appropriate . In another embodiment, when the cycloalkyl group is substituted by two 6 alkyl groups, the 132426-1:27-200916447 two alkyl groups may be bonded to form a secondary alkyl chain, such as Ci. - 3 alkyl chains. The cycloalkyl group having this parent structure includes a bicyclo[2 2 2]octyl group and a n-donating alkyl group. Examples of the substituent on the cycloalkenyl group include, but are not limited to, a nitro group, a cyano group, an alkyl group or a substituted alkyl group, and other examples of the group substituents described as examples of the alkyl substituent include but Not limited to spiro-linked or fused cyclic substituents, especially spiro-linked cycloalkyl, spiro-linked cycloalkenyl, spiro-linked heterocycle (excluding heteroaryl), fused cycloalkyl' A fused cycloalkenyl group, a fused heterocyclic ring or a fused aryl group, wherein the cycloalkyl, cycloalkenyl, heterocyclic and aryl substituents mentioned above may be optionally substituted by themselves. In another specific embodiment, when the cycloalkenyl group is substituted with two C16 alkyl groups, the two alkyl groups can be joined together to form a secondary alkyl chain, such as a c13 alkyl chain. Examples of substituents on the aryl group include, but are not limited to, nitro, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, cyano, alkyl or substituted alkyl' and The groups described above as examples of alkyl substituents. Other examples of substituents include, but are not limited to, fused cyclic groups, especially fused cycloalkyl, fused cycloalkenyl, fused heterocyclic or fused aryl 'which is mentioned above The cycloalkyl, cycloalkenyl, heterocyclic and aryl substituents may themselves be substituted as appropriate. Further examples of substituents on the aryl (phenyl, as a non-limiting example) include, but are not limited to, a halogen-based group and a group which is exemplified as an alkyl group substituent. In another embodiment, when the aryl system is substituted with two q-6 alkyl groups, the two alkyl groups can be joined together to form a secondary alkyl chain, such as a C!-3 alkyl chain. 134026-1 -28- 200916447 Examples of substituents on a heterocyclic group include, but are not limited to, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, nitro, keto ( That is, = 〇), cyano, affinity, substituted sulphide, and a group described as an example of a substituent for a nominee. (IV) Examples of other substituents on the cyclo-group include, but are not limited to, spiro-linked or fused cyclic substituents, at any point or point of attachment, such as a spiro-linked cycloalkyl, spiro-linked Cycloalkenyl-linked heterocyclic ring (excluding heteroaryl), fused cycloalkyl, fused cycloaliphatic, fused heterocyclic ring and fused aryl group, cyclized groups as mentioned before The cycloalkenyl, heterocyclic and aryl substituents may themselves be substituted as appropriate. In another embodiment, when the heterocycle is substituted with two Ci 6 alkyl groups, the two alkyl groups can be joined together to form a secondary alkyl chain, such as a secondary alkyl bond. In some embodiments, the 'cyclo & groups are substituted on carbon, nitrogen and/or sulfur at a plurality of positions. Examples of the substituent on the carbon include a group which is exemplified as an alkyl substituent. Examples of the substituent on the nitrogen include, but are not limited to, an alkyl group, an aryl group, an aryl group, a aryl group, a fluorenyl group, an aryl group, an aryl group, an oxygen group or an aromatic gas. Basic secret. Examples of substituents on sulfur include, but are not limited to, keto groups and Ci-6 alkyl groups. In certain embodiments, the nitrogen and sulfur heteroatoms can be independently oxidized as appropriate, and the nitrogen heteroatoms can be independently quaternized as appropriate. Exemplary substituents on the bad group such as aryl, heteroaryl, cycloalkyl and heterocyclic groups include _, alkoxy and alkyl. Exemplary substituents on the alkyl group include a sulfonate and a thiol group. Examples of substituents on aromatic polyterpenes including, but not limited to, mercapto and porphyrins include: 134026-1 -29- 200916447 including CVQ alkyl, cycloalkyl (eg cyclopropyl fluorenyl), oxyalkyl , i-based, an amine group, an alkyl group, an alkylamino group, an aminoalkyl group, an alkyl ketone, a nitrile, a slow-base group, a burnt-stone ruthenium group, an aryl sulfanyl group, an amine group, and, for example, An alkoxy group, wherein Raa is selected from the group consisting of H, Cl-C6 alkyl, c4_c9 cyclohexyl, (iv) heterocycloalkyl, aryl, heteroaryl, aryl, heteroaryl and -(CH2)Q .6ZaRbb, wherein the Za is selected from the group consisting of ruthenium, nr ", 5 and lanthanum, and the - is selected from the group consisting of H, Cl_C^, C4m, %, 杂环, Μ, aryl, aryl , mixed aryl and non-aryl polycyclic, • hetero-alkyl (for example, aryl) and heteroaryl (for example, carbyl methyl) m are selected from the group consisting of η, Cl_c, and anthracene , 杂环 heterocyclic, aryl, heteroaryl, aryl (eg, aryl), heteroaryl (eg pyridylmethyl) and amine fluorenyl. Examples of non-aromatic polycyclic rings include, but are not limited to, Double ring and triple ring condensed net system, Each ring may be 4-9 members, and each ring may contain zero, more than one money, and ?'s key. Suitable examples of non-aromatic polycyclic rings include, but are not limited to, decahydrourine, n. Hydrogen stupid cycloheptene and perhydrobenzo-(iv). Such a ancestral system is optionally substituted by, for example, but not limited to, qc:9 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. Unless otherwise indicated, a bicentric polycyclic ring includes an unsubstituted ring-based group, and a cycloalkyl group substituted with one or more suitable substituents including, but not limited to, Ci_C6 alkyl: fluorenyl a base, an amine alkyl group, a oxy group, a hospital amine group, and 0Raa, such as a 2-oxy group. Examples of the substituent for such a cycloalkyl group include a glutenyl group, a hydroxyl group, an oxy group, an oxyalkyl group, and an alkane. Amino and aminoalkyl. Mixed aryl and non-aryl polyfluorene consists of 4 columns including bicyclic and tricyclic slightly 134026-1 -30· 200916447 :=2 each ring can be 4-9[ And at least one ring is aromatic. Suitable examples of the mixed group and the non-aryl polycyclic ring include methylenedioxyphenylene, di-t-phenylphenyl, 1,2,3,4-tetrahydronaphthalene, dibenzo Cycloheptyl:::蕙The first group of this group Unsubstituted or substituted by nitro, with respect to non-aryl (d). Or as described above, polyheteroaryl includes bicyclic and tricyclic fused ring systems independently of 5 or 6 members and containing one or more heteroatoms , for example: , , 2: one: original:: selected from 〇, NW, so that the fused ring system is aromatic: suitable examples of multi-heterocyclic ring lines include materials, different 4 #, (4) and 10 wells, pyr 'And 咐 定 定 夫 并 并 并 并 并 并 并 并 并 并 并 P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P Unless otherwise indicated, = polyheteroaryl is unsubstituted or substituted with one or more aptamy substituents on a carbon atom. 'Substituents include, but are not limited to, straight and branched, as appropriate. Ci-c6 hospital base, unsaturated (meaning one or more double or ginseng c_c bond), brewing base, cycloalkyl, dentate, oxyalkyl, amphoteric, amine alkyl, fluorenyl An amine group and (d), such as an alkoxy group, and a substituent of the formula 〇 〇. Examples of suitable straight-chain and branched c"C6-based substituents include, but are not limited to, ethyl, ethyl, n-propyl, 2-propyl, n-butyl, second-butyl, third- Butyl groups, etc. Examples of the substituent include a group L group, a methoxy group, an oxyalkyl group, an amido group, and an amine group. The gas atom system is unsubstituted or substituted, for example, by RCC. Examples of substituents on the atom include hydrazine, Cl (4 alkyl, aryl, amine fluorenyl, and continuation groups. Examples of non-aromatic polyheterocyclic groups include, but are not limited to, bicyclic and tricyclic ring systems, wherein Each ring may be 4-9 members, containing _ or more heteroatoms, such as i, 134026-1 -31 - 200916447 2, 3 or 4 heteroatoms, which are delayed, N or s, and contain zero or one or A plurality of CC double or ginseng bonds. Suitable examples of non-rule 枣 t t t t 衣 包括 包括 包括 包括 包括 包括 包括 包括 包括 包括 包括 包括 包括 包括 包括 b b b b b b b b b b b b b b b b b b b b b b b Congqiqiqiyuan dilute base, 2,8-dioxobicyclo[3 3 〇]octane, hexahydro 4 pheno[[thiophene, perchlorine ten each [3 fields than Π, all hydrogen' fixed, all Hydrogen_1H-bicyclo-5 [b,e] shouted. The polyheterocyclic family is unsubstituted or substituted with one or more substituents on a carbon atom, and the substituents include, but are not limited to, straight-chain and branched-like Ci_C6 alkyl groups, unsaturation ( That is, there are - or a plurality of double or gin CC bonds), anthracenyl, cycloalkyl, (tetra), oxyalkyl, alkylamino, aminoalkyl, decylamino and 0Raa, such as alkoxy. Examples of L-line linear and knive-shaped q-C:6 alkyl substituents include, but are not limited to, methyl, ethyl, n-propyl, 2-propyl, n-butyl, second butyl, and third. -butyl, etc. Examples of the substituent include a halogen group, a hydroxyl group, an alkoxy group, an oxyalkyl group, an alkylamino group, and an aminoalkyl group. The nitrogen atom is unsubstituted or, for example,

Rcc取代。N取代基之實例包括H、Ci_c4烷基、醯基、胺醯 基及磺醯基。 混合之芳基與非芳基聚雜環類之實例包括但不限於雙環 狀與三環狀稠合環系統，其中各環可為4_9員，含有一或多 個雜原子，選自〇、N或S，且至少一個環必須為芳族。混 合之芳基與非芳基聚雜環類之適當實例包括2,3_二氫ρξ]嗓' 1,2,3,4-四氫喹啉、5，11-二氫-10H-二苯并[b，e][i，4]二氮七園烯、 5H-一本并[b，e][l，4]二氮七圜稀、1,2-二氫p比u各并[3,4七][1，5]苯并 二氮七圜、1，5-二氫吡啶并[2,3-b][l，4]二氮七圜 _4_酮、12,3,4,611_ 六氫-苯并[b]p比咬并[2,3-e][l，4]二氮七園稀_5_酮。除非另有指 134026-1 -32- 200916447 明，否則混合之芳基與非芳基多雜環族係為未經取代，或 在礙原子上被一或多個適當取代基取代，取代基包括但不 限於-N-OH、=N-OH、視情況經取代之烷基不飽和性（意即有 一或多個雙或參C-C鍵結）、醯基、環烷基、_基、氧基烷 基、燒胺基、胺基烧基、醯基胺基及〇Ra a ’例如烧氧基。 氮原子係為未經取代，或例如被Rcc取代。N取代基之實例 包括Η、q—4烷基、醯基胺醯基及磺醯基。 "_素”或"鹵基”術語，當於本文中採用時，係指氯、溴、 氟或碘。當於本文中採用時，”醯基” 一詞係指烷羰基或芳 基羰基取代基。”醯基胺基"一詞係指醯胺基，經連接於氮 原子上（意即R-CO—NH-)。"胺甲醯基"一詞係指醯胺基，經連 接於羰基碳原子上（意即NH2_c〇_)。醯基胺基或胺甲醯基取 代基之氮原子，係另外視情況經取代。”磺醯胺基"一詞係 指嶒醯胺取代基，藉由無論是硫或氮原子連接。，,胺基"— 詞係意謂包括NH2、烷胺基、二-烷基-胺基（其中烷基為相同 \ f不同）、芳胺基及環狀胺基6 ”脲基，，一詞當於本文_採用 時係指經取代或未經取代之脲部份基團。 於本文中使用之”自由基"一詞係意謂包含一或多個未成 對電子之化學部份基團。 在部份基團之選用取代基係選自”一或多個”基團之情 中’應明瞭的是’除非另有述及’否則此部份基團係視 況具有-個至高達最高數目之可取代氫在該部份基團上 破獨立選自所指定基團中之取代基置換。 此外，於環狀部份基團（意即環烧基、雜環基、芳基、 134026-1 -33- 200916447 ^之取代基，係包括m員單鲁至14項雙環狀部 々基團’經稠合至母體環狀部份基團，以形成雙或三 稠合環系統。於環狀部份基團上之取代基亦包括5_至6_員單_ 與9-至14-員雙環狀部份基團，萨 ❹共仏鍵連接至母體環狀 ::基：，以形成雙或三_環狀雙環系統。例如，視情況經 取笨基，括但予限於下列Rcc replaced. Examples of the N substituent include H, Ci_c4 alkyl, fluorenyl, amine sulfhydryl and sulfonyl. Examples of mixed aryl and non-aryl polyheterocycles include, but are not limited to, bicyclic and tricyclic fused ring systems wherein each ring can be a 4-9 member containing one or more heteroatoms selected from hydrazine, N or S, and at least one ring must be aromatic. Suitable examples of mixed aryl and non-aryl polyheterocycles include 2,3-dihydroρξ]嗓' 1,2,3,4-tetrahydroquinoline, 5,11-dihydro-10H-diphenyl And [b,e][i,4]diazepine, 5H-one and [b,e][l,4]diazepine, 1,2-dihydrop, and u 3,4 7][1,5]benzodiazepines, 1,5-dihydropyrido[2,3-b][l,4]diazepine-7-one, 12,3, 4,611_ Hexahydro-benzo[b]p ratio bites [2,3-e][l,4]diazepines _5-ketone. Unless otherwise indicated, 134026-1 -32- 200916447, the mixed aryl and non-aryl polyheterocyclic families are unsubstituted or substituted at the atom to one or more suitable substituents, and the substituent includes But not limited to -N-OH, =N-OH, optionally substituted alkyl unsaturation (meaning one or more double or gins CC bonds), fluorenyl, cycloalkyl, yl, oxy Alkyl, acrylamine, amine alkyl, decylamino and 〇Ra a ' are, for example, alkoxy groups. The nitrogen atom is unsubstituted or substituted, for example, by Rcc. Examples of the N substituent include anthracene, q-4 alkyl, mercaptoamine sulfhydryl and sulfonyl. The term "halogen" or "halo-based", as used herein, means chloro, bromo, fluoro or iodo. As used herein, the term "mercapto" refers to an alkylcarbonyl or arylcarbonyl substituent. The term "mercaptoamine" refers to a guanamine group attached to a nitrogen atom (ie, R-CO-NH-). The term "amine-methyl thiol" refers to the guanamine group, which is linked. On the carbonyl carbon atom (ie, NH2_c〇_). The nitrogen atom of the mercaptoamino group or the amine mercapto substituent is additionally substituted as appropriate. The term "sulfonylamino" refers to the substitution of indoleamine. The base is attached by either a sulfur or a nitrogen atom. , "amino" is used to mean NH2, alkylamino, di-alkyl-amine (wherein alkyl is the same \f different), arylamine and cyclic amine 6" Urea, The term "free radical" as used herein refers to a chemical moiety that contains one or more unpaired electrons. Group. In the case where a selected substituent of a group is selected from "one or more" groups, it should be understood that 'unless otherwise stated', otherwise the group has a - up to the highest A number of substitutable hydrogens are substituted on the moiety to independently substitute a substituent selected from the specified group. In addition, the substituents in the cyclic moiety (ie, cycloalkyl, heterocyclyl, aryl, 134026-1 -33- 200916447 ^) include m-membered single-lumen to 14-membered bicyclic fluorenyl groups. The group 'is fused to the parent cyclic group to form a double or triple fused ring system. The substituents on the cyclic moiety also include 5_ to 6_members _ and 9- to 14 a member of a bicyclic moiety, a samarium conjugated bond to the parent ring:: group: to form a double or triple _ ring double ring system. For example, depending on the case, the base is included, but is limited to the following

口、Μ或不餘和—_至八_員碳環為例如四-至七-員，或者五 員，或不飽和碳環。飽和或不飽和三_至 族兔之實例包括笨基、環丙基、環丁基、環戊基、環 及環庚基。 土 v 飽和或不飽和二-至八_員雜環含有至少一個雜原子，選 :氧、氮及硫原子。飽和或不飽和三-至八-員雜環含有例 式—或兩個雜原子，其中其餘環構成原子為碳原子。飽和 、不飽和二-至八項雜環為钶如飽和或不飽和西-至七項 ，或者，為飽和或不飽和五_或六-員雜環。飽和或不 飽和三-至八-員雜環族基團之實例包括嘧吩基、吡啶基、 =三哇[°米唾基、異号。坐基”比唾基、六氫基、 /氫咐呼基、六氫p比咬基、六氫峨咬基、嗎福口林基、嗎福 '土阿，、虱吡畊基、高六氫吡畊基、硫代嗎福啉基 '硫 弋馬福啉基、四氫吡咯基及一氮七園烷基。 於本文中使用之”組織蛋白去乙醯化酶„、"種類m組織蛋 脫乙醯酶或組織蛋白去乙醯化酶蛋白質"術語，係指組 134026-1 -34- 200916447 織蛋白去乙醯化酶脫乙醯酶蛋白質族群（例如指sir2族群） 之一個成員，其包括酵母Sir2、C. elegans Sir-2.1及人類SIRT1 與SIRT2蛋白質。其他族群成員包括四種其他酵母似Sir2基 因，稱為"HST基因”（Sir2之同系物），HST1、HST2、HST3及 HST4，及五種其他人類同系物 hSIRT3、hSIRT4、hSIRT5、hSIRT6 及 hSIRT7 (Brachmann 等人（1995) Genes Dev. 9 : 2888 與 Frye 等人 (1999) BBRC 260 : 273)。組織蛋白去乙醯化酶之實例為與 SIRT1，意即hSIRTl及，或Sir2共有較多相似性者，相較於與 SIRT2，譬如具有N-末端順序之至少一部份存在於SIRT1中而 不存在於SIRT2中（譬如SIRT3所具有）之成員。其他組織蛋白 去乙醯化酶為與SIRT7共有較多相似性者。組織蛋白去乙醯 化酶較佳為人類組織蛋白去乙醯化酶。在一些其他具體實 施例中，組織蛋白去乙醯化酶係衍生自原生動物或真菌來 源。 ”組織蛋白去乙醯化酶抑制劑"與”組織蛋白去乙醯化酶 之抑制劑”等術語係意指具有如本文所定義結構之化合物， 其係能夠直接或間接與組織蛋白去乙醯化酶交互作用且抑 制其酵素活性。 ”抑制組織蛋白去乙醯化酶酵素活性”一詞係意指降低組 織蛋白去乙醯化酶之功能性質或生物能力。例如，組織蛋 白去乙醒化酶活性之抑制可為至少約1 〇%。在本發明之一 些具體實施例中，組織蛋白去乙醯化酶活性之此種抑制係 為至少約50%，或者，至少約75%，及或者，至少約90%。 在其他具體實施例中，組織蛋白去乙醯化酶活性之抑制為 134026-1 -35· 200916447 至少95%，或者，至少99%。會降低組織蛋白去乙醯化酶之Oral, sputum or non-existent -_ to eight-member carbon rings are, for example, four- to seven-members, or five members, or unsaturated carbon rings. Examples of saturated or unsaturated tri- to rabbits include stupid, cyclopropyl, cyclobutyl, cyclopentyl, cyclo and cycloheptyl. Soil v Saturated or unsaturated two- to eight-membered heterocyclic rings containing at least one hetero atom, selected from the group consisting of oxygen, nitrogen and sulfur. The saturated or unsaturated three- to eight-membered heterocyclic ring contains a formula - or two hetero atoms in which the remaining ring constitutes an atom which is a carbon atom. The saturated, unsaturated, two- to eight-membered heterocyclic ring is, for example, a saturated or unsaturated West-to-seven term, or a saturated or unsaturated five- or six-membered heterocyclic ring. Examples of the saturated or unsaturated three- to eight-membered heterocyclic group include a pyrenyl group, a pyridyl group, = triwax [°m. Sit-base" is more than salivation, hexahydro, hydrazine, hexahydro-p, hexahydro, hexahydro, hexahydro, phlegm, phloem, turmeric, turmeric, hexa Hydropyridyl, thiomorpholine-thiolmatinoline, tetrahydropyrrolyl and hexa-octadecyl. As used herein, "tissue protein deacetylase", " Deacetylase or tissue protein deacetylase protein " term, refers to a member of the group 134026-134-200916447 woven protein deacetylase deacetylase protein group (for example, refers to the sir2 group), It includes yeast Sir2, C. elegans Sir-2.1 and human SIRT1 and SIRT2 proteins. Other population members include four other yeast-like Sir2 genes, called "HST gene" (sir2 homolog), HST1, HST2, HST3 and HST4, and five other human homologs, hSIRT3, hSIRT4, hSIRT5, hSIRT6, and hSIRT7 (Brachmann et al. (1995) Genes Dev. 9: 2888 and Frye et al. (1999) BBRC 260: 273). An example of a tissue protein deacetylase is one that shares more similarity with SIRT1, meaning hSIRT1 and or Sir2, as compared to SIRT2, for example, at least a portion of the N-terminal sequence is present in SIRT1 It is a member of SIRT2 (such as that owned by SIRT3). Other tissue proteins Deacetylases are more similar to SIRT7. The tissue protein deacetylase is preferably a human tissue protein deacetylase. In some other specific embodiments, the tissue protein deacetylase enzyme is derived from a protozoan or fungal source. The terms "tissue protein deacetylase inhibitor" and "inhibitor of tissue protein deacetylase" mean a compound having a structure as defined herein, which is capable of directly or indirectly interacting with a tissue protein. The interaction of deuterated enzymes and inhibition of their enzyme activity. The term "inhibition of tissue protein deacetylase enzyme activity" means to reduce the functional or biological ability of tissue protein deacetylase. For example, tissue protein deacetylation The inhibition of the activity of the enzyme may be at least about 1%. In some embodiments of the invention, the inhibition of tissue protein deacetylase activity is at least about 50%, or at least about 75%, and Or, at least about 90%. In other embodiments, the inhibition of tissue protein deacetylase activity is 134026-1 -35 · 200916447 at least 95%, or at least 99%, which reduces tissue protein deacetylation. Enzyme

活性至未被抑制酵素之5〇%之抑制劑濃度，係被測定為iCM 值0 ’’抑制有效量” 一詞係意欲表示足以造成組織蛋白去乙醯 化酶活性在細胞中之抑制之劑量，該細胞可在多細胞生物 體中夕 '細胞生物體可為例如植物、冑_或動物，較佳為 哺乳動物’更佳為人類。真菌可感染植物或哺乳動物，較 佳為人類，且因此可位於植物或哺乳動物中及/或於其上。 右組織蛋白去乙S!化酶係在多細胞生物體中，則根據本發 明此方面之方法係包括對該生物體投予根據本發明之化合 物或、’且“勿。投藥可藉任何途徑，包括但不限於非經腸、 口腔、舌下 '經皮、局部、鼻内、氣管内、靜脈内或直腸 内。在某些具體實施例中，本發明化合物係以靜脈内方式 在西% &中投藥。在某些其他具體實施例中，投藥可 如藉由口腔途徑。 μ 平乂1主慣況是 踯蛋白去乙醯化酶抑制係為寻—，意即 組織蛋白去乙醯化酶抑制劑會在低於為產生另: 生物學作用所需要抑制劑濃度之濃度下，降低= 乙酿化酶之功能性f或生物能力。❹，組織蛋白去 化西I每抑制活性所需要之抑制劑濃度為至少2_倍低於，或者， 至少5-倍低於’或者’至少1{)倍低於，及或者 低於為產生不相關生物學作用所需要之濃度。厲 化合t療上乂效量，，一詞，當於本文中採用時，係為本發明 “又予病患時，會誘出所要治療效果之量。治療 134026-1 -36- 200916447 效果係依被冶療之疾病及所要之結果而定。因此，治療效 果可為疾病狀態之治療。再者，治療效果可為組織蛋白去 乙醯化酶活性之抑制。構成"治療上有效量，， 物量將依化合物、— 疾病狀態及其嚴重性、待治療病患之 齡等而改變。t α〜、上有效量可例行性地由一般熟諳此蓺 測定。 匕π有 係！：發：之目的而言，"病患，，一詞，當於本文中採用時， 固、Τ人眉及其他動物，特別是哺乳動物，及其他生物體。 ::’本發明之化合物、組合物及方法係可應用於人類療 於另一項具體實施例中，病患為哺乳 動物，而於另-項具體實施例中，病患為人類。 於本文中使用之，，進行 在動物中疾病狀態之療作業專術語係涵蓋 康且包括以下之至少一 /阳· /·、 防疾病狀態發生，特 1預 尚未被診斷具有嗲佐广 淮心"亥疾病狀態但 即部份或完全= ⑼抑制該疾病狀態，意 該疾病狀態之徵候之 、，d，Μ即造成 ^ 、 ’或改善該疾病之徵候.及Γ、 该疾病狀態之逆轉或退 丙之抓及㈣ 於本發明之另-…眘&為§亥疾病之消除或治癒。 靈長類動物，例如人魅* # 》為哺乳動物，例如 使用之..進行：二。::些具體實施例中，於本文中 中疾病狀態之治療，且包括二·:術5吾，係涵蓋在生物體 正如此項技藝中& 4 ⑻、（叫及（1V)之至少一個。 體重、一般健康狀態、_、Μ身對局部之傳輸、年齡、 人 < 杈藥時間、藥物交互 134026-1 -37- 200916447 作用及症狀之嚴重性之調整可為必 由-般熟諸此藝者確定。 廣且可以例行實驗術’The concentration of the inhibitor which is 5% of the activity to the uninhibited enzyme is determined to be the iCM value of 0 ''the effective amount of inhibition'. The term is intended to mean a dose sufficient to cause inhibition of tissue protein deacetylase activity in the cell. The cell may be in a multicellular organism. The cell organism may be, for example, a plant, a cockroach or an animal, preferably a mammal, preferably a human. The fungus may infect a plant or mammal, preferably a human, and Thus, it may be located in and/or on a plant or mammal. The right tissue protein to the B-Sase enzyme is in a multicellular organism, and the method according to this aspect of the invention comprises administering the organism according to the present invention. The compound of the invention or 'and' does not. Administration can be by any means including, but not limited to, parenteral, buccal, sublingual, transdermal, topical, intranasal, intratracheal, intravenous or rectal. In certain embodiments, the compounds of the invention are administered intravenously in Western % & In some other specific embodiments, administration can be by oral route. The main habit of μ 乂 1 is that the prion protein deacetylase inhibitor system is found, meaning that the tissue protein deacetylase inhibitor will be lower than the concentration of the inhibitor required to produce another biological effect. Lower, lower = functional f or biological capacity of the brewing enzyme. ❹, the concentration of the inhibitor required for each inhibitory activity of the tissue protein depletion of West I is at least 2 times lower than, or at least 5-fold lower than 'or 'at least 1 {) times lower than, and or lower than being produced The concentration required for irrelevant biological effects. The effect of sputum and phlegm on the treatment of phlegm and blood stasis, the term, when used in this article, is the amount of the therapeutic effect that will be induced when the patient is "in patients. Treatment" 134026-1 -36- 200916447 It depends on the disease to be treated and the desired result. Therefore, the therapeutic effect can be the treatment of the disease state. Furthermore, the therapeutic effect can be the inhibition of the activity of the tissue protein deacetylase. It constitutes a therapeutically effective amount, The amount of the substance will vary depending on the compound, the state of the disease and its severity, the age of the patient to be treated, etc. t α~, the upper effective amount can be routinely determined by the general familiarity of this 。. 匕π有系!:发For the purposes of this purpose, "patients,", as used herein, solid, scorpion and other animals, particularly mammals, and other organisms. :: 'Compounds, combinations of the invention The method and method can be applied to human therapy in another specific embodiment, the patient is a mammal, and in another embodiment, the patient is a human. As used herein, in an animal. Terminology of the treatment of disease states Kang also includes at least one of the following / Yang · / ·, prevention of disease occurs, special 1 has not yet been diagnosed with 嗲 广 淮 淮 & 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥 亥The sign of the disease state, d, 造成 造成 造成 、 ' ' 或 或 或 或 或 或 或 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善 改善The elimination or cure of the disease. The primate, such as the human charm*# is a mammal, for example, used.. Performed: 2.: In some specific embodiments, the treatment of the disease state herein, and includes two ·: surgery 5 I, is covered in the organism as in this technique & 4 (8), (called and (1V) at least one. Weight, general health, _, body to local transmission, age, person &lt Drug withdrawal time, drug interaction 134026-1 -37- 200916447 The adjustment of the severity of the effects and symptoms can be determined by the general practitioners. Wide and routine experimentation'

在某些具體實施例中，SiR 為例如選自包括腦癌、乳癌、社腸广質所媒"之疾病或病症 睪丸癌及审也& 、、、0知癌、肝癌、脾臟癌症、 瓦及甲狀腺癌之疾病或病症。 於另—項具體實施例中，嫩蛋 症為例如選自包括與老化 、"疾病或病 及經降低之骨浐蘇“ 1聯之病症、皮下脂肪之失去 低之月礦物質密度之疾病或病症。 於另—項具體實施例中 症為例如選自包括第I型與 於另項具體實施例中 症為例如肥胖。 ’贈蛋白質所媒介之疾病或病 第11型糖尿病之疾病或病症。 SIRT蛋自質所媒介之疾病或病 L體貫施财，SIRT蛋白f所媒介之疾病或病 症為例如選自包括發炎、心臟衰竭、㈣退化 '細 應生熱作用之疾病或病症。In some embodiments, the SiR is, for example, a disease or condition selected from the group consisting of brain cancer, breast cancer, and a large amount of media, and is also known as a cancer or a disease, a cancer, a liver cancer, a spleen cancer, A disease or condition of pelvic and thyroid cancer. In another embodiment, the egg ovum is, for example, a disease selected from the group consisting of a mineral density including a aging, a disease or a disease, and a reduced bone sputum, a loss of subcutaneous fat. Or a condition. In another embodiment, the disease is, for example, selected from the group consisting of Type I and in another embodiment, such as obesity. 'Protein or disease-borne disease or disease type 11 diabetes disease or condition The SIRT protein is a disease or a disease that is mediated by the disease. The disease or condition mediated by the SIRT protein f is, for example, a disease or condition selected from the group consisting of inflammation, heart failure, and (4) degeneration.

本發明化合物會形成鹽，其亦在本發明之範圍内。本文 指稱本發明之化合物，例如式(I)化合物，應明瞭係包括指 稱其鹽’除非另有指出。 當於本文中採用時，”鹽.1一詞係表示以無機及/或有機酸 與鹼所形成之酸性及/或鹼性鹽。此外，當式（I)化合物含有 嶮性邵份丞團譬如但不限於吡啶或咪唑，與酸性部份基團 譬如但不限於鲮酸兩者時，可形成兩性離子（”内鹽"），且係 被包含在如本文中使用之"鹽"一詞内。藥學上可接受（意即 無毒性（顯示最少或沒有不期望之毒物學作用）、生理學上 134026-1 -38- 200916447 可接受）之鹽為較佳，惟其他鹽亦可例如使 步驟中，其可於製備期 你早離她 經—合物與一數量之 會™者，或在水性二::應在: 者冷来乾煉而形成。The compounds of the invention form salts which are also within the scope of the invention. Reference herein to a compound of the invention, such as a compound of formula (I), is intended to include reference to the salt, unless otherwise indicated. As used herein, the term "salt. 1" means an acidic and/or basic salt formed with an inorganic and/or organic acid and a base. In addition, when the compound of formula (I) contains an anthraquinone For example, but not limited to, pyridine or imidazole, a zwitterion ("internal salt") may be formed with an acidic moiety such as, but not limited to, citric acid, and is included in "salt" as used herein ; within the word. Salts which are pharmaceutically acceptable (i.e., non-toxic (showing minimal or no undesirable toxicological effects), physiologically 134026-1 -38 to 200916447 acceptable) are preferred, but other salts may also be used, for example, in the step It can be formed in the preparation period when you leave the compound and a quantity of the TM, or in the water 2:: should be: cold and dry.

^發Γ合物’其含有驗性部份基團，譬如但不限於胺 或f米唾環，可與多種有機與無機酸類形成鹽。舉例 之酸加成鹽包括醋酸鹽(譬如與醋酸或三齒基醋酸(例如三 氣醋酸）所形成者）、己二酸鹽 '海藻酸鹽、抗壞企酸鹽、 天冬月女酸鹽、本甲酸鹽、苯磺酸鹽、酸性硫酸鹽、硼酸鹽' 丁酸鹽:檸檬酸鹽、樟腦酸鹽、樟腦續酸鹽、環戊院丙酸 鹽、二葡萄糖酸鹽、十二基硫酸鹽、乙烷磺酸鹽、反丁烯 二酸鹽、葡萄糖庚酸鹽、甘油磷酸鹽、半硫酸鹽、庚酸鹽、 己酸鹽、鹽酸鹽、氫演酸鹽、氫礙酸鹽、經基乙炫績酸鹽（例 如2-經基乙烧項酸鹽）、乳酸鹽、順丁婦二酸冑、甲烧績酸 鹽、萘磺酸鹽（例如2-萘磺酸鹽）、菸鹼酸鹽、硝酸鹽、草酸 鹽、果膠酯酸鹽、過硫酸鹽、苯基丙酸鹽（例如3_苯基丙酸 14 Sst鹽 '告味酸鹽、三甲基醋酸鹽、丙酸鹽、柳酸鹽、 琥珀酸鹽、硫酸鹽（譬如與硫酸所形成者）、磺酸鹽、酒石 酸鹽 '硫氰酸鹽、甲苯磺酸鹽（譬如曱笨基磺酸鹽）、十一 烷酸鹽等。 本發明化合物’其含有酸性部份基團，譬如但不限於羧 ’可與多種有機與無機驗形成鹽。舉例之驗性鹽包括敍 鹽’驗金屬鹽，譬如鈉、鋰及鉀鹽，鹼土金屬鹽’譬如鈣 134026-1 -39- 200916447 與鎂鹽，與有機鹼（例如有機胺類）之鹽，該鹼類譬如芊星 (benzathine)、二環己基胺類、海巴胺（與N，N-雙（脫氫松香基） 乙二胺所形成）、N_曱基葡萄糖胺、N-甲基-D-葡萄糖醯胺、 第一-丁基胺類，及與胺基酸之鹽，該胺基酸譬如精胺酸、 離胺酸等。鹼性含氮基團可以作用劑四級化，譬如低碳烷 基鹵化物（例如曱基、乙基、丙基及丁基氯化物、溴化物及 碘化物）、二烷基硫酸鹽（例如二曱基、二乙基、二丁基及 二戊基硫酸鹽）、長鏈函化物（例如癸基、月桂基、肉豆蔻 基及硬脂基之氯化物、溴化物及碘化物）、芳烷基_化物㈠列 如芊基與苯乙基溴化物）及其他。 於本文中使用之"藥學上可接受鹽” 一詞，係意指會保持 上文所確s忍化合物之所要生物學活性，且顯示最少或無不 期望毒物學作用之鹽。 本發明之另一方面係提供組合物，其包含如本文中所述 根據本發明之化合物，化合物之N_氧化物、水合物、溶劑 合物、藥學上可接受之鹽、複合物或前體藥物，或其外消 旋混合物、非對映異構物、對掌異構物或互變異構物。例 如，於本發明之一項具體實施例中，組合物係包含如本文 中所述根據本發明之化合物，化合物之N_氧化物、水合物、 溶劑合物、藥學上可接受之鹽、複合物或前體藥物，以至 少約30%對掌異構物或非對映異構物過量存在。在本發明 之某些想要具體實施例中，化合物、N_氧化物、水合物、 溶劑合物、藥學上可接受之鹽、複合物或前體藥物係以至 少約50%，至少約80%，或甚至為至少約9〇%對掌異構物或 134026-3 -40- 200916447 非對映異構物過量存在。在本發明之某些其他想要具體實 施例中，化合物、N_氧化物、水合物、溶劑合物、藥學上 可接文之鹽、複合物或前體藥物係以至少約95%，或者， 至少約98%，及或者，至少約99%對掌異構物或非對映異構 物過量存在。在本發明之其他具體實施例中，化合物、N_ 氧：物、水合物、溶劑合物、藥學上可接受之鹽、複合物 或前體藥物係以實質上外消旋混合物存在。 k 本發明之—些化合物可具有對掌中心及/或幾何異構中 心（E-與Z_異構物），且應明瞭的是，本發明係涵蓋所有此種 光學、對掌異構物、非對映異構物及幾何異構物。本發明 亦包含本文中所揭示化合物之所有互變異構形式。在本發 明化合物包含之情況巾，本發㈣涵蓋此種化: 物之=掌異構上及/或非對映異構上純異構物，此種化合物 之對掌異構上及/或非對映異構物上富含之混合物，及此種 化合物之外消旋舆呈比例混合物。例b，組合物可包含式 (I)化口物之對掌異構物或非對映異構物之混合物，以至少 約3一0%非對映異構或對掌異構物過量。在本發明之某些具 體貫施例中’化合物係以至少約鄉對掌異構物或非對映 旦構物過里’以至少約8〇%對掌異構物或非對映異構物過 旦或甚至疋以至少約對掌異構物或非對映異構物過 ^予在。在本發明之某些具體實施例巾，化合物係以至少 =95% ’或者，係以至少約98%對掌異構物或非對映異構物 ^量’及或者，係以至少約99%對掌異構物或非對映 物過量存在。 134026-1 -41 - 200916447 本發明之對堂由、、1 物理方法解析，⑴有組態。外消旋形式可藉由 ? σ非對映異構衍生物之分級結晶、分離 或結晶化作用，或藉 刀離 構物可…6 ! 官柱層析之分離。個別光學異 藉任何::：：·對旱性先質’中間物，或自外消旋物開始， 光心！ “獲得，包括但不限於習用方法，例如與 予活性酸之鹽形成，接著為結晶化作用。 本發明亦包括本發明化合物之前體藥物。 詞係意謂本發明化合物之衍生物，其需要轉變二； 體内’以釋出活性化合物。前體藥物係經常地（惟並非必須 地）為藥理學上不活性，直到被轉化成母體化合物為止。含 有經基之化合物可被轉化成例如魏鹽、s旨或碳酸醉前體 樂物，其可於活體内轉，以提供經基化合物。含有胺基 之化合物可例如被轉化成胺基甲酸酯、醯胺、烯胺、亞胺、 N-膦酸基、Ν·德基或N_硫基前體藥物，其可於活體内水解， 以提供胺基化合物。羧酸化合物可被轉化成酯（包括矽烷基 酯類與硫酯）、醯胺或醯肼前體藥物，其係於活體内水解， 以提供羧酸化合物。關於具有不同於上文所列示之官能基 之藥物，其前體藥物係為熟練技師所習知。此外，前體藥 物可藉由化學或生物化學方法，在活體外環境中被轉化成 本發明化合物。例如，前體藥物當被放置在經皮貼藥儲器 中時，可以適當酵素或化學試劑，慢慢地被轉化成本發明 化合物。 本發明化合物之前體藥物包括其中羥基、胺基、敌基或 類似基團經修改之化合物。前體藥物之實例包括但不限於 134026-1 -42- 200916447 =t :物中之羥基或胺基官能基之酯類（例如醋酸酯、甲 u曰及本甲酸g|衍生物）、胺基甲酸醋類（例如顧_二甲胺美 厌基）’酸胺類（例如三氟乙醯胺基、乙醯胺基等）等。土 發月化口物可以本身或以前體藥物投予，例如呈活體 内可水解㈣活體内可水賴胺之形式。含錢基或經基 /本电月化合物之活體内彳水解醋，係'為例如藥學上可接 =之知’其係在人類或動物身體中水解，以產生母體酸或 醇。關於縣之適當藥學上可接受_，包括Ch_烧氧基 甲基酿類(例”氧基甲基)、C“-烷醯氧基甲基_類(例如 例如三甲基乙醒基氧基甲基）m類、C3 8_環烧氧基幾 基氧基C! γ烷基酯類（例如環己羰基氧基乙基广^-二氡 伍圜烯-2-酮基甲基酯類（例如5_曱基_u_二氧伍圜烯_2_酮基 甲基）’及Cl -6 -院氧幾基氧基乙基酯類（例如1-甲氧羰基氧基 乙基）’且可在本發明化合物中之任何羧基上形成。 含有說基之本發明化合物之活體内可水解酯，包括無機 醋類’譬如磷酸酯類與仏醯氧基烷基醚類，及相關化合物， 其係由於酯分解之活體内水解作用而得母體羥基。α_醯氧 基烧基醚類之實例包括乙醯氧基甲氧基與2,2_二甲基丙醯 氧基-甲氧基。羥基之活體内可水解酯形成基團之選擇係包 括烷醯基、笨甲醯基、苯乙醯基及經取代之苯甲醯基與笨 乙醯基、烷氧羰基（而得烷基碳酸酯類）、二烷基胺曱醯基 與Ν-(Ν，Ν-二烷胺基乙基）-Ν-烷基胺甲醯基（而得胺基曱酸酯 類）、Ν，Ν-二烷胺基乙醯基及羧基乙醯基。於苯甲醯基上之 取代基實例包括嗎福4基與略ρ井基，從環氮原子經由亞甲 134026-1 •43· 200916447 基連結至苯甲醯基環之3_或4_位置。含有羧基之本發明化合 物之活體内可水解醯胺之適當意義，係為例如N_c卜6_烷基 或RN-二-Ci-6^基醯胺，譬如N-甲基、N-乙基、N-丙基、Ν,Ν-二甲基、Ν-乙基-Ν-曱基或ν，Ν-二乙基醯胺。 在投予病患時，前體藥物係藉由代謝或化學過程進行化 學轉化，而產生本發明化合物或其鹽及/或溶劑合物。本發 明化合物之溶劑合物包括例如水合物。 典型上，在前體藥物中，極性官能基（例如羧酸、胺基、 羥基等）係被在生理學條件下為不安定之保護部份基團遮 蔽。••保護部份基團”係指一種保護基形式，當用以遮蔽化 合物分子内之官能基時，其係使藥物轉化成前體藥物。典 型上，保護部份基團係經由鍵結連接至化合物，該鍵結係 於活體内藉由酵素或非酵素方式分裂。 ’’保護"、”經保護"及，’保護作用”術語係意欲指稱一種製 程，其中在化合物中之官能基係選擇性地被非反應性官能 基遮蔽，以允許選擇性反應在該化合物上之別處發生。此 種非反應性官能基於此處係稱為，，保護基”。例如，”氮保護 基’’ 一詞係意指能夠選擇性地遮蔽氮（Ν)基團之反應性之基 團。”適當保護基"一詞係意指可使用於製備本發明化合物 之保護基。此種基團係通常能夠使用不會干擾主題化合物 之其他部份之溫和反應條件而選擇性地被引進及移除。適 用於本發明之製程與方法中之保護基係為習知，譬如但不 限於Bn-(或-CH2 Ph)、-CHPh2、烯丙氧基羰基（或Ch2 =CH Ch2 _ O-C(O)-)、BOC-、-Cbz (或 Z_)、_F_m〇c、（(ο)，、N 鄰苯二 134026-1 200916447 曱醯亞胺、l-Adoc-、TBDMS-、TBDPS-、TMS-、TIPS-、IPDMS-、 -SiR3、SEM-、t-Bu-、Tr-、THP-及烯丙基-。此等保護基可在 合宜階段下，使用得知自此項技藝之方法而被移除。此種 保護基之化學性質，關於此項技藝中已知之其引進及其移 除之方法，可參閱例如T. Greene與P. Wuls，亦襪合竑之保護J (第3版），John Wiley & Sons，NY (1999)，以其全文併於本文供參 考。’’去除保護”、”經去除保護”及”去除保護作用”術語係 意欲指稱自化合物移除保護基之製程。 在整個本專利說明書中，一或多個化學取代基之具體實 施例係經確認。亦涵蓋者係為特定具體實施例之組合。例 如，本發明係描述L在化合物中之特定具體實施例，且係 描述基團Y之特定具體實施例。因此，以下述作為實例， 亦意欲被涵蓋在本發明之範圍内者為其中L之特定實例係 如上述且其中基團Y之特定實例係如上述之化合物。 前文僅只是摘述本發明之一個方面及具體實施例，而在 本性上並不意欲成為限制。此方面及具體實施例係更完整 地描述於下文。 化合物 於一方面，本發明係提供式（I)化合物： Y——L——Z—-D (I) 及其N-氧化物、水合物、溶劑合物、藥學上可接受之鹽、 前體藥物及複合物，以及其外消旋與呈比例混合物、非對 映異構物及對掌異構物，其中 134026-1 -45- X 200916447 C’ S /M、〇b D係選自包括 义，x N c R X ， f ψ s FV ZN，N、c/M、Rb ^ R3 x Ψ ψ 一 Rh 〆丫 Ν\γΙ\ή' II Q Rb R«=The hair styling composition, which contains an exemplary moiety, such as, but not limited to, an amine or a f-salt ring, forms a salt with a variety of organic and inorganic acids. Exemplary acid addition salts include acetates (such as those formed with acetic acid or tridentate acetic acid (eg, tri-acetic acid)), adipate alginate, anti-hypoformate, aspartic acid , formate, besylate, acid sulfate, borate 'butyrate: citrate, camphorate, camphoroate, cyclopentate propionate, digluconate, dodeca Sulfate, ethanesulfonate, fumarate, glucose heptanoate, glycerol phosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrogenate, hydrogen hydrochloride , by base ethyl leuco acid salt (such as 2-aminoethyl phthalate), lactate, cis-butanyl citrate, formazan acid salt, naphthalene sulfonate (such as 2-naphthalene sulfonate) , nicotinic acid salt, nitrate, oxalate, pectin ester, persulfate, phenylpropionate (for example, 3 phenylpropionic acid 14 Sst salt 'sodium salt, trimethyl acetate , propionate, salicylate, succinate, sulfate (such as those formed with sulfuric acid), sulfonate, tartrate 'thiocyanate, tosylate (such as sulfonate) Salts, undecanoic acid salts, etc. The compounds of the present invention, which contain acidic moiety, such as, but not limited to, carboxylic acid, can form salts with various organic and inorganic salts. Exemplary test salts include the salt salt Such as sodium, lithium and potassium salts, alkaline earth metal salts such as calcium 134026-1 -39- 200916447 and magnesium salts, and organic bases (such as organic amines), such as such as comet (benzathine), two rings Hexylamines, seabamine (formed with N,N-bis(dehydrorosinyl)ethylenediamine), N_mercaptoglucosamine, N-methyl-D-glucoside, first-butyl Amines, and salts with amino acids, such as arginine, lysine, etc. Basic nitrogen-containing groups can be tetracyclized, such as lower alkyl halides (eg, sulfhydryl groups, Ethyl, propyl and butyl chloride, bromide and iodide), dialkyl sulfates (eg di-decyl, diethyl, dibutyl and dipentyl sulfate), long-chain complexes (eg Sulfhydryl, lauryl, myristyl and stearyl chlorides, bromides and iodides), aralkyl groups (a) Ethyl bromides), and others. The term "pharmaceutically acceptable salt," as used herein, is intended to mean a salt which will retain the desired biological activity of the compound as described above and which exhibits minimal or no undesirable toxicological effects. In another aspect is provided a composition comprising a compound according to the invention, an N-oxide, a hydrate, a solvate, a pharmaceutically acceptable salt, a complex or a prodrug of a compound, as herein described, or a racemic mixture, a diastereomer, a palmomer or a tautomer. For example, in one embodiment of the invention, the composition comprises a according to the invention as described herein. The compound, the N-oxide, hydrate, solvate, pharmaceutically acceptable salt, complex or prodrug of the compound, is present in excess of at least about 30% by weight of the palmo isomer or diastereomer. In certain desirable embodiments of the invention, the compound, N-oxide, hydrate, solvate, pharmaceutically acceptable salt, complex or prodrug is at least about 50%, at least about 80 %, or even at least about 9〇% Isomers or 134026-3 -40- 200916447 diastereoisomers are present in excess. In certain other preferred embodiments of the invention, compounds, N-oxides, hydrates, solvates, pharmaceutically An acceptable salt, complex or prodrug is present in an excess of at least about 95%, or at least about 98%, and or at least about 99% of the palmo isomer or diastereomer. In other specific embodiments of the invention, the compound, N-oxygen, hydrate, solvate, pharmaceutically acceptable salt, complex or prodrug is present as a substantially racemic mixture. Some of the compounds may have a palm center and/or geometric isomeric center (E- and Z-isomers), and it should be understood that the present invention encompasses all such optical, palmomere, diastereomeric, diastereomeric Constructs and geometric isomers. The invention also encompasses all tautomeric forms of the compounds disclosed herein. In the case of the compounds of the invention, the present invention (4) covers such characterization: Or diastereomeric upper pure isomers And/or a mixture enriched in diastereomers, and a mixture of racemic oximes in such a compound. Example b, the composition may comprise a palmomer isomer or a non-chemical formula of formula (I) a mixture of enantiomers in an amount of at least about 3% by weight diastereomeric or para-isomer. In some specific embodiments of the invention, the compound is at least about The diastereomeric or diastereomeric construct is at least about 8 % by weight of the palmomer or diastereomer or even at least about palmomere or diastereomer In some embodiments of the invention, the compound is at least = 95% 'or, at least about 98%, of the palmier isomer or diastereomer' and/or It is present in an excess of at least about 99% of the palmomer or diastereomer. 134026-1 -41 - 200916447 The invention is analyzed by the physical method, (1) has a configuration. The racemic form can be separated by fractional crystallization, separation or crystallization of ? σ diastereomeric derivatives, or by means of a knife-free separation. Individual opticals borrow any ::::· for the dry precursors 'intermediate, or from the racemate, light heart! "Acquired, including but not limited to conventional methods, such as formation with a salt of a pre-active acid followed by crystallization. The invention also includes prodrugs of the compounds of the invention. The word system means a derivative of a compound of the invention which requires a transformation 2; in vivo' to release the active compound. The prodrug is often (but not necessarily) pharmacologically inactive until it is converted to the parent compound. The compound containing the trans group can be converted to, for example, the salt of Wei , s- or carbonated precursor music, which can be converted in vivo to provide a trans-based compound. The amine-containing compound can be converted, for example, to a carbamate, a guanamine, an enamine, an imine, N a phosphonic acid group, a fluorenyl group or an N-thio group prodrug which can be hydrolyzed in vivo to provide an amine compound. The carboxylic acid compound can be converted into an ester (including a decyl ester and a thioester), A proguanamine or hydrazine prodrug which is hydrolyzed in vivo to provide a carboxylic acid compound. For drugs having functional groups different from those listed above, prodrugs are known to the skilled artisan. Precursor The drug can be converted to the compound of the invention in an in vitro environment by chemical or biochemical methods. For example, when the prodrug is placed in a transdermal patch, it can be slowly activated by appropriate enzymes or chemical reagents. Conversion to the compounds of the invention. Prodrugs of the compounds of the invention include compounds wherein the hydroxy, amine, enradyl or the like are modified. Examples of prodrugs include, but are not limited to, 134026-1 -42 - 200916447 = t: Esters of hydroxy or amino functional groups (such as acetate, methyl sulfonate and g | derivatives of g-formic acid), amino carboxylic acid vines (such as dimethyl amide), acid amines (such as three Fluoroacetamido, etidamine, etc.) The sulphate can be administered by itself or a prodrug, for example, in the form of in vivo hydrolyzable (iv) water-soluble lysine in vivo. Hydrolysis of vinegar in vivo or in the presence of a compound of the present invention, which is, for example, pharmaceutically acceptable; it is hydrolyzed in the human or animal body to produce a parent acid or alcohol. _, including Ch_Alkoxy Stuffed (for example "oxymethyl"), C"-alkyloxymethyl" (for example, trimethyl ethaneoxymethyl) m, C3 8 -cycloalkoxyoxy C! γ-alkyl esters (eg, cyclohexylcarbonyloxyethyl)-dioxazol-2-one methyl esters (eg, 5 fluorenyl _u_dioxosyl-2-ene) Ketomethylmethyl)' and Cl-6-oxooxyoxyethyl esters (e.g., 1-methoxycarbonyloxyethyl)' and can be formed on any of the carboxyl groups in the compounds of the present invention. In vivo hydrolysable esters of the compounds of the invention, including inorganic vinegars such as phosphates and decyloxyalkyl ethers, and related compounds which are derived from the in vivo hydrolysis of the ester to give the parent hydroxyl group. Examples of the 醯 methoxyalkyl ether include ethoxycarbonyl methoxy and 2,2-dimethylpropoxy-methoxy. The selection of the hydrolyzable ester-forming group of the hydroxyl group in vivo includes an alkane group, a benzamidine group, a phenethyl group and a substituted benzamidine group with a stupidinyl group and an alkoxycarbonyl group. Ester), dialkylamine fluorenyl and hydrazine-(hydrazine, hydrazine-dialkylaminoethyl)-hydrazine-alkylamine carbaryl (and amino phthalate), hydrazine, hydrazine- Dialkylaminoethyl carbonyl and carboxyethyl fluorenyl. Examples of the substituent on the benzamidine group include a ruthenium 4 group and a slightly ruthenium group, which are bonded from the ring nitrogen atom via the methylene 134026-1 •43·200916447 group to the 3_ or 4_ position of the benzamidine ring. . Suitable meanings of in vivo hydrolysable guanamines of the compounds of the invention containing a carboxy group are, for example, N-cb 6-alkyl or RN-di-Ci-6 decylamine, such as N-methyl, N-ethyl, N-propyl, hydrazine, hydrazine-dimethyl, hydrazine-ethyl-fluorenyl-fluorenyl or ν, fluorene-diethyl decylamine. When administered to a patient, the prodrug is chemically converted by metabolic or chemical processes to produce a compound of the invention or a salt and/or solvate thereof. Solvates of the compounds of the invention include, for example, hydrates. Typically, in prodrugs, polar functional groups (e.g., carboxylic acid, amine groups, hydroxyl groups, etc.) are masked by a protecting moiety that is unstable under physiological conditions. • • Protecting a moiety “refers to a form of protecting group that, when used to mask a functional group within a molecule of a compound, converts the drug into a prodrug. Typically, the protecting moiety is linked via a linkage. To a compound, the bond is cleavable in vivo by an enzyme or a non-enzymatic method. The terms 'protection', 'protected', and 'protective' are intended to refer to a process in which a functional group is present in a compound. It is selectively masked by non-reactive functional groups to allow selective reactions to occur elsewhere on the compound. Such non-reactive functionalities are based on what is referred to herein, the protecting group. For example, the term "nitrogen protecting group" is used to mean a group capable of selectively masking the reactivity of a nitrogen (Ν) group. The term "appropriate protecting group" means that it can be used to prepare a compound of the invention. Protection base. Such groups are typically capable of being selectively introduced and removed using mild reaction conditions that do not interfere with other portions of the subject compound. Protecting groups suitable for use in the processes and methods of the present invention are conventional, such as, but not limited to, Bn-(or -CH2 Ph), -CHPh2, allyloxycarbonyl (or Ch2 = CH Ch2 _ OC(O)- ), BOC-, -Cbz (or Z_), _F_m〇c, ((ο), N phthalate 134026-1 200916447 曱醯 imine, l-Adoc-, TBDMS-, TBDPS-, TMS-, TIPS -, IPDMS-, -SiR3, SEM-, t-Bu-, Tr-, THP-, and allyl-. These protecting groups can be removed at a convenient stage using methods known from the art. The chemical nature of such a protecting group, as described in the art for its introduction and removal, can be found, for example, in T. Greene and P. Wuls, also in the protection of socks (3rd edition), John. Wiley & Sons, NY (1999), the entire disclosure of which is incorporated herein by reference in its entirety in its entirety in the the the the the the the the the the the the the the the the the the Specific examples of one or more chemical substituents are identified throughout this patent specification. Also included are specific combinations of specific embodiments. For example, the present invention is described Specific embodiments of L in the compounds, and are specific embodiments of the group Y. Thus, the following examples are intended to be included within the scope of the invention, wherein the specific examples of L are as described above. The specific examples of the group Y are as described above. The foregoing is merely an overview of one aspect of the invention and specific embodiments thereof, and is not intended to be limiting in nature. This aspect and specific embodiments are more fully described in Hereinafter, the compound provides, in one aspect, a compound of formula (I): Y-L-Z--D (I) and its N-oxides, hydrates, solvates, pharmaceutically acceptable salts , prodrugs and complexes, as well as their racemic and proportional mixtures, diastereomers and palmomeris, 134026-1 -45- X 200916447 C' S /M, 〇b D Select from the meaning, x N c RX , f ψ s FV ZN, N, c / M, Rb ^ R3 x Ψ ψ a Rh 〆丫Ν \ γ Ι \ ή ' II Q Rb R « =

X oX o

XX

YY

R\y 〜义，R、irRa /R\y ~ meaning, R, irRa /

Lij^J Rc X 〇 V ,iLij^J Rc X 〇 V ,i

XX

Ra RbRa Rb

Ra X Rb 〔I RcRa X Rb [I Rc

I RC'W八wrRa 〜yI RC'W eight wrRa ~ y

7s7s

XX

ψ Rc -Raψ Rc -Ra

X 、Rb V|^rR； Rc'w/y»：n vw/)-R、％c 其中 v y X為〇或s ;Μ為氮、氧或硫 W為氮；W為氮、氧或硫；纟中當W為氣或硫時，㈣不存在，且 Μ為氮； 各Ra係獨立選自包括-Η、_Cl -C：6燒基、保護基、_Ci _c6燒基_ 芳基、芳基、-q -C6蝝基-雜芳基、雜芳基、-c! -C6烷基_ 環烷基、·環烷基、-CrC6烷基-雜環基、雜環基、_c(0)_a Ci-C6烷基、_c(〇)-〇-CrC6烷基-雜環基、_c⑼_〇_Ci_c6烧基-烯基、-C(0)-〇-C丨-C6烷基-芳基、-CO-CF3及丨人， 其每一個係視情況經取代，其中該保護基較佳係選自包 其中當M為氣或硫時，妒係不存在，且 134026-1 .46 - 200916447 括 Bn-(或-C^Ph)、-CHPh2、烯丙氧基羰基(^ch2=CH-CH2-O-C(O)-)、BOC-、-Cbz (或 Z-)、-F-moc、_C(0)-CF3、N-鄰苯 二曱酸亞胺、1-Adoc-、TBDMS-、TBDPS-、TMS-、TIPS-、 IPDMS-、-SiR3、SEM_、t-Bu-、Tr-、THP-及烯丙基；且 當M為氮時’ Ra係另外選自_c(〇)_H ;X, Rb V|^rR; Rc'w/y»: n vw/)-R, %c where vy X is 〇 or s; Μ is nitrogen, oxygen or sulfur W is nitrogen; W is nitrogen, oxygen or sulfur When W is gas or sulfur, (4) is absent, and niobium is nitrogen; each Ra is independently selected from the group consisting of -Η, _Cl -C:6 alkyl, protecting group, _Ci _c6 alkyl _ aryl, aromatic , -q -C6 decyl-heteroaryl, heteroaryl, -c! -C6 alkyl-cycloalkyl, cycloalkyl, -CrC6 alkyl-heterocyclyl, heterocyclyl, _c(0 )_a Ci-C6 alkyl, _c(〇)-〇-CrC6 alkyl-heterocyclyl, _c(9)_〇_Ci_c6 alkyl-alkenyl, -C(0)-〇-C丨-C6 alkyl-aryl Each of the groups, -CO-CF3 and oxime, is optionally substituted, wherein the protecting group is preferably selected from the group consisting of: when M is gas or sulfur, the lanthanide is absent, and 134026-1.46 - 200916447 includes Bn-(or -C^Ph), -CHPh2, allyloxycarbonyl (^ch2=CH-CH2-OC(O)-), BOC-, -Cbz (or Z-), -F-moc , _C(0)-CF3, N-phthalic acid imide, 1-Adoc-, TBDMS-, TBDPS-, TMS-, TIPS-, IPDMS-, -SiR3, SEM_, t-Bu-, Tr- , THP- and allyl; and when M is nitrogen, the 'Ra line is additionally selected from _c(〇)_H;

Rb與Rc ’當存在時’係獨立選自包括_H、_〇H、_CN、_〇_ 烷基、-〇-烷基-芳基、-〇-烷基-雜芳基、_Ci _c6烷基、_c(〇)_ 烷基、-NH2、-NH-烷基、-C(0)_H、保護基、_Ci_C6烷基_ 方基、芳基、_Cl_C6燒基_雜芳基、-雜芳基、（1(6烧基_ 環烷基、環烷基、-Cl 烷基-雜環基、雜環基、 烷基-芳基、-C(0>C〇_C3烷基.芳基，_c〇_c3烷基環 烷基、-c(o)-cvC3烷基-雜環基、_c(〇)_〇_c「c6烷基、 -聊叫％院基.雜環基、_C(QKK^院基，基、 •C(0)_0-Cl'C6燒基-芳基、-CO-CF3及 ，其每 個係視情況經取代； 八 其中當Μ為氮時，”Rb和彼等所連接之氮 況形成3至9-員雜環基、 趣視障 雜芳美，装在、 雜絃基-方基或雜環基_ ’、土 _ 、母個係視情況經取代.且 其中當以為-⑽基、-c雜-芳基、物… 基、-c】-Q烧基-雜環基或μ烧基 ^ 烷基時，則…與!^係視情 汉為义<：6 員雜環基、雜環基二和兔原子連接’以形成5至瓜 基或雜環基-環烷Α雜％基-雜環 烷基其每-個係視情況經取代； 134026-1 -47- 200916447Rb and Rc 'when present, are independently selected from the group consisting of _H, _〇H, _CN, _〇_alkyl, -〇-alkyl-aryl, -〇-alkyl-heteroaryl, _Ci_c6 Base, _c(〇)_alkyl, -NH2, -NH-alkyl, -C(0)_H, protecting group, _Ci_C6 alkyl group, aryl group, _Cl_C6 alkyl group, heteroaryl group, heteroaryl Base, (1 (6 alkyl)cycloalkyl, cycloalkyl, -Cl alkyl-heterocyclyl, heterocyclyl, alkyl-aryl, -C(0>C〇_C3 alkyl.aryl , _c〇_c3 alkylcycloalkyl, -c(o)-cvC3 alkyl-heterocyclyl, _c(〇)_〇_c"c6 alkyl, - Talk for % 院. Heterocyclyl, _C (QKK^院基,基,•C(0)_0-Cl'C6 alkyl-aryl, -CO-CF3 and each of them is substituted as appropriate; VIII where Μ is nitrogen, “Rb and The nitrogen conditions to which they are attached form a 3 to 9-membered heterocyclic group, which is substituted with a heterocyclic group, a heterocyclic group or a heterocyclic group _ ', a soil _, and a parent. And when it is thought that -(10) group, -c hetero-aryl group, substance group, -c]-Q alkyl group-heterocyclic group or μ alkyl group, the alkyl group is ... <: 6 member heterocyclic group, heterocyclic group II and rabbit atomic linkage ' To 5 to melon or heterocyclyl group - a cycloalkyl group Α heteroaryl% - heterocycloalkyl each of which is - optionally substituted departments; 134026-1-47- 200 916 447

Rf係選自包括Η、Cl_c6烷基；Rf is selected from the group consisting of hydrazine and Cl_c6 alkyl;

Rh係選自台杯Rh is selected from the cup

:其0H、-CN、-Cl職、QW-O-Co-Q 二：：土、-C。☆烷基-〇-Q-c6烷基-雜芳基，其中各該烷 土、方基及雜芳基係視情況經取代；或Rh與π和彼等所 連接之原子—起視情況形成3至9-員雜環基、雜芳基、雜 環基雜方基雜 HA為視情況經取代㈣…、固係視情況經取代； 環㈣=代之雜環基' 雜芳基、雜環基-芳基或雜 Z =:共價鍵'物基I侧娜院基 3 -C〇_C3烧基必必烯基-cvc3烷基·、_c c 烷基-c2-c8炔美 r r h i 〇-C3 C 其3基-、（0七㈤基-芳基-c〇-c6烧基-、 C〇 C6：^ 基 π 基 _c c r r P # 烧某、r r 6雜说基c〇-Q燒基-環炫基-C〇-C6 ::C6燒基-環燒基_c2_c6雜烧基_〜6雜環基· 方巷l〇 -C6燒基-、_已r I®甘p 。 仏必雜％基-方基-CVC6雜烷基·、 # ^ A C c〇4 Q # % ^ "C〇"C6 ^ ^ ' 'C〇'C6 ^ ^ -Q-C6- c C ' -〇-c6^^^^-c0_c6r^.. -C〇-C6-烧基-雜芳基_c Γ Γ oC6雜烷基_、-c4-c6雜環基_雜芳基 0 6、元土…_C4_C6雜環基-雜芳基-C0-C6雜烷基… 炫基-芳基-C3_c6炔基…c〇_c6烧基-雜芳基〜6快基0_、6 -Co-Q烷基-環烷基弋夂炔基…Q_C6炫基 ^•-c〇-c6r^-^_C2.c^^.C2_C6^_；；c-- 基-方基-C2-C6稀基_、_c〇_c6烧基-雜芳基々、美6'元 -Co-Q烷基-環院基弋夂烯基…㈣烷基^芙= 稀基-、-0rc6烷基-芳基_芳基_Q C6烷基、（。二院2美6 134026-1 •48· 200916447 芳基-雜芳基-QrC6烷基-、-C0-C6烷基-雜芳基-芳基_C()_C6_ 烧基·、-c〇-c6炫基-雜芳基-雜芳基-(：0-(：6_烧基·、_C()_C3 烧基-雜芳基_〇> -CI3院基-C2 -C8烯基-C〇 -C3 -燒基-、-C0 -C3烧 基-^基-C〇 -C；3 炫基-C2 -Cs 烯基-C〇 -C3 -燒基-、_c〇 -C3 燒基― 雜環基-CQ -C3炫基-C2 -C8稀基-C〇 -C3 -烧基-、_〇) -C3燒基·環 烧基-C0 -C3炫《基-C；2 -Cs稀基-C〇 -C3 -烧基-' _c〇 -C3烧基-雜芳 基-C〇 -C3燒基-C2 -C8炔基-C〇 -C3 -烧基-、-Cq -C3烧基-芳基 -C0-C3燒基_c2-C8炔基-CQ-C3-烧基-、-C〇-C3炫基-雜環基 -C0-C3燒基-C^-Cg炔基-Cq-C3-烧基-及-CQ-C3炫基-環烧基 -C0 -C3院基_c2 -Cg炔基-C〇 -C3 -烧基-’其中各烧基、烯基、 炔基、雜烷基、芳基、雜芳基、雜環基及環烷基部份基 團係視情況經取代；且 當W為N時，Z係進一步選自包括-Q-C8烷基-c(0)-、-(^-(^烷 基-S(0)2-、-芳基-C〇-Cg烧基-S(0)2-、-雜芳基-C〇-C8烧基 -S(0)2 _、_環烷基_C〇 -C8烷基-S(0)2 -、_雜環烷基-C0 -C8烷基 _s(0)2_、-CVCg 烷基-CH=、-CVCs 烷基-C(CH3)=、_〇)-<：6烷基 -CH=CH-C(0)、-C〇-C4 烷基-C(O)-、-CVCg 烷基-(NH2)C=、-c0-c3 烷基-c! -c8雜烷基-c〇 -c3烷基-c(o)-、-c〇 -c3烷基-c2 -c8烯基 -C〇 -C3 烧基-C(O)-、-C〇 -C3 烧基-C〗-Cg 快基-C〇 -C3 烧基-C(O)-、 -C〇-C6烧基-芳基-C〇-Cg烧基-C(O)-、-C〇-C6烧基-芳基-C2-C6雜 烷基-c(o)-、-c〇-c6 烷基-環烷基-CG-C6 烷基-c(o)-、-CQ-C6 烷 基-環烷基-c2-c6雜烷基-c(o)-、-c4 -c6雜環基-芳基-CQ-c6烷 基-C(O)-、-C4 -C6 雜環基 _芳基-C〇 <6 雜烧基-C(〇)-、-C〇 -C6 烧 基-C4 -C6 -雜環基-C〇 -C6烧基-C(O)-、-C〇 -C6烧基-c4 -C6 -雜環基 ^4026-1 -49- 200916447 -C〇 -C6 雜院基-c(o)-、-C〇 -c6 -烧基-雜芳基-c0 -C6 烧基-c(o)-、 -c0 -C：6 -烧基-雜芳基-c0 -c6雜烷基-C(O)-、-c4 -C6雜環基-雜芳 基-C0-C6烧基-c(0)-、-c4-c6雜環基-雜芳基_c〇_c6雜烷基 -C(O)-、-c0 -C6 烧基-芳基 _c3 _c6 炔基 _c(〇)-、-C〇 _c6 烷基雜芳 基-c2-c6 炔基-c(0)-、<vc6 烷基-環烷基 _c3_c6 炔基 _c(〇)_、 -C〇 -C6烧基-雜環基-c3 -c6炔基-c(0)-、-CG -c6烧基-芳基-c2 -c6 炔基-C2 -C6 烯基-c(0)-、-Q _c6 烷基-芳基 _c2 _c6 烯基 _c(〇)_、 -c0 -Q烧基-雜芳基-C2 -c6烯基-c(0)-、-c0 -C6烷基-環烷基 -c2 -C6 烯基-C(0)_、-c0 -c6 烷基-雜環基 _gvc6 烯基 _c(〇)_、 -c0 -Q烷基-芳基-芳基_Cq 烷基_c(0)…_c〇 _c6烷基_芳基雜 芳基-c0 -Q烧基-c(0)-、_C〇 _c6烷基-雜芳基_芳基_c〇 _c6 _院基 -C(o)-及-C〇 -C：6烧基-雜芳基_雜芳基_c〇 _c6 _烧基_c(〇)_ ;或 z-w係選自包括-Cl-c8烷基_(NH2)C=N_、_CH烷基_C=N_及 -C! _8烧基-C(CH3 )=N-，當RC係不存在時； L係選自包括共價鍵、-q-Q烷基-、-c0-c6烷基-(CRkCR3)"-c0-c6炫基-' -Co-Q燒基-(CsQh-Co-Q烧基-、-C〇-C6烷 基-芳基-C0-C6烧基-、-C〇-C6烧基-雜芳基_c〇-C6烧基-、 -C0-C3烧基-雜環基-CQ-C3烧基-、-CQ-C3烧基-環烧基-C〇-C3 炫基-、-C〇-C6 烧基-芳基-(CR^CR'.rCo-Q 烷基-、-C〇-C6 烧基-^基-(C = Ch 2 -c0 -C6烧基·、-C0 -C6烧基-雜芳基 -(CRO^h-rCo-q烷基-、-C0-C6 烷基-雜芳基-(CEQn-c0-c6烧基-、-CQ-C6烷基-N(R3)-C(〇KVC3烷基-、-c〇-c6烷 基-N(R3)-C(S)-C〇-C3 院基-、-C0-C6 烷基-N(R3)-C(0)-烯基 -c〇-c3 烷基-、-C〇-C6 烷基-N(R3)-C(s)-烯基-C〇-C3 烷基-、 134026-1 -50- 200916447 -c0-c6 烷基-n(r3)-c(o)-炔基-C〇-C3 烷基-、-c〇-c6 烷基 -N(R3 )-C(S)-炔基-C〇 -C3 烷基-、-C〇 -C6 烷基-N(R3 )-(：(0)-(：: -C3 烷基-n(r3)-c(o)-、-c〇-c6 烷基nkrskxskvc^ 烷基 -N(R3 )-C(0)-、-C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-N(R3 )-C(0)-(^-(^烷基…-匸^仏烷基召妒^:⑸-心-^烷基-风圮)-!^。)-C〇 -C3 烷基-、-CG -C6 烷基-N(R3 )-0:(0)-(^ -C3 烷基-N(R3 )-C(S)-C〇 -C3 烷基-、-C〇 -C6 烷基-N(R3 -C3 烷基-N(R3 )-C(S)- C0-C3 烷基-、-CG-C6 烷基-CCOH^Rq-Co-C^ 烷基-、-(：〇-(：6烷 基-C(S)-N(R3 )-C〇 -C3 烷基-、-C〇 -C6 烷基-C(0)-N(R3 )-C2 -C4 烷基 -0-CQ -C3 烷基-、-C〇 -C6 烷基-C(S)-N(R3 )-C2 -C4 烷基-O-Q -C3 烷 基-、-CQ-C6 烷基-C(0)-N(R3)-C2-C4 烷基-N(R3)-C〇-C3 烷基-、 -c〇-c6 烷基-C(S)-N(R3)-C2-C4 烷基-N(R3)-C〇-C3 烷基-、-c0-c6 烷基-C(0)-CQ-C3 烷基-、-CQ-C6 烷基-C(NOH)-C〇-C3 烷基-、 -C0 -C6 烷基-C(O)-烯基-CG -C3 烷基-、-CG -C6 烷基-C(NOH)-烯基 -(^-(^烷基…-仏-^烷基名㈦^-:^”^^-^烷基-、-!^·^ 烷基-N(R3 )-S(0)2 -CG -C3 烷基-、-C〇 -C3 烷基-N(R3 )-S(0)2 -N(R3 )-c〇-c3 烷基-、-C〇-C6 烷基-C(0)-N(R3)-S(0)2-CQ-C3 烷基-、 -c0 -C6 烷基-N(R3 )-CG -C3 烷基-、-CG -C6 烷基-N(R3 -C3 烷基 -烯基-、-C〇-C6烷基烷基-炔基-、-〇)-(：6烷基 -N(R7)-Cq-C3 烧基-、-Cg-Cg 烧基-N(R7)-Ci -C3 烧基-稀基-、 -LJ〇 -(J6 烧基-Ν(Κ/ )-Ci -C3 院基-炔基-、-C〇 院基-N(R3 )-C2 -C4 烷基-N(R3)-C(0)-烷基-、-C〇-C6 烷基-N(R3)-C2-C4 烷基 -N(R3 )-C(S)-烷基-、-CQ -C6 烷基-0-C2 -C4 烷基-N(R3 )C(O)-C0 -C3 烷基-、-C〇-C6 烷基-S-C2-C4 烷基-N(R3)C(0)-CQ-C3 烷基-、 134026-1 -51 - 200916447 -C〇-C6 烷基-0-C2-C4 烷基-N(R3 )C(S)-CG-C3 烷基-、-Co-c6 炫基 -S-C2 -C4 炫基-N(R3 )C⑸-C。-C3 烧基-、-C。-C6 烧基-N(R3 )-C2 -C3 雜烷基-、-CQ-C6烷基-N(R7)-C2-C3雜烷基-、-QrQ炫基 -C(0)-N(R3 )-C2 -C3 雜烷基-、-C〇 -C6 烷基-C(S)-N(R3 )-C2 -C3 雜炫* 基-、-C〇-C6 烷基-C(0)-N(R7)-C2-C3 雜烷基-、-C〇-C6 烷基 -C(S)-N(R7 )-C2 -C3 雜烷基-、-C〇 -C6 烷基-N(R3 )-C(0)-C〇 -C3 雜烷 基-、-CQ-C6 烷基-N(R3)-C(S)-C〇-C3雜烷基-、-CG-C6 烷基 -N(R7 )-C(0)-C〇 -C3 雜烷基-、-C〇 -C6 烷基-N(R7 )-C(S)-C〇 -C3 雜烷 基-、-C〇 -C6 炫> 基-S-C〇 -C3 烧基-、-C〇 -C6 烧基 _0-C〇 -C3 炫基-、 -C〇 -C6 烧基-S(0)-C〇 -C3 炫基-、-C〇 -Cg 烧基-S(0)2 -C〇 -C3 炫基-、 -c〇-c6 烧基-n(r3)-c(o)-n(r3)-c〇-c3 烧基-、-C0-C6 烷基 -N(R3)-C(S)-N(R3)-CQ-C3烷基-、-C0-C6 烷基-0-C〇-C3 烷基-雜 %基-、-C〇 -C6焼> 基-0-C〇 -C3烧基-環烧基-、-C〇 -Cg烧基 -S(0)〇 - 2 -C〇 -C3 烧基-雜環基-、-C〇 -C6 烧基-S(O)0 _ 2 -C〇 -C3 燒基 -環烷基-、-CG-C6 烷基-N(R3)-C()-C3 烷基-雜環基-、_Cq_C6 炫基-N(R3)-Cq-C3炫基-環炫《基-、-雜環基-C〇-C6院基 -0-C〇 -C3烧基-、-環烧基-C〇 -C6烧基-0-C〇 -C3烧基-、-雜環 基-C〇-C6烧基-S(0)q-2-Cg-C3炫> 基-、-環烧基_cG-c6燒基 -S(〇)〇 - 2 -C〇 -C3 烧基 _、-雜環基-C〇 -C6 烧基-N(R3 )-C〇 -C3 烧基 _、 -環烷基-Cg-Q烷基-N(R3)-CG-C3烷基-、-Cq_C6提基 -Ν(Ι^)-C(O)-O-C0-C3 炊基-、-C〇-C6院基-N(R3)-C(S)-〇-C0~c 院 基-、-CVC6 烷基-0-0(0)-Ν(Κ3Κν(：3烷基-、七〇<：6 烷基 -0-C(S)-N(R3 )-C〇 -C3 烧基-、-C〇 -C3 院基-N(R3 )-C(0)-〇_雜譬久 -C〇 -C3 烧基-、-C。-C3 烧基-N(R3 )-C(S)-0-雜環基 _C〇 _C3 垸基、 134026-1 -52- 200916447 -c〇-c3烷基-n(r3)—c(o)-〇-環烷基-C〇-C3烷基-、-Cq-C3烷基 -N(R3 )-C(S)-0-環烷基-C〇 -C3 烷基-、-Q -C6 烷基-S(0)2 -雜環基 -C〇 -C3 烧基-、-C〇 -Cg 烧基-S(0)2 -¾ 烧基--C3 烧基-、-C〇 -Cg 烷基-N(R3)-S(0)2-雜環基 _Q-C3 烷基-、-CG-C6 烷基-N(R3)-S(〇)2 -¼烧基-Cq -C3烧基-、-C〇 -C3炫》基-雜環基-C〇 -C3燒基 -0-C〇 -C3烧基-、-C〇 -C3烧基-環烧基-C〇 -C3烧基-〇-C〇 -C3烧基― 、-C〇-C3烷基-雜環基-C〇-C5烷基-N(R3)-C〇-C3烷基-、-C〇-C3 烷基-環烷基-CG-C5烷基-N(R3)-C〇-C3烷基-、-CG-C3烷基 -0-C〇 -C3烷基-雜環基-c〇 -C3烷基-、-C〇 -C3烷基-0-C〇 -C3烷基 -環烷基-CG-C3烷基-、_cG_c3烷基-雜環基-CQ-C3烷基 -S-CG -C3烷基-、-C〇 -c3烷基-環烷基-C〇 -C3烷基-S-C〇 -C3烷基_、 -c0 -C：3 烷基-N(R3 )-〇) -C3 烷基-雜環基-CQ -C3 烷基-、-CG -c3 燒 基-N(R3)-Cq-C3烷基-環烷基-C(rC3烷基-、_Cq_C3烷基 -S-C〇 -C：3烷基-雜環基-C3烷基-、-C〇 -C：3烷基-S-C〇 -c3烷基 -環烧基-〇)-(：3烧基-、-CQ-C3 烧基-S(0)2N(R3)-CQ-C3燒基-雜 環基-CG -C3 烷基-、_cG -c3 烷基-S(0)2 N(R3 )-CG -C3 烷基-環烷 基-c。-C3 院基-' _C。_c3 烷基 _C(0)_N(R3 )_c。_c3 烷基 _雜環基 -C〇-C3 烷基-、_Cg_c3 烷基 _c(〇)_n(r3)_Cg_C3 烷基 _ 環烷基 _c〇_C3 炫·基-、-cG-C3 院基-c(s)-n(r3)-〇)-C3 烷基-雜環基 -C〇-C3烷基_、_Cg_c3烷基_c⑶_n(r3)_Cg_C3烷基_環烷基 -C〇-C3院基-、_C()_C3坑基_c(〇)-雜環基心^院基-、_c〇A 烷基-C(O)-環烷基_Cq_C3烷基_、_Cq_C3烷基_〇_c(0)_雜環基 -Co -c3 烷基 _、_Cq _c3 烷基 _0_c(0)_環烷基 _C() _c3 烷基 _、^ 烧基-0-C(0)-N(R3)-Q-C3 烷基-雜環基 _Q-C3 烷基-、-Cq<：3 134026-1 -53- 200916447 烷基-o-c(o)-n(r3)-cg-c3 烷基-環烷基-C〇-C3 烷基-、-C0-c3 烧基-0-C⑸-N(R3 )-C〇 -C3烧基-雜環基-C〇 -C3炫基-' _C〇 -C3燒 基-0-C(S)-N(R3 )-C〇 -C3 烷基-環烷基-C〇 -C3 烷基-、-C〇 -C3 烷基 -N(R3 )-C(0)-N(R3 )-C〇 -C3 烷基-雜環基-C〇 -C3 烷基-、-C〇 -C3 烷 基-N(R3)-C(0)-N(R3)-C〇-C3烷基-環烷基-CD-C3烷基-、-C0-C3 烷基-N(R3)-C(S)-N(R3)-C〇-C3 烷基-雜環基-CQ-C3 烷基-、 -C〇 -C3 烷基-N(R3 )-C(S)-N(R3 )-C〇 -c3 烷基-環烷基-CQ -C3 烷基-、 -C0-C3 炫基-N(R3)-C(0)-雜環基-C0-C3 烧基-、-C0-C3 淀基 -N(R3 )-C(0)-環烷基-C〇 -C3 烷基-、-CG -C3 烷基-N(R3 )-C(S)-雜環 基-C〇 -C3 院基-、-C〇 -C3 烧基-N(R3 )-C(S)-i哀烧基-C〇 -C3 烧基-、 -C〇 -C3 烷基-N(R3 )-S(0)2 -N(R3 )-CG -C3 烷基-雜環基-CQ -C3 烷基_ 、-CG -C3 烷基-N(R3 )-S(0)2 -N(R3 )-CQ -C3 烷基-環烷基-CQ -C3 烷 基-、-C〇 -C6烧基-雜環基-C(0)-C〇 -Cg烧基-、-C〇 -C6院基-環 烷基-C(0)-CQ-C6 烷基-、-CG-C6 烷基-n(r3)-c(o)-雜環基 -C(0)-CVC6 烷基-、-CQ -C6 烷基-N(R3 )-C(0)-環烷基-C(O)-C0 -c6 烷基-、-c〇-c6 烷基-n(r3)-c(s)-雜環基-c(o)-c〇-c6 烷基-、 -C〇 -C6 烷基-N(R3 )-C(S)-環烷基-C(0)-C(rC6 烷基-、-C〇 -C6 烷基 -雜環基-S(0)2 -C〇 -C6 烷基-' -c〇 -c6 烷基-環烷基-s(o)2 -c〇 -c6 烷基-、-C〇-C6烷基-雜環基-n(r3)-c(o)-c〇-c6烷基-、-c〇-c6 烷基-環烷基-N(R3)-C(0)-C〇-C6烷基-、-CG-C6烷基-雜環基 -0-C(0)-C〇 -C6 烷基-、-CQ -C6 烷基-環烷基-0-(：(0)-(：〇 -c6 烷基-、 -c0 -C6 烷基-雜環基-N(R3 )-C(S)-C〇 -C6 烷基-、-Q -C6 烷基-環 烷基-n(r3)-c(s)-c〇-c6 烷基-、-c〇-c6 烷基-雜環基-o-c(s)-C〇 -C6 烧基-、-C〇 -C6 烧基-環烧基-〇-C(S)-C〇 -Cg 烧基-、-C〇 -C3 134026-1 •54- 200916447 烷基-CttN-O-Co-Cg 烷基-、-cG-c3 烷基-c=n(oh)c(o)-N(R3 )-C2 -C4 -烧基-S-S-烷基-、-c。-C6烷基-雜烷基-Q -c6烷基 -C(0)-N(R3)-CQ-C3 烷基-、-C〇-C6 烷基-雜烷基-CG-C6 烷基 -C(S)-N(R3 )-C0 -C3 烷基-、-QrQ 烧基-芳基-雜芳基-C〇 -C6 烷 基-、-C0-C6烷基-雜芳基-芳基-Q-Q烷基-、-C〇-C6烷基-雜芳基-雜芳基-C0-C6烷基-、-C〇-C6烷基-芳基-芳基-C0-C6 烷基-、-Ci -C3 烷基-N(R3 )-(:(0)-(^ -C7 烷基-、-C3 烷基 -N(R3 -C7 烷基-、-C〇 -C3 烷基-烯基-C(0)-C〇 -C6 烷基-、 -C〇 -C6 烷基-N(R3 )-C(0)-N(R3 )-S(0)。 2 -C。-C3 烧基-、-C。-C3 燒 基-O-芳基-C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C0 -C3 烷基-s-芳基-C〇 -C6烷基-N(R3 χχο)^ -C3烷基-、-C〇 -C3烷基_a芳基 -C〇 -C6烷基-N(R3厂⑸必-C3烷基-、-C〇 -C3烷基各芳基_c〇 _c6 烧基-N(R3 )C(S)-C] -C；3 院基-、-C0 -C3 烧基-〇-雜芳基 _c〇 (6 燒 基-N(R3 )-(：(〇)-0：! -C3 烷基-、-C〇 -C3 烷基-S-雜芳基 _c〇 _Q 燒基 -N(R3 -C3 烧基-、-C〇-C3 烧基-O-雜芳基 _c〇_c6 燒式 -N(R3-C3 烷基-、-C0-C3 烷基-S-雜芳基 _c〇 C6 燒基 -N(R3 -C3烷基-、-CG -C3烷基-0-雜環基& %燒基 -N(R3 )-(：(0)-(：! -C3 炫基-、-C0-C3 炫基-S-雜環基 _c〇_C6 燒武 -N(R3)-(:(0)-(^-C：3 烷基-、-C0-C3 烷基-O-雜環基 炫臭 -NO^-CXSKVCs 烷基-、-CG-C3 烷基-S-雜環基 _Cg_c6 燒義 -Ν(Ι^ -C3 烧基-、-C〇-C3 烧基-0-環燒基 _Cq_c6 燒義 -N(R3 )-0(0)-0^ -C3 烷基-、-CG -C3 烷基-S-環燒基 ％ & 烧義 -Na^-cxcoA-C3炫基-、-eve：3烧基-o-環燒基_c〇_C6燒式 -N(R3)-C⑸-C3烧基-、-C〇-C3烧基-S-環燒基_c〇_Q燒美 134026^1 -55- 200916447 -N(R3 hCOCi -C3 烷基-、-C〇 -C3 烷基-N(R3)-芳基-C〇 -C6 烷基 -N(R3 )-(:(0)-^ -C3 烷基-、-C〇 -C3 烷基-N(R3)-芳基-C〇 -C6 烷基 -N(R3 yCXS)-^ -C3 烧基-、-C〇 -C3 烧基-N(R3 )-雜芳基-C〇 -C6 烧 基-N(R3 -C3 烧基-、-C〇 -C3 烧基-N(R3)-雜芳基-C〇 -C6 炫基-N(R3)-C(S)-Ci_C3 烧基-、-CQ-C3 烧基-N(R3)-雜環基 -C0-C6 烷基-NO^KXOKVCs 烷基-、-CQ-C3 烷基-N(R3)-雜環 基-CG-C6 烷基-N^KXSKVQ 烷基-、-CQ-C3 烷基-N(R3)-環 烷基-CQ -C6 烷基-N(R3 )((0)-(^ -C3 烷基-、-C。-C3 烷基-N(R3 )_ 環烷基-C〇-C6烷基-N^KXSKVCs烷基-、-C〇-C3烷基 -N(R3)-C(0)-0-芳基-C0-C6 烷基-NCRq-CXCO-Ci-Cs 烷基-' -C0 -C3 烧基-N(R3 )-C(S)-0-芳基-C0 -C6 烧基-N(R3 )((0)-(：! -C3 烷 基-、-C0-C3 烧基-N(R3)-C(0)-S-芳基-C〇-C6 烧基-N(R3)-C(0)-CVC3 烷基-、-c0-c3 烷基-n(r3)-c(o)-o-芳基-C〇-C6 烷基 -N(R3 KXSXi -C3 烷基-、-C〇-C3 烷基-N(R3 )-C(S)-0-芳基-C〇-C6 烷基-N(R3 -C3 烷基-、-C〇 -C3 烷基-N(R3 )-C(0)-S-芳基 -C〇 -C6 烷基-N(R3 )-C(S)-C, -C3 烷基-、-C〇 -C3 烷基-N(R3 )-C(0)-0-雜芳基-C〇-C6烷基-N^KXOKVq烷基·、-C0-C3烷基 -N(R3)-C(S)-0-雜芳基-C〇-C6 烷基-N(R3)-0(0)-(^-C3 烷基-、 -C〇 -C3 烷基-N(R3 )-C(0)各雜芳基-C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C〇 -C3 烷基-N(R3 )-C(0)-0-雜芳基-C〇 -C6 烷基-N(R3 )-(:⑸-匚丨-C3 烷基-、-C0 -C3 烷基-N(R3 )-C(S)-0-雜芳基-C。-C6 烷 基-N(R3-C3烧基-、-CQ-C3烧基-N(R3)-C(0)-0-雜環基 -C0 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C。-C3 烷基-N(R3 )-C(S)-0-雜環基-CG-C6 烷基-N(R3 )-(:(0)-(^-C3 烷基-、-CG-C3 烷基 134026-1 56· 200916447 -N(R3)-C(0)-0-雜環基烷基 _N(R3)_C⑸·Ci_c3 烷基 _、 -C〇 -C3 烷基-N(R3 )-C(S)-0-雜環基 _c〇 -c6 烷基-N(R3 VCXSyCi -C3 烧基-、-C〇 -C3 院基-N(R3 )-C(〇)-〇-環烧基-C。-c6 烧基-N(R3 )-CXCO-CrCg烧基-、_cG-C3 烷基 _N(R3)_C⑸_〇_環烷基 _Cg_C6 烷 基-N(R3)-(:(0)-(^-C3烷基-、_〇)-(：3烷基-N(R3)-C(0)-0-環烷基 -C〇 -C6 烧基-N(R3 VQSK〗-C3 烷基-、_c〇 -C3 烷基-N(R3 )-C(S)-0-環烷基-CG-C6烧基-N(R3)-C⑸烧基-、-CG-C3烷基 -C(0)-N(R3)-芳基-C〇-C6 烷基烷基-、-C〇-C3 烷基-C(S)-N(R3)-芳基-c0 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、 -C〇-C3 烧基-C(0)-N(R3)-芳基 _c0-C6 烷基-N(R3 -C3 烷 基-、-C〇 -C3 烷基-C⑸-N(R3)-芳基 _c〇 -C6 烷基-N(R3 )-C⑸-C〗-C3 烷基-、-C〇 -C3 烷基-C(0)-N(R3)-雜芳基-Q -C6 烷基-N(R3 )C(0)-CVC3 烷基-、-C〇-C3 烷基-C(S)-N(R3)-雜芳基-C0-C6 烷基 -N(R3 )(:(0)-(^ -C3 烷基-、-C0 -C3 烷基-C(0)-N(R3)-雜芳基-C〇 -C6 烷基-N(R3 KXSKi -C3 烷基-、_c〇 -C3 烷基-C(S)-N(R3)-雜芳基 -C〇-C6 烧基-N^XXSHI：】-C3 烧基-、-C0-C3 烧基-C(0)-N(R3)-雜環基-C〇-C6 烧基-N(R3 )-(:(0)-(^-C3 烧基-、-C〇-C3 烷基 -C⑸-N(R3)-雜環基-C〇-C6 烷基-N^KXOKVQ 烷基-、 -C0-C3 烷基-C(0)-N(R3)-雜環基-C〇-C6 烷基-N^KXSK^ -C3 烷基-、-Co -C3 烷基-C(S)-N(R3)-雜環基-C〇 -C6 烷基-N(R3 )-C(S)-Ci-Q 烷基-、-C〇-C3 烷基-C(0)-N(R3)-環烷基-Cq-Q 烷基 -N^y-QOKVC^ 烷基-、-C〇-C3 烷基-C(S)-N(R3)-環烷基 -C〇 -C6 烧基-N(R3 -C3 院基-、-C〇 -C3 烧基-C(0)-N(R3)- 環烷基-C〇-C6烷基-N^H^SKVCg烷基-、-C〇-C3烷基 134026-1 •57- 200916447 -C⑸-N(R3)-環烷基-C〇 -C6 烷基-N(R3 )-C⑶-C3 烷基-、-C0 -C3 烷基-0-C(0)-N(R3)-芳基-C〇 -C6 烷基-N(R3 )-(:(0)4 -C3 烷基-、 -C〇-C3 烷基-O-C⑸-N(R3)-芳基-C0-C6烷基-N(R3)-(:(0)-(^ -C3 烷 基-、-C〇-C3 烷基-0-C(0)-N(R3)-芳基-C〇-C6 烷基-N(R3)-C(S)-烷基-、-C〇-C3 烷基-0-C⑸-N(R3)-芳基-C0-C6 烷基 -NCI^KXSKVQ 烷基-、-C0-C3 烷基-0-C(0)-N(R3)-雜芳基 -C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C〇 -C3 烷基-0-C⑸-N(R3 )-雜芳基-C0-C6 烷基-C3 烷基-、-C〇-C3 烷基 -0-C(0)-N(R3)-雜芳基-C〇-C6 烷基-Nil^KXSKVC^ 烷基-、 -C〇 -C3 烷基-0-C(S)-N(R3)-雜芳基-C〇 -C6 烷基-N(R3 -C3 烷基-、-C〇 -C3 烷基-0-C(0)-N(R3)-雜環基-C〇 -C6 烷基-N(R3 )-CCOKVC3 烷基-、-C〇-C3 烷基-0-C(S)-N(R3)-雜環基-C〇-C6 烷 基-N(R3 Κ(0)·Α -C3 烷基-、-C〇 -C3 烷基-0-C(0)-N(R3)-雜環基 -C〇 -C6 烷基-N(R3 -C3 烷基-、-C〇 -C3 烷基-0-C(S)-N(R3 )- 雜環基-C〇-C6烷基-N(R3)-C⑸-CVC3烷基-、-C〇-C3烷基 -0-C(0)-N(R3)-環烷基-CG-C6 烷基-I^RSKXOKVCs 烷基-、 -C〇 -C3 烷基-O-C⑸-N(R3 )-環烷基-C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C〇-C3 烷基-0-C(0)-N(R3)-環烷基-C〇-C6 烷基 -r^Ri-CO-CVC^ 烷基-、-C〇-C3 烷基-0-C(S)-N(R3)-環烷基 -C〇-C6 烷基-Nil^KXSKVCs 烷基-、-C〇-C3 烷基-S(0)2-N(R3)-芳基-1〇七6 烧基-N(R3 )_c(〇)-Ci -C〗烧基-、-C〇-C3 烧基-S(0)2· N(R3 )-芳基-C〇 -C6 烷基-N(R3 -C3 烷基-、-C〇 -C3 烷基 -S(0)2-N(R3)-雜芳基-C0-C6 烷基-I^R'CCOKVCs 烷基-、 -C0 -C3 烷基-S(0)2 -N(R3)-雜芳基-C0 -C6 烷基-N(R3 -C3 134026-1 -58· 200916447 烷基-、-c〇-c3 烷基-s(o)2-n(r3)-雜環基 _q_C6 烷基 _n(R3)-C(0)-C〗-C3 烧基-、-C〇 -C3 烧基-S(0)2 -N(R3)-雜環基-C〇 -C6 烧基 -N(R3)-C⑸-Q-C3 烧基-、-C〇-C3 院基 _s(〇)2-N(R3)-環烧基 -C0-C6炫基-NO^KXOKVCg烧基-、-C〇_c3烧基 _s(0)2-N(R3)-環烷基-Q-Q烧基-N^KXSKVq烧基-、-C(rC3烷基 -N(R3 )-S(0)2 -N(R3)-芳基-C0 -C6 烷基-N(R3 )-C(0)_Cl _c3 烷基—、 -匚0-(：3烷基-；^(113)-3(〇)2顿113)-芳基-(：0-(：6烷基-：^(113)-(：(8)-Q -C3 烧基-、-C〇 -C3 烧基-N(R3 )-S(0)2 -N(R3)-雜芳基-C0 -C6 烧 基-N(R3 )-(:(0)-(^ -C3 烷基-、-C〇 -C3 烷基-N(R3 )-S(0)2 -N(R3)-雜 芳基-C0 -Q 烧基-N(R3 -C3 炫基-、-C〇 _c3 烷基 _N(R3 )_ S(0)2-N(R3)-雜環基-c0-c6 烧基-N(R3 )-(:(0)-(:^3 烧基-、 -(^-(^烷基-风心^⑼厂风尺”-雜環基—仏心烷基-风的-匸⑸-q -C3 烷基-、-CQ -C3 烷基-N(R3 )-S(0)2 -N(R3)-環烷基-CQ -C6 烷 基-ι^ι^κχοκνο^烷基-、-c〇-c3 烷基-n(r3)-s(o)2-n(r3)-環 烧基-C〇 -Q烧基-N(R3丨-匚⑻-心-C3烧基_、-CQ -C3烧基-雜環基 -〇-芳基-C〇 -C6 烧基-N(RJ )-0(0)-(^ -C3 烧基-、-C〇 -C3 烧基-雜 環基-S-芳基-C〇 -Q 烧基-N(R3 )-(:(0)-(^ -C3 烧基-、-C〇 -C3 烷基 -雜環基-0-芳基-C0 -C6 烧基-N(R3 ycXSK! -C3 烧基-、_c〇 -C3 烷基-雜環基-s-芳基-Co-q烷基-n^kxskvq烷基_、 -C0-C3 烷基-雜環基-〇-雜芳基 _c〇_C6 烷基 _N(R3)_c(〇)_Ci & 烷基-、-C〇 -C3烷基-雜環基-s-雜芳基_c〇 -C6烷基-N(R3 )-(：(；〇)-CVC：3烧基-、-C0-C3烧基-雜環基_〇_雜芳基_c〇_c6烧基 -N(R3 yCXShC! -C3 烷基-、-C0 -C3 烷基-雜環基-S-雜芳基 _Cq & 烧基-N(R3 hQS)% -C：3烷基-、-Cq 4烷基-雜環基_〇_雜環基 134026-1 •59- 200916447 -C〇 -C6 烷基-N(R3 )_c(0)_Cl _c3 烷基-、-Q -C3 烷基-雜環基-s-雜環基-CG -c6烷基-N(R3 )-(:(0)-(^ -C3烷基-、-CG -C3烷基-雜環 基-〇-雜環基-CQ -C6烷基-N(R3 )-C⑸-Ci -C3烧基-、-CVC3烷基 -雜環基-s-雜環基_c。_C6烧基_N(R3 )_c⑸_Ci _C3院基_、_c〇 燒基-雜環基_〇_環烷基_Cq _C6烷基_N(R3 )_c(〇)_Ci _C3烷基… -C〇 -c3烷基-雜環基_s_環烷基_c。_c6烷基_N(R3 )_c(〇)_Ci _c3烷 基…-C〇-C3烷基-雜環基-0_環烷基-Cq_C6烷基-N(R3)_c(s)_ 烷基·、_C()_C3烷基-雜環基_s_環烷基_Cg_c6烷基 _N(R3)-C⑸-Ci-Q烷基·、-C0-C3烷基-C(O)-雜環基-ο-芳基 -C0 -C6 烷基-N(R3 )_c(0)_Ci _c3 烷基 _、_c〇 _c3 烷基 _c⑸_雜環基 -O-芳基-C0 -C6 烧基-N(R3 )-0(0)-(^ -C3 烧基-、-C0 -C3 烧基-c(0)_ 雜環基-S-芳基-C〇 -Q 烷基-N(R3 )-(:(0)% -C3 烷基-、-c0 -c3 烷 基-C(O)-雜環基_〇_芳基_C(rC6烷基_N(R3 )_c⑸^ _C3烷基_、 -C〇 -C：3 烷基-C(s)-雜環基-s-芳基-c0 -C6 烷基-N(R3 )-(:(0)4 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基-N(R3)-C(S)-雜環基-N(R3)-雜芳基-C0-C6 烷基-N(R3)-C(0)-C! -C3 烧基-、-C〇 -C；3 烧基-N(R3 )-C(0)-雜環基 _N(R3)-雜芳基 -C〇 -C6 烧基-N(R3 -C3 烧基-、-C。-C3 烧基-N(R3 )-C(S)- 雜環基-N(R3)-雜芳基-C0 -C6烷基-N(R3 )-C⑸-C3烷基_、 -C0-C3 烷基-N(R3)-C(0)-雜環基-N(R3)-雜環基-C0-C6 烷基 -n(r3)-c(〇)-ci-c3 烷基-、-C〇-C3 烷基·ν(ϊ13)-(：(8)-雜環基 -N(R3)-雜環基-CQ-C6 烷基烷基-、-C〇-C3 烷 基-N(R3)-C(0)-雜環基-N(R3)-雜環基-Cq_c6 烷基-N(R3)_C⑸_ Ci -C3 烷基-、-C〇-C3 烷基-N(R3)-C(S)-雜環基-N(R3)-雜環基 -C0-C6 烷基-N^KXSKVCg 烷基-、-C(rC3 烷基 _N(R3)_c(〇)_ 雜環基-N(R3)-環烧基-C〇 -C6 烧基-N(R3 )-0:(0)-(^ -C3 烷基-、 -C0-C：3 烧基-N(R3)-C(S)-雜環基-N(R3)-環烷基-Qj-Q 烷基 -N^KXOHVCs 院基-、-C〇-C3 烧基-N(R3)-C(0)-雜環基 -N(R3)-環烷基-Cq _c6 烷基-N(R3 )_c(s)_Ci & 烷基—、& 烷 基-n(r3)-c(s)-雜環基 _n(r3)_環烷基 _Cq_C6 烷基 _N(R3)_C⑸_ 烧基-、-C〇-C3 烷基-S(0)2-雜環基-N(R3)-芳基-C0-C6 烷 基-NiRM-CCOKVCs 烷基-、-C〇-C3 烷基-S(〇)2-雜環基-N(R3)-芳基-Q) -c6 烷基 _n(r3 )-C⑸_Cl _c3 烷基 _、_c〇 _C3 烷基 _s(〇)2 _ 雜環基-N(R3)-雜芳基_c〇 _C6炫基_N(R3 )_c(〇)_Ci ^院基—、 -c0-C3 烧基-s(o)2_雜環基 _n(R3)_雜芳基 _c〇_C6 烷基 _n(R3)_ C(S>Cl _C3 燒基-、-C〇-C3 烷基-S(0)2-雜環基-N(R3)-雜環基 -C〇-C6 烷基-N(R3)_c(〇)_Ci_C3 烷基-、_C()_C3 烷基 _s(〇)厂雜環 基-N(R3)-雜環基 _C()_C6 烷基 _n(r3)_c ⑶ _Ci_C3烷基-、_c〇_c3 烷基-s(o)2_雜環基-N(R3)_環烷基 _Cg_C6 烷基 _n(R3)-C(〇)_ 134026-1 -66- 200916447 q -C3 烷基-、-C〇 -C3 烷基-S(0)2 -雜環基-N(R3)-環烷基-C〇 -C6 烷基-N(R3 -C3 烷基-、-C。-C6 烷基-N(R3 )-C(O)-C0 -C6 烷基-雜環烧基-C(0)-C〇-C3烷基-、-C〇-C6烷基-N(R3)-C⑸-c0 -C6 烷基-雜環烷基-c(0)-c〇 -C3 烷基-、-C〇 -C6 烷基-N(R3 )-c(o)-c〇-c6烧基-雜環烧基-C⑸-CG-C3烧基-、-CG-C6烷基 -N(R3 -C6 烷基-雜環烷基-C(S)-C〇 -C3 烷基-、-C〇 -C6 烷 基-N(R3 )-C(0)-CQ -C6 烷基-雜環烷基-C(0)-N(R3 )-CQ -C3 烷基-、-C〇-C6 烷基-N(R3)-C(S)-CG-C6 烷基-雜環烷基-C(0)-N(R3)-C〇-C3 烧基-、-C〇-C6 烧基-N(R3)-C(0)-C〇-C6 烧基-雜環烧基 •C(S)-N(R3 )-C〇 -C3 烷基-、-C0 -C6 烷基-N(R3 )-C(S)-C〇 -C6 烷基-雜環烷基-C(S)-N(R3 )-CG -C3 烷基-、-C〇 -C6 烷基-C(O)-C0 -C6 烷 基-雜 院基-C(0)-N(R3 )-C〇 -C3 烧基-、-C〇 -C6 烧基-C(S)-C〇 -Cg 烷基-雜環烷基-C(0)-N(R3)-CG-C3 烷基-、-CQ-C6 烷基-C(0)-C〇-C6 烷基-雜環烷基 _c(S)-N(R3)-CQ-C3 烷基-、-CG-C6 烷基 -C(S)-C。-C6 烷基-雜環烷基-C(S)-N(R3 )-C。-C3 烷基…-c。-c6 燒 基-0-Q)-C3 烷基-c(o)-n(r3)-cg-c3 烧基-及-C〇-C6 烷基 -〇-C(S)-N(R3 )-C〇 -C：3院基-’其中前文所提及L之各烧基、 烯基、炔基、雜烷基、環烷基、雜環烷基、雜環基、芳 基及雜芳基部份基團係視情況經取代；其中 各Y係獨立選自包括Η、烧基、雜炫基、環烧基、雜環基、 環烷基烷基、雜環基烷基、芳基、芳烷基、雜芳基、雜 芳烧基、芳基-雜芳基、芳基-雜芳烷基、雜芳基_烷基芳 基、芳基-芳基、芳基-芳烷基、芳基-炫基芳基、芳基_C()_C3 烧基-0-C〇 -C3炫>基-芳基、芳基_c〇 -C3烧基-S(0)〇 __ 2 _c〇 _c3燒 134026-1 •67- 200916447 基-芳基、-C0-C3烷基ACOoi-Co-q烷基-芳基、芳基-c〇-c3 烷基-N(R3 )-C〇 -C3 烷基-芳基、芳基-C0 -C3 烷基-C(0)-N(R3 )-C〇-C3烷基-芳基、芳基-C〇-C3烷基-C(S)-N(R3)-C〇-C3烷基-芳 基、芳基-C〇 -C3烷基-N(R3 )-C(O)-C0 -C3烷基-芳基、芳基-C0 -C3 烷基-N(R3)-C(S)-C0-C3烷基-芳基、雜芳基-雜芳基、雜芳基 -芳基、雜芳基-芳烷基、芳基-烷基雜芳基、雜芳基-芳基 -芳基、芳基-芳基-芳基、芳基-雜芳基-芳基、芳基-雜芳 基-雜芳基、雜芳基-雜芳基-雜芳基、雜芳基-雜芳基-芳 基、芳基-芳基-雜芳基、雜芳基-芳基-芳烷基、芳基-芳基 -烷基雜芳基、雜芳基-芳基-烷基芳基、芳基-芳基-烷基芳 基、芳基-芳基-芳烷基、芳基-芳基-雜芳烷基、雜芳基-芳基-雜芳基、雜芳基-芳基-雜芳烷基、雜芳基-芳基-烧基 雜芳基、雜芳基-雜芳烷基、雜芳基-烷基雜芳基、雜環 基-雜芳基、環烷基-芳基、環烷基-雜芳基、雜芳基-雜環 基、雜芳基-環烷基、芳基-環烷基、雜環基-芳基、芳基-雜環基、雜環基-烷基-芳基、雜環基-烷基雜芳基、環烷 基-烷基芳基、環烷基-烷基雜芳基、芳基-烷基-雜環基、 芳基-烷基環烷基、雜芳基-烷基環烷基、雜芳基-烷基雜 環基、芳烷基-芳基、芳基-芳烷基、芳基-雜芳烷基、雜 芳基-芳烷基、雜芳基-雜芳烷基、雜芳基-C〇-C3烷基 -o-c〇-c3烷基-芳基、雜芳基-c0-c3烷基-o-c0-c3烷基-雜芳 基、芳基-c〇-c3烷基-o-c0-c3烷基-雜芳基、雜芳基-c0-c3 烷基-N(R3 )-C0-C3 烷基-芳基、芳基-C0-C3 烷基-N(R3 )-C〇-C3 烷基-雜芳基、雜芳基烷基-N(R3)-C〇-C3烷基-雜芳 134026-1 -68- 200916447 基、雜芳基-c〇-c3烷基-C(O)-N(R3)-C0-C3烷基-芳基、芳基 -C0 -C3烧基-C(0)-N(R3 )-C0 -C3烧基-雜芳基、雜芳基-C〇 -C3烧 基-C(0)-N(R3)-C〇-C3烷基-雜芳基、芳基-c0-c3烷基 -C(S)-N(R3 )-C〇 -C3 烧基-芳基、芳基-C〇 -C3 烧基-C ⑸-N(R3 )-C〇 -C3烷基-雜芳基、雜芳基-C0 -C3烷基-C(S)-N(R3 )-C0 -C3烷 基-芳基、雜芳基-C0-C3烷基-C(S)-N(R3)-C〇-C3烷基-雜芳 基、雜芳基-c〇-c3烷基-n(r3)-c(o)-c〇-c3烷基-芳基、雜芳 基-c0-c3烷基-N(R3)-C(0)-C〇-C3烷基-雜芳基、芳基-(^-(^烷 基-N(R3)-C(O)-C0-C3 烧基-雜芳基、芳基-C〇-C3 烧基-N(R3)-cxs)-c0 -C3 烷基-芳基、芳基-c0 -C3 烷基-N(R3 )-C(S)-C〇 -C3 烷基 -雜芳基、雜芳基-C〇 -C3烷基-N(R3 )-C(S)-C〇 -C3烷基-芳基、 雜芳基-C〇 -C3烷基-N(R3 )-C(S)-C〇 -C3烷基-雜芳基、R3 -雜環 基-CQ-C3 烷基、R3-環烷基-CG-C3 烷基、（R3)(R3a)N-C2-C4 烷 基-〇-芳基-、（R3)(R3a)N-C2-C4 烷基-S(0)〇_2-芳基-、 (R3)(R3a)N-C2-C4 院基-〇-雜芳基-、（R3)(R3a)N_c2_C4 烷基 -S(O)0-2-雜芳基-、C〇-C3烷基-芳基-C〇-C3烷基、〇：〇-0：3烷基-雜芳基-C〇-C3烷基、芳基-Q-Q烷基-雜芳基、芳基 烷基-芳基、雜芳基-Ci-Cg烷基-芳基、雜芳基烷基-雜芳基、R3 -雜環基-C〇 -C3烷基-N(R3 )-C(0)-N(R3)-雜芳基-、 R3-雜環基-C0-C3 烷基-N(R3)-C(0)-N(R3)-芳基-、R3-環烷基 -C〇 -C3 烷基-N(R3 )-C(0)-N(R3)-雜芳基-、R3 -環烷基-C〇 -C3 烷 基-N(R3)-C(0)-N(R3)-芳基-、R3-雜環基-C0-C3 烷基-N(R3)-C(S)-N(R3)-雜芳基-、r3 _雜環基 _c〇 _C3 烷基 _n(r3 )_c(s)_n(r3 )_ 芳基-、R3 -環烷基·〇) -C3 烷基-N(R3 )-C(S)-N(R3)-雜芳基-、R3 - 134026-1 •69· 200916447 環烷基-C0-C3烷基-N(R3)-C(S)-N(R3)-芳基-、雜芳基 -C(O)-C0-C6烷基-雜芳基-、雜芳基_C(0)_C〇_C6烷基_芳基-、 芳基-C(O)-C0-C6烷基-芳基_、芳基_C(0)_C〇_C6烷基_雜芳基_ 、雜芳基-C(0)-N(R3 )-C0-C6 烧基-芳基-、雜芽基 _c(〇)-N(R3 )-c0-c：6烧基-雜芳基-、雜芳基_S(0)2_C()_C6烷基_雜芳基_、雜 芳基-S(O)2-C0-C6烧基-芳基-、芳基_s(〇)0_2_c0-C6烧基-芳 基、务基 -C3 烧基-S(O)0 - 2 -C〇 -Cg 烧基-雜芳基、R3 -〇-C(〇)_ N(R3 )-C0 -C3 烷基-雜芳基·、R3 _〇_c(〇)-N(R3 )-C〇-C3 烷基-芳基 -、R3 -0-C(S)-N(R3 )-C0 -C3 烧基-雜芳基-、R3 _〇_c(s)-N(R3 )_ C0-C3烷基-芳基-、R3-C(0)-雜環基-C0-C3烷基-雜芳基_、 R3 -C(O)-雜環基-C〇 -C3烷基-芳基-、r3 _c(〇)_環烷基_C〇_C3燒 基-雜芳基-、R3-C(0)-環烷基-C0-C3烷基-芳基-、R3_雜環基 -C〇 -C3 烧基-N(R3 )-C(0)-N(R3 )-C〇 -C3 院基-雜芳基-、_雜環 基-C〇 -C3烧基-N(R3 )-S(0)2 -C〇 -C3烧基-雜芳基—、R3 -雜環基 -C〇 -C3 烧基-N(R3 )-S(0)2 -C〇 -C3 烧基-芳基·、R3 _環烷基 _c。_Cg 烷基-N(R3 )-S(0)2-C0-C3烷基-雜芳基-、R3_環烷基_c〇_C3院 基-N(R3)-S(0)2-C〇-C3烷基-芳基-' R3-雜環基-C0-C3烷基 -N(R3)-C(O)-C0-C3烷基-雜芳基-、R3-雜環基-C0-C3燒基 -N(R3)-C(0)-C〇-C3 烷基-芳基-、R3-環烷基-C〇-C3 烷基 -N(R3)-C(O)-C0-C3烷基-雜芳基-、R3-環烷基-C〇-C3垸基 -Ν(Κ°)-(^(0)-0〇-Ε3 炫•基-方基 _、R3-雜 ί辰基-Cq-C〗览基 -N(R3)-C(S)-C〇-C3烷基-雜芳基-、R3-雜環基-c0-c3燒基 -N(R3KXS)-C〇-C3烷基-芳基-、R3 -環烷基-C〇-C3烷基 -N(R3)-C(S)-C0-C3烷基-雜芳基-、R3-環烷基-C〇-C3烷基 134026-1 -70- 200916447 -N(R3 )-C(S)-C〇-C3 烷基-芳基-、R3 _c(〇)_c〇 & 烷基-雜芳基 _、 R3-C(0)-C〇-C3烷基-芳基_、雜環*_c(〇)_、芳族多環、非 芳族多環、混合之芳基與非芳基多環、多雜芳基、非芳 族多雜環及混合之芳基與非芳基多雜環，其每一個係視 情況被一或多個選自R3、R4或R7之基團取代； 或 各Y係獨立選自包括 A2 a -芳基-c0 -c3 烷基-N(R3 -c7 烷基-，其中 q -C7 烷基係 視情況被部份基團取代，該部份基團選自包括 _N(R3 烧基-(C2-C4 稀基烧基-0-A2b、 -N(R3)-C(0)-N(R3 -C5 烧基-(C2-C4 烯基）〇_]-(：!-C3 烷基 •O-A2 b、-N(R3 )-(:(0)-0-(^ -C5 烷基-(C2 -C4 烯基）〇 -丨-C3 烷基 -0-A2b、烷基-(C2-C4 烯基 烷基 -〇_A2b、-N(R3)_s(〇)2_N(R3)_c]_C5 烷基 _(C2_c4 烯基）q 烷基-O-A2 b 及-N(R3 )-S(0)2 -C5 烷基-(C2 -C4 烯基）。_ 丨-C3 烷基-0-A2b， A2 a -次雜芳基-C〇 -C3 烷基-N(R3 )-(：(0)-(：! -C7 烷基-，其中 q -C7 烷基係視情況被部份基團取代，該部份基團選自包括 -N(R3)-0(0)-(^-C5 烷基-(C2-C4 烯基 Vi-Ci-q 烷基-0-A2b、 -NCRM-CCC^-N^SKVCs 烷基-(C2-C4 烯基 Vi-CVQ 烷基 -O-A2 b、-N(R3 )-(:(0)-0-(^ -C5 烷基-(C2 -C4 烯基）0 -1 -C3 烷基 _〇·A2 b、-C5 烷基-(C2-C4 烯基）(^-CVQ 烷基 -O-A2 b、-N(R3 )4(0)2-^113)-(^-C5 烷基-(C2-C4 烯基）〇」-(：!-C3 烧基-0-A2b 及-N(R3)-S(0)2-Ci -C5 烧基-(C2-C4 稀基）〇-1 -Q -C3 134026-1 -71 · 200916447 烷基-0-A2b，及 b2-b] -NR3 -B3 取代， 烷基 其中烷基係視情況被: Its 0H, -CN, -Cl jobs, QW-O-Co-Q II:: soil, -C. ☆ alkyl-fluorene-Q-c6 alkyl-heteroaryl, wherein each of the alkane, alkyl and heteroaryl groups are optionally substituted; or Rh and π and the atoms to which they are attached - depending on the situation 3 to 9-membered heterocyclic group, heteroaryl group, heterocyclic group heteroaryl group HA is optionally substituted (4), and the solid is optionally substituted; ring (tetra) = substituted heterocyclic group 'heteroaryl, hetero Cyclo-aryl or heterozygous Z =: covalent bond 'substance I flavonine 3 -C〇_C3 alkyl bis-cvc3 alkyl, _c c alkyl-c2-c8 acetylene rrhi 〇-C3 C, its 3-yl-, (0-(5)-yl-aryl-c〇-c6 alkyl-, C〇C6:^-based π-based _ccrr P # 烧, rr 6 heterogeneous c〇-Q Anthracenyl-cyclohexyl-C〇-C6::C6 alkyl-ring group _c2_c6 miscellaneous group _~6 heterocyclic group · square lane l〇-C6 alkyl group-, _ has r I® Gan p.仏必杂基基-方基-CVC6 heteroalkyl·, # ^ AC c〇4 Q # % ^ "C〇"C6 ^ ^ ' 'C〇'C6 ^ ^ -Q-C6- c C ' -〇-c6^^^^-c0_c6r^.. -C〇-C6-alkyl-heteroaryl_c Γ Γ oC6 heteroalkyl-, -c4-c6 heterocyclyl-heteroaryl 0 6, Soil..._C4_C6heterocyclyl-heteroaryl-C0-C6 heteroalkyl... leuko-aryl-C3_c6 alkynyl...c〇_c6 -heteroaryl~6 fast radical 0_,6-Co-Qalkyl-cycloalkylnonynyl...Q_C6 炫基••-c〇-c6r^-^_C2.c^^.C2_C6^_;; C--yl-aryl-C2-C6 dilute _, _c〇_c6 alkyl-heteroaryl fluorene, 6'-membered-Co-Q alkyl-cyclohexyl decyl group (tetra)alkyl芙 = dilute-,-0rc6 alkyl-aryl-aryl_Q C6 alkyl, (. Eryuan 2 US 6 134026-1 • 48· 200916447 aryl-heteroaryl-QrC6 alkyl-, -C0 -C6 alkyl-heteroaryl-aryl_C()_C6_alkyl, -c〇-c6 leu-heteroaryl-heteroaryl-(:0-(:6_alkyl,·_C( )_C3 alkyl-heteroaryl_〇> -CI3 fen-C2 -C8 alkenyl-C〇-C3 -alkyl-, -C0-C3 alkyl-yl-C-C; -C2 -Cs alkenyl-C〇-C3 -alkyl-, _c〇-C3 alkyl-heterocyclyl-CQ-C3 leuco-C2 -C8 dilute-C〇-C3 -alkyl-, _〇 -C3 alkyl group, cycloalkyl group-C0-C3 Hyun "based-C; 2 -Cs dilute-C〇-C3 -alkyl-' _c〇-C3 alkyl-heteroaryl-C〇-C3 -C2 -C8 alkynyl-C〇-C3 -alkyl-, -Cq-C3 alkyl-aryl-C0-C3 alkyl _c2-C8 alkynyl-CQ-C3-alkyl-, -C〇 -C3 leuko-heterocyclyl-C0-C3 alkyl-C^-Cg alkynyl-Cq-C3-alkyl- and -CQ-C3 leuko-cycloalkyl-C0- C3-based _c2-Cg alkynyl-C〇-C3-alkyl--in which each alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, heterocyclic and cycloalkyl moiety The group is optionally substituted; and when W is N, the Z system is further selected from the group consisting of -Q-C8 alkyl-c(0)-, -(^-(^-alkyl-S(0)2-, -aryl-C〇-Cg alkyl-S(0)2-,-heteroaryl-C〇-C8 alkyl-S(0)2 _,_cycloalkyl-C〇-C8 alkyl-S (0)2-, _heterocycloalkyl-C0-C8 alkyl _s(0)2_, -CVCg alkyl-CH=, -CVCs alkyl-C(CH3)=, _〇)- <:6 alkyl-CH=CH-C(0), -C〇-C4 alkyl-C(O)-, -CVCg alkyl-(NH2)C=, -c0-c3 alkyl-c! -c8heteroalkyl-c〇-c3alkyl-c(o)-, -c〇-c3 alkyl-c2 -c8 alkenyl-C〇-C3 alkyl-C(O)-, -C〇- C3 alkyl-C--Cg fast-C〇-C3 alkyl-C(O)-, -C〇-C6 alkyl-aryl-C〇-Cg alkyl-C(O)-, -C 〇-C6 alkyl-aryl-C2-C6 heteroalkyl-c(o)-, -c〇-c6 alkyl-cycloalkyl-CG-C6 alkyl-c(o)-, -CQ-C6 Alkyl-cycloalkyl-c2-c6 heteroalkyl-c(o)-, -c4 -c6 heterocyclyl-aryl-CQ-c6 alkyl-C(O)-, -C4 -C6 heterocyclic _aryl-C〇 <6 miscible-C(〇)-, -C〇-C6 alkyl-C4-C6-heterocyclyl-C〇-C6 alkyl-C(O)-, -C〇-C6 alkyl- C4 -C6 -heterocyclic group ^4026-1 -49- 200916447 -C〇-C6 complex base-c(o)-, -C〇-c6-alkyl-heteroaryl-c0-C6 alkyl-c (o)-, -c0 -C:6-alkyl-heteroaryl-c0-c6heteroalkyl-C(O)-, -c4 -C6 heterocyclyl-heteroaryl-C0-C6 alkyl- c(0)-, -c4-c6heterocyclyl-heteroaryl_c〇_c6heteroalkyl-C(O)-, -c0 -C6 alkyl-aryl_c3 _c6 alkynyl_c(〇 )-, -C〇_c6 alkylheteroaryl-c2-c6 alkynyl-c(0)-, <vc6 alkyl-cycloalkyl-c3_c6 alkynyl_c(〇)_, -C〇-C6 alkyl-heterocyclyl-c3 -c6 alkynyl-c(0)-, -CG-c6 alkyl -aryl-c2 -c6 alkynyl-C2 -C6 alkenyl-c(0)-, -Q _c6 alkyl-aryl _c2 _c6 alkenyl_c(〇)_, -c0 -Q alkyl-hetero Aryl-C2-c6 alkenyl-c(0)-, -c0-C6 alkyl-cycloalkyl-c2-C6 alkenyl-C(0)-, -c0-c6 alkyl-heterocyclyl_gvc6 Alkenyl_c(〇)_, -c0 -Qalkyl-aryl-aryl-Cq alkyl_c(0)..._c〇_c6alkyl-arylheteroaryl-c0-Q alkyl- c(0)-, _C〇_c6 alkyl-heteroaryl_aryl_c〇_c6 _ 院-C(o)- and -C〇-C: 6 alkyl-heteroaryl_hetero Base_c〇_c6_alkyl group_c(〇)_; or zw is selected from the group consisting of -Cl-c8 alkyl_(NH2)C=N_, _CH alkyl_C=N_ and -C! _8 The group -C(CH3)=N-, when the RC system is absent; the L system is selected from the group consisting of a covalent bond, -qQ-alkyl-, -c0-c6-alkyl-(CRkCR3)"-c0-c6 -'-Co-Q alkyl-(CsQh-Co-Q alkyl-, -C〇-C6 alkyl-aryl-C0-C6 alkyl-, -C〇-C6 alkyl-heteroaryl-c 〇-C6 alkyl-, -C0-C3 alkyl-heterocyclic-CQ-C3 alkyl-, -CQ-C3 alkyl-cycloalkyl-C〇-C3 炫-, -C〇-C6 Base-aryl-(CR^CR'.rCo-Q alkyl- , -C〇-C6 alkyl-yl-(C = Ch 2 -c0 -C6 alkyl, -C0 -C6 alkyl-heteroaryl-(CRO^h-rCo-qalkyl-, -C0 -C6 alkyl-heteroaryl-(CEQn-c0-c6 alkyl-, -CQ-C6 alkyl-N(R3)-C (〇KVC3 alkyl-, -c〇-c6 alkyl-N (R3) )-C(S)-C〇-C3 院-,-C0-C6 alkyl-N(R3)-C(0)-alkenyl-c〇-c3 alkyl-, -C〇-C6 alkyl -N(R3)-C(s)-alkenyl-C〇-C3 alkyl-, 134026-1 -50- 200916447 -c0-c6 alkyl-n(r3)-c(o)-alkynyl-C 〇-C3 alkyl-, -c〇-c6 alkyl-N(R3)-C(S)-alkynyl-C〇-C3 alkyl-, -C〇-C6 alkyl-N(R3)-( :(0)-(:: -C3 alkyl-n(r3)-c(o)-, -c〇-c6 alkyl nkrskxskvc^alkyl-N(R3)-C(0)-, -C〇 -C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-N(R3)-C(0)-(^-(^alkyl...-匸^仏alkyl call 妒^ :(5)-Heart-^Alkyl-Wind)-!^. )-C〇-C3 alkyl-, -CG-C6 alkyl-N(R3)-0:(0)-(^-C3 alkyl-N(R3)-C(S)-C〇-C3 alkane Base-, -C〇-C6 alkyl-N(R3-C3 alkyl-N(R3)-C(S)-C0-C3 alkyl-, -CG-C6 alkyl-CCOH^Rq-Co-C ^alkyl-,-(:〇-(:6-alkyl-C(S)-N(R3)-C〇-C3 alkyl-, -C〇-C6 alkyl-C(0)-N(R3 )-C2 -C4 alkyl-0-CQ-C3 alkyl-, -C〇-C6 alkyl-C(S)-N(R3)-C2 -C4 alkyl-OQ-C3 alkyl-, -CQ -C6 alkyl-C(0)-N(R3)-C2-C4 alkyl-N(R3)-C〇-C3 alkyl-, -c〇-c6 alkyl-C(S)-N(R3 )-C2-C4 alkyl-N(R3)-C〇-C3 alkyl-, -c0-c6 alkyl-C(0)-CQ-C3 alkyl-, -CQ-C6 alkyl-C(NOH )-C〇-C3 alkyl-, -C0-C6 alkyl-C(O)-alkenyl-CG-C3 alkyl-, -CG-C6 alkyl-C(NOH)-alkenyl-(^- (^alkyl...-仏-^alkyl name (seven)^-:^"^^-^alkyl-,-!^·^ alkyl-N(R3)-S(0)2 -CG-C3 alkyl -, -C〇-C3 alkyl-N(R3)-S(0)2 -N(R3)-c〇-c3 alkyl-, -C〇-C6 alkyl-C(0)-N(R3 )-S(0)2-CQ-C3 alkyl-, -c0-C6 alkyl-N(R3)-CG-C3 alkyl-, -CG-C6 alkyl-N (R3-C3 alkyl-ene Base-, -C〇-C6 alkylalkyl-alkynyl-, -〇)-(:6-alkyl-N(R7)-Cq-C3 -, -Cg-Cg alkyl-N(R7)-Ci-C3 alkyl-dilutyl-, -LJ〇-(J6 alkyl-oxime (Κ/)-Ci-C3)-alkynyl-,- C〇院基-N(R3)-C2 -C4 alkyl-N(R3)-C(0)-alkyl-, -C〇-C6 alkyl-N(R3)-C2-C4 alkyl-N (R3)-C(S)-alkyl-, -CQ-C6 alkyl-0-C2 -C4 alkyl-N(R3)C(O)-C0-C3 alkyl-, -C〇-C6 alkane --S-C2-C4 alkyl-N(R3)C(0)-CQ-C3 alkyl-, 134026-1 -51 - 200916447 -C〇-C6 alkyl-0-C2-C4 alkyl-N (R3)C(S)-CG-C3 Alkyl-, -Co-c6 leu-S-C2-C4 leu-N(R3)C(5)-C. -C3 burnt base -, -C. -C6 alkyl-N(R3)-C2 -C3 heteroalkyl-, -CQ-C6 alkyl-N(R7)-C2-C3 heteroalkyl-, -QrQ ndyl-C(0)-N( R3)-C2 -C3 heteroalkyl-, -C〇-C6 alkyl-C(S)-N(R3)-C2 -C3 杂*, yl-, -C〇-C6 alkyl-C(0) -N(R7)-C2-C3 heteroalkyl-, -C〇-C6 alkyl-C(S)-N(R7)-C2-C3 heteroalkyl-, -C〇-C6 alkyl-N ( R3)-C(0)-C〇-C3 heteroalkyl-, -CQ-C6 alkyl-N(R3)-C(S)-C〇-C3 heteroalkyl-, -CG-C6 alkyl- N(R7)-C(0)-C〇-C3 heteroalkyl-, -C〇-C6 alkyl-N(R7)-C(S)-C〇-C3 heteroalkyl-, -C〇- C6 炫> base-SC〇-C3 烧基-, -C〇-C6 烧基_0-C〇-C3 炫基-, -C〇-C6 烧基-S(0)-C〇-C3 Base-, -C〇-Cg alkyl-S(0)2-C〇-C3 炫-, -c〇-c6 alkyl-n(r3)-c(o)-n(r3)-c〇 -c3 alkyl-, -C0-C6 alkyl-N(R3)-C(S)-N(R3)-CQ-C3 alkyl-, -C0-C6 alkyl-0-C〇-C3 alkyl -heteroyl-, -C〇-C6焼> base-0-C〇-C3 alkyl-cycloalkyl-, -C〇-Cg alkyl-S(0)〇- 2 -C〇-C3 Alkyl-heterocyclyl-, -C〇-C6 alkyl-S(O)0 _ 2 -C〇-C3 alkyl-cycloalkyl-, -CG-C6 alkyl-N(R3)-C( )-C3 alkyl-heterocyclyl-, _Cq_C6 炫-N(R3)-Cq-C3 炫基-环炫 "基-,-heterocyclyl-C〇-C6 yard base-0-C〇-C3 alkyl-,-cycloalkyl-C〇-C6 burn Base-0-C〇-C3 alkyl-,-heterocyclic-C〇-C6 alkyl-S(0)q-2-Cg-C3 Hyun> base-,-cycloalkyl group_cG-c6 --S(〇)〇-2 -C〇-C3 alkyl _,-heterocyclyl-C〇-C6 alkyl-N(R3)-C〇-C3 alkyl _, -cycloalkyl-Cg- Q-alkyl-N(R3)-CG-C3 alkyl-, -Cq_C6 taki-Ν(Ι^)-C(O)-O-C0-C3 fluorenyl-, -C〇-C6 yard-N (R3)-C(S)-〇-C0~c 院基-,-CVC6 alkyl-0-0(0)-Ν(Κ3Κν(:3 alkyl-, 〇 <:6 alkyl-0-C(S)-N(R3)-C〇-C3 alkyl-, -C〇-C3 院-N(R3)-C(0)-〇_杂譬久-C〇-C3 burnt base-, -C. -C3 alkyl-N(R3)-C(S)-0-heterocyclyl_C〇_C3 fluorenyl, 134026-1 -52- 200916447 -c〇-c3alkyl-n(r3)-c( o)-〇-cycloalkyl-C〇-C3 alkyl-, -Cq-C3 alkyl-N(R3)-C(S)-0-cycloalkyl-C〇-C3 alkyl-, -Q -C6 alkyl-S(0)2-heterocyclyl-C〇-C3 alkyl-, -C〇-Cg alkyl-S(0)2 -3⁄4 alkyl-C3 alkyl-, -C〇 -Cg alkyl-N(R3)-S(0)2-heterocyclyl_Q-C3 alkyl-, -CG-C6 alkyl-N(R3)-S(〇)2 -1⁄4 alkyl-Cq -C3 alkyl-, -C〇-C3 Hyun"-heterocyclyl-C〇-C3 alkyl--0-C〇-C3 alkyl-, -C〇-C3 alkyl-cycloalkyl-C〇 -C3 alkyl-〇-C〇-C3 alkyl-, -C〇-C3 alkyl-heterocyclic-C〇-C5 alkyl-N(R3)-C〇-C3 alkyl-, -C〇 -C3 alkyl-cycloalkyl-CG-C5 alkyl-N(R3)-C〇-C3 alkyl-, -CG-C3 alkyl-0-C〇-C3 alkyl-heterocyclyl-c〇 -C3 alkyl-, -C〇-C3 alkyl-0-C〇-C3 alkyl-cycloalkyl-CG-C3 alkyl-, _cG_c3 alkyl-heterocyclyl-CQ-C3 alkyl-S- CG-C3 alkyl-, -C〇-c3 alkyl-cycloalkyl-C〇-C3 alkyl-SC〇-C3 alkyl _, -c0 -C:3 alkyl-N(R3)-〇) -C3 alkyl-heterocyclyl-CQ-C3 alkyl-, -CG-c3 alkyl-N(R3)-Cq-C3 alkyl-naphthenic -C(rC3 alkyl-, _Cq_C3 alkyl-SC〇-C: 3 alkyl-heterocyclyl-C3 alkyl-, -C〇-C: 3 alkyl-SC〇-c3 alkyl-cycloalkyl -〇)-(:3 alkyl-, -CQ-C3 alkyl-S(0)2N(R3)-CQ-C3 alkyl-heterocyclyl-CG-C3 alkyl-, _cG-c3 alkyl- S(0)2 N(R3)-CG-C3 alkyl-cycloalkyl-c.-C3 院-' _C._c3 alkyl_C(0)_N(R3)_c._c3 alkyl_heterocycle --C〇-C3 alkyl-, _Cg_c3 alkyl _c(〇)_n(r3)_Cg_C3 alkyl _ cycloalkyl _c〇_C3 炫·基-, -cG-C3 院基-c(s) -n(r3)-〇)-C3 alkyl-heterocyclyl-C〇-C3 alkyl_, _Cg_c3 alkyl_c(3)_n(r3)_Cg_C3 alkyl-cycloalkyl-C〇-C3 yard--, _C ()_C3 Pit base _c(〇)-Heterocyclic group heart^--, _c〇A alkyl-C(O)-cycloalkyl_Cq_C3 alkyl _, _Cq_C3 alkyl _ 〇_c(0) _heterocyclyl-Co-c3 alkyl _, _Cq _c3 alkyl_0_c(0)_cycloalkyl_C() _c3 alkyl _, ^ calcyl-0-C(0)-N(R3)- Q-C3 alkyl-heterocyclyl_Q-C3 alkyl-, -Cq <:3 134026-1 -53- 200916447 Alkyl-oc(o)-n(r3)-cg-c3 alkyl-cycloalkyl-C〇-C3 alkyl-, -C0-c3 alkyl--0 -C(5)-N(R3)-C〇-C3 alkyl-heterocyclyl-C〇-C3 leuko-' _C〇-C3 alkyl--0-C(S)-N(R3)-C〇-C3 Alkyl-cycloalkyl-C〇-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-N(R3)-C〇-C3 alkyl-heterocyclyl-C 〇-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-N(R3)-C〇-C3 alkyl-cycloalkyl-CD-C3 alkyl-, -C0 -C3 alkyl-N(R3)-C(S)-N(R3)-C〇-C3 alkyl-heterocyclyl-CQ-C3 alkyl-, -C〇-C3 alkyl-N(R3) -C(S)-N(R3)-C〇-c3 alkyl-cycloalkyl-CQ-C3 alkyl-, -C0-C3 leu-N(R3)-C(0)-heterocyclyl- C0-C3 alkyl-, -C0-C3 decyl-N(R3)-C(0)-cycloalkyl-C〇-C3 alkyl-, -CG-C3 alkyl-N(R3)-C( S)-heterocyclyl-C〇-C3 院--,-C〇-C3 alkyl-N(R3)-C(S)-i smoldering-C〇-C3 alkyl-, -C〇- C3 alkyl-N(R3)-S(0)2-N(R3)-CG-C3 alkyl-heterocyclyl-CQ-C3 alkyl_, -CG-C3 alkyl-N(R3)-S (0)2-N(R3)-CQ-C3 alkyl-cycloalkyl-CQ-C3 alkyl-, -C〇-C6 alkyl-heterocyclyl-C(0)-C〇-Cg alkyl -, -C〇-C6 yard base-ring alkyl-C(0)-CQ-C6 alkyl-, -CG-C6 alkyl-n(r3)-c(o)-heterocyclyl-C(0)-CVC6 alkyl-, -CQ-C6 Alkyl-N(R3)-C(0)-cycloalkyl-C(O)-C0-c6 alkyl-, -c〇-c6 alkyl-n(r3)-c(s)-heterocyclyl -c(o)-c〇-c6 alkyl-, -C〇-C6 alkyl-N(R3)-C(S)-cycloalkyl-C(0)-C(rC6 alkyl-, -C 〇-C6 alkyl-heterocyclyl-S(0)2-C〇-C6 alkyl-'-c〇-c6 alkyl-cycloalkyl-s(o)2-c〇-c6 alkyl-, -C〇-C6 alkyl-heterocyclyl-n(r3)-c(o)-c〇-c6 alkyl-, -c〇-c6 alkyl-cycloalkyl-N(R3)-C(0 )-C〇-C6 alkyl-, -CG-C6 alkyl-heterocyclyl-0-C(0)-C〇-C6 alkyl-, -CQ-C6 alkyl-cycloalkyl-0-( :(0)-(:〇-c6 alkyl-, -c0-C6 alkyl-heterocyclyl-N(R3)-C(S)-C〇-C6 alkyl-, -Q-C6 alkyl- Cycloalkyl-n(r3)-c(s)-c〇-c6 alkyl-, -c〇-c6 alkyl-heterocyclyl-oc(s)-C〇-C6 alkyl-, -C〇 -C6 alkyl-cycloalkyl-indole-C(S)-C〇-Cg alkyl-, -C〇-C3 134026-1 •54- 200916447 alkyl-CttN-O-Co-Cg alkyl-, -cG-c3 alkyl-c=n(oh)c(o)-N(R3)-C2 -C4-alkyl-SS-alkyl-, -c. -C6 alkyl-heteroalkyl-Q-c6 alkyl-C(0)-N(R3)-CQ-C3 alkyl-, -C〇-C6 alkyl-heteroalkyl-CG-C6 alkyl- C(S)-N(R3)-C0-C3 alkyl-, -QrQ alkyl-aryl-heteroaryl-C〇-C6 alkyl-, -C0-C6 alkyl-heteroaryl-aryl -QQ alkyl-, -C〇-C6 alkyl-heteroaryl-heteroaryl-C0-C6 alkyl-, -C〇-C6 alkyl-aryl-aryl-C0-C6 alkyl-, -Ci -C3 alkyl-N(R3)-(:(0)-(^-C7 alkyl-, -C3 alkyl-N(R3-C7 alkyl-, -C〇-C3 alkyl-alkenyl) -C(0)-C〇-C6 alkyl-, -C〇-C6 alkyl-N(R3)-C(0)-N(R3)-S(0). 2 -C.-C3 alkyl -, -C.-C3 alkyl-O-aryl-C〇-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-, -C0-C3 alkyl-s- aryl-C〇-C6 alkyl-N(R3 χχο)^-C3 alkyl-, -C〇-C3 alkyl-a aryl-C〇-C6 alkyl-N (R3 plant (5) must-C3 alkane --, -C〇-C3 alkyl aryl _c〇_c6 alkyl-N(R3)C(S)-C] -C; 3 fen--, -C0-C3 alkyl-indole-hetero Aryl-c〇(6 alkyl-N(R3)-(:(〇)-0:! -C3 alkyl-, -C〇-C3 alkyl-S-heteroaryl_c〇_Q alkyl -N(R3 -C3 alkyl-, -C〇-C3 alkyl-O-heteroaryl_c〇_c6 calcined-N (R3-C3 alkyl-, -C0-C3 Alkyl-S-heteroaryl_c〇C6 alkyl-N (R3-C3 alkyl-, -CG-C3 alkyl-0-heterocyclic group & % alkyl-N(R3)-(:( 0)-(:! -C3 炫基-, -C0-C3 炫基-S-heterocyclic group_c〇_C6 烧武-N(R3)-(:(0)-(^-C:3 alkane --, -C0-C3 alkyl-O-heterocyclic odor-NO^-CXSKVCs alkyl-, -CG-C3 alkyl-S-heterocyclic group_Cg_c6 烧义-Ν(Ι^ -C3 烧Base-, -C〇-C3 alkyl group-0-cycloalkyl group _Cq_c6 -Synthesis-N(R3)-0(0)-0^-C3 alkyl-, -CG-C3 alkyl-S-ring %% & calcination-Na^-cxcoA-C3 leuko-, -eve: 3 alkyl-o-cycloalkyl _c〇_C6-sinter-N(R3)-C(5)-C3 alkyl-,- C〇-C3 alkyl-S-cycloalkyl _c〇_Q 烧美134026^1 -55- 200916447 -N(R3 hCOCi -C3 alkyl-, -C〇-C3 alkyl-N(R3)- aryl-C〇-C6 alkyl-N(R3)-(:(0)-^-C3 alkyl-, -C〇-C3 alkyl-N(R3)-aryl-C〇-C6 alkyl -N(R3 yCXS)-^ -C3 alkyl-, -C〇-C3 alkyl-N(R3)-heteroaryl-C〇-C6 alkyl-N (R3 -C3 alkyl-, -C〇 -C3 alkyl-N(R3)-heteroaryl-C〇-C6 leu-N(R3)-C(S)-Ci_C3 alkyl-, -CQ-C3 alkyl-N(R3)-heterocyclic -C0-C6 alkyl-NO^KXOKVCs alkyl-, -CQ-C3 alkyl-N(R3)-hetero --CG-C6 alkyl-N^KXSKVQ alkyl-, -CQ-C3 alkyl-N(R3)-cycloalkyl-CQ-C6 alkyl-N(R3)((0)-(^-C3 Alkyl-, -C. -C3 alkyl-N(R3)-cycloalkyl-C〇-C6 alkyl-N^KXSKVCs alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-0-aryl -C0-C6 alkyl-NCRq-CXCO-Ci-Cs alkyl-'-C0-C3 alkyl-N(R3)-C(S)-0-aryl-C0-C6 alkyl-N(R3) ((0)-(:! -C3 alkyl-, -C0-C3 alkyl-N(R3)-C(0)-S-aryl-C〇-C6 alkyl-N(R3)-C( 0)-CVC3 alkyl-, -c0-c3 alkyl-n(r3)-c(o)-o-aryl-C〇-C6 alkyl-N (R3 KXSXi-C3 alkyl-, -C〇 -C3 alkyl-N(R3)-C(S)-0-aryl-C〇-C6 alkyl-N(R3-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C (0)-S-aryl-C〇-C6 alkyl-N(R3)-C(S)-C, -C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0 -0-heteroaryl-C〇-C6 alkyl-N^KXOKVq alkyl·,-C0-C3 alkyl-N(R3)-C(S)-0-heteroaryl-C〇-C6 alkane --N(R3)-0(0)-(^-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0) each heteroaryl-C〇-C6 alkyl-N (R3)-(:(0)-(^-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-0-heteroaryl-C〇-C6 alkyl-N (R3)-(:(5)-匚丨-C3 alkyl-, -C0-C3 alkyl-N(R3)-C(S)-0-heteroaryl-C.-C6 alkyl-N(R3- C3 alkyl-, -CQ-C3 alkyl-N(R3)-C(0)-0-heterocyclic-C0-C6 alkyl-N(R3)-(:(0)-(^-C3 alkane Base-, -C.-C3 alkyl-N(R3)-C(S)-0-heterocyclyl-CG-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl -, -CG-C3 alkyl 134026-1 56· 200916447 -N(R3)-C(0)-0-heterocyclylalkyl_N(R3)_C(5)·Ci_c3 alkyl-, -C〇-C3 alkane --N(R3)-C(S)-0-heterocyclyl-c〇-c6 alkyl-N (R3 VCXSyCi-C3 alkyl-, -C〇-C3)-N(R3)-C( 〇)-〇-cycloalkyl-C.-c6 alkyl-N(R3)-CXCO-CrCg alkyl-, _cG-C3 alkyl_N(R3)_C(5)_〇_cycloalkyl-Cg_C6 alkyl- N(R3)-(:(0)-(^-C3 alkyl-, 〇-)-(:3 alkyl-N(R3)-C(0)-0-cycloalkyl-C〇-C6基-N(R3 VQSK-C3 alkyl-, _c〇-C3 alkyl-N(R3)-C(S)-0-cycloalkyl-CG-C6 alkyl-N(R3)-C(5) alkyl -, -CG-C3 alkyl-C(0)-N(R3)-aryl-C〇-C6 alkylalkyl-, -C〇-C3 alkyl-C(S)-N(R3)- Aryl-c0-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-, -C〇-C3 alkyl-C(0)-N(R3)-aryl_c0 -C6 alkyl-N(R3 -C3 alkyl-, -C〇-C3 alkyl-C(5)-N(R3)-aryl-c〇-C6 alkyl-N(R3)-C(5)-C--C3 Alkyl-, -C〇-C3 alkyl-C(0)-N(R3)-heteroaryl-Q-C6 alkyl-N(R3)C(0)-CVC3 alkyl-, -C〇- C3 alkyl-C(S)-N(R3)-heteroaryl-C0- C6 alkyl-N(R3)(:(0)-(^-C3 alkyl-, -C0-C3 alkyl-C(0)-N(R3)-heteroaryl-C〇-C6 alkyl- N(R3 KXSKi -C3 alkyl-, _c〇-C3 alkyl-C(S)-N(R3)-heteroaryl-C〇-C6 alkyl-N^XXSHI:]-C3 alkyl-,- C0-C3 alkyl-C(0)-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-, -C〇- C3 alkyl-C(5)-N(R3)-heterocyclyl-C〇-C6 alkyl-N^KXOKVQ alkyl-, -C0-C3 alkyl-C(0)-N(R3)-heterocyclyl- C〇-C6 alkyl-N^KXSK^-C3 alkyl-, -Co-C3 alkyl-C(S)-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)- C(S)-Ci-Q alkyl-, -C〇-C3 alkyl-C(0)-N(R3)-cycloalkyl-Cq-Q alkyl-N^y-QOKVC^ alkyl-, -C〇-C3 alkyl-C(S)-N(R3)-cycloalkyl-C〇-C6 alkyl-N(R3-C3 院-, -C〇-C3 alkyl-C(0) -N(R3)-cycloalkyl-C〇-C6 alkyl-N^H^SKVCg alkyl-, -C〇-C3 alkyl 132046-1 •57- 200916447 -C(5)-N(R3)-cycloalkane --C〇-C6 alkyl-N(R3)-C(3)-C3 alkyl-, -C0-C3 alkyl-0-C(0)-N(R3)-aryl-C〇-C6 alkyl- N(R3)-(:(0)4-C3 alkyl-, -C〇-C3 alkyl-O-C(5)-N(R3)-aryl-C0-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C〇-C3 alkyl-0-C(0 )-N(R3)-aryl-C〇-C6 alkyl-N(R3)-C(S)-alkyl-, -C〇-C3 alkyl-0-C(5)-N(R3)-aryl -C0-C6 alkyl-NCI^KXSKVQ alkyl-, -C0-C3 alkyl-0-C(0)-N(R3)-heteroaryl-C〇-C6 alkyl-N(R3)-( :(0)-(^-C3 alkyl-, -C〇-C3 alkyl-0-C(5)-N(R3)-heteroaryl-C0-C6 alkyl-C3 alkyl-, -C〇-C3 Alkyl-0-C(0)-N(R3)-heteroaryl-C〇-C6 alkyl-Nil^KXSKVC^alkyl-, -C〇-C3 alkyl-0-C(S)-N (R3)-heteroaryl-C〇-C6 alkyl-N(R3-C3 alkyl-, -C〇-C3 alkyl-0-C(0)-N(R3)-heterocyclyl-C〇 -C6 alkyl-N(R3)-CCOKVC3 alkyl-, -C〇-C3 alkyl-0-C(S)-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3 Κ (0)·Α-C3 alkyl-, -C〇-C3 alkyl-0-C(0)-N(R3)-heterocyclyl-C〇-C6 alkyl-N (R3-C3 alkyl- , -C〇-C3 alkyl-0-C(S)-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)-C(5)-CVC3 alkyl-, -C〇-C3 alkane -0-C(0)-N(R3)-cycloalkyl-CG-C6 alkyl-I^RSKXOKVCs alkyl-, -C〇-C3 alkyl-O-C(5)-N(R3)-cycloalkane --C〇-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-, -C〇-C3 alkyl-0-C(0)-N(R3)-cycloalkane --C〇-C6 alkyl-r^Ri-CO-CVC^ alkyl-, -C〇-C3 alkane -0(C)-N(R3)-cycloalkyl-C〇-C6 alkyl-Nil^KXSKVCs alkyl-, -C〇-C3 alkyl-S(0)2-N(R3) -aryl-1〇7-6 alkyl-N(R3)_c(〇)-Ci-C]alkyl-, -C〇-C3 alkyl-S(0)2·N(R3)-aryl- C〇-C6 alkyl-N(R3 -C3 alkyl-, -C〇-C3 alkyl-S(0)2-N(R3)-heteroaryl-C0-C6 alkyl-I^R'CCOKVCs Alkyl-, -C0-C3 alkyl-S(0)2-N(R3)-heteroaryl-C0-C6 alkyl-N (R3-C3 134026-1 -58· 200916447 alkyl-, -c 〇-c3 alkyl-s(o)2-n(r3)-heterocyclyl_q_C6 alkyl_n(R3)-C(0)-C--C3 alkyl-, -C〇-C3 alkyl -S(0)2 -N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)-C(5)-Q-C3 alkyl-,-C〇-C3 _s(〇)2 -N(R3)-cycloalkyl-C0-C6 leuko-NO^KXOKVCg alkyl-, -C〇_c3 alkyl _s(0)2-N(R3)-cycloalkyl-QQ alkyl- N^KXSKVq alkyl-, -C(rC3 alkyl-N(R3)-S(0)2-N(R3)-aryl-C0-C6 alkyl-N(R3)-C(0)_Cl _c3 Alkyl-, -匚0-(:3 alkyl-;^(113)-3(〇)2 ton 113)-aryl-(:0-(:6-alkyl-:^(113)-(: (8)-Q-C3 alkyl-, -C〇-C3 alkyl-N(R3)-S(0)2-N(R3)-heteroaryl-C0-C6 alkyl-N(R3)- (:(0)-(^ -C3 alkyl-, -C〇-C3 alkyl-N(R3) )-S(0)2 -N(R3)-heteroaryl-C0-Q alkyl-N(R3-C3 炫-, -C〇_c3 alkyl_N(R3)_S(0)2 -N(R3)-heterocyclyl-c0-c6 alkyl-N(R3)-(:(0)-(:^3 alkyl-, -(^-(^-alkyl-fengxin^(9) factory wind尺"-Heterocyclyl-Cytoalkyl-Wind-匸(5)-q-C3 Alkyl-,-CQ-C3 Alkyl-N(R3)-S(0)2-N(R3)-cycloalkyl -CQ -C6 alkyl-ι^ι^κχοκνο^alkyl-, -c〇-c3 alkyl-n(r3)-s(o)2-n(r3)-cycloalkyl-C〇-Q --N(R3丨-匚(8)-heart-C3 alkyl group_,-CQ-C3 alkyl-heterocyclic-indole-aryl-C〇-C6 alkyl-N(RJ)-0(0)- (^ -C3 alkyl group-, -C〇-C3 alkyl group-heterocyclic group-S-aryl-C〇-Q alkyl group-N(R3)-(:(0)-(^-C3 alkyl group- , -C〇-C3 alkyl-heterocyclyl-0-aryl-C0-C6 alkyl-N (R3 ycXSK! -C3 alkyl-, _c〇-C3 alkyl-heterocyclyl-s-aryl -Co-qalkyl-n^kxskvqalkyl-, -C0-C3 alkyl-heterocyclyl-fluorene-heteroaryl_c〇_C6 alkyl_N(R3)_c(〇)_Ci & Base-, -C〇-C3 alkyl-heterocyclyl-s-heteroaryl_c〇-C6 alkyl-N(R3)-(:(;〇)-CVC: 3 alkyl-, -C0- C3 alkyl-heterocyclyl-〇_heteroaryl_c〇_c6 alkyl-N (R3 yCXShC! -C3 alkyl-, -C0-C3 alkyl-hetero --S-heteroaryl_Cq & aryl-N(R3 hQS)% -C:3 alkyl-, -Cq 4 alkyl-heterocyclyl-〇-heterocyclyl 1300026-1 • 59- 200916447 -C〇-C6 alkyl-N(R3)_c(0)_Cl _c3 alkyl-, -Q-C3 alkyl-heterocyclyl-s-heterocyclyl-CG-c6alkyl-N(R3)- (:(0)-(^-C3 alkyl-, -CG-C3 alkyl-heterocyclyl-fluorenyl-heterocyclyl-CQ-C6 alkyl-N(R3)-C(5)-Ci-C3 alkyl- -CVC3 alkyl-heterocyclyl-s-heterocyclyl-c. _C6 alkyl _N(R3)_c(5)_Ci _C3 院基_,_c〇alkyl-heterocyclyl_〇_cycloalkyl_Cq _C6 alkyl_N(R3)_c(〇)_Ci _C3 alkyl... -C〇 -c3 alkyl-heterocyclyl_s_cycloalkyl-c. _c6alkyl_N(R3)_c(〇)_Ci_c3 alkyl...-C〇-C3 alkyl-heterocyclyl-0-cycloalkyl-Cq_C6 alkyl-N(R3)_c(s)_alkyl ·, _C()_C3 alkyl-heterocyclyl_s_cycloalkyl-Cg_c6 alkyl_N(R3)-C(5)-Ci-Q alkyl·, -C0-C3 alkyl-C(O)- Cyclo-o-aryl-C0-C6 alkyl-N(R3)_c(0)_Ci _c3 alkyl_,_c〇_c3 alkyl_c(5)_heterocyclyl-O-aryl-C0-C6 -N(R3)-0(0)-(^-C3 alkyl-, -C0-C3 alkyl-c(0)_heterocyclyl-S-aryl-C〇-Q alkyl-N ( R3)-(:(0)% -C3 alkyl-, -c0-c3 alkyl-C(O)-heterocyclyl-〇_aryl_C(rC6alkyl_N(R3)_c(5)^ _C3 Base_, -C〇-C: 3 alkyl-C(s)-heterocyclyl-s-aryl-c0-C6 alkyl-N(R3)-(:(0)4-c3 alkyl-, -C0-C3 alkyl-C(S)-heterocyclyl-o-aryl-C〇-C6 alkyl-N(R3)-QSKVC3 alkyl-, -C0-C3 alkyl-c(0)- Heterocyclyl-s-aryl-C〇-C6^--N(R3 KXSK:! -C:3 alkyl-, -C0-C3 alkyl-C(s)-heterocyclyl-S-aryl -c0 -C6 alkyl-N(R3)-C(5)-C, -C3 alkyl-, -Q-c3 alkyl-C(oxime)-heterocyclyl-O-heteroaryl-C0-C6 alkyl- Nd^-CCO)-^-C3 alkyl-, -C0-C3 alkyl-C(S)-heterocyclyl-0-heteroaryl-C〇-c6 alkyl-N(R3)-(:( 0)-(^ - C3 alkyl_, -c0-c3 alkyl-c(o)-heterocyclyl-s-heteroaryl_c〇_C6 alkyl_n(r3)_c(〇)_ q -C:3 alkyl -, -C0 -C3 alkyl-C(O)-heterocyclyl-indole_heteroaryl_c〇_c6alkyl-N (R3 & alkyl-, c0-C3 alkyl-C(S) -heterocyclyl-s-heteroaryl-C〇-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl·, -C〇_c3 alkyl_c(s)_ Heterocyclic group 134026-1 •60- 200916447 -〇-heteroaryl-C0-C6 alkyl-N(R3)_C(3)_Ci_c3 alkyl...alkyl-C(9)-heterocyclyl-s-heteroaryl_C〇A —N(R3 )_c(8)_Ci _C3 alkyl group - -c〇-c: 3 alkyl group _c(5)-heterocyclyl heteroaryl group _c〇_C6 alkyl_N(R3K(3)· Cl -C3 alkyl-, - C〇-C: 3 alkyl-C(O)-heterocyclyl-0-heterocyclyl_c〇_c6 alkyl-N(R3)-C(〇)-Cl-C:3 alkyl-, -Q -C3 alkyl group-C(s)-heterocyclic group_〇_heterocyclyl-Co-Q alkyl-N(R3)_C(0)_Cl-c:3 alkyl...c〇弋alkyl_ c(〇)heterocyclyl-S-heterocyclyl-QC: 6 alkyl-NdOAc^CpC3 alkyl-, _c. -^alkyl-C(O)-heterocyclyl-0-heterocyclyl-C() _c6alkyl_N(R3)_c(8)Cl _C3 alkyl, -Q-C3 alkyl-c(5)-heterocyclyl_ s-heterocyclyl_c〇_C6alkyl_N(R3)_c(〇)· c! -C3 alkyl-, -CG-c3 alkyl-C(5)-heterocyclyl-0-heterocyclyl_Cq _c6alkyl-N(R3 -C3 alkyl-, -C〇-C3 alkyl-C(oxime)-heterocyclyl_s_heterocyclyl-oxime)%alkyl-N(r3h:(5)_Cl_C3 alkyl- , _Q_C3 alkyl._c(3)-heterocyclyl-S-heterocyclyl-QQ alkyl-N^KXSKVC3 alkyl-, _C〇_C3 alkyl; C(0)-heterocyclyl-fluorenyl-cycloalkyl- Q) -C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl_, -C〇-〇3 alkyl-C(S)-heterocyclyl-fluorene-cycloalkyl- Q) -C6 alkyl-N(R3)_C(〇)-C1-C3 alkyl-, _CQ-C3 alkyl-C(O)-heterocyclyl-s-cycloalkyl-C (rC6 alkyl) N(R-C; 3 alkyl-, -C〇-C; 3 alkyl-C(O)-heterocyclyl-〇-cycloalkyl-C0 alkyl-N (R3-Cs alkyl-, - C〇-C3 alkyl-C(s)-heterocyclyl-S-cycloalkyl-QQalkyl-N(R3)-(:(0)々-C3 alkyl-, -Cq_C3 alkyl-C( S)-heterocyclyl-fluorenylcycloalkyl-Cq _c:6-alkyl-N(R3)_c(5)_Ci &alkyl-, -C〇-C3 alkyl-C(〇)-heterocyclyl-S- Cycloalkyl-Q-C6 alkyl-N(R3)-C(5)-q-C:3 alkyl-, -Q _c: 3-alkyl-(:(5)-heterocyclylcycloalkyl-Cq alkyl-N(R3)-C(5)-Ci-Q alkyl-, -c〇-c3 leu-n(r3)-c( o)·Heterocyclyl_〇_ aryl-C〇-C6 alkyl-N^KXOKVC^alkyl-,-c〇-c3 alkyl 134026-1 -61 - 200916447 -N(R3 )-C(S -heterocyclyl-oxime-aryl_C〇_c6 alkyl_n(R3-C3 alkyl-, -C0-C3 alkyl-N(R3)-C(0)-heterocyclyl-S- Aryl-C〇-C6 alkyl-N(R3)-CCCO-Ci-Cg alkyl-, -Co-Q alkyl-N(R3)-C(0)-heterocyclyl-o-aryl- C〇-C6 alkyl-N(R3-C3 alkyl-, -C.-C3 alkyl-N(R3)-C(S)-heterocyclyl-S-aryl-C0-C6 alkyl-N (R3)-(:(0)4-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-heterocyclyl-indole_aryl_c〇_C6 alkyl_ N(R3)_c(5)_Ci_C3 alkyl-, -QC:3 alkyl-N(R3)-C(0)-heterocyclyl-S-aryl-C〇-C6 alkyl_N(R3)_C(S -Ci-C3 alkyl-, -C0-C3 alkyl-N(R3)-C(S)-heterocyclyl-s-aryl-CQ-C6 alkyl-N(R3)-C(5)-Q- C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(O)-heterocyclyl-fluorene-heteroaryl_C〇_C6 alkyl_n(r3)_c(〇)_Ci _C3 Alkyl, -C0-C3 alkyl-N(R3)-C(S)-heterocyclyl-indole-heteroaryl (0% alkyl-N(R3)-(:(0)-(^-C3) Alkyl-, _CQ-C3 alkyl- N(R3)-C(0)-heterocyclyl-s-heteroaryl-C0-C6 alkyl-N(R3 alkyl-, -C0-C3 alkyl-N(R3)-C(0)- Heterocyclyl-〇·heteroaryl_c〇% alkyl_N(R3)_c(s)_Ci & alkyl-, -Q-C3 alkyl-N(R3)-C(S)-heterocyclic --s-heteroaryl-C0-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-, -C〇_C3 alkyl_N(R3)_C(5)_ heterocyclyl_ 〇_heteroaryl-C〇-C6 alkyl-N^KXSK^-Cg alkyl-, -C0-C3 alkyl-N(R3)-C(0)-heterocyclyl_S_heteroaryl_ C〇% alkyl_N(R3^(8) force ☆ alkyl-, -c0-c3 alkyl_n(r3)-c(s)-heterocyclyl_s_heteroaryl_c〇_C6 alkyl -N(R3 WSyq A alkyl-, alkyl_N(R3)_c(〇)_heterocyclylhetero-cG-c6 alkyl-n(r3)-C(0)_Ci_C3 alkyl _, _C "C3 alkyl-n(r3)-c(3)-heterocyclylheterocyclyl-c〇(6 alkyl _n(r3)_ 七7 1 alkyl-, -Q-C3 alkyl-N(R3) _C(0)_heterocyclyl_s_heterocyclyl-c〇夂alkyl-N(R3)-C(0)-Cl-C3 alkyl-, -Cq C3 alkyl _N(R3)_c( 〇)_Heterocyclyl_〇_ 134026-1 -62- 200916447 Heterocyclyl-C0-C6 alkyl-NO^-QSK^C3 alkyl-, -C(rC3alkyl-N(R3)-C( S)-heterocyclyl_s-heterocyclyl_C() ☆alkyl_N(R3)_c(〇)_Ci & alkyl-, -c〇-c3 alkyl_n(r3)-c(5)- Heterocyclyl-indole_heterocyclyl_C()_C6 alkyl-N(R3 KXSK^-C3 alkyl group·, <ν(:3 alkyl group_零3 KXC〇_heterocyclyl-based group-QQ alkyl-N(R3)-C(S)_Ci_C3 alkyl-, alkyl-N(R3)-C(S) -heterocyclyl-s-heterocyclyl-Co-C6 alkyl-N(R3XOC-C3 alkyl-, -c〇-c3 alkyl-n(r3)-c(o)-heterocyclyl-oxime -cycloalkyl-C()-C6 alkyl-N(R3)-(:(0)-(:!-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(S)- Heterocyclic group; cycloalkyl-C〇-C6 alkyl-N^KXCO-CVCs alkyl-, -Cg_c3 alkyl-N(R3)-C(0)-heterocyclylcycloalkyl_C〇_ C6 alkyl-N(R3)_c(〇)_Ci & alkyl-, -CG-C3 alkyl-N(R3)-C(0)-heterocyclyl-fluorenyl-cycloalkyl-Cq_C6 alkyl- N(r3)_C(5)_C1-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(5)-heterocyclyl-s-cycloalkyl-c.-c6 fen-N(R3)-(: (0)-(^-C3 alkyl group-, -CQ-C3 alkyl group-N(R3)-C(S)-heterocyclic-indole-cycloalkyl-Q-C6 alkyl-N (R3-C3 Alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-heterocyclyl-S-cycloalkyl-CQ-C6 alkyl-N(R3)_CXSKi-C3 alkyl-, -Q-C3 alkyl-N(R3)-C(S)-heterocyclyl-S-cycloalkyl-C〇-C6 alkyl-N (R3 VCXSKi-C3 alkyl-, -C.-C3 alkane --S(0)2 -heterocyclyl-〇_方方_C〇-C6 alkyl-C3 炫基-,-〇)-C3 alkyl-S(0)2-hetero Base-s-aryl-c0-C6 alkyl-N (R3 KXCO-q-C3 alkyl-, -c〇-c3 alkyl-s(0)2-heterocyclyl-o-aryl-C0- C6 alkyl-N(R3)-C(s)-Ci-C3 alkyl-, -C0-C3 alkyl-s(o)2-heterocyclyl-s-aryl-c〇-c6 alkyl- N(R3 -C3 alkyl-, -C〇-C3 alkyl-S(0)2-heterocyclyl-indole-heteroaryl-C〇-C6 alkyl-N(R3)-(:(0) -(^ -c3 alkyl-, -c〇-c3 alkyl-s(o)2-heterocyclyl-S-heteroaryl-c0-C6 alkyl-N(R3)((0)-(^ -C3 alkyl-, -C〇-C3 alkyl 134026-1 -63- 200916447 -s(o)2 -heterocyclyl-αheteroaryl_c〇_c6alkyl_n(r3)_c(5)_C1 alkyl _, -C〇_C3 alkyl-S(0)2'heterocyclyl-S-heteroaryl-CG-C6 alkyl_N(R3)_C(5)_Cl-C3 alkyl-, -C〇-c3 --S(〇)2-heterocyclyl-o-heterocyclyl_C() _c6alkyl-N(R3)-(:(0)-(^-C:3 alkyl_, -Q _C3 alkane Base _s(〇)2 _heterocyclyl each heterocyclic group-C〇-C6 alkyl-N (R3k: (〇KVC3 alkyl-, _c〇_C3 alkyl_s(〇)2_heterocyclyl) -o-heterocyclyl-CG-c6alkyl-N (R3 ycoq -C3 alkyl_, _cQ _c3 alkyl-S(0)2 -heterocyclyl_S_heterocyclyl_Q alkyl-n ( R3)_c(5)Benyl group... -Co-c:3 Alkyl-S(0)2_Heterocyclyl-〇-cycloalkyl-Cg_c6 Alkyl_n(r3)c(〇) _ q -C:3 alkyl-, -cG _(:3 alkyl_s(0)2 _heterocyclylcycloalkyl-Cq alkyl-N(R3)-C(0)_Cl _C3 alkyl _, _Cq alkyl_s(〇)2 _heterocyclyl-〇-cycloalkyl-C0-C6 alkyl-N(R3 KXS)-^-C3 alkyl...-c. -C3 alkyl-s(0)2-heterocyclyl-S-cycloalkyl-CG-Q-alkyl-N(R3-Cs-alkyl-, -Q-c3alkyl-heterocyclyl-N(R3) -aryl-C0-C6 alkyl-N^KXOK^;alkyl-, -C〇-C3-homo-heterocyclyl_N(R3)_aryl-c〇%alkyl_n(r3)_c(5)&amp ; & calcinyl-, -C〇-C3 alkyl-heterocyclyl-N(R3)_heteroaryl_c〇%alkyl_n(r3)_-C3 cyclyl-, -C0-C3 -heterocyclyl-N(R3)-heteroaryl_c〇_c6]-N(R-C3 alkyl-, -CG-C3 alkyl-heterocyclyl-n(R3)-heterocyclyl -CQ-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl-, -CG-c3 alkyl-heterocyclyl-N(R3)-heterocyclyl-C(rC6 alkane --N(R3)-C(5)alkyl-, -CG-C3 alkyl-heterocyclyl-N(R3)-cycloalkyl-C〇-C6 alkyl-N(R3)-(:(0)- (^-C3 alkyl_, -C0-C3 alkyl-heterocyclyl-N(R3)-cycloalkyl-CQ-C6 alkyl-N(R3)-C(s)-Ci-C;3 -'-C〇-C3 alkyl-C(O)-heterocyclyl-N(R3)-aryl-C0-C6 alkyl-N(R3)-0(0)-(^-C3 alkyl -, -C〇-C3 alkyl-C(S)-heterocyclyl-N(R3)-aryl-C〇-C6 alkyl-N (R3 KXCO-C!-C3 alkyl-, -C. -C3 alkyl-C(0)-heterocyclyl 1300026-1 200916447 -N(R3)_aryl_Q &alkyl_n(r3) c(s)_Ci & alkyl-, _c〇 々alkyl-c(s)-heterocyclyl_N(R3)_aryl_Q-butyl-N(R3)c(5)-m-alkyl, -Q-C3 alkyl-c(0)-heterocyclyl _N(R3)_heteroaryl_c〇_C6 alkyl-QOKVC3 alkyl_ ' _Q_C3 alkyl_c(5)-heterocyclyl_N(R3),heteroaryl-C〇-C:6 alkyl_ N(R3)_c(0)_Ci_C3 alkyl_,_c〇alkyl_c(〇)_heterocyclyl-N(R3)_heteroaryl_c〇_c6 alkyl_n(r3)_c(5)_Ci alkane Base-, fluorenyl-c(s)-heterocyclyl-N(R3)_heteroaryl-C〇alkyl_N(R3)_c(5)_Ci_c3alkyl-, -C〇-C3 alkyl-C( O)-heterocyclyl-N(R3)-heterocyclyl-C(rc6alkyl-N(R3)-C(0)_Cl _c3 alkyl_, _c3 alkyl_c(5)_heterocyclyl_n(r3 )-heterocyclyl-C(rC6 alkyl_N(R3)-(:(0)-(^-C3 alkyl-, -C〇-C3 alkyl-c(0)-heterocyclyl-N ( R3)-heterocyclyl-Q _Q alkyl _N(R3 )_c(5)_Ci _c3 alkyl-, _c〇4 alkyl-C(S)-heterocyclyl_N(R3)_heterocyclyl_Q _Q alkyl _N(R3) c(5)_Ci ^ alkyl-, -CQ-C3 alkyl-C(O)-heterocyclyl, N(R3)-cycloalkyl-CG-C6 alkyl-N(R3)-(:( 0)-(^-c3 alkyl-, -CQ-c3 alkyl-C(s)-heterocyclyl-N(R3)-cycloalkyl-CG-C6 alkyl-N (R3 ycxco-q -c3 Alkyl-, -CQ-c3 alkyl-c(0)-heterocyclyl-N(R3)-rings _Q_c6 alkyl-N(R3ycxsvc! -C3 院-, -C〇-C3 alkyl-C(s)-heterocyclyl_N(R3)_cycloalkyl_cG_c6alkyl_N(R3)_c(5)_Ci Alkyl-,-C0-C3 alkyl-N(R3)-C(0)-heterocyclyl_N(R3)-aryl-(:0-(:6-alkyl-N^KXCO-C] - C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-aryl-C〇_c6 alkyl_N(R3)_c(〇) Seven plants Q alkyl _, _c〇_C3 alkyl-n(r3)-c(o)-heterocyclyl_N(R3)_ aryl_c〇_C6 alkyl_N(R3)_C(5)_Ci_C3 alkyl -, -c0 -C:3 alkyl-N(R3)-C(S)-heterocyclyl_n(R3)-aryl-c0-C6 alkyl-N^KXSKVQ alkyl-, -C〇- C3 alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-heteroaryl-c0-C6 alkyl-N(R3)-(:(0)-(^-C3 alkyl -, -C0 -C3 alkane 134026-1 -65- 200916447 yl-N(R3)-C(S)-heterocyclyl-N(R3)-heteroaryl-C0-C6 alkyl-N(R3)- C(0)-C! -C3 alkyl-, -C〇-C; 3 alkyl-N(R3)-C(0)-heterocyclyl_N(R3)-heteroaryl-C〇-C6 Burning base - N (R3 - C3 alkyl group -, -C. -C3 alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-heteroaryl-C0-C6 alkyl-N(R3)-C(5)-C3 alkyl_, -C0-C3 Alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-heterocyclyl-C0-C6 alkyl-n(r3)-c(〇)-ci-c3 alkyl-,- C〇-C3 alkyl·ν(ϊ13)-(:(8)-heterocyclyl-N(R3)-heterocyclyl-CQ-C6 alkylalkyl-, -C〇-C3 alkyl-N ( R3)-C(0)-heterocyclyl-N(R3)-heterocyclyl-Cq_c6 alkyl-N(R3)_C(5)_Ci-C3 alkyl-, -C〇-C3 alkyl-N(R3)- C(S)-heterocyclyl-N(R3)-heterocyclyl-C0-C6 alkyl-N^KXSKVCg alkyl-, -C(rC3 alkyl_N(R3)_c(〇)_ heterocyclyl -N(R3)-cycloalkyl-C〇-C6 alkyl-N(R3)-0:(0)-(^-C3 alkyl-, -C0-C:3 alkyl-N(R3)- C(S)-heterocyclyl-N(R3)-cycloalkyl-Qj-Q alkyl-N^KXOHVCs, deuterium-, -C〇-C3 alkyl-N(R3)-C(0)-hetero Cyclo-N(R3)-cycloalkyl-Cq _c6 alkyl-N(R3)_c(s)_Ci & alkyl-, & alkyl-n(r3)-c(s)-heterocyclyl _n(r3)_cycloalkyl_Cq_C6 alkyl_N(R3)_C(5)_alkyl-, -C〇-C3 alkyl-S(0)2-heterocyclyl-N(R3)-aryl-C0 -C6 alkyl-NiRM-CCOKVCs alkyl-, -C〇-C3 alkyl-S(〇)2-heterocyclyl-N(R3)-aryl-Q)-c6 alkyl_n(r3)- C(5)_Cl _c3 alkyl _ _c〇_C3 alkyl_s(〇)2 _heterocyclyl-N(R3)-heteroaryl_c〇_C6 炫基_N(R3)_c(〇)_Ci^院基—, -c0- C3 alkyl-s(o)2_heterocyclyl_n(R3)_heteroaryl_c〇_C6 alkyl_n(R3)_ C(S>Cl _C3 alkyl-, -C〇-C3 Alkyl-S(0)2-heterocyclyl-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)_c(〇)_Ci_C3 alkyl-, _C()_C3 alkyl_s (〇)厂 Heterocyclic-N(R3)-heterocyclic group_C()_C6 alkyl_n(r3)_c (3) _Ci_C3 alkyl-, _c〇_c3 alkyl-s(o)2_heterocycle --N(R3)_cycloalkyl-Cg_C6 alkyl_n(R3)-C(〇)_ 134026-1 -66- 200916447 q -C3 alkyl-, -C〇-C3 alkyl-S(0 2 -Heterocyclyl-N(R3)-cycloalkyl-C〇-C6 alkyl-N (R3-C3 alkyl-, -C. -C6 alkyl-N(R3)-C(O)-C0-C6 alkyl-heterocycloalkyl-C(0)-C〇-C3 alkyl-, -C〇-C6 alkyl-N (R3 )-C(5)-c0-C6 alkyl-heterocycloalkyl-c(0)-c〇-C3 alkyl-, -C〇-C6 alkyl-N(R3)-c(o)-c〇-c6 Alkyl-heterocyclic alkyl-C(5)-CG-C3 alkyl-, -CG-C6 alkyl-N (R3-C6 alkyl-heterocycloalkyl-C(S)-C〇-C3 alkyl-, -C〇-C6 alkyl-N(R3)-C(0)-CQ-C6 alkyl-heterocycloalkyl-C(0)-N(R3)-CQ-C3 alkyl-, -C〇- C6 alkyl-N(R3)-C(S)-CG-C6 alkyl-heterocycloalkyl-C(0)-N(R3)-C〇-C3 alkyl-, -C〇-C6 alkyl -N(R3)-C(0)-C〇-C6 alkyl-heterocyclic alkyl group C(S)-N(R3)-C〇-C3 alkyl-, -C0-C6 alkyl-N ( R3)-C(S)-C〇-C6 alkyl-heterocycloalkyl-C(S)-N(R3)-CG-C3 alkyl-, -C〇-C6 alkyl-C(O)- C0 -C6 alkyl-hetero-based-C(0)-N(R3)-C〇-C3 alkyl-, -C〇-C6 alkyl-C(S)-C〇-Cg alkyl-heterocyclic alkyl-C(0)-N(R3)-CG-C3 alkyl-, -CQ-C6 alkyl-C(0)-C〇-C6 alkyl-heterocycloalkyl-c(S)-N (R3)-CQ-C3 alkyl-, -CG-C6 alkyl-C(S)-C.-C6 alkyl-heterocycloalkyl-C(S)-N(R3)-C.-C3 alkane Base...-c.-c6 alkyl group-0-Q)-C3 alkyl-c(o)-n(r3)-cg-c3 alkyl group- -C〇-C6 alkyl-〇-C(S)-N(R3)-C〇-C: 3 院-', wherein each of the above-mentioned L, alkyl, alkenyl, alkynyl, heteroalkyl The cycloalkyl, heterocycloalkyl, heterocyclyl, aryl and heteroaryl moiety are optionally substituted; wherein each Y is independently selected from the group consisting of an anthracene, a pyrenyl group, a heterodole group, and a cycloalkyl group. ,heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl, aryl-heteroaryl, aryl-heteroarylalkyl, heteroaryl -Alkylaryl, aryl-aryl, aryl-aralkyl, aryl-arylaryl, aryl_C()_C3 alkyl--0-C〇-C3 Hyun> Base, aryl group _c〇-C3 alkyl group-S(0)〇__ 2 _c〇_c3 burn 134026-1 •67- 200916447 base-aryl group, -C0-C3 alkyl ACOoi-Co-q alkyl group -aryl, aryl-c〇-c3 alkyl-N(R3)-C〇-C3 alkyl-aryl, aryl-C0-C3 alkyl-C(0)-N(R3)-C〇 -C3 alkyl-aryl, aryl-C〇-C3 alkyl-C(S)-N(R3)-C〇-C3 alkyl-aryl, aryl-C〇-C3 alkyl-N ( R3)-C(O)-C0-C3 alkyl-aryl, aryl-C0-C3 alkyl-N(R3)-C(S)-C0-C3 alkyl-aryl, heteroaryl-hetero Aryl, heteroaryl-aryl , heteroaryl-aralkyl, aryl-alkylheteroaryl, heteroaryl-aryl-aryl, aryl-aryl-aryl, aryl-heteroaryl-aryl, aryl- Heteroaryl-heteroaryl, heteroaryl-heteroaryl-heteroaryl, heteroaryl-heteroaryl-aryl, aryl-aryl-heteroaryl,heteroaryl-aryl-aralkyl , aryl-aryl-alkylheteroaryl, heteroaryl-aryl-alkylaryl, aryl-aryl-alkylaryl, aryl-aryl-aralkyl, aryl- Aryl-heteroarylalkyl, heteroaryl-aryl-heteroaryl, heteroaryl-aryl-heteroarylalkyl, heteroaryl-aryl-alkylheteroaryl, heteroaryl-heteroaryl Alkyl, heteroaryl-alkylheteroaryl, heterocyclyl-heteroaryl, cycloalkyl-aryl, cycloalkyl-heteroaryl, heteroaryl-heterocyclyl, heteroaryl-cycloalkane , aryl-cycloalkyl, heterocyclyl-aryl, aryl-heterocyclyl, heterocyclyl-alkyl-aryl, heterocyclyl-alkylheteroaryl, cycloalkyl-alkylaryl , cycloalkyl-alkylheteroaryl, aryl-alkyl-heterocyclyl, aryl-alkylcycloalkyl, heteroaryl-alkylcycloalkyl, heteroaryl-alkylheterocyclyl , aralkyl-aryl, aryl-aralkyl, aryl -heteroarylalkyl,heteroaryl-aralkyl,heteroaryl-heteroarylalkyl,heteroaryl-C〇-C3alkyl-oc〇-c3alkyl-aryl,heteroaryl-c0- C3 alkyl-o-c0-c3 alkyl-heteroaryl, aryl-c〇-c3 alkyl-o-c0-c3 alkyl-heteroaryl, heteroaryl-c0-c3 alkyl-N ( R3)-C0-C3 alkyl-aryl, aryl-C0-C3 alkyl-N(R3)-C〇-C3 alkyl-heteroaryl,heteroarylalkyl-N(R3)-C〇 -C3 alkyl-heteroaryl 134026-1 -68- 200916447 yl, heteroaryl-c〇-c3 alkyl-C(O)-N(R3)-C0-C3 alkyl-aryl, aryl-C0 -C3 alkyl-C(0)-N(R3)-C0-C3 alkyl-heteroaryl,heteroaryl-C〇-C3 alkyl-C(0)-N(R3)-C〇-C3 Alkyl-heteroaryl, aryl-c0-c3 alkyl-C(S)-N(R3)-C〇-C3 alkyl-aryl, aryl-C〇-C3 alkyl-C(5)-N (R3)-C〇-C3 alkyl-heteroaryl,heteroaryl-C0-C3 alkyl-C(S)-N(R3)-C0-C3 alkyl-aryl,heteroaryl-C0- C3 alkyl-C(S)-N(R3)-C〇-C3 alkyl-heteroaryl,heteroaryl-c〇-c3alkyl-n(r3)-c(o)-c〇-c3 Alkyl-aryl,heteroaryl-c0-c3alkyl-N(R3)-C(0)-C〇-C3 alkyl-heteroaryl, aryl-(^-(^alkyl-N() R3)-C(O)-C0-C3 alkyl-heteroaryl, aryl-C〇-C3 alkyl- N(R3)-cxs)-c0 -C3 alkyl-aryl, aryl-c0-C3 alkyl-N(R3)-C(S)-C〇-C3 alkyl-heteroaryl, heteroaryl -C〇-C3 alkyl-N(R3)-C(S)-C〇-C3 alkyl-aryl, heteroaryl-C〇-C3 alkyl-N(R3)-C(S)-C 〇-C3 alkyl-heteroaryl, R3 -heterocyclyl-CQ-C3 alkyl, R3-cycloalkyl-CG-C3 alkyl, (R3)(R3a)N-C2-C4 alkyl-〇- Aryl-, (R3)(R3a)N-C2-C4 alkyl-S(0)〇_2-aryl-, (R3)(R3a)N-C2-C4-homo-indole-heteroaryl- (R3)(R3a)N_c2_C4 alkyl-S(O)0-2-heteroaryl-, C〇-C3 alkyl-aryl-C〇-C3 alkyl, 〇:〇-0:3 alkyl -heteroaryl-C〇-C3 alkyl, aryl-QQ alkyl-heteroaryl, arylalkyl-aryl, heteroaryl-Ci-Cg alkyl-aryl, heteroarylalkyl- Heteroaryl, R3 -heterocyclyl-C〇-C3 alkyl-N(R3)-C(0)-N(R3)-heteroaryl-, R3-heterocyclyl-C0-C3 alkyl-N (R3)-C(0)-N(R3)-aryl-, R3-cycloalkyl-C〇-C3 alkyl-N(R3)-C(0)-N(R3)-heteroaryl- , R 3 -cycloalkyl-C〇-C3 alkyl-N(R3)-C(0)-N(R3)-aryl-, R3-heterocyclyl-C0-C3 alkyl-N(R3)- C(S)-N(R3)-heteroaryl-, r3_heterocyclyl_c〇_C3 alkyl_n(r3)_c(s)_n(r3)_ aryl -, R3 -cycloalkyl·〇) -C3 alkyl-N(R3)-C(S)-N(R3)-heteroaryl-, R3 - 134026-1 •69· 200916447 Cycloalkyl-C0- C3 alkyl-N(R3)-C(S)-N(R3)-aryl-,heteroaryl-C(O)-C0-C6 alkyl-heteroaryl-,heteroaryl_C(0 )_C〇_C6 alkyl-aryl-, aryl-C(O)-C0-C6 alkyl-aryl, aryl_C(0)_C〇_C6 alkyl_heteroaryl_, miscellaneous aryl-C(0)-N(R3)-C0-C6 alkyl-aryl-, aryl-c(〇)-N(R3)-c0-c: 6 alkyl-heteroaryl-, Heteroaryl_S(0)2_C()_C6alkyl_heteroaryl_,heteroaryl-S(O)2-C0-C6 alkyl-aryl-, aryl_s(〇)0_2_c0-C6 Alkyl-aryl, keto-C3 alkyl-S(O)0 - 2 -C〇-Cg alkyl-heteroaryl, R3 -〇-C(〇)_ N(R3)-C0 -C3 alkane -heteroaryl, R3 _〇_c(〇)-N(R3)-C〇-C3 alkyl-aryl-, R3 -0-C(S)-N(R3)-C0 -C3 -heteroaryl-, R3 _〇_c(s)-N(R3)_C0-C3 alkyl-aryl-, R3-C(0)-heterocyclyl-C0-C3 alkyl-hetero Base, R3 -C(O)-heterocyclyl-C〇-C3 alkyl-aryl-, r3 _c(〇)_cycloalkyl_C〇_C3 alkyl-heteroaryl-, R3-C (0)-Cycloalkyl-C0-C3 alkyl-aryl-, R3_heterocyclyl-C〇-C3 alkyl-N(R3)-C(0)-N(R3)-C〇-C3-heteroaryl-,heterocyclyl-C〇-C3 alkyl-N(R3)-S(0)2-C〇-C3 alkyl-heteroaryl-, R3-heterocyclyl-C〇 -C3 alkyl-N(R3)-S(0)2 -C〇-C3 alkyl-aryl-, R3-cycloalkyl-c. _Cg alkyl-N(R3)-S(0)2-C0-C3 alkyl-heteroaryl-, R3_cycloalkyl-c〇_C3, and -N(R3)-S(0)2- C〇-C3 alkyl-aryl-' R3-heterocyclyl-C0-C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-heteroaryl-, R3-heterocyclyl- C0-C3 alkyl-N(R3)-C(0)-C〇-C3 alkyl-aryl-, R3-cycloalkyl-C〇-C3 alkyl-N(R3)-C(O)- C0-C3 alkyl-heteroaryl-, R3-cycloalkyl-C〇-C3 fluorenyl-Ν(Κ°)-(^(0)-0〇-Ε3 炫•基-方基_, R3-杂 辰 - -Cq-C 〗 〖N-(R3)-C(S)-C〇-C3 alkyl-heteroaryl-, R3-heterocyclyl-c0-c3 alkyl-N (R3KXS) -C〇-C3 alkyl-aryl-, R3-cycloalkyl-C〇-C3 alkyl-N(R3)-C(S)-C0-C3 alkyl-heteroaryl-, R3-cycloalkane --C〇-C3 alkyl 134026-1 -70- 200916447 -N(R3)-C(S)-C〇-C3 alkyl-aryl-, R3 _c(〇)_c〇& alkyl-hetero Aryl, R3-C(0)-C〇-C3 alkyl-aryl, heterocyclic *_c(〇)_, aromatic polycyclic, non-aromatic polycyclic, mixed aryl and non-aryl a polycyclic, polyheteroaryl, non-aromatic polyheterocyclic ring and a mixed aryl group and a non-aryl polyheterocyclic ring, each of which is optionally substituted by one or more groups selected from R3, R4 or R7; Or each Y series is selected from the package A2 a -aryl-c0 -c3 alkyl-N (R3 -c7 alkyl-, wherein the q-C7 alkyl group is optionally substituted with a partial group selected from the group consisting of _N (R3 burned) Base-(C2-C4 dilute alkyl-0-A2b, -N(R3)-C(0)-N(R3-C5 alkyl-(C2-C4 alkenyl)〇_]-(:!-C3 Alkyl•O-A2 b,-N(R3)-(:(0)-0-(^-C5 alkyl-(C2-C4 alkenyl)〇-丨-C3 alkyl-0-A2b, alkyl -(C2-C4 alkenylalkyl-oxime_A2b, -N(R3)_s(〇)2_N(R3)_c]_C5 alkyl-(C2_c4 alkenyl)q alkyl-O-A2 b and -N( R3)-S(0)2-C5 alkyl-(C2-C4 alkenyl). 丨 C-C3 alkyl-0-A2b, A2 a-heteroaryl-C〇-C3 alkyl-N (R3 )-(:(0)-(:! -C7 alkyl-, wherein the q-C7 alkyl group is optionally substituted by a partial group selected from the group consisting of -N(R3)-0(0) )-(^-C5 alkyl-(C2-C4 alkenyl Vi-Ci-q alkyl-0-A2b, -NCRM-CCC^-N^SKVCs alkyl-(C2-C4 alkenyl Vi-CVQ alkyl) -O-A2 b, -N(R3)-(:(0)-0-(^-C5 alkyl-(C2-C4 alkenyl)0-1-C3 alkyl_〇·A2 b, -C5 alkane -(C2-C4 alkenyl)(^-CVQ alkyl-O-A2 b, -N(R3)4(0)2-^113)-(^-C5 alkyl-(C2-C4 alkenyl) 〇"-(:!-C3 burnt base-0-A2b and -N(R3) -S(0)2-Ci -C5 alkyl-(C2-C4 dilute)〇-1 -Q -C3 134026-1 -71 · 200916447 alkyl-0-A2b, and b2-b] -NR3 -B3 Substituted, alkyl, wherein alkyl is optionally

，以形成肽 A2a B1 鍵；且其中To form the peptide A2a B1 bond; and wherein

各R3與R3 a係獨立選自 包括-H、-OH、-C(0)H、雜環基、（:i -C6 烧基、c2 -c6 稀基、c2 _c6 炔基、_c2 _Q 烷基 _〇Ra、c(〇) 〇 C2 _c4 t然或合成胺基酸，且當任何Bi、B2 守，其係藉由肽鍵連結在一起； 烷基-NRaRa、雜烷基、 、C〇-C6烧基雜芳基、c(0)CF3、Each of R3 and R3a is independently selected from the group consisting of -H, -OH, -C(0)H, heterocyclyl, (:i-C6 alkyl, c2-c6, c2-c6 alkynyl, _c2_Q alkyl _〇Ra, c(〇) 〇C2 _c4 t or synthesize amino acids, and when any Bi, B2 is held, they are linked together by peptide bonds; alkyl-NRaRa, heteroalkyl, C〇- C6 alkylidene, c(0)CF3,

烧基芳基、雜芳基-芳基、芳基及烷基雜芳基，其中各烷 基、烯基、炔基、雜烷基、環烷基、雜環基、芳基及雜 芳基部份基團係視情況經取代； 各R4係獨立選自包括-H、-C(NRa)-N(Ra)2、CVC6烷基、c2-c6 烯基 ' C2 -C6 炔基、-C6 烷基-Ra、-C〇 -C6 烷基-O-Ra、_c。-C6 烷基-S(0)〇_2-Ra、-CQ-C6 烷基-C(0)-0Ra、-CG-C6 烷基-(：(0)-N(R3)(R3a)、_C〇_C6烷基_C⑸_N(R3)(R3a)、_CH=CH-C(0)-0Ra、 -CH=CH-C(0)-N(R3)(R3a)、-CH=CH-C(S)-N(R3)(R3a)、-N(R3)-C(0)-CF3、-N(R3)-C2-C6 烷基-N(R3)(R3a)、-C〇-C6 烷基 •N(R3)(R3a)、-C6烷基-R3、-NCI^KXSKVCVJ^ 基-R3、-N(R3 )-S(0)2 A -C6 烷基-R3、-S(〇)2 _N(R3 )R3 a、-0-C2 -C6 烷基-N(R3)(R3a)、-S(0)〇-2-C2-C6 烷基 _N(R3)(R3a)、-S-R3、 -SCO、- 2-C2-C6 烧基-R3、_C3-C6 環炫基、_c3-C6 環烧基-Ra、 ^4026-1 • 72- 200916447An alkyl, heteroaryl-aryl, aryl and alkylheteroaryl group, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl Some of the groups are optionally substituted; each R4 is independently selected from the group consisting of -H, -C(NRa)-N(Ra)2, CVC6 alkyl, c2-c6 alkenyl 'C2-C6 alkynyl, -C6 Alkyl-Ra, -C〇-C6 alkyl-O-Ra, _c. -C6 alkyl-S(0)〇_2-Ra, -CQ-C6 alkyl-C(0)-0Ra, -CG-C6 alkyl-(:(0)-N(R3)(R3a), _C〇_C6 alkyl_C(5)_N(R3)(R3a), _CH=CH-C(0)-0Ra, -CH=CH-C(0)-N(R3)(R3a), -CH=CH-C (S)-N(R3)(R3a), -N(R3)-C(0)-CF3, -N(R3)-C2-C6 alkyl-N(R3)(R3a), -C〇-C6 Alkyl•N(R3)(R3a), -C6alkyl-R3, -NCI^KXSKVCVJ^-R3, -N(R3)-S(0)2 A-C6 Alkyl-R3,-S(〇 ) 2 _N(R3 )R3 a,-0-C2 -C6 alkyl-N(R3)(R3a), -S(0)〇-2-C2-C6 alkyl_N(R3)(R3a),- S-R3, -SCO, - 2-C2-C6 alkyl-R3, _C3-C6 cyclodextrin, _c3-C6 cycloalkyl-Ra, ^4026-1 • 72- 200916447

烷基-雜環基（當烷基係經由雜環基中之N連結時）、 -S(O)2-C0-C4 虎基-雜環基、_0_C〇_C4 烷基 _雜環基 _c(〇)_〇ra -S(O)0 _ i -C0 -C4烷基-雜環基_c(0)_0Ra (當烷基係經由雜環基 卜）、-0-C2 -C4烧基-雜環 7之N連結時）、-0_環 -0-雜芳基-C(0)-0Ra、Alkyl-heterocyclic group (when the alkyl group is bonded via N in the heterocyclic group), -S(O)2-C0-C4, fluorenyl-heterocyclyl, _0_C〇_C4 alkyl-heterocyclyl c(〇)_〇ra -S(O)0 _ i -C0 -C4 alkyl-heterocyclyl_c(0)_0Ra (when the alkyl group is via a heterocyclic group), -0-C2 -C4 When the N-heterocyclic ring 7 is N-linked, -0_cyclo-0-heteroaryl-C(0)-0Ra,

(當烷基係經由雜環基中之C連結時） 基-C(0)-0Ra (當院基係經由雜環基中 烧基-C(0)-0Ra、-0-芳基 _c(0) 〇Ra、〔 -S(〇)0-2-C0-C4烷基-芳基、_〇_c〇_c4烷基-雜芳基、 -S(O)0_2-C0-C4 烧基-雜芳基、_〇_c(〇) n(r3) c〇 C4 烷基芳 基、-O-QSH^Kvq 烷基-芳基、_0_c(0)_n(r3)_c〇_C4 烷基 -雜芳基、-OC⑸-风於)<：0-(：4烷基-雜芳基、_ac(〇)_N(R3：)_ C0-C4烷基-環烷基、_0_c⑸_n(r3)_c〇_C4烷基_環烷基、 -uc(〇)-n(r3 -C4 烷基·雜環基、_0_C(S)_N(R3 )_Cg _c4 烷基- 雜環基、-O-Co-C4烷基-雜環基_芳基（當烷基係經由雜環基 中之C連結時）、-o-Q-C4烷基-雜環基-芳基（當烷基係經 由雜環基中之N連結時）、_〇_C〇_C4烷基_雜環基_雜芳基 134026-1 -73- 200916447 (當烧基係經由雜環基中之c連結時）、_aC2_c道基-雜環 基-雜芳基（當烷基係經由雜環基中之N連結時）、(When the alkyl group is bonded via C in the heterocyclic group) -C(0)-0Ra (when the pendant is via a heterocyclic group, a group -C(0)-0Ra, -0-aryl-c (0) 〇Ra, [ -S(〇)0-2-C0-C4 alkyl-aryl, _〇_c〇_c4 alkyl-heteroaryl, -S(O)0_2-C0-C4 -heteroaryl, _〇_c(〇) n(r3) c〇C4 alkylaryl, -O-QSH^Kvq alkyl-aryl,_0_c(0)_n(r3)_c〇_C4 alkane -heteroaryl, -OC(5)-wind)<:0-(:4 alkyl-heteroaryl, _ac(〇)_N(R3:)_C0-C4 alkyl-cycloalkyl, _0_c(5)_n(r3 )_c〇_C4 alkyl-cycloalkyl, -uc(〇)-n(r3 -C4 alkyl.heterocyclyl,_0_C(S)_N(R3)_Cg_c4 alkyl-heterocyclyl, -O- Co-C4 alkyl-heterocyclyl-aryl (when the alkyl group is linked via C in the heterocyclic group), -oQ-C4 alkyl-heterocyclyl-aryl (when the alkyl group is via a heterocyclic group) In the case of N-bonding, _〇_C〇_C4 alkyl-heterocyclyl-heteroaryl 134026-1 -73- 200916447 (when the alkyl group is linked via c in the heterocyclic group), _aC2_c a heterocyclic group-heteroaryl group (when the alkyl group is linked via N in the heterocyclic group),

烷基-雜ί哀基-環烷基（當烷基係經由雜環基中之C連社 時）、-O-Q-C：4烷基-雜環基_環烷基（當烷基係經由雜環: 中之N連結時）、-叫。4炫基-雜環基_雜環基（當烧基^ 經由雜環基中之C連結時卜⑽2%烧基_雜環基_雜環基 (當烷基係經由雜環基中之N連結時）、_s(〇)〇广C〇 <4烷^ -雜環基-芳基（當烷基係經由雜環基中之c連結時）^ ACOoq-C^-C4烷基-雜環基_芳基（當烷基係經由雜環基中 之N連結時）、_S(0)2_C〇_C4烷基_雜環基_芳基、娜〇] C0-C4烷基-雜環基_雜芳基（當烷基係經由雜環基中之^ 連結時）、-SCC^q-CVC4烷基-雜環基_雜芳基（當烷基係經 由雜環基中之N連結時）' _s(〇)2_c0-C4烷基-雜環基_雜芳 基、-S^h-CVC4烷基-雜環基_環烷基（當烷基係經由雜 %基中之C連結時）、_C4烷基_雜環基_環烷基 (當烷基係經由雜環基中之N連結時）、_S(〇)2_C〇_C4烷基 雜環基-環烷基、-SCOX^-Q-C：4烷基-雜環基_雜環基（當烷 基係經由雜環基中之C連結時）、-S(0)〇 烷基_雜環 基-雜環基（當烧基係經由雜環基中之N連結時）、 -S(0)2-CG-C4烷基-雜環基_雜環基、_N(R3)_C2_C4烷基-雜環 基、-n(r3k：2-C4烷基-環烷基、-N(R3)_C2_C4烷基_雜芳基、 -N(R3 )-C2 -c4 烷基-芳基、-N(R3 )-C(0)-N(R3 )-C〇 -C4 烷基-雜環基 -R3、-N(R3)-C(S)-N(R3)-C〇-C4 烧基-雜環基 _r3、_n(R3)_c(〇)_ N(R3 )-C〇 -C4烷基-環烷基-R3、_n(R3…⑸召妒)_c。、烷基_ 134026-1 ，74- 200916447 環烷基-R3、-N(R3)-C(O)-N(R3)-C0-C4 烷基-芳基-R3、-N(R3)-C(S)-N(R3 )-C。-C4 烷基-芳基，R3、-N(R3 )-C(0)-N(R3 )-C〇 -C4 烷基-雜芳基-R3、-N(R3)-C(S)-N(R3)-C〇-C4烷基-雜芳基-R3、-C0-C4 烷基-0-C(0)-Ra、-〇)-C4 烷基-N(R3)-C(0)-0-Ra、-C〇-C4 烷基 -N(R3 )-C(S)-0-Ra、-C〇 -C4 烷基-雜環基-C(0)-0-Ra、-CG -C4 烷基 -環烷基-C(0)-0-Ra、-C0-C4 烧基-雜芳基 _c(〇)-〇-Ra、_c〇-C4 烷基-芳基-C(0)-0-Ra、-N(R3 )-C2 -C4烷基-雜環基、 -N(R3)-C2-C4烷基-環烷基、_n(R3)-C2-C4烷基-雜芳基、 -N(R3)-C2-C4 院基-芳基、F、Cl ' Br、I、-CF3、-S03H、-CN、 芳基、雜芳基 '環烷基及雜環基，其中前文所提及R4之 各烷基、烯基、炔基、環烷基、雜環基、芳基及雜芳基 部份基團係視情況經取代； 各R7與R7a係獨立選自包括_H、Ci _C6烷基_、C2_C6烯基、C2_C6 炔基、CVQ雜烷基、Ra_〇_C2_C6烷基 _、RHrC2_C6 烷基-、NO^XR^KVC6烷基…保護基、〔A烷基Alkyl-heteroyl-cycloalkyl (when the alkyl group is bonded via C in the heterocyclic group), -OQC: 4 alkyl-heterocyclyl-cycloalkyl (when the alkyl group is via a heterocyclic ring) : When N is connected,) - call. 4histyl-heterocyclyl-heterocyclyl (when the alkyl group is bonded via C in the heterocyclic group) (10) 2% alkyl group-heterocyclyl group-heterocyclic group (when the alkyl group is via a heterocyclic group) When linking, _s(〇)〇广〇C〇<4 alkyl^-heterocyclyl-aryl (when the alkyl group is linked via c in the heterocyclic group) ^ ACOoq-C^-C4 alkyl-hetero Cyclo-aryl (when the alkyl group is bonded via N in the heterocyclic group), _S(0)2_C〇_C4 alkyl_heterocyclyl-aryl, Natto] C0-C4 alkyl-heterocycle a base-heteroaryl group (when the alkyl group is bonded via a heterocyclic group), -SCC^q-CVC4 alkyl-heterocyclyl-heteroaryl (when the alkyl group is linked via N in the heterocyclic group) ' _s(〇) 2_c0-C4 alkyl-heterocyclyl-heteroaryl, -S^h-CVC4 alkyl-heterocyclyl-cycloalkyl (when the alkyl group is linked via C in the heteropoly group) , _C4 alkyl-heterocyclyl-cycloalkyl (when the alkyl group is linked via N in the heterocyclic group), _S(〇)2_C〇_C4 alkylheterocyclyl-cycloalkyl, -SCOX ^-QC: 4 alkyl-heterocyclyl-heterocyclyl (when the alkyl group is bonded via C in the heterocyclic group), -S(0)decyl-heterocyclyl-heterocyclic group (when burned) When the base is linked via N in the heterocyclic group), -S (0) 2-CG-C4 alkyl-heterocyclyl-heterocyclyl, _N(R3)_C2_C4 alkyl-heterocyclyl, -n(r3k:2-C4alkyl-cycloalkyl, -N(R3) )_C2_C4 alkyl-heteroaryl, -N(R3)-C2-c4 alkyl-aryl, -N(R3)-C(0)-N(R3)-C〇-C4 alkyl-heterocyclyl -R3, -N(R3)-C(S)-N(R3)-C〇-C4 alkyl-heterocyclyl-r3, _n(R3)_c(〇)_ N(R3)-C〇-C4 Alkyl-cycloalkyl-R3, _n(R3...(5) 妒)_c., alkyl group _ 134026-1 , 74- 200916447 cycloalkyl-R3, -N(R3)-C(O)-N(R3 )-C0-C4 alkyl-aryl-R3, -N(R3)-C(S)-N(R3)-C.-C4 alkyl-aryl, R3, -N(R3)-C(0 )-N(R3)-C〇-C4 alkyl-heteroaryl-R3, -N(R3)-C(S)-N(R3)-C〇-C4 alkyl-heteroaryl-R3,- C0-C4 alkyl-0-C(0)-Ra, -〇)-C4 alkyl-N(R3)-C(0)-0-Ra, -C〇-C4 alkyl-N(R3)- C(S)-0-Ra, -C〇-C4 alkyl-heterocyclyl-C(0)-0-Ra, -CG-C4 alkyl-cycloalkyl-C(0)-0-Ra, -C0-C4 alkyl-heteroaryl_c(〇)-〇-Ra, _c〇-C4 alkyl-aryl-C(0)-0-Ra, -N(R3)-C2 -C4 alkyl -heterocyclyl, -N(R3)-C2-C4 alkyl-cycloalkyl, _n(R3)-C2-C4 alkyl-heteroaryl, -N(R3)-C2-C4 aryl-aryl , F, Cl ' Br, I, -CF3, -S03H, -CN, a heteroaryl 'cycloalkyl group and a heterocyclic group, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl moiety groups of R4 mentioned hereinbefore Substituted as appropriate; each R7 and R7a are independently selected from the group consisting of _H, Ci_C6 alkyl group, C2_C6 alkenyl group, C2_C6 alkynyl group, CVQ heteroalkyl group, Ra_〇_C2_C6 alkyl group, RHrC2_C6 alkyl group, NO^XR^KVC6 alkyl...protective group, [A alkyl group

-〇-c(〇)‘、芳基 _c〇_C4 烧基 _〇_c(〇)_、雜芳基 _c〇 c4 烷基-〇-c(〇)‘, aryl _c〇_C4 alkyl _〇_c(〇)_, heteroaryl _c〇 c4 alkyl

-O-C(o)-、苄基_〇_c(〇)_、雜環基Cl 烷基_、環烷基Cl Q 烷基-、雜芳基-Cl-C：6烷基_、芳基_Ci_Q烷基…其中各烷 基、烯基、炔基、雜烧基、芳基、雜芳基、環烧基、爷 ”基及雜環基部份基團係獨立視情況經取代；其條件是 K為货，當連接至㈣基部份基團之N原子時；且 其中一在娜Μ”基團中，R3與一和彼等所連接之氮原子 一起視情況形成雜環基。 在本發明之—項具體實施例中，Y，L，Z，Ra，Rb，RHR3a 134026-1 -75- 200916447 之各烷基、烯基、炔基、雜烷基、環烷基、雜環基、芳基 及雜芳基部份基團係獨立視情況被一或多個獨立選自r4之 基團取代。 於本發明之另—項具體實施例中，Y，L，Z，Ra，Rb, Rc，…及 R3a之各烷基、烯基、炔基、雜烷基、環烷基、雜環基、芳 基及雜芳基部份基團係獨立視情況被一或多個基團取代， 取代基獨立選自酮基、-OH、_CN、Ci _Q烷基、q -(：6烷氧基、 -N02、-N(Ra )2、-N(R7 )(R7 a)' 鹵基、_SH、_s c厂Q 烷基、_s(〇)_Ci % 烷基、-s-cxokvC6烷基及單-至全-鹵tCi_C6烷基。 於本發明之另一項具體實施例中，R42Ci_C6烷基部份基 團係視情況被取代基取代，取代基選自包括_〇H、_N〇2及 C〇-C6 烷基-C(0)-N(R3)(R3a)。 於本發明之另一項具體實施例中，Z之各烧基、烯基' 炔基、雜烷基、芳基、雜芳基、環烷基及雜環基部份基團 係獨立視情況被一或多個取代基取代，取代基獨立選自包 括酮基、-OH、-CN、烷基、（^-(^烷氡基、_N02、 -N(R3 )(R3 a)、鹵基、_sh及單-至全_ _化q _C6烷基。 於本發明之另一項具體實施例中，L係選自包括 -C〇 -C6炫基-N(R3 )-C0 -C3烷基-，其中當_c〇 _C6烷基為_Ci _C6烷 基時，其係視情況被取代基取代，取代基選自包括_Ci _c3 烷基-ORa、-C]-C3 烷基-N(Rj)(R3a)、_Cq_C3 烷基 _C(；⑺〇Ra 及 C〇 -C3 烷基-C(0)-N(R3 )(R3 a); -C〇 -C6 烧基-N(R3 )-C(O)-C0 -C3 烧基-，其中當 _c〇 _q 烧基為 q -C6 燒基時’其係視情況被取代基取代，取代基選自包括 134026-1 -76- 200916447 -C3 烧基-〇Ra、_Ci _c3 烧基 _nr3 r3 a、& q 烧基 _c(〇)〇Ra 及 C〇 -C3 烷基-C(0)-N(R3 )(R3 a); -C〇 -Q 院基-N(R3 )-(：(〇)-(：〇 -C3 烧基-，其中 _C〇 _c3 烧基為 Cl _C3 烷 基’其係視情況被取代基取代，取代基選自包括_n(r3)_ 0；0)-(：0-(：3烧基-丫、-1^(113)-〇；8)-(：〇-(：3烧基-丫、-(：(0)-1\[(113)-C〇-C3 院基-Y、-C(S)-N(R3)-C〇-C3 烧基-Y、-N(R3)-C(0)-C〇-C3 烧基-c4-c6環規基-、-n(r3)-c⑸-CG-C3烧基-C4-C6環烷基-、-N(R3)-C〇-C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-c4-c6 雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基 -ORa、-N(R3 )-C。-C3 烧基-C。-C3 雜烧基-Y、-N(R3 )-C(O)-〇-C0 -C3 烷基-Y、-N(R3)-C(S)-0-C〇-C3 烷基-Y、-N(R3)-S(0)2-C〇-C3 烷 基-Y、-N(R3 )-C(0)-N(R3 )-C〇 -C3 烧基-Y、-N(R3 )-C⑸-N(R3 )-c0-c3 烷基-Y、-n(r3)-c(0)-cq-c3 烷基-CG-C3 雜環基、 -N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環基、-N(R3 )-C(0)-C〇 -C3 烷基 -C〇 -C3 雜環基-Y、-N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環基-Y 及 -N(R3 >S(0)2 -N(R3 )-C〇 -C3 烷基-Y ; -C0 -C6 烷基-N(R3 )-C(S)-C〇 -C3 烷基-，其中-C〇 -C3 烷基為 q -C3 烷 基，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、 -c(o)-n(r3)-c〇-c3 烷基-Y、-C⑸-N(R3)-C〇-C3 烷基-Y、 -N(R3 )-C(0)-CQ -C3 烷基-C4 -C6 環烷基-、-N(R3 )-C(S)-CG -C3 烷基 -(：4-(：6環烷基-、-叫113)-〇)-(：3烷基-丫、-风113)(1133)、-风113)-C0-C3 烷基-(：4-(：6雜環基、-N(R3)-C2-C3烷基-N(R3)(R3a)、 -N(R3 )-C2 -C3 烷基-ORa、-N(R3 )-CG -C3 烷基-CG -C3 雜烷基-Y、 134026-1 -77- 200916447 -n(r3)-c(o)-o-c〇-c3 烷基-Υ、-n(r3)-c(s)-o-c〇-c3 烷基-Υ、 -N(R3)-S(O)2-C0-C3 烷基-Υ、-N(R3)-C(O)-N(R3)-C0-C3 烷基-Υ、 -N(R3 )-C(S)-N(R3 )-CQ -C3 烷基-Υ、-N(R3 )-C(0)-CQ -C3 烷基-C0 -C3 雜環基、-N(R3)-C(S)-C〇-C3 烷基-CG-C3 雜環基、-N(R3)-c(o)-c〇-c3 烷基-C〇-C3 雜環基-Υ、-N(R3)-C(S)-C〇-C3 烷基 -C〇 -C3 雜環基-Y 及-N(R3 )-S(0)2 -N(R3 )-C〇 -C3 烷基-Υ ; -C0 -C6烷基-C(O)-C0 -C3烷基-，其中當-C0 -C6烷基為q -C3烷基 時，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、 -C(0)-N(R3)(R3a)、-C(S)-N(R3)(R3a)、-C(0)-N(R3)-C〇-C3 烷基 -Υ、-C(S)-N(R3)-C〇-C3 烷基-Υ、-N(R3)-C(0)-Cq-C3 烷基-c4-c6 環烷基-、-N(R3 )-C(S)-CG -C3 烷基-C4 -C6 環烷基-、-N(R3 )-C〇 -C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-(V^*-C4-C6雜環基、 -N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基-ORa-、 -N(R3)-C〇-C3 雜烷基-Y、-N(R3)-C(0)-0-C〇-C3 烷基-Y、 -叫尺3)-(：(8)-0-(：()-<：3烷基-丫、-风113)-5(0)2-〇)-(：3烷基-丫、 -N(R3)-C(0)-N(R3)-Cq-C3 烷基-Y、-N(R3)-C(S)-N(R3)-C〇-C3 烷基 -Y ' -n(r3)-c(o)-c〇-c3 烷基-c0-c3雜環基、-n(r3)-c(s)-c0-c3 烷基-C〇 -C3 雜環基、-N(R3 )-(:(0)-(^ -C3 烷基-C〇 -C3 雜環基-Y、 -N(R3)-C(S)-C〇-C3 烷基-C〇-C3 雜環基-Y 及-IsKI^-SlOh-^Rq-Co-C^ 烷基-Y ; -C〇 -Cg炫基-C(S)-C〇 -C3烧基-’其中當-C0 -C6烧基為Ci -C3院基 時，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-Cq-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、 134026-1 •78- 200916447 -C(0)-N(R3)(R3a)、-C(S)-N(R3)(R3a)、-C(0)-N(R3)-C〇-C3 烷基 -Y ' -C(S)-N(R3)-Q-C3 烷基-Y、-n(r3)-c(o)-c〇-c3 烷基-C4-C6 環烷基-、-N(R3 )-C⑸-CG -C3 烷基-C4 -C6 環烷基-、-N(R3 )-C〇 -C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-C4-C6 雜環基、 -N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基-ORa-、 -N(R3)-C〇-C3 雜烷基-Y、-N(R3)-C(0)-0-C〇-C3 烷基-Y、 以(113)-(：(5)-0-〇)-(：3烷基-丫、-风113)-5(0)2-(：()-(：3烷基-丫、 -N(R3 )-C(0)-N(R3 )-C〇 -C3 烷基-Y、-N(R3 )-C(S)-N(R3 )-〇) -C3 烷基 -Y、-N(R3)-C(0)-C〇-C3烷基-C0-C3雜環基、-N(R3)-C(S)-C0-C3 炫基-C〇 -C3 雜壞基 ' -N(R3 )-C(〇)-C〇 -C3 烧基-C〇 -C3 雜環基-Y、 -N(R3)-C(S)-C〇-C3 烷基-C0-C3 雜環基-Y 及-n(r3)-s(o)2-n(r3)-c0-c3 烷基-Y ; -C0 -C6炫基-’其中當-C〇 -C6院基為c! -C6烧基時，其係視情況 被取代基取代，取代基選自包括-N(R3)-C(0)-CQ-C3烷基 -Y、-N(R3)-C(O)-C0-C3烷基-雜環基及_N(R3)-C(0)-C〇-C3烷基- 壤烧基； -C〇 -C6 烷基-C(0)-N(R3 )-C0 -C3 烷基-，其中當 _c0 -c3 烷基為 q -c3 烷基時，其係視情況被取代基取代，取代基選自包括 -C(0)-N(R3)-C〇-C3烷基-Y、-c(0)-雜環基、_c(〇)-N(R3)(R3a)、 芳基-芳基、芳基-雜芳基、-雜芳基-芳基、雜芳基-雜芳基、 雜芳基、雜環基-雜芳基及雜環基； 'c0 -C：6烧基-雜烧基-C0 -C6烧基-C(0)-N(R3 )_c0 -C：3烧基-，其中當 -C0-C3烷基為Ci -C：3烷基時’其係視情況被取代基取代， 取代基選自包括-C(0)-N(R3 )-C〇 -C3烷基-Y、-c(0)_雜環基、 134026*1 -79- 200916447 -C(0)-N(R3)(R3a)、芳基-芳基、芳基-雜芳基、-雜芳基芳 基、雜芳基-雜芳基、雜芳基、雜環基-雜芳基及雜環基； -Q -c6烷基-c(o)-n(r3 )-c〇 -c3烷基-’其中當-c0 -c6烷基為Ci义 烷基時，其係視情況被取代基取代，取代基選自包括 -N(R7)(R7a)、-N(R3)(R3a)、-N(R3)-C(O)-C0-C3 烷基 _γ、 -N(R3)-C(0)-0-Q-C3 烷基-Υ、-n(r3)-c(o)-n(r3)-q-c3 烷基 _γ 及-N(R3 )-S(0)2 -CG -C3 烷基-Υ ; _C〇 -Cg烧基-雜芳基-C〇 -C3烧基-’其中當-C0 -C3烧基為q -C3燒 基時，其係視情況被取代基取代，取代基選自包括_CQ_C3 烷基-N(R3 )-C(O)-C0 -C3 烧基-N(R3 )(R3 a)、-N(R3 )-C(0)-C。-C3 烷 基-Y、-N(R3)-C(0)-0-C〇-C3 烧基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及-N(R3 )-S(0)2 -CG -C3 烷基-Y ; -c〇-c6烷基-芳基-C〇-C3烷基-，其中當-C〇-C3烷基為(^-(：3烷基 時，其係視情況被取代基取代，取代基選自包括-N(R3 )-(：(〇)-〇)-(：3烷基-丫、-风113)七(〇)-(：0-(：3烷基-丫、->^3)-(：(〇)-0-C〇-C3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及-N(R3)-S(0)2-C〇-C3 烷基-Y ; -c0-c6烷基-芳基-雜芳基-C〇-C3烷基-，其中當-c〇-c3烷基為 烷基時，其係視情況被取代基取代，取代基選自包 括-n(r3)-c(o)-c〇-c3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-Y、 -N(R3)-C(0)-0-C〇-C3 烷基-γ、-Ν(Κ3 )-€Χ〇)-Ν(3Κ3)-〇)-(：3 烷基-Y 及-N(R3 )-S(0)2 -C〇 -C3 烷基-Υ ; -c〇-c6烷基-雜芳基-雜芳基-CQ-C3烷基-，其中當-c0-c3烷基為 c] -c3烷基時，其係視情況被取代基取代，取代基選自包 134026-1 -80- 200916447 括-N(R3)-C(0)-C〇-C3 烷基-Υ、-N(R3)-C(0)-C〇-C3 烷基-Υ、 -N(R3)-C(0)-0-C〇-C3 烷基-Υ、-Ν(Ι13Κ：(0)-Ν(Κ3Κν(：3 烷基-Υ 及-N(R3 )-S(O)2-C0-C3 烷基-Υ ; -C〇-C6烷基-雜芳基-C〇-C3烷基-，其中當-c0-c3烷基為（ν〇3烷 基時，其係視情況被取代基取代，取代基選自包括-N(R3)-C(0)-C〇-C3 烷基-Y 、 -n(r3)-c(o)-cg-c3 烷基-Y 、 -N(R3 )-C(0)-0-C〇 -C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-CQ -C3 烷基-Y 及-N(R3 )-S(0)2 -C〇 -C3 烷基-Y ; -C〇-C6 烷基-O-C(O)-N(R3)-C0-C3 院基-，其中當-C〇-C3 烧基為 c〗-C3烷基時，其係視情況被基團取代，取代基選自 -C(0)-0Ra、-C(S)-ORa、-C(0)-N(R3 )-Q -C3 烷基、-C⑸-N(R3 )-C^C3 烷基、-C(0)-N(R3)(R3a)-、-C(S)-N(R3)(R3a)-、-C(0)-N(R3)-C0-C3 烷基-芳基、-C⑸-N(R3)-C〇-C3 烷基-芳基、-C(0)-N(R3)-C0-C3烷基-雜芳基、-C(S)-N(R3)-C〇-C3烷基-雜芳基、 -C(O)-N(R3)-C0-C3 烷基-環烷基、-C(S)-N(R3)-C〇-C3 烷基-環烷 基、-C(O)-雜環基、-C⑸-雜環基、-C(0)-N(R3 )-C〇-C3 烷基-Y、 -C(S)-N(R3KVC3 烷基-Y、-C(0)-N(R3)-雜環基、-C(s)-N(R3)-雜環基、-C(0)-N(R3 )-CQ -C3 烷基-雜環烷基及-C(S)-N(R3 )-C0 -C3烧基-雜環烧基； -C0-C6 烷基-O-CXS)-N(R3)-C0-C3 烷基-，其中當-c0-c3 烷基為 Cl -c3烷基時，其係視情況被基團取代，取代基選自 -C(0)-0Ra、-C(S)-ORa、-C(0)-N(R3 )-(^ -C3 烷基、·ί：(5)-Ν(Ι13 )-烷基、-C(0)-N(R3)(R3a)-、-C(S)-N(R3)(R3a)-、-C(0)-N(R3)-C〇-C3 烷基-芳基、-C⑸_N(r3)_Cq_C3 烷基 _芳基、_c(〇)_n(R3)_ 134026-1 -81 · 200916447 c〇-c3烷基-雜芳基、-C⑸-N(R3)-C〇-C3烷基-雜芳基、 -C(0)-N(R3 )-C。-c3 烷基-環烷基、-C(S)-N(R3 )-C。_c3 烷基-環烷 基、-C(O)-雜環基、-C(S)-雜環基、-C(0)-N(R3)-C〇-C3 烷基-Y、 -C(s)-N(R3)-C0-C3 烷基-Y、-C(0)-N(R3)-雜環基、-C(s)-N(R3)-雜環基、-C(0)-N(R3)-C〇-C3烷基-雜環烷基及-c⑸-N(R3)-C〇-C3烷基-雜環烷基；且-OC(o)-, benzyl_〇_c(〇)_, heterocyclic group C alkyl group, cycloalkyl group C Q alkyl group, heteroaryl-Cl-C: 6 alkyl group, aryl group _Ci_Qalkyl, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, aryl and heterocyclyl moiety is independently substituted; The condition is that K is a cargo, when attached to the N atom of the (iv) base moiety; and one of them is in the Natto group, R3 optionally forms a heterocyclic group together with the nitrogen atom to which they are attached. In a specific embodiment of the invention, each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycle groups of Y, L, Z, Ra, Rb, RHR3a 134026-1 -75- 200916447 The aryl, aryl and heteroaryl moiety are independently substituted with one or more groups independently selected from r4, as appropriate. In another embodiment of the invention, each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl groups of Y, L, Z, Ra, Rb, Rc, ... and R3a, The aryl and heteroaryl moiety are independently substituted by one or more groups, and the substituents are independently selected from the group consisting of keto, -OH, -CN, Ci_Q alkyl, q-(:6 alkoxy, -N02, -N(Ra)2, -N(R7)(R7 a)' Halo, _SH, _s c plant Q alkyl, _s(〇)_Ci % alkyl, -s-cxokvC6 alkyl and mono- To a per-halo tCi_C6 alkyl group. In another embodiment of the invention, the R42Ci_C6 alkyl moiety is optionally substituted with a substituent selected from the group consisting of 〇H, _N〇2, and C〇. -C6 alkyl-C(0)-N(R3)(R3a). In another embodiment of the invention, each of the alkyl, alkenyl 'alkynyl, heteroalkyl, aryl, hetero The aryl, cycloalkyl and heterocyclyl moiety are independently substituted by one or more substituents, the substituents being independently selected from the group consisting of keto, -OH, -CN, alkyl, (^-(^ Alkanoyl, _N02, -N(R3)(R3a), halo, _sh, and mono- to all-_q_C6 alkyl. Another embodiment of the present invention In the example, L is selected from the group consisting of -C〇-C6 leu-N(R3)-C0-C3 alkyl-, wherein when _c〇_C6 alkyl is _Ci_C6 alkyl, it is optionally Substituted by a substituent selected from the group consisting of _Ci_c3 alkyl-ORa, -C]-C3 alkyl-N(Rj)(R3a), _Cq_C3 alkyl-C(;(7)〇Ra and C〇-C3 alkyl -C(0)-N(R3)(R3 a); -C〇-C6 alkyl-N(R3)-C(O)-C0-C3 alkyl-, wherein when _c〇_q is a When q-C6 is calcined, it is optionally substituted by a substituent selected from the group consisting of 134026-1 -76- 200916447 -C3 alkyl-hydrazine Ra, _Ci _c3 alkyl _nr3 r3 a, & q alkyl _c(〇)〇Ra and C〇-C3 alkyl-C(0)-N(R3)(R3 a); -C〇-Q 院-N(R3)-(:(〇)-(: 〇-C3 alkyl-, wherein _C〇_c3 is a C1-C3 alkyl group, which is optionally substituted with a substituent selected from the group consisting of _n(r3)_0;0)-(:0- (:3 alkyl-丫, -1^(113)-〇; 8)-(:〇-(:3 alkyl-丫, -(:(0)-1\[(113)-C〇-C3 Deutero-Y,-C(S)-N(R3)-C〇-C3 alkyl-Y,-N(R3)-C(0)-C〇-C3 alkyl-c4-c6 ring-based group- , -n(r3)-c(5)-CG-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y, -N(R3) (R3a), -N(R3)-C〇-C3 alkyl-c4-c6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)- C2-C3 alkyl-ORa, -N(R3)-C. -C3 burnt base-C. -C3 miscible group -Y, -N(R3)-C(O)-〇-C0 -C3 alkyl-Y, -N(R3)-C(S)-0-C〇-C3 alkyl-Y , -N(R3)-S(0)2-C〇-C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C〇-C3 alkyl-Y,-N( R3)-C(5)-N(R3)-c0-c3 alkyl-Y, -n(r3)-c(0)-cq-c3 alkyl-CG-C3 heterocyclic group, -N(R3)-C( S)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-C(0)-C〇-C3 alkyl-C〇-C3 heterocyclic group-Y, -N(R3 -C(S)-C〇-C3 alkyl-C〇-C3 heterocyclyl-Y and -N(R3 >S(0)2-N(R3)-C〇-C3 alkyl-Y; -C0 -C6 alkyl-N(R3)-C(S)-C〇-C3 alkyl-, wherein -C〇-C3 alkyl is q-C3 alkyl, which is optionally substituted by a substituent The group is selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -c(o)- n(r3)-c〇-c3 alkyl-Y, -C(5)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(0)-CQ-C3 alkyl-C4- C6 cycloalkyl-, -N(R3)-C(S)-CG-C3 alkyl-(: 4-(:6-cycloalkyl-, -113)-〇)-(:3 alkyl-oxime , - wind 113) (1133), - wind 113) -C0-C3 alkyl-(: 4-(:6 heterocyclyl, -N(R3)-C2-C3 alkyl-N(R3)(R3a) , -N(R3)-C2 -C3 alkyl-ORa, -N(R3)-CG-C3 alkyl-CG-C3 -Y, 134026-1 -77- 200916447 -n(r3)-c(o)-oc〇-c3 alkyl-Υ, -n(r3)-c(s)-oc〇-c3 alkyl-Υ -N(R3)-S(O)2-C0-C3 alkyl-oxime, -N(R3)-C(O)-N(R3)-C0-C3 alkyl-oxime, -N(R3) -C(S)-N(R3)-CQ-C3 alkyl-oxime, -N(R3)-C(0)-CQ-C3 alkyl-C0-C3 heterocyclic group, -N(R3)-C (S)-C〇-C3 alkyl-CG-C3 heterocyclic group, -N(R3)-c(o)-c〇-c3 alkyl-C〇-C3 heterocyclic group-Υ, -N(R3 -C(S)-C〇-C3 alkyl-C〇-C3 heterocyclyl-Y and -N(R3)-S(0)2-N(R3)-C〇-C3 alkyl-hydrazine; -C0 -C6 alkyl-C(O)-C0-C3 alkyl-, wherein when -C0-C6 alkyl is q-C3 alkyl, it is optionally substituted with a substituent selected from the group consisting of - N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -C(0)-N(R3)( R3a), -C(S)-N(R3)(R3a), -C(0)-N(R3)-C〇-C3 alkyl-Υ, -C(S)-N(R3)-C〇 -C3 alkyl-fluorene, -N(R3)-C(0)-Cq-C3 alkyl-c4-c6 cycloalkyl-, -N(R3)-C(S)-CG-C3 alkyl-C4 -C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C〇-(V^*-C4-C6 heterocycle , -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl-ORa-, -N(R3)-C〇-C3 heterocycloalkane -Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y, - is called 3)-(:(8)-0-(:()-<:3 alkyl -丫, -风113)-5(0)2-〇)-(:3 alkyl-oxime, -N(R3)-C(0)-N(R3)-Cq-C3 alkyl-Y,- N(R3)-C(S)-N(R3)-C〇-C3 alkyl-Y '-n(r3)-c(o)-c〇-c3 alkyl-c0-c3 heterocyclic group, - n(r3)-c(s)-c0-c3 alkyl-C〇-C3 heterocyclic group, -N(R3)-(:(0)-(^-C3 alkyl-C〇-C3 heterocyclic group -Y, -N(R3)-C(S)-C〇-C3 alkyl-C〇-C3 heterocyclyl-Y and -IsKI^-SlOh-^Rq-Co-C^ alkyl-Y; C〇-Cg 炫-C(S)-C〇-C3 alkyl-' wherein when the -C0-C6 alkyl group is a Ci-C3 group, the substituent is optionally substituted by a substituent selected from the group consisting of -N(R3)-C(0)-Cq-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, 134026-1 •78- 200916447 -C(0 )-N(R3)(R3a), -C(S)-N(R3)(R3a), -C(0)-N(R3)-C〇-C3 alkyl-Y '-C(S)- N(R3)-Q-C3 alkyl-Y, -n(r3)-c(o)-c〇-c3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C(5)-CG-C3 Alkyl-C4 -C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C〇-C3 alkyl-C4- C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl-ORa-, -N(R3)-C〇 -C3 heteroalkyl-Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y, with (113)-(:(5)-0-〇)-(:3 alkane Base-丫,-风113)-5(0)2-(:()-(:3alkyl-丫, -N(R3)-C(0)-N(R3)-C〇-C3 alkyl -Y, -N(R3)-C(S)-N(R3)-〇) -C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-C0-C3 Cyclic group, -N(R3)-C(S)-C0-C3 炫-C〇-C3 heteroatom'-N(R3)-C(〇)-C〇-C3 alkyl-C〇-C3 Heterocyclyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-C0-C3 heterocyclyl-Y and -n(r3)-s(o)2-n(r3)- C0-c3 alkyl-Y; -C0-C6 leuko-' wherein when the -C〇-C6 group is c!-C6 alkyl, it is optionally substituted by a substituent selected from the group consisting of -N (R3)-C(0)-CQ-C3 alkyl-Y, -N(R3)-C(O)-C0-C3 alkyl-heterocyclyl and _N(R3)-C(0)-C 〇-C3 alkyl-leaf-based; -C〇-C6 alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when _c0-c3 alkyl is q-c3 alkyl , which is optionally substituted by a substituent selected from the group consisting of -C(0)-N(R3)-C〇-C3 alkyl-Y, -c(0)-heterocyclyl, _c(〇)- N(R3)(R3a), aryl-aryl, aryl-heteroaryl, -heteroaryl-aryl,heteroaryl-heteroaryl,heteroaryl,heterocyclyl-heteroaryl Heterocyclic group; 'c0-C: 6 alkyl group-heteroalkyl group-C0-C6 alkyl group-C(0)-N(R3)_c0-C: 3 alkyl group-, wherein when -C0-C3 alkyl group is When Ci-C: 3 alkyl group is substituted with a substituent, the substituent is selected from the group consisting of -C(0)-N(R3)-C〇-C3 alkyl-Y, -c(0)- Ring group, 134026*1 -79- 200916447 -C(0)-N(R3)(R3a), aryl-aryl, aryl-heteroaryl, -heteroarylaryl,heteroaryl-heteroaryl , heteroaryl, heterocyclyl-heteroaryl and heterocyclic; -Q-c6 alkyl-c(o)-n(r3)-c〇-c3 alkyl-' wherein -c0-c6 When the group is a Ci-alkyl group, it is optionally substituted by a substituent selected from the group consisting of -N(R7)(R7a), -N(R3)(R3a), -N(R3)-C(O). -C0-C3 alkyl_γ, -N(R3)-C(0)-0-Q-C3 alkyl-Υ, -n(r3)-c(o)-n(r3)-q-c3 alkane Base _γ and -N(R3)-S(0)2-CG-C3 alkyl-Υ; _C〇-Cg alkyl-heteroaryl-C〇-C3 alkyl-' where -C0-C3 burns When the group is a q-C3 alkyl group, it is optionally substituted by a substituent selected from the group consisting of _CQ_C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-N(R3) (R3) a), -N(R3)-C(0)-C. -C3 alkyl-Y,-N(R3)-C(0)-0-C〇-C3 alkyl-Y,-N(R3)-C(0)-N(R3)-C〇-C3 alkane -Y and -N(R3)-S(0)2-CG-C3 alkyl-Y; -c〇-c6alkyl-aryl-C〇-C3 alkyl-, wherein -C〇-C3 When the alkyl group is (^-(:3 alkyl group, it is optionally substituted by a substituent selected from -N(R3)-(:(〇)-〇)-(:3 alkyl-oxime, - wind 113) seven (〇)-(:0-(:3 alkyl-丫,->^3)-(:(〇)-0-C〇-C3 alkyl-Y, -N(R3) -C(0)-N(R3)-C〇-C3 alkyl-Y and -N(R3)-S(0)2-C〇-C3 alkyl-Y; -c0-c6alkyl-aryl -heteroaryl-C〇-C3 alkyl-, wherein when -c〇-c3 alkyl is alkyl, it is optionally substituted with a substituent selected from the group consisting of -n(r3)-c(o )-c〇-c3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3)-C(0)-0-C〇-C3 alkyl -γ, -Ν(Κ3 )-€Χ〇)-Ν(3Κ3)-〇)-(:3 alkyl-Y and -N(R3)-S(0)2 -C〇-C3 alkyl-Υ -c〇-c6 alkyl-heteroaryl-heteroaryl-CQ-C3 alkyl-, wherein when -c0-c3 alkyl is c]-c3 alkyl, it is optionally substituted with a substituent, The substituent is selected from the group 134026-1 -80- 200916447 including -N(R3)-C(0)-C〇-C3 alkyl-Υ, -N(R3)-C( 0)-C〇-C3 alkyl-Υ, -N(R3)-C(0)-0-C〇-C3 alkyl-Υ,-Ν(Ι13Κ:(0)-Ν(Κ3Κν(:3 alkane) - ( and -N(R3)-S(O)2-C0-C3 alkyl-oxime; -C〇-C6 alkyl-heteroaryl-C〇-C3 alkyl-, wherein -c0-c3 When the alkyl group is (ν〇3 alkyl group, it is optionally substituted by a substituent selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y, -n(r3) -c(o)-cg-c3 alkyl-Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y, -N(R3)-C(0)-N(R3 )-CQ-C3 alkyl-Y and -N(R3)-S(0)2 -C〇-C3 alkyl-Y; -C〇-C6 alkyl-OC(O)-N(R3)-C0 -C3 院基-, wherein when -C〇-C3 alkyl is c-C3 alkyl, it is optionally substituted by a group selected from -C(0)-0Ra, -C(S) -ORa, -C(0)-N(R3)-Q-C3 alkyl, -C(5)-N(R3)-C^C3 alkyl, -C(0)-N(R3)(R3a)-,- C(S)-N(R3)(R3a)-, -C(0)-N(R3)-C0-C3 alkyl-aryl, -C(5)-N(R3)-C〇-C3 alkyl-aryl , -C(0)-N(R3)-C0-C3 alkyl-heteroaryl, -C(S)-N(R3)-C〇-C3 alkyl-heteroaryl, -C(O) -N(R3)-C0-C3 alkyl-cycloalkyl, -C(S)-N(R3)-C〇-C3 alkyl-cycloalkyl, -C(O)-heterocyclyl, -C(5) -heterocyclyl, -C(0)-N(R3)-C〇-C3 alkyl- Y, -C(S)-N (R3KVC3 alkyl-Y, -C(0)-N(R3)-heterocyclyl, -C(s)-N(R3)-heterocyclyl, -C(0 )-N(R3)-CQ-C3 alkyl-heterocycloalkyl and -C(S)-N(R3)-C0-C3 alkyl-heterocyclic alkyl; -C0-C6 alkyl-O-CXS -N(R3)-C0-C3 alkyl-, wherein when -c0-c3 alkyl is Cl-c3 alkyl, it is optionally substituted by a group selected from -C(0)-0Ra , -C(S)-ORa, -C(0)-N(R3)-(^-C3 alkyl, ·ί:(5)-Ν(Ι13)-alkyl, -C(0)-N( R3)(R3a)-, -C(S)-N(R3)(R3a)-, -C(0)-N(R3)-C〇-C3 alkyl-aryl, -C(5)_N(r3)_Cq_C3 alkane Base-aryl, _c(〇)_n(R3)_ 134026-1 -81 · 200916447 c〇-c3 alkyl-heteroaryl, -C(5)-N(R3)-C〇-C3 alkyl-heteroaryl -C(0)-N(R3)-C. -c3 alkyl-cycloalkyl, -C(S)-N(R3)-C. _c3 alkyl-cycloalkyl, -C(O)-heterocyclyl, -C(S)-heterocyclyl, -C(0)-N(R3)-C〇-C3 alkyl-Y, -C (s)-N(R3)-C0-C3 alkyl-Y, -C(0)-N(R3)-heterocyclyl, -C(s)-N(R3)-heterocyclyl, -C( 0) -N(R3)-C〇-C3 alkyl-heterocycloalkyl and -c(5)-N(R3)-C〇-C3 alkyl-heterocycloalkyl;

Ci -〇3烧基-N(R3 )-C(〇)-Ci -C7烧基-’其中C! -C3炫> 基係視情況 被-C(0)N(R3 )-^ -C3烷基-A1 a取代，且Q -C7烷基係視情況被 取代基取代，取代基選自包括-N(R3 )-(:(0)-0-(^ -C3烷基 -A1 b、-N(R3 )-(:(0)-(^-C3 烷基-A1 b、-N(R3 )-8(0)2-(^-C3 烷基 -八11领尺3)-5(〇)2领尺3)-(：1-0：3烷基-八11以(113)-0：(〇)召(尺3)- Q -C3 烷基-A1 b 及-N(R3 )-S(0)2 -N(R3 -C3 烷基-A1 b，其中 A1 3與八113係獨立選自包括烷基、烯基及保護基；或 Ala與Alb —起經由·〇2·(：6次烷基_、_C2_Q次烯基_、_c2_C6次 块基-或-Co-C：3烷基-雜芳基-C0-C3烷基-連結基形成視情 況經取代之環。 於本發明之另一項具體實施例中，L係選自包括 -CrC6烷基-N(R3)-C〇-C3烷基-’其中q-Q烷基係視情況被取 代基取代，取代基選自包括_C〗_C4烷基_〇Ra、_Ci_C6烧基 -N(R3)(R3a)_、烷基 _c(〇)〇Ra 及 _c〇 C3 烷基·c(〇)_ N(R3)(R3a); -C〇 -Q烧基-N(R3 )-C(0)_C〇 A烷基_，其中Ci 烷基係視情況 被取代基取代，取代基選自包括_Ci_C4烷基_〇(Ra)_、_Cq_C6 燒基-C(0)0(Ra 及 _Cl _C6 烷基 _N(r3 )(r3 a ;及 134026-1 -82 - 200916447 -C0 -C6烷基-C(0)-N(R3 )-C〇 -C3烧基-，其中q -C6烧基係視情況 被取代基取代，取代基選自包括-CQ-C6烷基-0(Ra)-、_cq-C6 烷基-C(0)0(Ra)-、-C。-C3 烷基-C(0)-N(R3 )(R3 a)及-C〇 -C6 燒基 -N(R3)(R3a)-。 於本發明之另一項具體實施例中，L係選自包括 -C0 -Q烧基-N(R3 -〇7烧基-，其中q -C?烧基係視情況 被取代基取代，取代基選自包括-N(R7)(R7a)、-N(R3 C〇-C3 烷基·雜環基、-N(R3)-C(O)-C0-C6 烷基芳基 _Ra、 中雜環基係視情況經取代； -C0 -Q烷基-C(0)-N(R3 -C?烷基-，其中q -C6烷基係視情況 被-N(R7)(R7a)取代； -C〇 -C6烷基-C(0)-N(R3 -C7烷基-，其中q -C7烷基係視情況 被取代基取代，取代基選自包括芳基-芳基、芳基-雜芳 基、雜芳基-雜芳基、雜芳基-芳基及雜芳基；及 … -Ci -C3烷基-N(ie )-(:(0)-(^ -C7烷基-，其中C〗-C3烷基係視情況 被-C(0)N(R3 )-C〗-C3烧基-A1 a取代，且Ci -Gy烧基係視情況被 取代基取代，取代基選自包括-N(R3 )-(:(0)0-(^ -C3烷基-A1 b 、-N(R3 )-(：(0)-(：〗-C3 烷基-A1 b、-N(R3 )^(0)2-(^-(:3 烷基-A1 b、 -NCRq-CCCO-N^KVCs 烷基-Alb 及-N^VSCOVN^HVCj 烷基-A1 b，其中Ci -〇3 alkyl-N(R3)-C(〇)-Ci-C7 alkyl-'where C! -C3 Hyun> The base is optionally -C(0)N(R3)-^ -C3 Alkyla-A1 a is substituted, and Q-C7 alkyl group is optionally substituted with a substituent selected from the group consisting of -N(R3)-(:(0)-0-(^-C3 alkyl-A1b, -N(R3)-(:(0)-(^-C3 alkyl-A1 b, -N(R3)-8(0)2-(^-C3 alkyl-八11领尺3)-5( 〇)2 collar ruler 3)-(:1-0:3 alkyl-eight-11 to (113)-0:(〇)call (foot 3)-Q-C3 alkyl-A1 b and -N(R3) -S(0)2 -N(R3 -C3 alkyl-A1 b, wherein A1 3 and VIII 113 are independently selected from the group consisting of alkyl, alkenyl and protecting groups; or Ala and Alb are via 〇2·( : 6th alkyl-, _C2_Q-alkenyl-, _c2_C6-branched- or -Co-C:3 alkyl-heteroaryl-C0-C3 alkyl-linker forms an optionally substituted ring. In another embodiment of the invention, L is selected from the group consisting of -CrC6 alkyl-N(R3)-C〇-C3 alkyl-' wherein the qQ alkyl group is optionally substituted with a substituent selected from the group consisting of _C〗_C4 alkyl_〇Ra, _Ci_C6 alkyl-N(R3)(R3a)_, alkyl_c(〇)〇Ra and _c〇C3 alkyl·c(〇)_ N(R3)( R3a); -C〇-Q alkyl-N(R3)-C(0)_C〇Aalkyl_, The Ci alkyl group is optionally substituted with a substituent selected from the group consisting of _Ci_C4 alkyl_〇(Ra)_, _Cq_C6 alkyl-C(0)0 (Ra and _Cl_C6 alkyl_N(r3) ( R3 a ; and 134026-1 -82 - 200916447 -C0 -C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein the q-C6 alkyl group is optionally substituted by a substituent, The substituent is selected from the group consisting of -CQ-C6 alkyl-0(Ra)-, _cq-C6 alkyl-C(0)0(Ra)-, -C.-C3 alkyl-C(0)-N(R3 (R3 a) and -C〇-C6 alkyl-N(R3)(R3a)-. In another embodiment of the invention, the L is selected from the group consisting of -C0-Q alkyl-N (R3) - 〇7 alkyl-, wherein the q-C? alkyl group is optionally substituted with a substituent selected from the group consisting of -N(R7)(R7a), -N(R3C〇-C3 alkyl.heterocyclyl) , -N(R3)-C(O)-C0-C6 alkylaryl-Ra, the intermediate heterocyclic group is optionally substituted; -C0 -Q alkyl-C(0)-N(R3 -C? Alkyl-, wherein q-C6 alkyl is optionally substituted by -N(R7)(R7a); -C〇-C6 alkyl-C(0)-N(R3-C7alkyl-, wherein q-C7 The alkyl group is optionally substituted with a substituent selected from the group consisting of an aryl-aryl group, an aryl-heteroaryl group, a heteroaryl-heteroaryl group, a heteroaryl-aryl group, and a heteroaryl group; and Ci -C3 alkyl-N(ie)-(:(0)-(^-C7 alkyl-, wherein C-C3 alkyl is optionally treated by -C(0)N(R3)-C-C3 Substituting -A1 a, and Ci -Gy alkyl is optionally substituted by a substituent selected from -N(R3)-(:(0)0-(^-C3 alkyl-A1 b , -N (R3)-(:(0)-(:〗-C3 alkyl-A1 b, -N(R3)^(0)2-(^-(:3 alkyl-A1 b, -NCRq-CCCO-N ^KVCs alkyl-Alb and -N^VSCOVN^HVCj alkyl-A1 b, of which

Ala與Alb係獨立選自包括烷基、烯基及保護基；或 Ala與Alb —起經由-C2-C6次烷基、-C2-C6次烯基、-(：2-(：6次炔 基、-C〇-C3烷基-雜芳基-CVC3烷基-連結基或-C〇-C3烷基- 134026-1 -83- 200916447 芳基-c〇 -c3烧基-連結基形成視情況經取代之環，且 於本發明之另一項具體實施例中，L係選自包括 -c0 -C7烷基-N(R3 )-C(0)-雜環基-C0 -C6烷基-，其中c〗-C7烷基係 視情況被-C〇 -C3烧基-C(0)0Ra或-C〗-C3烧基-ORa取代；與 -c0 -〇7烷基-o-c(o)-雜環基，CG -C6烷基-，其中Ci -c7烷基係視情 況被-C〇 -C3烷基-C(0)0Ra或-C〇 -C3烷基-〇Ra取代。 於本發明之另一項具體實施例中，L係選自包括共價鍵、 -(CH2h-4-、-(CH2)0.4-(CR3=CR3)-(CH2)0.4-、-(CH2)0.4-(CEC)- (CH2)〇.4- ' -(CH2)〇.3N(R3)C(0)- ' -(CH2)〇.3-C(0)N(R3)---(CH2)〇.3 N(R3 )C(0)-(CRa =CRa)-、-(CH2 )G. 3. N(R3 )-(CH2 )2.4 N(R3 )C(0)-、 -(CH2 )〇. 3 -0-(CH2 )2.4 -N(R3 )C(0)-、-(CH2 )。. 3 C(0)-(CH2 )〇. 3 -、 -(CH2 )〇. 3 -(CRa =CRa )-C(0)-(CH2 )〇. 3 -、-(CH2)0 — 3C(O)-(CRa=CRa)-(CH2)〇.3-、-C〇-C6烷基-N(R3)-C(0)-雜環基-C〇-C3烷基-、-c0-c6 烷基-S(0)2 -雜環基-c。-C3 烷基-、-((^2)0-3-8(〇)2-风尺3)-((^2)0-3-、-(CH2)0_3N(R3)-S(O)2-(CH2)0.3-、-(CH2)0.3N(R3)-(CH2)0.3-、 -(^2)0.3^^)-(^2)^3-(0^=0^)- ' -(CH2)0.3C=N-O-(CH2)0.3-、-(CH2)0.3N(R7)-(CH2)0_3-、-(CH2)0.3S-(CH2)0_3-、-(CH2)0.3〇-(CH2)0_3-、-(CH2)0.3S(O)-(CH2)0.3-、_(ch2)0.3s(o)2-(ch2)0.3-、 -(CH2)0-3CH=CH-(CH2)2.3-、-(CH2)0.3N(R3)-C(O)-N(R3)-(CH2)0-3、 -(CH2 )〇. 3 N(R3 )-C(0)-0-(CH2 )〇. 3 ' -(CH2 )〇. 3 0-C(0)-N(R3 )-(CH2 )〇. 3 - 、-(ch2)0-3n(r3)-c(o)-n(r3)-s(o)2-(ch2)0.3-及-(ch2)0.3n(r3)-c(o)-n(r3)-c(o)-(ch2)0-3-。 於本發明之另一項具體實施例中，B!、B2及B3係獨立選 自包括 D-Gly、L-Gly、D-Pro、L-Pro、D-Tyr、L-Tyr、D-Tyr(ORa)、 -84- 134026-1 200916447 ^-iyr(UKa; D-Ala、L-AIa、D-ProR3、L-ProR3、D-Ile、L-Ile、D-Leu、L-Leu D-PheR3、L-PheR3、D-Pip 及 L-Pip。 於本發明之另一項具體實施例中，R7與R7a之各烷基、词 基、炔基、雜烷基、苄基及雜環基部份基團係獨立視情況 被一或多個取代基取代，取代基選自包括酮基、_〇h、-CN、 yc6烧基、Cl_c6炫氧基、_N〇2、娜3)(R3a) 1基、卻及 單-至全-iS化c】-c6烷基。 於本發明之另-項具體實施例中 笔佐夕讲^ 係獨立選自包括 非芳族多環、混合之芳基與非芳基多環 雜環，其每 方基、非方族多雜環、混合之芳基及非芳 夕’、 一個係視情況經取代。 土 於本發明之另—項具體實施例中，各 芳基、芳基-芳基、雜 . 糸獨立選自包和 環烧基、㈣^雜„僻基，^基-芳基、 代。 /、母個係视情況經取Ala and Alb are independently selected from the group consisting of alkyl, alkenyl and protecting groups; or Ala and Alb are via -C2-C6 alkyl, -C2-C6-alkenyl, -(:2-(:6-acetylene) , -C〇-C3 alkyl-heteroaryl-CVC3 alkyl-linker or -C〇-C3 alkyl- 134026-1 -83- 200916447 aryl-c〇-c3 alkyl-linker formation a substituted ring, and in another embodiment of the invention, L is selected from the group consisting of -c0 -C7 alkyl-N(R3)-C(0)-heterocyclyl-C0-C6 alkyl - wherein c-C7 alkyl is optionally substituted by -C〇-C3 alkyl-C(0)0Ra or -C--C3 alkyl-ORa; with -c0-〇7 alkyl-oc(o a heterocyclic group, CG-C6 alkyl-, wherein the Ci-c7 alkyl group is optionally substituted by -C〇-C3 alkyl-C(0)0Ra or -C〇-C3 alkyl-〇Ra. In another embodiment of the invention, the L is selected from the group consisting of a covalent bond, -(CH2h-4-, -(CH2)0.4-(CR3=CR3)-(CH2)0.4-, -(CH2)0.4 -(CEC)- (CH2)〇.4- ' -(CH2)〇.3N(R3)C(0)- ' -(CH2)〇.3-C(0)N(R3)---(CH2 ) 〇.3 N(R3 )C(0)-(CRa =CRa)-, -(CH2 )G. 3. N(R3 )-(CH2 )2.4 N(R3 )C(0)-, -(CH2 ) 〇. 3 -0-(CH2 )2.4 -N(R3 )C(0)-, -(CH2 ). 3 C(0)-(CH2 )〇. 3 -, -(CH2 )〇. 3 -(CRa =CRa )-C(0)-(CH2 )〇. 3 -, -(CH2)0 — 3C(O)-(CRa=CRa)-(CH2) 、.3-, -C〇-C6 alkyl-N(R3)-C(0)-heterocyclyl-C〇-C3 alkyl-, -c0-c6 alkyl-S(0)2-heterocycle Base-c.-C3 alkyl-, -((^2)0-3-8(〇)2-wind ruler 3)-((^2)0-3-, -(CH2)0_3N(R3)- S(O)2-(CH2)0.3-, -(CH2)0.3N(R3)-(CH2)0.3-, -(^2)0.3^^)-(^2)^3-(0^=0 ^)- ' -(CH2)0.3C=NO-(CH2)0.3-, -(CH2)0.3N(R7)-(CH2)0_3-, -(CH2)0.3S-(CH2)0_3-,-( CH2)0.3〇-(CH2)0_3-, -(CH2)0.3S(O)-(CH2)0.3-, _(ch2)0.3s(o)2-(ch2)0.3-, -(CH2)0- 3CH=CH-(CH2)2.3-, -(CH2)0.3N(R3)-C(O)-N(R3)-(CH2)0-3, -(CH2)〇. 3 N(R3)-C (0)-0-(CH2)〇. 3 ' -(CH2 )〇. 3 0-C(0)-N(R3 )-(CH2 )〇. 3 - , -(ch2)0-3n(r3) -c(o)-n(r3)-s(o)2-(ch2)0.3- and -(ch2)0.3n(r3)-c(o)-n(r3)-c(o)-(ch2 ) 0-3-. In another embodiment of the invention, B!, B2 and B3 are independently selected from the group consisting of D-Gly, L-Gly, D-Pro, L-Pro, D-Tyr, L-Tyr, D-Tyr. (ORa), -84- 134026-1 200916447 ^-iyr(UKa; D-Ala, L-AIa, D-ProR3, L-ProR3, D-Ile, L-Ile, D-Leu, L-Leu D- PheR3, L-PheR3, D-Pip and L-Pip. In another embodiment of the invention, each alkyl, aryl, alkynyl, heteroalkyl, benzyl and heterocyclic group of R7 and R7a Part of the group is independently substituted by one or more substituents, including a keto group, _〇h, -CN, yc6 alkyl, Cl_c6 methoxy, _N〇2, Na 3) (R3a ) 1 base, but mono-to-all-iS c]-c6 alkyl. In another embodiment of the present invention, the pens are independently selected from the group consisting of non-aromatic polycyclic, mixed aryl and non-aryl polycyclic heterocycles, each of which is hetero- and non-aromatic Rings, mixed aryl groups and non-fang Xi', one system is replaced as appropriate. In another embodiment of the present invention, each of the aryl, aryl-aryl, and heterocyclic groups is independently selected from the group consisting of a ketone group and a cycloalkyl group, (4) a heterocyclic group, a aryl group, and an aryl group. /, the mother is taken as the case

Rc·!—w、 ,Rh 中 例 施 實 體 具 項Rc·!—w, ,Rh in the example of the physical item

為 D 0 H—w cnxIs D 0 H—w cnx

a R—M b 或a R—M b or

X 於本發明之另 於本發明之另X is another according to the invention of the invention

Rc 項具體貫施例中，〇為 項具體貫施例中，D為In the specific example of the Rc term, 〇 is the specific example, and D is

Rafr Rb xRafr Rb x

Rc -RhRc -Rh

II X 134026-1 -1、 -85- 200916447 ψ ΐ本發明之另-項具體實施例中，D為 N、 /CHs 、c/CH3 Μ s 例如 s 於本毛明之另一項具體實施例中，x為o。 於本叙明之另-項具體實施例中X為s。 於本發明之另—音 “化 汽施例中，RaHRc係獨立，s 自包括-Η、C, -C，焓其r ^ τ词立4 -Cl職……C6環烧基、芳基、雜芳基及芳基 於本發明之另一項具體實施例中，以與於和彼等所連接 之亂原子-起形成3至9_員雜環基、雜芳基或雜環基-芳美 其中各雜環基 '雜芳基及雜環基·芳基係視情況經取代: 於本發明之另—項具體實施例中，R3與R3a係獨立選自包 括-H、0H、Cl % 院基、Q & 環烧基、（(ο)%、c_、 烧基-C_Ra '雜環基、_C2_C4烧基_〇Ra、C2 _C4次燒基；C# 烯基、（VC：6搜烷基_q_C6烷基芳基、芳基、_CG_C6烷基雜劳 基及A -C3烷基_c(0)N(Ra)#芳基。 於本發明之另一項具體實施例中，R3與R3a係獨立選自包 括-ci 烷基芳基、第三_丁基、芊基及芳基。 於本發明之另一項具體實施例中，r3與係獨立選自包 括乙醇、四氫-2H-哌喃、苯基及芊基。 於本發明之另一項具體實施例中，R3與R3a係獨立為Q _C4 院基。 於本發明之另一項具體實施例中，在-N(R3)(R3〇基團中， 134026-1 • 86- 200916447 R3與R3a和彼等所連接之氮原子一起視情況形成環，選自包 括嗎福啉基、六氫吡哨·基、六氫吡啶基、四氫吡咯基及一 氮四圜基。 於本發明之另一項具體實施例中，R4係選自包括-H、 -CH3、-S(0)2 -N(R3 )(R3 a)、_S〇3 H、_0_c2 _c4 烷基 _雜環基、_ac〇 Q 烷基-芳基、-o-c0-C4烷基-雜芳基、_0_C(0)N(R3)_C〇_C4烷基_ 芳基、-0-C(0)N(R3 )-C0 -C：4烷基-雜芳基、_0_c〇 _C4烷基-雜環基 -芳基、-o-c0 -C：4烷基-雜環基·雜芳基、_N(R3 )_c2 _C4烷基-雜環 基、-(CH2)〇.4ORa、-(CH2)0_4N(R3)(R3a)、_f、-ci、-Br、-CF3、 -CN、-CH2OH、-OH、-OCH3、-N02、Ph、芳基、雜芳基、 -N(R3)C(0)CH2R3、-N(R3)S02CH2Ra、-〇(CH2)2_4N(R3)(R3a)、 -SRa、-S(O)CH2R3、-SO2CH2Ra、-(CH2)0_4C(O)ORa、-CH=CH- C(0)0Ra、-CH=CHC(0)N(R3)(R3a)、-N(R3)c(0)CF3&_n(r3)(CH2)2_ N(R3)(R3a)。 於本發明之另一項具體實施例中，Rh為_Ch3。 / 於本發明之另一項具體實施例中，Rh為_CF3。 於本發明之另一項具體實施例中，L係選自包括 nr R NR Αί ΛII X 134026-1 -1, -85- 200916447 另 另 In another embodiment of the invention, D is N, /CHs, c/CH3 Μ s, eg s in another embodiment of the present invention , x is o. In another embodiment of the present description, X is s. In the other embodiment of the invention, the RaHRc system is independent, and the s self includes -Η, C, -C, 焓其r^ τ 词立 4 -Cl jobs... C6 cycloalkyl, aryl, Heteroaryl and aryl are based on another embodiment of the invention, forming a 3 to 9-membered heterocyclic group, a heteroaryl group or a heterocyclic group with a chaotic atom attached to the same. Each heterocyclyl 'heteroaryl and heterocyclyl-aryl is optionally substituted: In another embodiment of the invention, R3 and R3a are independently selected from the group consisting of -H, 0H, Cl% , Q & cycloalkyl, ((ο)%, c_, alkyl-C_Ra 'heterocyclyl, _C2_C4 alkyl 〇 Ra, C2 _C4 alkyl; C# alkenyl, (VC: 6 search alkyl _ Q_C6 alkylaryl, aryl, _CG_C6 alkyl aryl, and A-C3 alkyl _c(0)N(Ra)# aryl. In another embodiment of the invention, R3 and R3a are Independently selected from the group consisting of -ci alkylaryl, tert-butyl, decyl and aryl. In another embodiment of the invention, the r3 and the independently selected are selected from the group consisting of ethanol and tetrahydro-2H-periphere. , phenyl and fluorenyl. In another embodiment of the invention, R3 and R3a are Independently a Q _C4 hospital base. In another embodiment of the invention, in the -N(R3) (R3 fluorene group, 134026-1 • 86- 200916447 R3 and R3a and the nitrogen atom to which they are attached Forming a ring together, optionally comprising a morpholinyl group, a hexahydropyrrolyl group, a hexahydropyridyl group, a tetrahydropyrrolyl group, and a nitrotetradecyl group. In another embodiment of the invention, R4 Is selected from the group consisting of -H, -CH3, -S(0)2-N(R3)(R3a), _S〇3 H, _0_c2 _c4 alkyl-heterocyclyl, _ac〇Q alkyl-aryl, - o-c0-C4 alkyl-heteroaryl, _0_C(0)N(R3)_C〇_C4 alkyl_aryl,-0-C(0)N(R3)-C0-C:4 alkyl- Heteroaryl, _0_c〇_C4 alkyl-heterocyclyl-aryl, -o-c0-C:4 alkyl-heterocyclyl-heteroaryl, _N(R3)_c2_C4 alkyl-heterocyclyl, -(CH2)〇.4ORa, -(CH2)0_4N(R3)(R3a), _f, -ci, -Br, -CF3, -CN, -CH2OH, -OH, -OCH3, -N02, Ph, aryl ,heteroaryl, -N(R3)C(0)CH2R3, -N(R3)S02CH2Ra, -〇(CH2)2_4N(R3)(R3a), -SRa, -S(O)CH2R3, -SO2CH2Ra,- (CH2)0_4C(O)ORa, -CH=CH-C(0)0Ra, -CH=CHC(0)N(R3)(R3a), -N(R3)c(0)CF3&_n(r3) (CH2)2_ N(R3)(R3a) . In another embodiment of the invention, Rh is _Ch3. / In another embodiment of the invention, Rh is _CF3. In another embodiment of the invention, L is selected from the group consisting of nr R NR Αί Λ

134026-1 -87· 200916447134026-1 -87· 200916447

134026-1 -88- 200916447134026-1 -88- 200916447

134026-1 -89- 200916447134026-1 -89- 200916447

134026-1 -90- 200916447134026-1 -90- 200916447

4, 4,4, 4,

一 J 7 (R3a)(R3)N^)〇·3 RA J 7 (R3a)(R3)N^)〇·3 R

33

134026-1 -91 · 200916447134026-1 -91 · 200916447

134026-1 •92_ 200916447134026-1 •92_ 200916447

其中among them

Ala與Alb係獨立選自包括烷基、烯基及保護基，且 各A係獨立選自N、CH或C (當A係連接至Y或Z時），其中 可以有0、1、2或3個氮。 於本發明之另一項具體實施例中，Z係選自包括Ala and Alb are independently selected from the group consisting of alkyl, alkenyl and protecting groups, and each A is independently selected from N, CH or C (when A is attached to Y or Z), which may be 0, 1, 2 or 3 nitrogens. In another embodiment of the invention, the Z series is selected from the group consisting of

,A i..- κ A.·, A i..- κ A.·

6 a \ >/vw 丄o ,A.6 a \ >/vw 丄o , A.

,(ch2S K3 A>,(ch2S K3 A>

,(CH2)〇_3 (CH2)^ '(CH2)〇-3,(CH2)〇_3 (CH2)^ '(CH2)〇-3

,A -A ,/K A', A -A , /K A'

A、广(Chyt,A, Guang (Chyt,

• A• A

A 。行、A. Row,

Ay、2' -s. / > A^A^(CH2)〇-7 , α"α·^ι ΗΊAy, 2' -s. / > A^A^(CH2)〇-7 , α"α·^ι ΗΊ

1-3 。增 o，l 134026-1 -93- 2009164471-3. Increase o, l 134026-1 -93- 200916447

其中各A係獨立為氮、-CH=或-C(R4)=，其中可以有0、1、2 或3個氮。 於本發明之另一項具體實施例中，各Υ係獨立選自包括Each of the A lines is independently nitrogen, -CH= or -C(R4)=, which may have 0, 1, 2 or 3 nitrogens. In another embodiment of the invention, each tether is independently selected from the group consisting of

R3 ， ^4 134026-1 -94- 200916447R3, ^4 134026-1 -94- 200916447

134026-1 -95- 200916447134026-1 -95- 200916447

134026-1 -96- 200916447134026-1 -96- 200916447

134026-1 -97- 200916447134026-1 -97- 200916447

134026-1 -98- 200916447134026-1 -98- 200916447

134026-1 •99- 200916447134026-1 •99- 200916447

134026-1 -100- 200916447134026-1 -100- 200916447

134026-1 -101 200916447134026-1 -101 200916447

RfRf

其中 各A係獨立為氮、 3個氮； -C(H)=或-C(R4 )= 其中可以有0、1、2或Wherein each A is independently nitrogen and 3 nitrogens; -C(H)= or -C(R4)= which may have 0, 1, 2 or

及B各獨立為天然或合成胺基酸；And B are each independently a natural or synthetic amino acid;

Ml_M2係選自包括共價鍵、姆3)CH2-、-CH2N(R3).、-S(O)0.2 CH2、-CH2S(〇)Q_2-、-〇-CH2-、-CH2-〇-、-C(0)N(Ra)-、 -N(R3)C(0)- ' -S02N(R3)- > -N(R3)S02- > -CH(Ra)CH2- ' -CH2CH(Ra)-、-N=C(Ra)_、-C(Ra)=N-、-CH2-CH2-、-CH=CH-、 CH(Ra)-CH(Ra)-、-C(Ra)=C(Ra)- · -CH2-、-c(Ra)(Ra)-、-S-、Ml_M2 is selected from the group consisting of a covalent bond, m3)CH2-, -CH2N(R3)., -S(O)0.2CH2, -CH2S(〇)Q_2-, -〇-CH2-, -CH2-〇-, -C(0)N(Ra)-, -N(R3)C(0)- '-S02N(R3)- > -N(R3)S02- > -CH(Ra)CH2- ' -CH2CH( Ra)-, -N=C(Ra)_, -C(Ra)=N-, -CH2-CH2-, -CH=CH-, CH(Ra)-CH(Ra)-, -C(Ra) =C(Ra)- · -CH2-, -c(Ra)(Ra)-, -S-,

-N(R3)-及不存在 *ΛΛΛ/ M3係選自包括 m4係選自包括 134026-1 -102· 200916447 (〇)〇-2 ，^ry、’欠〇〆，，及共價鍵-N(R3)- and absent *ΛΛΛ/ M3 is selected from the group consisting of m4 series including 134026-1 -102· 200916447 (〇)〇-2, ^ry, 'nack, and covalent bond

RsRs

I 其中當Mi -M2為共價鍵時，M4為I wherein when Mi -M2 is a covalent bond, M4 is

Di -D2係選自包括 Ί γ Ί y Ύ ¥、，Di-D2 is selected from the group consisting of Ί γ Ί y Ύ ¥,,

其中*表示對Q之連接點； D3係選自包括共價鍵Where * represents the point of attachment to Q; D3 is selected from the group consisting of covalent bonds

vy、 ^))〇2 、，〇〆'，及 其中'^、與^A係視情況經取代 V... > d4係選自包括及^； 其中θ係視情況經取代， ε2係選自包括Vy, ^)) 〇2,, 〇〆', and its '^, and ^A are replaced by V... > d4 is selected from the group consisting of and ^; where θ is replaced by ε2 Selected from

選自包括-c(o)-、_C(S)-、-ch2-、-c(〇H)2-及 c Ν 3 選自包括-Η、-Q -c6烷基、-CVQ烯基、-C2-C6炔基、-二6 I烷基、雜環基-c〇-c6炫基-、芳基_c〇_C6烷基雜 134026-2 • 103- 200916447 -C〇-C6炫基-、（：3-(：6環燒基-Q-Q烧基 _、N(R3)(R3a)_Ci_C6 烷基-、N(R3 )(R3 3)((0)4 -c6 炫基-及 N(R3 )(R3 a)-C(S)·。! -c6 烷基其中各烷基、烯基、炔基、雜烷基、環烷基、 芳基、雜芳基或雜環基部份基團係視情況經取代。 於本發明之另一項具體實施例中’ R6之各烷基、烯基、 炔基、雜烷基、環烷基、芳基、雜芳基及雜環基部份基團 係獨立視情況被一或多個獨立選自R4之基團取代。 於本發明之另一項具體實施例中，R6係選自包括Selected from the group consisting of -c(o)-, _C(S)-, -ch2-, -c(〇H)2-, and c Ν 3 are selected from the group consisting of -Η, -Q-c6 alkyl, -CVQ alkenyl, -C2-C6 alkynyl, -2 6 I alkyl, heterocyclyl-c〇-c6 leu-, aryl _c〇_C6 alkyl 134026-2 • 103- 200916447 -C〇-C6 炫-, (: 3-(:6-cycloalkyl-QQ alkyl), N(R3)(R3a)_Ci_C6 alkyl-, N(R3)(R3 3)((0)4 -c6 炫- and N (R3)(R3 a)-C(S)·!! -c6 alkyl wherein each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, heteroaryl or heterocyclic moiety The group is optionally substituted. In another embodiment of the invention, each alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and heterocyclic group of 'R6 Part of the group is independently substituted by one or more groups independently selected from R4. In another embodiment of the invention, R6 is selected from the group consisting of

於根據本發明之另一項具體實施例中，R7係選自包括_H、 視情況經取代之Ci_C6烷基、-(CH2)2 4〇Ra、_〇Me、In another embodiment of the present invention, R7 is selected from the group consisting of _H, optionally substituted Ci_C6 alkyl, -(CH2)2 4〇Ra, _〇Me,

-C(0)0-苄基、-(CH2)2- D為 ； ； w與M為氮；-C(0)0-benzyl, -(CH2)2-D is ; ; w and M are nitrogen;

Ra 與 Re 為 _Η; 或-ο-烷基-雜芳基，其中該烷基、芳基及Ra and Re are _Η; or -ο-alkyl-heteroaryl, wherein the alkyl group, the aryl group and

Rb為-〇-烷基-芳基 134026-2 200916447 雜芳基部份基團係視情況經取代； Z為-Ci -Cg烧基-; L 為共價鍵、-C0-C6 烷基 _N(R3)C(0)_C(3_C3 烷基 _、_C()_C6 烷基 -N(R3)C(S)-C〇-C3 烷基-、_C()_C6 烷基 _C(0)N(R3)_C()_C3 烷基 _ 或-C〇 -C6 烧基-C(S)N(R3 )-C〇 -C3 烧基-;且 Y係選自包括烷基、芳基、雜芳基、芳基_芳基、雜芳基_ 芳基-、芳基-雜芳基-及多環，其中各烷基、芳基、雜芳 基及多環係視情況經取代。在一項替代具體實施例中， 烷基、芳基、雜芳基及多環基團係視情況被芳基_c〇_C6 烷基-〇-、雜芳基-C0-C6烷基-Ο-、雜芳基-0-或芳基_取代， 該芳基-C〇 -C6烧基-0-、雜芳基-C〇 -C6烧基-〇-、雜芳基_〇_ 或芳基-係進一步視情況例如被取代基取代，取代基選 自包括鹵基、經基、氰基、酮基、叛基、曱醯基、；6肖基、 胺基、甲脒基、胍基、q-C0烧基及烧氧基。在—項替代 具體實施例中’ L為-C〇 -C6烷基-N(R3 )C(O)-C0 -C3烷基-或 -C〇-C6 烷基-N(R3)C(S)-CG-C3 烷基-。 於根據本發明之另一項具體實施例中，Rb is -〇-alkyl-aryl 134026-2 200916447 Heteroaryl moiety is optionally substituted; Z is -Ci-Cg alkyl-; L is a covalent bond, -C0-C6 alkyl_ N(R3)C(0)_C(3_C3 alkyl_, _C()_C6 alkyl-N(R3)C(S)-C〇-C3 alkyl-, _C()_C6 alkyl_C(0) N(R3)_C()_C3 alkyl_ or -C〇-C6 alkyl-C(S)N(R3)-C〇-C3 alkyl-; and Y is selected from the group consisting of alkyl, aryl, hetero Aryl, aryl-aryl, heteroaryl-aryl-, aryl-heteroaryl- and polycyclic, wherein each alkyl, aryl, heteroaryl and polycyclic ring is optionally substituted. In alternative embodiments, the alkyl, aryl, heteroaryl, and polycyclic groups are optionally aryl-c〇_C6 alkyl-〇-, heteroaryl-C0-C6 alkyl-Ο- , heteroaryl-0- or aryl-substituted, the aryl-C〇-C6 alkyl--0-, heteroaryl-C〇-C6 alkyl-hydrazine-, heteroaryl-〇- or aryl Further, as the case may be, for example, substituted by a substituent selected from the group consisting of a halogen group, a thiol group, a cyano group, a ketone group, a thiol group, a fluorenyl group, a 6 schyl group, an amine group, a fluorenyl group, a fluorenyl group, q-C0 alkyl group and alkoxy group. In the alternative embodiment, 'L is -C -C6 alkyl-N(R3)C(O)-C0-C3 alkyl- or -C〇-C6 alkyl-N(R3)C(S)-CG-C3 alkyl-. According to the invention In another specific embodiment,

Rc 4—/Rh D為 妄； W為氮；Rc 4—/Rh D is 妄; W is nitrogen;

Re 為-H ; R*1為-C〇 -C6烧基-〇_C〇 -C6烧基-方基或-C〇 -Cg统基-O-Cq -C6炫ι其_ 雜芳基，其中烷基、芳基及雜芳基部份基團係視情況經 取代； 134026-2 -105- 200916447 Z為-Ci -Cg烧基-; L為共價鍵、-C〇-C6烷基_N(r3 )(：(0)-(：〇-c3烷基或-C〇-C6烷基 -c(o)n(r3)-cg-c3烷基；且 Y係選自包括烷基、芳基、雜芳基、芳基-芳基、雜芳基_ 芳基-、芳基-雜芳基-及多環’其中各烷基、芳基、雜芳 基及多環係視情況經取代。在一項替代具體實施例中， 院基、^'基、雜务基及多環基團係視情況被芳基_c〇 _c6 烧基-Ο-、雜^•基-C〇 -C6烧基-Ο-、雜芳基-〇-或芳基_取代， 該芳基-C0 -C6炫基-0-、雜芳基-C0 -C6院基-〇-、雜芳基_〇_ 或芳基-係進一步視情況例如被取代基取代，取代基選 自包括i基、經基、氰基、酮基、羧基、甲酿基、s肖基、 胺基、甲脒基、脈基、C! -C6烧基及烧氧基。在一項替代 具體實施例中，L為-C0-C6烷基-N(R3)C(O)-C0-C3燒基。 於根據本發明之另一項具體實施例中，化合物係以式（11)Re is -H; R*1 is -C〇-C6 alkyl-〇_C〇-C6 alkyl-aryl or -C〇-Cg----O-Cq-C6 炫ι__heteroaryl, Wherein the alkyl, aryl and heteroaryl moiety is optionally substituted; 134026-2 -105- 200916447 Z is -Ci -Cg alkyl-; L is a covalent bond, -C〇-C6 alkyl _N(r3)(:(0)-(:〇-c3 alkyl or -C〇-C6 alkyl-c(o)n(r3)-cg-c3 alkyl; and Y is selected from the group consisting of alkyl , aryl, heteroaryl, aryl-aryl, heteroaryl-aryl-, aryl-heteroaryl- and polycyclic' wherein each alkyl, aryl, heteroaryl and polycyclic ring system Substituted. In an alternative embodiment, the phenyl group, the thiol group, the hydroxy group, and the polycyclic group are optionally substituted by an aryl group _c〇_c6 alkyl group-Ο-, hetero group----C 〇-C6 alkyl-hydrazine-, heteroaryl-hydrazine- or aryl-substituted, the aryl-C0-C6 leumino--0-, heteroaryl-C0-C6-indolyl-indole-, heteroaryl _〇_ or aryl- is further substituted, for example, by a substituent selected from the group consisting of i group, thiol group, cyano group, keto group, carboxyl group, mercapto group, s Schottky group, amine group, formazan group. , pulse base, C! -C6 alkyl and alkoxy. In an alternative specific Embodiment, L is -C0-C6 alkyl group -N (R3) C (O) -C0-C3 burn group. According to another embodiment of the present invention, a compound is represented by the formula (11)

或其N-氧化物、水合物、溶劑合物、藥學上可接受之鹽、 前體藥物或複合物’及其外消旋與呈比例混合物、非對映 異構物及對掌異構物’其中R係選自包括：Or its N-oxide, hydrate, solvate, pharmaceutically acceptable salt, prodrug or complex' and its racemic and proportional mixture, diastereomer and palmomer 'where R is selected from:

134026-2 -106- 200916447134026-2 -106- 200916447

其中Ri為選用之取代基，且nl為0-4。 於根據本發明之另一項具體實施例中， 134026-2 -107- 200916447Wherein Ri is an optional substituent and nl is 0-4. In another embodiment in accordance with the invention, 134026-2 -107- 200916447

w為氮或氧； Μ為氮；w is nitrogen or oxygen; hydrazine is nitrogen;

Ra、Rb 及 Rc 為 _Η; ζ為-C〗-C8烷基-或_Ci _c8烷基_c(〇)_ ; L為-C0-C6 烷基 _N(R3)c(〇)_c〇_C3烷基；且 Y為烷基、芳基、雜芳基、雜芳基_芳基或芳基.芳基，其 中烷基、芳基及雜芳基係視情況經取代。在—項替代且 體實施例中，烷基'芳基及雜芳基係視情況被取代基: 代，取代基選自包括烷氧基、烷基、芳基、_〇_燒基-雜芳 基及-0-烷基-芳基。 於根巧本發明之另一項具體實施例中，Ra, Rb and Rc are _Η; ζ is -C〗-C8 alkyl- or _Ci _c8 alkyl _c(〇)_ ; L is -C0-C6 alkyl_N(R3)c(〇)_c 〇_C3 alkyl; and Y is alkyl, aryl, heteroaryl, heteroaryl-aryl or aryl.aryl, wherein alkyl, aryl and heteroaryl are optionally substituted. In the alternative and in the embodiment, the alkyl 'aryl and heteroaryl are optionally substituted: the substituent is selected from the group consisting of alkoxy, alkyl, aryl, 〇 〇 烧 - Aryl and -O-alkyl-aryl. In another specific embodiment of the invention,

Rc —W\ /Rh D為 S ; W鈞1L玖乳；Rc —W\ /Rh D is S ; W钧1L is milk;

Rc 為-H ;Rc is -H;

Rh為H或-CKC6烷基，其中該烷基係視情況經取代； Z為-Ci -C8烷基-或_c】-c8烷基-C(0)-; L 為-C0-C6 烷基 _N(;R3)C(〇)_C〇_C3烷基；且 Y為烷基、芳基、雜芳基、雜芳基_芳基或芳基_雜芳基’其 中烧基、芳基及雜芳基係視情況經取代。在一項替代具 體實施例中’烷基、芳基及雜芳基係視情況被取代基取 代，取代基選自包括烷氧基、烷基、芳基、_〇_烷基_雜芳 134026-2 •108- 200916447 基及-〇-烷基-芳基。 於根據本發明之另一項具體實施例中， I Ψ ψ W\ /Μ 、c Rb D為 ϊ ； w與M為氮；Rh is H or -CKC6 alkyl, wherein the alkyl group is optionally substituted; Z is -Ci-C8 alkyl- or _c]-c8 alkyl-C(0)-; L is -C0-C6 alkane —N(;R3)C(〇)_C〇_C3 alkyl; and Y is alkyl, aryl, heteroaryl, heteroaryl-aryl or aryl-heteroaryl, wherein alkyl, aromatic The base and heteroaryl groups are optionally substituted. In an alternative embodiment, 'alkyl, aryl and heteroaryl are optionally substituted with a substituent selected from the group consisting of alkoxy, alkyl, aryl, 〇-alkyl-heteroaryl 134026 -2 •108- 200916447 base and -〇-alkyl-aryl. In another embodiment of the invention, I Ψ ψ W\ /Μ, c Rb D is ϊ; w and M are nitrogen;

Ra、Rb&Rc 為-Η; R3為-H或Q-C6烷基； Z為視情況經取代之_Ci _Q烷基_ ; L係選自包括 -c〇-c6 烧基-C(0)_N(R3)_C(rC3 烷基…_CcrC6 垸基 _n(r3w〇> N(R3KVC3 烷基-或-Q-Q 烷基-O-Q-q 烷基 _c(〇)_n(r3)_ c0-C3烷基-，其中當c〇_C3烷基為Cl_C3烷基時，此^ ^ 烷基係視情況被-C(O)-N(R3)-C0-C3烷基-Y、芳基、雜芳基、 -雜芳基-芳基、-芳基-雜芳基、-芳基-芳基、雜芳基-雜芳 基、-N(R3)(R3a)或_N(R3)_Y取代，其中各雜芳基或芳基部 , 份基團係視情況經取代； i - -c0 -C6烷基-雜烷基-c0 -C6烷基-C(0)-N(R3 )-C0 -C3烷基-，其中當 C〇 -C3院基為C! -C3院基時’此Ci -C3烧基係視情況被雜芳 基、-N(R3)(R3a)或-N(R3)-Y 取代；及 -C0 -C6 烧基-N(R3 )C(O)-C0 -C3 烧基-，其中當 Q -C3 烧基為 q -C3 太完基時，此C, -C3烧基係視情沉被_n(r3 )(R3 a)、_N(R3 )_γ、 -N(R3)-C(0)-0-C〇-C3 烷基-Y、-NH2、-NH-S(0)2-Y、-ΝΗ-αρ)- NH-C。-C3 烷基-Y、-NH-雜芳基 _芳基或 _N(R3 )c(〇)_c。_c3 烷基 -Y取代；且 134026-2 -109- 200916447 各Y係獨立選自包括Η、烷基、環烷基、芳基、雜環基、雜 芳基-芳基、芳基-雜芳基、雜環基_〇·、芳基_N(R3)c(〇)_ 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(r3)_c(〇)芳基、 雜環基-Q-C：6 烷基-N(R3)_C(0)_ 雜芳基及 B2_Bl_N(R3)_c(〇)_ q-C7烷基-，其中烷基、環烷基、芳基、雜芳基及雜環 基部份基團係視情況經取代，且（^-(^烷基係視情況被 -NR3-B3取代，及B3之胺係與B2之酸連接，以形成肽鍵， 且其中當Y為Β2 -βΐ -N(R3 )-0(0)-(^ -C7烷基-時，則z與l為 共價鍵；其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B1、B2及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 於根據本發明之另一項具體實施例中，Ra, Rb & Rc is -Η; R3 is -H or Q-C6 alkyl; Z is optionally substituted _Ci _Q alkyl _; L is selected from the group consisting of -c〇-c6 alkyl-C(0 )_N(R3)_C(rC3 alkyl..._CcrC6 fluorenyl_n(r3w〇> N(R3KVC3 alkyl- or -QQ alkyl-OQq alkyl-c(〇)_n(r3)_ c0-C3 alkane Base-, wherein when c〇_C3 alkyl is a C1-C3 alkyl group, this alkyl group is optionally taken as -C(O)-N(R3)-C0-C3 alkyl-Y, aryl, heteroaryl , -heteroaryl-aryl, -aryl-heteroaryl, -aryl-aryl,heteroaryl-heteroaryl, -N(R3)(R3a) or _N(R3)_Y, Wherein each heteroaryl or aryl moiety, the moiety is optionally substituted; i - -c0 -C6 alkyl-heteroalkyl-c0 -C6 alkyl-C(0)-N(R3)-C0-C3 Alkyl-, wherein when the C〇-C3 substituent is C!-C3, the Ci-C3 alkyl group is optionally heteroaryl, -N(R3)(R3a) or -N(R3)- Y substituted; and -C0 -C6 alkyl-N(R3)C(O)-C0-C3 alkyl-, wherein when the Q-C3 alkyl group is q-C3, the C, -C3 alkyl group Depending on the situation, _n(r3)(R3 a), _N(R3)_γ, -N(R3)-C(0)-0-C〇-C3 alkyl-Y, -NH2, -NH-S (0) 2-Y, -ΝΗ-αρ)-NH-C.-C3 alkyl-Y, -NH-heteroaryl-aryl Or _N(R3)c(〇)_c._c3 alkyl-Y substituted; and 134026-2 -109- 200916447 each Y is independently selected from the group consisting of an anthracene, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic group, Heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇, aryl_N(R3)c(〇)_heteroaryl,heteroaryl-N(R3)-C(0) -heteroaryl, aryl_n(r3)_c(〇)aryl, heterocyclyl-QC:6 alkyl-N(R3)_C(0)_heteroaryl and B2_Bl_N(R3)_c(〇) _ q-C7 alkyl-, wherein the alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moiety are optionally substituted, and (^-(^ alkyl is optionally taken by -NR3) -B3 substitution, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein when Y is Β2 -βΐ -N(R3)-0(0)-(^-C7 alkyl-, then z And l is a covalent bond; wherein when any of B1, B2 and B3 are linked together, they are linked by a peptide bond, and B1, B2 and B3 are independently selected from the group consisting of D-Pro, L-ile and D- Phe-4-CF3. In another embodiment in accordance with the present invention,

Rc Ί—W、，Rh D為 2 ; W為氮；Rc Ί—W,, Rh D is 2; W is nitrogen;

Rc 為-Η ;Rc is -Η;

Rh為Η或-q -C6烧基，其中該炫基係視情況經取代； R3為烷基； z為視情況經取代之_Ci _c8烷基_ ; L係選自包括 -c〇-c6 烷基-c(0)_n(R3)_Cq_C3 烷基-、_C()_C6 烷基 _n(r3)-c(o)-N(R3)-C0-C3 烷基-或-c0-c6 烧基-0-C〇-C3 烷基-C(0)-N(R3)-C〇-C3烷基-，其中當c〇_c3烷基為Cl_c3烷基時’此CVC3 烧基係視情況被-C(O)-N(R3)-C0-C3烷基-Y、芳基、雜芳基、 134026-2 200916447 -雜芳基-芳基、-芳基-雜芳基、-芳基_芳基、雜芳基雜芳 基、-N(R3)(R3a)或_N(R3)_Y取代，其中各雜芳基或芳基部 份基團係視情況經取代； -C〇 -Q烷基-雜烷基_C〇 烷基_c(〇)_N(R3 )_c〇 _C3烷基_，其中當 c0 -C：3烧基為Ci -C3烧基時’此Ci -C3烧基係視情況被雜芳 基、取代；及 -C〇 烧基-N(R3 )C(0)-C〇必烧基-，其中當c〇 _C3烧基為q七3 烷基時’此（VQ烷基係視情況被-N(R3)(R3a)、-N(R3)-Y、 -N(R )-C(O)-〇-C0-C3 烧基-Y、-NH2、-NH-S(0)2-Y、-NH-C(0)-NH-Rh is an anthracene or a -q-C6 alkyl group, wherein the leuco group is optionally substituted; R3 is an alkyl group; z is optionally substituted _Ci_c8 alkyl group; L is selected from the group consisting of -c〇-c6 Alkyl-c(0)_n(R3)_Cq_C3 alkyl-, _C()_C6 alkyl_n(r3)-c(o)-N(R3)-C0-C3 alkyl- or -c0-c6 Base-0-C〇-C3 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when c〇_c3 alkyl is Cl_c3 alkyl, this CVC3 alkyl group is optionally -C(O)-N(R3)-C0-C3 alkyl-Y, aryl, heteroaryl, 134026-2 200916447 -heteroaryl-aryl, -aryl-heteroaryl, -aryl a aryl, heteroarylheteroaryl, -N(R3)(R3a) or _N(R3)_Y substitution wherein each heteroaryl or aryl moiety is optionally substituted; -C〇- Qalkyl-heteroalkyl-C〇alkyl_c(〇)_N(R3)_c〇_C3 alkyl_, wherein when the c0-C:3 alkyl group is a Ci-C3 alkyl group, this Ci-C3 The alkyl group is optionally substituted by a heteroaryl group; and -C〇alkyl-N(R3)C(0)-C〇-carbyl-, wherein when the c〇_C3 alkyl group is q-s-7 alkyl group 'This (VQ alkyl group is optionally -N(R3)(R3a), -N(R3)-Y, -N(R)-C(O)-〇-C0-C3 alkyl-Y, -NH2 , -NH-S(0)2-Y, -NH-C(0)-NH-

c0 -C3 烧基-Y、_NH-雜芳基-芳基或-N(R3 )C(O)-C0 -C3 烷基-Y 取代；且 各Y係獨立選自包括H、烧基、環烧基、芳基、雜環基、雜 芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_N(R3)_c(〇)_ 雜芳基、雜芳基-n(r3)-c(0)-雜芳基、芳基_N(R3 )·(：(〇)_芳基、 雜環基-C〇-C6 烷基-N(R3)-C(0)-雜芳基及 Q-C：7烷基_，其中烷基、環烷基、芳基、雜芳基及雜環 基部份基團係視情況經取代，且基係視情況被 -NR _B3取代，及B3之胺係與B2之酸連接，以形成肽鍵， 且其中當Y為B2-B1 -N(R3 )-(:(0)-(^ -C7烧基-時，則z與L·為 共價鍵； 其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B、B2及B3係獨立選自包括D-Pr〇、L-ile及D-Phe-4-CF3。 於根據本發明之另一項具體實施例中， 134026-2 200916447C0 -C3 alkyl-Y, _NH-heteroaryl-aryl or -N(R3)C(O)-C0-C3 alkyl-Y substituted; and each Y is independently selected from the group consisting of H, alkyl, and ring Anthracenyl, aryl, heterocyclic, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇, aryl_N(R3)_c(〇)_heteroaryl, heteroaryl -n(r3)-c(0)-heteroaryl, aryl_N(R3)·(:(〇)_aryl, heterocyclyl-C〇-C6 alkyl-N(R3)-C( 0)-heteroaryl and QC:7 alkyl-, wherein the alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moiety are optionally substituted, and the group is optionally taken by -NR _B3 is substituted, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein when Y is B2-B1 -N(R3)-(:(0)-(^-C7 alkyl-, then z And L· is a covalent bond; wherein when any of B1, B2 and B3 are linked together, they are linked by a peptide bond, and B, B2 and B3 are independently selected from the group consisting of D-Pr〇, L-ile and D-Phe-4-CF3. In another embodiment in accordance with the invention, 134026-2 200916447

W與Μ為氮；W and Μ are nitrogen;

Ra、Rb 及 Re 為 _Η; R3為^或^-心烷基； z為視情況經取代之_Ci _c8烷基_ ; L係選自包括 -C〇-C6 烧基 _C(〇)_n(R3)_C()_C3 烧基-、_C〇_C6 烧基 _n(r3)_c(〇)_ N(R3)-C0-C3 烷基-或-C0-C6 烷基-0-C〇-C3 烷基-C(0)-N(R3)-c0-C3烷基-，其中當c〇_C3烷基為Ci_C3烷基時，此Ci_C3 院基係視情況被-C(0)-N(R3 )-C0 -C3烷基-Y、-雜芳基-芳基、 雜芳基、雜芳基-雜芳基、-N(R3)(R3a)或-N(R3)-Y取代，其 中各雜方基或芳基部份基團係視情況經取代；Ra, Rb and Re are _Η; R3 is ^ or ^-alkylalkyl; z is optionally substituted _Ci _c8 alkyl _; L is selected from the group consisting of -C〇-C6 alkyl _C(〇) _n(R3)_C()_C3 alkyl group, _C〇_C6 alkyl group_n(r3)_c(〇)_ N(R3)-C0-C3 alkyl- or -C0-C6 alkyl-0-C 〇-C3 alkyl-C(0)-N(R3)-c0-C3 alkyl-, wherein when the c〇_C3 alkyl group is a Ci_C3 alkyl group, the Ci_C3 base system is optionally -C(0) -N(R3)-C0-C3 alkyl-Y,-heteroaryl-aryl, heteroaryl, heteroaryl-heteroaryl, -N(R3)(R3a) or -N(R3)-Y Substituting wherein each heteroaryl or aryl moiety is substituted as appropriate;

-C〇 -C：6烷基-雜烷基-C〇 -C6烷基-C(0)-N(R3 )-C〇 -C3烷基-，其中當 C〇 -C3烧基為Ci -C3烧基時’此Ci -C3烧基係視情況被雜芳 基、-N(R3)(R3a)或-N(R3)-Y 取代；及 -C〇 -C6 烷基-N(R3 )C(O)-C0 -C3 烷基-，其中當 C〇 -C3 烧基為 C! -C3 烷基時，此CVQ烷基係視情況被-N(R3)-C(0)-0-CG-C3烷基 -Y、-NH2、-NH-S(0)2-Y、-NH-C(O)-NH-C0-C3 烷基-Y、-NH-雜芳基-芳基、-N(R3)C(O)-C0-C3 烷基-γ、-N(R3)(R3a)或 -N(R3)-Y取代；且 各Y係獨立選自包括Η、烷基、環烷基、芳基、雜芳基、雜 芳基-芳基、芳基-雜芳基、雜環基·0-、芳基-N(R3)-C(0)-雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(R3)-C(〇)-芳 134026-2 200916447 基、雜環基-C〇-C6烧基-N(R3)-C(0)-雜芳基及bLbLN^3)-C(0)-C1_C7烷基-，其中環烷基、芳基、雜芳基、雜環基 及烷基部份基團係視情況被一、二或三個（或者，一或 兩個’或者’ 一個）取代基取代’取代基選自包括_基、 烧氧基 '視情況經取代之Cl-C6烷基、烷氧羰基-、_〇H、 -CN、-C(0)-〇H、視情況經取代之芳基、視情況經取代之 -烷基芳基、視情況經取代之雜芳基、視情況經取代之 -o-q -c：6烧基-芳基、視情況經取代之_c(〇)_〇 Ci %烧基、 •nH2、視情況經取代之_芳基-雜環基及視情況經取代之稠 合雜環，且C〗-C7烷基係視情況被_NR3-B3取代，及B3之胺 係與B2之酸連接，以形成肽鍵，且其中當Y為 B B -N(R )-0(0)-(^ -C7烧基-時’則Z與L為共價鍵；其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B1、B2及B3係獨立選自包括D_Pro、L_ile及D_phe_4_CF3。 於根據本發明之另一項具體實施例中， 卜 W、/Rh D為 t ； W為氮；-C〇-C: 6-alkyl-heteroalkyl-C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when C〇-C3 alkyl is Ci- When C3 is burned, 'this Ci-C3 alkyl group is optionally substituted with a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; and -C〇-C6 alkyl-N(R3) C(O)-C0 -C3 alkyl-, wherein when the C〇-C3 alkyl group is C!-C3 alkyl, the CVQ alkyl group is optionally taken as -N(R3)-C(0)-0- CG-C3 alkyl-Y, -NH2, -NH-S(0)2-Y, -NH-C(O)-NH-C0-C3 alkyl-Y, -NH-heteroaryl-aryl, -N(R3)C(O)-C0-C3 alkyl-γ, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of hydrazine, alkyl, and ring. Alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl·0-, aryl-N(R3)-C(0)-heteroaryl, heteroaryl --N(R3)-C(0)-heteroaryl, aryl_n(R3)-C(〇)-aryl 134026-2 200916447 yl, heterocyclyl-C〇-C6 alkyl-N (R3 -C(0)-heteroaryl and bLbLN^3)-C(0)-C1_C7 alkyl-, wherein cycloalkyl, aryl, heteroaryl, heterocyclyl and alkyl moiety groups The situation is replaced by one, two or three (or one or two 'or 'one) substituents. The substituent is selected from the group consisting of Alternate substituted C-C6 alkyl, alkoxycarbonyl-, 〇H, -CN, -C(0)-〇H, optionally substituted aryl, optionally substituted - alkane Alkylaryl, optionally substituted heteroaryl, optionally substituted -oq-c: 6 alkyl-aryl, optionally substituted _c(〇)_〇Ci% alkyl, nH2 Optionally substituted aryl-heterocyclic group and optionally substituted fused heterocyclic ring, and C-C7 alkyl group is optionally substituted by _NR3-B3, and amine of B3 is linked to acid of B2 To form a peptide bond, and wherein when Y is BB -N(R )-0(0)-(^ -C7 alkyl-- then Z and L are covalent bonds; wherein when any B1, B2 and B3 are When linked together, they are joined by peptide bonds, and B1, B2, and B3 are independently selected from the group consisting of D_Pro, L_ile, and D_phe_4_CF3. In another embodiment in accordance with the present invention, w, /Rh D is t ; W is nitrogen;

Re 為-H ; R為Η或-C：6烷基’其中該烷基係視情況經取代； R3為七或^-心烷基； Z為視情況經取代之_Ci _C8烷基_ ·， L係選自包括 _c〇-C6 烷基-C(0)-N(R3)-Cg-C3 烷基-、-CQ-C6 烷基-N(R3)-C(0)- 134026-2 -113- 200916447 N(R3)-C〇-C3 烷基-或-C0-C6 烷基-〇-C0-C3 烷基-C(0)-N(R3)-C〇 -C3烧基-，其中當C0 -C3烧基為q -C3烧基時，此q -C3 烷基係視情況被-C(0)-N(R3 )-C〇 -c3烷基-Y ' -雜芳基-芳基、 雜芳基、雜芳基-雜芳基、-N(R3 )(R3 a)或-N(R3 )-Y取代，其 中各雜芳基或芳基部份基團係視情況經取代； -C〇 -C：6烷基-雜烷基_c0 -C：6烷基-C(0)-N(R3 )-C0 -C3烷基-，其中當 C〇 Cg烧基為C! -C3院基時’此Cl -C3烧基係視情況被雜芳 基、-叫113)(1^)或_风]^3)_¥取代；及 -C〇 -C6 烧基-N(R3 )c(0)_c〇 _c3 烧基-，其中當 c〇 _c3 烧基為 Ci _c3 烧基時，此C! -C3烷基係視情況被-N(R3 )-C(0)-0-C〇 -c3烷基 -γ、NH2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-Y、-NH-雜芳基-芳基、-N(R3)C(0)-C〇-C3 烷基-Y、-N(R3)(R3a)或 -N(R3)-Y取代；且 各Y係獨立選自包括H、烷基、環烷基、芳基、雜芳基、雜 芳基-芳基、芳基-雜芳基、雜環基-〇-、芳基-n(r3)-c(o)-雜芳基、雜芳基_N(R3)-C(〇)-雜芳基、芳基_N(R3)_C(0)_芳基、 雜 ％ 基 C0-C6 烷基-N(R3)-C(〇)-雜芳基及 bLbLN^KXO)-q-C7燒基其中環烷基、芳基、雜芳基、雜環基及烷 基°卩份基團係視情況被一、二或三個（或者，一或兩個， 或者’ 一個）取代基取代’取代基選自包括鹵基、烷氧 基、視情況經取代之c! -C6烷基、烷氧羰基_、-OH、-CN、 -C(0)-〇H、視情況經取代之芳基、視情況經取代之-烷基 芳基、視情況經取代之雜芳基、視情況經取代之_〇_Ci _c6 烷基 '芳基、視情況經取代之-CCCO-O-Ci -C6烷基、-NH2、視 134026-2 -114- 200916447 情況經取代之-芳基-雜環基及視情況經取代之稠合雜 環’且q -C：7烧基係視情況被_nr3 -B3取代，及B3之胺係與 B之酸連接’以形成肽鍵，且其中當γ為B2_gi _n(r3 )_C(〇)_Re is -H; R is hydrazine or -C: 6 alkyl' wherein the alkyl group is optionally substituted; R3 is a hexa- or aryl-alkyl group; Z is optionally substituted _Ci_C8 alkyl _ , L is selected from the group consisting of _c〇-C6 alkyl-C(0)-N(R3)-Cg-C3 alkyl-, -CQ-C6 alkyl-N(R3)-C(0)-134026- 2 -113- 200916447 N(R3)-C〇-C3 alkyl- or -C0-C6 alkyl-oxime-C0-C3 alkyl-C(0)-N(R3)-C〇-C3 alkyl- Wherein, when the C0-C3 alkyl group is a q-C3 alkyl group, the q-C3 alkyl group is optionally taken as -C(0)-N(R3)-C〇-c3 alkyl-Y'-heteroaryl -aryl, heteroaryl, heteroaryl-heteroaryl, -N(R3)(R3a) or -N(R3)-Y substituted, wherein each heteroaryl or aryl moiety is as appropriate Substituted; -C〇-C: 6-alkyl-heteroalkyl-c0-C: 6-alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when C〇Cg is alkyl C! -C3 yard base 'This Cl -C3 base is replaced by heteroaryl, -113) (1^) or _ wind]^3)_¥; and -C〇-C6 burnt base - N(R3)c(0)_c〇_c3 alkyl group, wherein when the c〇_c3 alkyl group is a Ci_c3 alkyl group, the C!-C3 alkyl group is optionally taken as -N(R3)-C( 0)-0-C〇-c3 alkyl-γ, NH2, -NH-S(0)2-Y, -NH-C(0)-NH-C〇-C3 Base-Y, -NH-heteroaryl-aryl, -N(R3)C(0)-C〇-C3 alkyl-Y, -N(R3)(R3a) or -N(R3)-Y And each Y is independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-indole-, aryl-n (r3)-c(o)-heteroaryl,heteroaryl_N(R3)-C(〇)-heteroaryl, aryl_N(R3)_C(0)_aryl, heteropoly group C0 -C6 alkyl-N(R3)-C(〇)-heteroaryl and bLbLN^KXO)-q-C7 alkyl wherein cycloalkyl, aryl, heteroaryl, heterocyclic and alkyl The group is optionally substituted by one, two or three (or one or two, or 'one) substituents. The substituent is selected from the group consisting of halo, alkoxy, and optionally substituted c!-C6 alkane. Alkyloxycarbonyl, -OH, -CN, -C(0)-oxime H, optionally substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl, Substituted _〇_Ci _c6 alkyl 'aryl, optionally substituted - CCCO-O-Ci-C6 alkyl, -NH2, 134026-2 -114- 200916447 case substituted - aryl -heterocyclic group and optionally substituted fused heterocyclic ring 'and q -C:7 Based group optionally substituted _nr3 -B3, and B3 of the amine acid B is connected 'to form a peptide bond, and wherein when γ is B2_gi _n (r3) _C (square) _

Cl -C?烷基-時，則Z與L為共價鍵； 其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B1、於及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 . 於根據本發明之另一項具體實施例中，When Cl -C?alkyl-, then Z and L are covalent bonds; wherein when any of B1, B2 and B3 are linked together, they are linked by a peptide bond, and B1, and B3 are independently selected from Including D-Pro, L-ile and D-Phe-4-CF3. In another embodiment in accordance with the present invention,

Rb D為 J . w與Μ為氮；Rb D is J. w and Μ are nitrogen;

Ra、Rb及俨為_Η ; R3為—Η或CKC6烷基； z為視情況經取代之_Ci_c8烷基_ ; L為 ()七0乇6烷基"N(R3 >°(0)-c〇 - A烷基…其中當C〇 -C3烷基為q -C3 烷基時’此Ci -C：3烷基係視情況被_N(R3 )_c(〇)_〇_Cg _c3烷基 -Y、-nh2、_NH_S(0)2_Y、_NH C(〇) NH C〇 q 烷基 γ NH 雜芳基·芳基、领R3)C⑼_c〇_C3烷基_γ、_N(R3)(R3a)或 _N(R3)-Y取代；且 合Y係獨立選自包括Η、烷基、環烷基、芳基、雜芳基、雜 芳基-芳基、芳基_雜芳基、雜環基_α、芳基_n(r3) c(0)_ 雜芳基、雜芳基-n(r3)-c(0)-雜芳基、芳基_n(r3)_c(0)_芳基、 雜 J衣基-C0-(：6 烷基-N(R3)-C(0)-雜芳基及 b2_bi_n(R3)-C(0)- 134026*2 *115- 200916447Ra, Rb and 俨 are _Η; R3 is -Η or CKC6 alkyl; z is optionally substituted _Ci_c8 alkyl _; L is () 七乇6 alkyl "N(R3 >°( 0) -c〇- Aalkyl...wherein when C〇-C3 alkyl is q-C3 alkyl, 'Ci-C:3 alkyl is optionally taken as _N(R3)_c(〇)_〇_ Cg _c3 alkyl-Y, -nh2, _NH_S(0)2_Y, _NH C(〇) NH C〇q alkyl γ NH heteroaryl·aryl, collar R3)C(9)_c〇_C3 alkyl _γ, _N( R3) (R3a) or _N(R3)-Y substituted; and Y is independently selected from the group consisting of anthracene, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-hetero Aryl, heterocyclyl-α, aryl_n(r3) c(0)_heteroaryl, heteroaryl-n(r3)-c(0)-heteroaryl, aryl_n(r3) _c(0)_aryl, hetero-J-yl-C0-(:6-alkyl-N(R3)-C(0)-heteroaryl and b2_bi_n(R3)-C(0)-134026*2 *115 - 200916447

Cl c7烷基·，其中環烷基、芳基、雜芳基、雜環基及烷 、二視If况經取代，且q -〇7烷基係視情況被_NR3 _B3取 代，’ 之胺係與B2之酸連接，以形成肽鍵，且其中當 ' ' B N(R -C7烧基-時，則z與[為共價鍵； 其中 可B B及B3係連接在一起時，其係藉由肽鍵連接， B B及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 於根$本發明之另一項具體實施例中， -卜W、/Rh D為 t ； W為氮；Cl c7 alkyl, wherein cycloalkyl, aryl, heteroaryl, heterocyclyl and alkane, di-substitution, are substituted, and q-〇7 alkyl is optionally substituted by _NR3_B3, 'amine Is linked to the acid of B2 to form a peptide bond, and wherein when ''BN(R-C7 alkyl group-), then z and [is a covalent bond; wherein BB and B3 are linked together, Linked by peptide bonds, BB and B3 are independently selected from the group consisting of D-Pro, L-ile and D-Phe-4-CF3. In another embodiment of the invention, -W, /Rh D Is t; W is nitrogen;

Rc 為-H ; R為Η或-C】-C：6烷基，其中該烷基係視情況經取代； R3為-Η或q -C6燒基； z為視情況經取代之_Ci _C8烷基_ ; L為 -C〇 -C6 烷基-N(R3 )c(0)_C(rc3 烷基 _，其中當 c〇 _c3 烷基為 Ci _c3 烧基時’此C! -C：3烷基係視情況被-N(R3 )-C(0)-0-CG -C3烷基 -Y、-NH2、-NH-S(0)2_Y、-NH-C(0)-NH-C〇-C3 烧基-Y、-NH- 雜芳基·芳基、-N(R3)C(0)_C〇_C3 烷基 _γ、_N(R3)(R3a)或 -N(R3)-Y取代；且 各Y係獨立選自包括η、烷基、環烷基、芳基、雜芳基、雜 芳基-芳基、芳基_雜芳基、雜環基_〇_、芳基_n(r3)_c(〇)_ 雜芳基、雜芳基-n(r3)-c(o)-雜芳基、芳基-n(r3)-c(o)-芳 134026-2 -116- 200916447 基、雜％基-cvc：6烷基_n(R3)_c(〇)·雜芳基及 ()1C7烷基_，其中環烷基、芳基、雜芳基、雜環基 及烧基係視情況經取代，且Ci_c#基係視情況被_nr3_b3 取代及B之胺係與於之酸連接，以形成肤鍵，且其中 田Y為B B N(R )_c(〇)_c】-C7烧基-時，則z與L為共價鍵； 其中 ' 田任何B B及B3#、連接在—起時，其係藉由肽鍵連接， 且B B及B係獨立選自包括Dpr〇、及。 於根^本發明之另一項具體實施例中， K J'RbRc is -H; R is hydrazine or -C]-C: 6 alkyl, wherein the alkyl group is optionally substituted; R3 is -Η or q-C6 alkyl; z is optionally substituted _Ci_C8 Alkyl _ ; L is -C〇-C6 alkyl-N(R3 )c(0)_C(rc3 alkyl_, wherein when c〇_c3 alkyl is Ci _c3 alkyl) 'This C! -C: The 3 alkyl group is optionally taken as -N(R3)-C(0)-0-CG-C3alkyl-Y, -NH2, -NH-S(0)2_Y, -NH-C(0)-NH- C〇-C3 alkyl-Y, -NH-heteroaryl-aryl, -N(R3)C(0)_C〇_C3 alkyl_γ, _N(R3)(R3a) or -N(R3) -Y substituted; and each Y is independently selected from the group consisting of η, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇, aryl Base_n(r3)_c(〇)_heteroaryl,heteroaryl-n(r3)-c(o)-heteroaryl, aryl-n(r3)-c(o)-aryl 134026-2 -116- 200916447, hexyl-cvc: 6-alkyl-n(R3)_c(〇)·heteroaryl and ()1C7alkyl-, wherein cycloalkyl, aryl, heteroaryl, heterocyclic The base and the alkyl group are optionally substituted, and the Ci_c# base is optionally substituted by _nr3_b3 and the amine of B is linked to the acid to form a skin bond, and wherein Y is BBN(R)_c(〇) _c]-C7 burning base-, z and L are covalent bonds; wherein 'any BB and B3#, when linked, are linked by peptide bonds, and BB and B are independently selected from the group consisting of Dpr〇, and In another specific embodiment, K J'Rb

Rb D為 χ ； W與M為氮；Rb D is χ; W and M are nitrogen;

Ra、Rb 及 R^-H ; R3為^或心-仏烷基； z為視情況經取代之_Ci _c8烷基_ ; L為 -C0-C6烷基-N(R3)c(0)_c〇烷基_，其中當c。％烷基為Ci必 烷基時，此Ci -C：3烷基係視情況被_N(R3 )_c(〇)_〇_Cg _c3烷基 -γ、-ΝΉ2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-Y、-NH-雜芳基-芳基、-N(R3)C(O)-C0-C3 烷基-Υ、-N(R3)(R3a)或 -N(R3)-Y取代；且 各Y係獨立選自包括H、烷基、環烷基、芳基、雜芳基、雜 芳基-芳基、芳基-雜芳基、雜環基-〇_、芳基-n(r3)-c(o)-雜芳基、雜芳基-N(R3)-C(〇)-雜芳基、芳基芳 134026-2 -117- 200916447 基、雜環基-C0-C6烷基_n(R3)-C(〇)-雜芳基及BlB1-!^3)-CXCO-q-C7烷基-，其中環烷基、芳基、雜芳基、雜環基 及烷基係視情況被一 '二或三個（或者，—或兩個，或 者’ 一個）取代基取代，取代基選自包括_基、烷氧基、 視情況經取代之Q -C6烷基、烷氧羰基_、_〇H、-CN、 -C(0)-0H、視情況經取代之芳基、視情況經取代之_烷基 芳基、視情況經取代之雜芳基、視情況經取代之_〇_Ci _C6 烷基-芳基、視情況經取代之_c(〇)_〇_Ci &烷基、_NH2、視 情況經取代之-芳基_雜環基及視情況經取代之稠合雜 環’且C! -C7烧基係視情況被_NR3 _B3取代，及¥之胺係與 B2之酸連接，以形成肽鍵，且其中當γ為B2_Bl_N(R3)_c(0y C1-C7烷 基-時 ，則乙與乙為共價鍵； 其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B1、B2及B3係獨立選自包括]〇_1>1>〇、。 於根^本發明之另一項具體實施例中，Ra, Rb and R^-H; R3 is ^ or cardio-alkyl; z is optionally substituted _Ci _c8 alkyl _; L is -C0-C6 alkyl-N(R3)c(0) _c〇alkyl_, where c. When the % alkyl group is a Ci-containing alkyl group, the Ci-C:3 alkyl group is optionally treated by _N(R3)_c(〇)_〇_Cg_c3 alkyl-γ, -ΝΉ2, -NH-S(0). ) 2-Y, -NH-C(0)-NH-C〇-C3 alkyl-Y, -NH-heteroaryl-aryl, -N(R3)C(O)-C0-C3 alkyl- Υ, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl , aryl-heteroaryl, heterocyclyl-oxime, aryl-n(r3)-c(o)-heteroaryl, heteroaryl-N(R3)-C(〇)-heteroaryl, Aryl aromatic 134026-2 -117- 200916447 base, heterocyclic group-C0-C6 alkyl_n(R3)-C(〇)-heteroaryl and BlB1-!^3)-CXCO-q-C7 alkyl - wherein cycloalkyl, aryl, heteroaryl, heterocyclyl and alkyl are optionally substituted by a 'two or three (or, or two) or 'one' substituents selected from Including _ group, alkoxy group, optionally substituted Q-C6 alkyl group, alkoxycarbonyl group, _〇H, -CN, -C(0)-0H, optionally substituted aryl group, as the case may be Substituted _alkylaryl, optionally substituted heteroaryl, optionally substituted _〇_Ci _C6 alkyl-aryl, optionally substituted _c ( )_〇_Ci & alkyl, _NH2, optionally substituted-aryl-heterocyclic group and optionally substituted fused heterocyclic ring ' and C! -C7 alkyl group are replaced by _NR3 _B3 as appropriate And amines of B are linked to the acid of B2 to form a peptide bond, and wherein when γ is B2_Bl_N(R3)_c (0y C1-C7 alkyl-, then B is a covalent bond with B; wherein when any B1 When B2 and B3 are linked together, they are linked by peptide bonds, and B1, B2 and B3 are independently selected from the group consisting of: 〇_1 > 1 > 〇, 于根^ Another embodiment of the present invention In the example,

RC c D為 x ; W為氮；RC c D is x ; W is nitrogen;

Rc 為-Η ;Rc is -Η;

Rh為H或-CVC：6烷基，其中該烷基係視情況經取代； K*"為-H 或 基； Z為視情況經取代之-c! -c8烷基-; L為 -C〇 -Q烷基-N(R3 )c(0)-c〇 -C：3烷基_ ’其中當c〇 _c3烷基為q必 134026-2 -118- 200916447 烷基時，此C! -C：3烷基係視情況被_n(R3 )-C(〇)-〇-CQ -C3烷基 -Y、-NH2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-γ、-NH- 雜芳基-芳基、-N(R3)C(0)-C〇-C3 烷基-Y、-N(R3)(R3a)或 -N(R3)-Y取代；且 各Y係獨立選自包括H、烷基、環烷基、芳基、雜芳基、雜 芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_N(R3)_c(〇)_ 雜芳基、雜芳基-n(r3)-c(0)-雜芳基、芳基-n(r3)-c(o)-芳基、 雜環基-Q-Q 烷基-N(R3)-C(0)-雜芳基及 W-Bi-N^KXO)- q-c：7烷基_，其中環烷基 '芳基、雜芳基、雜環基及烷 基係視情況被一、二或三個（或者，一或兩個，或者， 一個）取代基取代’取代基選自包括_基、烷氧基、視 情況經取代之q -C6烷基、烷氧羰基-、_〇H、_CN、 -C(0)-〇H、視情況經取代之芳基、視情況經取代之_烷基 芳基、視情況經取代之雜芳基、視情況經取代之_〇_c】_匸6 烷基-芳基、視情況經取代之_c(〇)_〇_Ci _C6烷基、_NH2、視 情況經取代之-芳基-雜環基及視情況經取代之稠合雜 環’且Cl -C7院基係視情況被-NR3 -B3取代，及B3之胺係與 B之酸連接，以形成肽鍵，且其中當Y為Rh is H or -CVC: 6 alkyl, wherein the alkyl group is optionally substituted; K*" is -H or a group; Z is optionally substituted -c!-c8 alkyl-; L is - C〇-Qalkyl-N(R3)c(0)-c〇-C:3alkyl_' wherein C is c-_3 alkyl is q 134026-2 -118- 200916447 alkyl, this C -C:3 alkyl group is optionally treated as _n(R3)-C(〇)-〇-CQ-C3 alkyl-Y, -NH2, -NH-S(0)2-Y, -NH-C (0)-NH-C〇-C3 alkyl-γ, -NH-heteroaryl-aryl, -N(R3)C(0)-C〇-C3 alkyl-Y, -N(R3)( R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, Heterocyclyl-〇_, aryl_N(R3)_c(〇)_heteroaryl, heteroaryl-n(r3)-c(0)-heteroaryl, aryl-n(r3)-c (o)-aryl, heterocyclyl-QQ alkyl-N(R3)-C(0)-heteroaryl and W-Bi-N^KXO)-qc:7alkyl-, wherein cycloalkyl The aryl, heteroaryl, heterocyclyl and alkyl groups are optionally substituted by one, two or three (or one or two, or one) substituents. The substituent is selected from the group consisting of benzyl and alkoxy. , optionally substituted q-C6 alkyl, alkoxy Base-, _〇H, _CN, -C(0)-〇H, optionally substituted aryl, optionally substituted _alkylaryl, optionally substituted heteroaryl, optionally substituted _〇_c]_匸6 alkyl-aryl, optionally substituted _c(〇)_〇_Ci _C6 alkyl, _NH2, optionally substituted-aryl-heterocyclyl and, as appropriate Substituted fused heterocyclic ring' and the Cl-C7 nodal system is optionally substituted by -NR3 -B3, and the amine of B3 is linked to the acid of B to form a peptide bond, and wherein Y is

Cl<：7烷基-時，則Z與L·為共價鍵； 其中 田任何B、y及Bj係連接在一起時，其係藉由肽鍵連接， 且B B及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 於根據本發明之另一項具體實施例中， 134026-2 200916447 ,^ Ψ ^—W\c/M、Rb D為 χ ; W與M為氮；When Cl<:7 alkyl-, then Z and L· are covalent bonds; wherein any B, y and Bj lines of the field are linked together by peptide bonds, and BB and B3 are independently selected from the group consisting of D-Pro, L-ile and D-Phe-4-CF3. In another embodiment of the present invention, 134026-2 200916447 , ^ Ψ ^—W\c/M, Rb D is χ; W and M are nitrogen;

Ra、Rb 及 Rc 為-Η ; R3 為-Η ; R4為Η或F ; Z為視情況經取代之-Ci -Cg烧基-; L係選自包括 -c〇 -C6 烷基-C(0)_N(R3 )_C〇 _c3 烷基-，其中當 c〇 _C3 烷基為 ^ & 烧基時’此Ci -C：3烷基係視情況被-C(0)-N(R3 )-CQ -c3烧基 -Y、-雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； -C〇 -Q烷基-雜烷基_C〇 (6烷基_c(〇)_N(R3 )_c〇 a烷基-，其中當 C〇-C3烷基為Q-C：3烷基時，此q-C：3烷基係視情況被雜芳 基、-N(R3)(R3a)或-N(R3)_Y取代；及 _C〇夂烧基-n(r3 )C(O)-C0-C3烧基-，其中當Q-C3烧基為Cl七3 燒基時’此C]-C3烷基係視情被-N(R3)C(0)-C()-C3烷基-Y、 -N(R3)(R3a)或·n(r3)_Yw取代；且 各γ係獨立選自包括烷基、芳基、雜芳基、雜芳基_芳基、 芳基-雜芳基及B2_Bi_N(R3)_c(〇)_Ci_C7烷基_，其中芳基與 雜芳基係視情況經取代，且Ci _C7烧基係視情況被_NR3 _B3 取代，及之胺係與B2之酸連接，以形成肽鍵’且其中 當Y為烷基-時，則Z與L為共價 鍵；其中 田任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 134026-2 -120- 200916447 且B1、B2及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 於根據本發明之另一項具體實施例中，Ra, Rb and Rc are -Η; R3 is -Η; R4 is Η or F; Z is optionally substituted -Ci-Cg alkyl-; L is selected from -c〇-C6 alkyl-C ( 0) _N(R3)_C〇_c3 alkyl-, wherein when c〇_C3 alkyl is ^ & burnt, 'this Ci-C:3 alkyl is optionally taken as -C(0)-N ( R3)-CQ-c3 alkyl-Y,-heteroaryl-aryl, heteroaryl, -N(R3)(R3a) or -N(R3)-Y substituted; -C〇-Qalkyl-hetero Alkyl_C〇(6-alkyl-c(〇)_N(R3)_c〇aalkyl-, wherein when C〇-C3 alkyl is QC:3 alkyl, this qC:3 alkyl group is optionally Substituted by a heteroaryl group, -N(R3)(R3a) or -N(R3)_Y; and _C〇夂alkyl-n(r3)C(O)-C0-C3 alkyl-, wherein when Q- When the C3 alkyl group is a Cl-7 alkyl group, the 'C'-C3 alkyl group is optionally taken as -N(R3)C(0)-C()-C3 alkyl-Y, -N(R3)(R3a) Or ·n(r3)_Yw is substituted; and each γ is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl and B2_Bi_N(R3)_c(〇)_Ci_C7 Alkyl group, wherein the aryl group and the heteroaryl group are optionally substituted, and the Ci_C7 alkyl group is optionally substituted by _NR3_B3, and the amine group is bonded to the acid of B2 to form a peptide bond 'and wherein Y Is an alkyl group - When Z and L are covalent bonds; wherein any of B1, B2 and B3 are linked together, they are linked by a peptide bond, 134026-2 -120-200916447 and B1, B2 and B3 are independently selected from Including D-Pro, L-ile, and D-Phe-4-CF3. In another embodiment in accordance with the present invention,

Rc Ί—Wx ^R11 D為x ； w為氮；Rc Ί—Wx ^R11 D is x; w is nitrogen;

Rc 為-Η ; R為Η或-C^ -C6烧基，其中該烧基係視情況經取代； R3 為-H ; R4為Η或F ; ζ為視情況經取代之-c8烷基-; L係選自包括 -0) 烷基-C(0)-N(R3 )-C0 -C3 烷基-，其中當 C0 -C3 烷基為 C] -C3 烷基時’此Q -C3烷基係視情況被-C(0)-N(R3)-C〇-C3烷基 -Y、-雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； -C0 -C6烷基-雜烷基-C0 -C6烷基-C(0)-N(R3 )-C〇 -C3烷基-，其中當 C〇 -C：3烷基為C! -C3烷基時，此q -C3烷基係視情況被雜芳 基、-N(R3)(R3a)或-N(R3)-Y取代；及 -C〇 -Q 烧基-N(R3 )C(O)-C0 -C3 烧基-，其中當 C〇 -C3 烧基為 C! -C3 烷基時，此C〗-C3烷基係視情況被-N(R3)C(0)-CG-C3烷基 -丫、-风1^3)(1^)或_风113)_丫取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳基、 芳基-雜芳基及BkBLNCR'CCOKVC；烷基-，其中芳基與 雜芳基係視情況經取代；且(^-(：7烷基係視情況被-NR3-B3 取代，及B3之胺係與b2之酸連接，以形成肽鍵，且其中 134026-2 200916447 當Y為B2也傳3 )_c(〇)_Ci _c7烷基_時，則z與L為共價鍵； 其中 當任何B1、B2及B3係'連接在—起時，其係、藉由肽鍵連接， 且B1、B2及B3係獨立選自包括D_pr〇、L ^及d phe 4 CF3。 於根巧本發明之另一項具體實施例中， y Ra “\，Rb D為 ϊ ; W與Μ為氮；Rc is -Η; R is hydrazine or -C^-C6 alkyl, wherein the alkyl group is optionally substituted; R3 is -H; R4 is hydrazine or F; hydrazine is optionally substituted -c8 alkyl- ; L is selected from the group consisting of -0) alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when the C0-C3 alkyl group is a C]-C3 alkyl group, the Q-C3 alkane The base system is optionally -C(0)-N(R3)-C〇-C3 alkyl-Y,-heteroaryl-aryl, heteroaryl, -N(R3)(R3a) or -N(R3 -Y substituted; -C0-C6 alkyl-heteroalkyl-C0-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when C〇-C:3 alkyl When C?-C3 alkyl, the q-C3 alkyl group is optionally substituted by a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; and -C〇-Q alkyl group- N(R3)C(O)-C0-C3 alkyl-, wherein when the C〇-C3 alkyl group is C!-C3 alkyl, the C-C3 alkyl group is optionally taken as -N(R3)C (0)-CG-C3 alkyl-hydrazine, -wind 1^3) (1^) or _wind 113)_丫 substituted; and each Y is independently selected from the group consisting of alkyl, aryl, heteroaryl, hetero Aryl-aryl, aryl-heteroaryl and BkBLNCR 'CCOKVC; alkyl-, wherein the aryl and heteroaryl are optionally substituted; and (^-(:7 alkyl is optionally -NR3- B3 substitution, and the amine of B3 and the acid of b2 To form a peptide bond, and wherein 134026-2 200916447 when Y is B2 also transmits 3)_c(〇)_Ci_c7alkyl_, then z and L are covalent bonds; wherein when any B1, B2 and B3 are ' When the linker is attached, it is linked by a peptide bond, and B1, B2 and B3 are independently selected from the group consisting of D_pr〇, L^ and d phe 4 CF3. In another embodiment of the invention , y Ra "\, Rb D is ϊ; W and Μ are nitrogen;

Ra、Rb 及 Rc 為-Η ; R3 為-Η ; R4為Η或F ; z為視情況經取代之-C8烷基-; L係選自包括 -C〇 -C6 烧基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當 c〇 -C3 烷基為 c! -C3 垸基時，此C! -eg烷基係視情況被-C(〇)-N(R3 )-CVC3烧基 -Ύ、-雜芳基-芳基、雜芳基、_N(R3XR3a)或_N(R3)_Y取代； •co - A烷基-雜烷基_c〇 -C：6烷基-C(0)-N(R3 )-C〇 -C：3烷基-，其中當 C〇 -C3烧基為Ci -C；3烧基日守’此Ci -C；3烧基係視情況被雜芳 基、-N(R3)(R3a)或-N(R3)-Y取代；及 -C〇 -C6 烷基-N(R3 )C(O)-C0 -C3 烧基-，其中當 C〇 -C3 烧基為 Cl & 燒基時，此c] -C：3烧基係視情況被-N(R3 )0(0)-(^-(:3 ：；：完基 -Y、-N(R3)(R3a)或-N(R3)-Y 取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳基、 芳基-雜芳基及BkBlNCI^KXOKVC7烷基-，其中芳基與 134026-2 -122- 200916447 雜芳基係視情況被一、二或三個（或者，一或兩個’或 者，一個）取代基取代，取代基選自包括鹵基、炫氧基、 視情況經取代之q-C6烷基、烷氧羰基-、-0H、-CN、 -C(0)-0H、視情況經取代之芳基、視情況經取代之-烷基 芳基、視情況經取代之雜芳基、視情況經取代之-0-C! -C6 烷基-芳基 '視情況經取代之_c(〇)_〇_Ci _c6烷基、-NH2、視 情況經取代之-芳基-雜環基及視情況經取代之稠合雜 環’且Ci-C：7烷基係視情況被_NR3_B3取代，及B3之胺係與 B2之酸連接，以形成肽鍵，且其中當Y為BLBi-NCRq-CCO)-C! -Ο?烷基-時，則z與L為共價鍵；其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B1、B2及B3係獨立選自包括D_pro、L-ile及D-Phe-4-CF3。 於根據本發明之另一項具體實施例中，Ra, Rb and Rc are -Η; R3 is -Η; R4 is Η or F; z is optionally substituted -C8 alkyl-; L is selected from -C〇-C6 alkyl-C(0) -N(R3)-C〇-C3 alkyl-, wherein when c〇-C3 alkyl is c!-C3 fluorenyl, this C!-eg alkyl group is optionally taken as -C(〇)-N ( R3)-CVC3 alkyl-hydrazine, -heteroaryl-aryl, heteroaryl, _N(R3XR3a) or _N(R3)_Y substituted; •co-Aalkyl-heteroalkyl-c〇-C: 6-alkyl-C(0)-N(R3)-C〇-C:3 alkyl-, wherein when C〇-C3 alkyl is Ci-C; 3 alkyl base is 'this Ci-C; 3 burns The base is optionally substituted with a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; and -C〇-C6 alkyl-N(R3)C(O)-C0-C3 alkyl - wherein, when the C〇-C3 alkyl group is a Cl & burn group, this c] -C:3 alkyl group is optionally treated by -N(R3)0(0)-(^-(:3 :;: Substituting -Y, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl -heteroaryl and BkBlNCI^KXOKVC7 alkyl-, wherein the aryl group and the 134026-2 -122-200916447 heteroaryl group are optionally substituted by one, two or three (or one or two 'or one') substituents take a substituent selected from the group consisting of halo, decyloxy, optionally substituted q-C6 alkyl, alkoxycarbonyl-,-0H, -CN, -C(0)-0H, optionally substituted aryl Substituted -alkylaryl, optionally substituted heteroaryl, optionally substituted -O-C! -C6 alkyl-aryl 'optionally substituted _c(〇)_ 〇_Ci _c6 alkyl, -NH2, optionally substituted -aryl-heterocyclic group and optionally substituted fused heterocyclic ring' and Ci-C:7 alkyl group is optionally substituted by _NR3_B3, and The amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein when Y is BLBi-NCRq-CCO)-C!-Ο?alkyl-, then z and L are covalent bonds; wherein when any B1 When B2 and B3 are linked together, they are linked by a peptide bond, and B1, B2 and B3 are independently selected from the group consisting of D_pro, L-ile and D-Phe-4-CF3. In a specific embodiment,

Rc W、/Rh D為 ϊ ; W為氮；Rc W, /Rh D is ϊ; W is nitrogen;

Rc 為-Η ;Rc is -Η;

Rh為Η或-C：6烷基，其中該烷基係視情況經取代； R3 為-H ; R4為Η或F ; ζ為視情況經取代之_Ci -c8烷基-; L係選自包括 -C〇 -C6烷基-C(0)_N(R3 )_c〇 _C3烷基_，其中當c〇七3烷基為A —A 烧基時’此Q -C：3烷基係視情況被_c(〇)-N(R3 )_Cq _C3烧基 134026-2 -123- 200916447 -Υ、-雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； -C〇 -C6烷基-雜烷基_c0 -C6烷基-C(0)-N(R3 )-C0 -C3烷基-，其中當 C0-C3烷基為q -C3烷基時，此q -A烷基係視情況被雜芳 -C0 垸基-N(R3 )C(0)-C〇 -c3 烷基-，其中當 C〇 _C3 烷基為 q _C3 烷基時’此Ci -C3烷基係視情況被-N(R3 )C(0)-CG -C3烷基-Υ、 -N(R3 )(R3 a )或-n(r3 )_γ 取代；且 各Υ係獨立選自包括烷基、芳基、雜芳基、雜芳基_芳基、 芳基-雜芳基及BkBLN^KXOKVG；烷基_，其中芳基與 雜方基係視情況被一、一或三個（或者，一或兩個，或 者’一個）取代基取代，取代基選自包括_基、烷氧基、 視情況經取代iCl_C6烷基、烷氧羰基-、_〇H、_CN、 C(〇)-〇H、視情況經取代之芳基、視情況經取代之_烧基 芳基、視情況經取代之雜芳基、視情況經取代之_〇_Ci _c6Rh is hydrazine or -C:6 alkyl, wherein the alkyl group is optionally substituted; R3 is -H; R4 is hydrazine or F; hydrazine is optionally substituted _Ci-c8 alkyl-; Including -C〇-C6 alkyl-C(0)_N(R3)_c〇_C3 alkyl_, wherein when c〇7-3 alkyl is A—A alkyl group, this Q-C:3 alkyl group Depending on the case, _c(〇)-N(R3)_Cq_C3 alkyl 134026-2 -123- 200916447 - fluorene, -heteroaryl-aryl, heteroaryl, -N(R3)(R3a) or - N(R3)-Y substituted; -C〇-C6 alkyl-heteroalkyl-c0-C6 alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein C0-C3 alkyl When q-C3 alkyl, this q-A alkyl group is optionally heteroaryl-C0 fluorenyl-N(R3)C(0)-C〇-c3 alkyl-, wherein when C〇_C3 alkyl When it is q _C3 alkyl, 'this Ci-C3 alkyl group is optionally -N(R3)C(0)-CG-C3alkyl-Υ, -N(R3)(R3 a ) or -n(r3 ) _γ substituted; and each lanthanide is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, and BkBLN^KXOKVG; alkyl-, wherein aryl and hetero-aryl Substituting one, one or three (or one or two, or 'one) substituents, the substituents being selected from the group consisting of An oxy group, optionally substituted iCl_C6 alkyl, alkoxycarbonyl-, 〇H, _CN, C(〇)-〇H, optionally substituted aryl, optionally substituted arylalkyl, Substituted heteroaryl, as appropriate _〇_Ci _c6

烷基'芳基、視情況經取代之-QOKKVQ烷基、-NH2、視 情況經取代之-芳基-雜環基及視情況經取代之稠合雜 環，且_C：7烧基係視情況被-NR3 -B3取代，及B3之胺係與 B之酸連接，以形成肽鍵，且其中當γ為B2 -B1 -N(R3 )-C(0)-Ci -C7貌基-時，則z與L為共價鍵；其中 田任何βΐ、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B及B3係獨立選自包括D-pro、L-ile及D-Phe-4-CF3。 π很錁本發明Alkyl 'aryl, optionally substituted -QOKKVQ alkyl, -NH2, optionally substituted-aryl-heterocyclyl, and optionally substituted fused heterocycle, and _C:7 alkyl Substituted by -NR3 -B3, and the amine of B3 is linked to the acid of B to form a peptide bond, and wherein γ is B2 -B1 -N(R3)-C(0)-Ci-C7 Wherein, z and L are covalent bonds; wherein any βΐ, B2 and B3 lines are linked together by a peptide bond, and B and B3 are independently selected from the group consisting of D-pro, L-ile and D-Phe-4-CF3. π is very simple invented by the present invention

Ra 1,Μ D為Ra 1, Μ D is

Rb 134026-2 -124- 200916447 W與Μ為氮；Rb 134026-2 -124- 200916447 W and hydrazine are nitrogen;

Ra、Rb及把為-Η ; R3 為-Η ; R4為Η或F ; z為視情況經取代之-Cl -c8烧基' ; L為 _C〇 -C6 烷基-N(R3 )C(O)-C0 -C3 炫基-，其中當 C0 -C3 院基為 Ci (3 烷基時，此Ci -C3烷基係視情況被_N(R3 )C(0)-CQ -C3烧基 -Y、-N(R3)(R3a)或-N(R3)-Y取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基_芳基、 芳基-雜芳基及ΒΙΒΙΝ^ΚΧΟΚ：〆7烷基-，其中芳基與 雜芳基係視情況經取代，且(^-^烷基係視情況被_NR3_b3 2代，及B3之胺係與b2之酸連接，以形成肽鍵，且其中 當Y為妒-B! _N(R3 )_c(〇)_Ci _C7烷基-時，則z與l為共價鍵； 其中Ra, Rb and put are -Η; R3 is -Η; R4 is Η or F; z is optionally substituted -Cl-c8 alkyl group; L is _C〇-C6 alkyl-N(R3)C (O)-C0 -C3 炫-, wherein when the C0-C3 base is Ci (3 alkyl, this Ci-C3 alkyl is optionally _N(R3)C(0)-CQ-C3 Substituted with -Y, -N(R3)(R3a) or -N(R3)-Y; and each Y is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl- Heteroaryl and ΒΙΒΙΝ^ΚΧΟΚ: 〆7-alkyl-, wherein the aryl and heteroaryl groups are optionally substituted, and (^-^alkyl groups are optionally treated by _NR3_b3 2, and B3 amines and b2 The acid is linked to form a peptide bond, and wherein when Y is 妒-B! _N(R3 )_c(〇)_Ci _C7 alkyl-, then z and l are covalent bonds;

可1 2B及B3係連接在-起時，其係藉由肽鍵連接， 及B係獨立選自包括D-pr〇、L-ile及D-Phe-4-CF3 cThe 1 2B and B 3 lines may be linked by a peptide bond, and the B line may be independently selected from the group consisting of D-pr〇, L-ile and D-Phe-4-CF3 c.

於根據本發明$ H R<= 月之另一項具體實施例中， -5-Wx ^Rh D為 t ； W為氮；In another embodiment of the invention according to the invention, $5 R <= month, -5-Wx ^Rh D is t; W is nitrogen;

Rc 為-Η ;Rc is -Η;

Rh 為 Η 或-C&ι ^ R3為H · 疋土，/、中該烷基係視情況經取代； 134026-2 -125- 200916447 R4為Η或F ; z為視情況經取代之_Ci 烷基_ ; L為 -C〇 -C：6烧基-N(R3 )c(〇)_c〇 _c3烷基…其中當c〇_c3烷基為Ci; 烧基時’此Ci -C3烷基係視情況被_N(R3 )(:(0)-0)-(¾烷基 -丫、-1^3)〇^)或_风尺3)_丫取代；且 各γ係獨立選自包括烷基、芳基、雜芳基、雜芳基_芳基、 芳基-雜芳基及B2_B1 _N(R3)_c(〇)_Ci _C7烷基_，其中芳基與 雜芳基係視情況經取代’且CpCy烷基係視情況被_NR3-B3 取代’及B3之胺係與B2之酸連接，以形成肽鍵，且其中 當y為b^bincrM-cxohvc?烷基-時，則Z與L為共價鍵； 其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連接， 且B]、B2及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 於根據本發明之另一項具體實施例中， ψ Ra W ώRh is Η or -C&ι ^ R3 is H · bauxite, /, the alkyl group is optionally substituted; 134026-2 -125- 200916447 R4 is Η or F; z is replaced by _Ci as appropriate Alkyl _ ; L is -C〇-C: 6 alkyl-N(R3 )c(〇)_c〇_c3 alkyl...wherein c〇_c3 alkyl is Ci; when calcined 'this Ci-C3 The alkyl group is optionally substituted by _N(R3)(:(0)-0)-(3⁄4 alkyl-丫,-1^3)〇^) or _ wind ruler 3)_丫; and each γ is independent Selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl and B2_B1_N(R3)_c(〇)_Ci_C7 alkyl_, wherein aryl and heteroaryl are Substituting 'and CpCy alkyl is optionally substituted by _NR3-B3' and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein when y is b^bincrM-cxohvc?alkyl- , Z and L are covalent bonds; wherein when any of B1, B2 and B3 are linked together, they are linked by a peptide bond, and B], B2 and B3 are independently selected from the group consisting of D-Pro, L- Ile and D-Phe-4-CF3. In another embodiment in accordance with the invention, ψ Ra W ώ

Rb D為 x ； W與M為氮；Rb D is x; W and M are nitrogen;

Ra、Rb及把為-Η ; R3 為-Η ; R4為Η或F ; Z為視情況經取代之_q烷基_ ; L為 -C0 -C6 烷基-N(R3 )C(〇)-C0 -C3 烧基-，其中當 C〇 _c3 烷基為 Cl _C3 134026-2 •126- 200916447 烷基時，此C! -C3烷基係視情況被-N(R3 )C(0)-Cg -C3烷基 -Y、-N(R3)(R3a)或-N(R3)-Y取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳基、 芳基-雜芳基及Β2 -Β1 -N(R3 )-(:(0)-(^ -C7烷基-，其中芳基與 雜芳基係視情況被一、二或三個（或者，一或兩個，或 者，一個）取代基取代，取代基選自包括_基、烷氧基、 視情況經取代之（：丨-C6烷基、烷氧羰基-、-oh、-CN、 -C(0)-〇H、視情況經取代之芳基、視情況經取代之_烷基 芳基、視情況經取代之雜芳基、視情況經取代之_0_Ci _c6 烧基-芳基、視情況經取代之_c(0)_0_Ci _c6烷基、_Νη2、視 情況經取代之-芳基-雜環基及視情況經取代之铜合雜 環，且C! -C7烧基係視情況被_nr3 -Β3取代，及Β3之胺係與 B2之酸連接，以形成肽鍵，且其中當γ為B2_Bl_N(R3)·c(o)_ C1 -C7 烷 基-時 ，則 z 與 L 為共 價鍵； 其中 當任何Β1、Β2及Β3係連接在一起時，其係藉由肽鍵連接， 且Β1、Β2及Β3係獨立選自包括D_Pr〇、L ne及D phe 4 cF3。 於根$本發明之另一項具體實施例中， -!一 Rh c D為 4 ; W為氮；Ra, Rb and P are -Η; R3 is -Η; R4 is Η or F; Z is optionally substituted _q alkyl _; L is -C0 -C6 alkyl-N(R3)C(〇) -C0 -C3 alkyl group, wherein when C〇_c3 alkyl is Cl _C3 134026-2 • 126- 200916447 alkyl, this C!-C3 alkyl group is optionally taken as -N(R3)C(0) -Cg -C3 alkyl-Y, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl Alkyl, aryl-heteroaryl and Β2 -Β1 -N(R3)-(:(0)-(^-C7 alkyl-, wherein the aryl and heteroaryl groups are optionally one, two or three ( Alternatively, one or two, or one, substituents are substituted, and the substituent is selected from the group consisting of a benzyl group, an alkoxy group, and optionally substituted (: 丨-C6 alkyl, alkoxycarbonyl-, -oh, -CN , -C(0)-〇H, optionally substituted aryl, optionally substituted _alkylaryl, optionally substituted heteroaryl, optionally substituted _0_Ci _c6 alkyl-aryl a _c(0)_0_Ci _c6 alkyl group, _Νη2, an optionally substituted aryl-heterocyclic group, and optionally a substituted copper heterocyclic ring, and a C!-C7 alkyl group, as the case may be substituted _nr3 as appropriate - Β3 substitution, and the amine of Β3 is linked to the acid of B2 to form a peptide bond, and wherein when γ is B2_Bl_N(R3)·c(o)_C1 -C7 alkyl-, z and L are covalently a bond; wherein when any of the Β1, Β2, and Β3 lines are linked together, they are linked by a peptide bond, and the Β1, Β2, and Β3 are independently selected from the group consisting of D_Pr〇, L ne, and D phe 4 cF3. In another embodiment of the invention, -! - Rh c D is 4; W is nitrogen;

Rc 為-Η ;Rc is -Η;

Rh為Η或A-Q烧基’其中該烧基係視情況經取代； R3 為-H ; R4為Η或F ; 134026-2 -127- 200916447 Z為視情況經取代之_C1 -cs烧基-; L為 -C0 -C6 烷基-N(R3 )C(O)-C0-C3 烷基-，其中當 C〇-C3 炫基為 Q -C3 烧基時，此q -C3院基係視情況被-N(R3)C(〇)-C〇-C3烧基 -Y、-N(R3)(R3a)或-N(R3)-Y取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳基、 芳基-雜芳基及W-B1 -N(R3 )-(:(0)-(^ -C7烷基-，其中芳基與 雜芳基係視情況被一、二或三個（或者，一或兩個，或 者，一個）取代基取代，取代基選自包括鹵基、烷氧基、 視情況經取代之C〗-C6烷基、烷氧羰基-、-OH、-CN、 -C(0)-0H、視情況經取代之芳基、視情況經取代之-烷基 芳基、視情況經取代之雜芳基、視情況經取代之-O-q -C6 院基-芳基、視情況經取代之_(：(0)-0-(：〗-c6烷基、-nh2、視 情況經取代之-芳基-雜環基及視情況經取代之稠合雜 環，且C]-C7烷基係視情況被_NR3_B3取代，及B3之胺係與 B之酸連接’以形成肽鍵，且其中當Y為β-Β1 -N(R3)-CCCO-Ci -G；烷基-時，則z與L為共價鍵；其中 菖任何B B及B3係連接在一起時，其係藉由肽鍵連接， 且B B及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 疒於根據本發明之另一項具體實施例中’選自包括視情況 、’、τ代之芳基視情況經取代之-烧基芳基' 視情況經取代 厂、^ 土視晴'兄經取代之-0_ci _匸6烧基-芳基、視情況經取 ，之基、視情況經取代之_芳基_雜環基及視 it况經取代之稠合雜環之取代基係本身進—步視情況在炫 134026-2 -128· 200916447 、芳基雜芳基或雜環基部份基團上被取代基取代，取 代基選自包括-0-C]_C6烷基_烷氧基、_CF3、_〇_芳基、烷氧基、 -NH-QCO-C】-C6烧基、齒素、Ci_c々基、_〇 (函基取代之烧基） 及-0-烷基-N(烷基）2。 於根據本發明之另一項具體實施例中， 各Y係獨立選自包括烷基、芳基、芳基芳基、雜芳基、芳 基-雜芳基、雜芳基-芳基、環烷基、雜環基及雜環基-雜 芳基，其每一個係視情況經取代； L係選自包括 -0) -C6烷基-N(R3 )-C0 -c3烷基-，其中當_C〇 _c6烷基為_Ci _c6烷 基時’其係視情況被取代基取代，取代基選自包括_Ci _c3 烧基-0Ra、-C] -C：3 烷基-N(R3 )(R3 a)、-C。-C3 烷基-C(0)0Ra 及 C〇 -C3 烷基-C(0)-N(R3 )(R3 a); -C〇 -C6 烷基-N(R3 )-C(O)-C0 -C3 烷基-，其中當-C〇 -C6 烷基為 q -C6 烧基時，其係視情況被取代基取代，取代基選自包括 _Ci -C3 烷基-0Ra、-C3 烷基-NR3 R3 3、_cG C3 烷基-C(0)0Ra 及 C〇 -C3 烷基-C(0)-N(R3 )(R3 a); -C0 -C6 烷基-N(R3 )-C(O)-C0 -C3 烷基-，其中-C〇 -C3 烷基為 C! -C3 烷 基，其係視情況被取代基取代，取代基選自包括-N(R3 )-(^(^-(^-(^烷基-丫…叫圮:^⑸-仏-^烷基-丫、-^。：^^3)-C〇-C3 烷基-Y、-C(S)-N(R3)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-C4 -C6 環烷基-、-N(R3 )-C(S)-CG -C3 烷基-C4 -C6 環烷基-、 -N(R3)-C〇-C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-C4-C6 雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3K：2-C3 烷基 134026-2 -129- 200916447 -ORa、-N(R3 )-C〇 -C3 烷基-C〇 -C3 雜烷基-Υ、-N(R3 )-C(O)-O-C0 -C3 烷基-Y、-N(R3)-C(S)-0-CG-C3 烷基-Y、 基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y、-NCRq-CeVNCR^-Co-C^ 烷基 -Y 、 -NKRq-CCOKVC^ 烷基 -C〇-C3 雜 環基、 -N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環基、-N(R3 )-C(0)-C〇 -C3 烷基 -C〇 -C3 雜環基-Y、-N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環基-Y 及 -N(R3 )-S(0)2 -N(R3 )-C〇 -C3 烷基-Y ; -C〇 -C6 烷基-N(R3 )-C(S)-C〇 -C3 烷基-，其中-C〇 -C3 烷基為 q -C3 烷 基，其係視情況被取代基取代，取代基選自包括-N(R3 )-C(0)-CQ-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、-C(0)-N(R3)-c〇-c3 烷基-Y、-C(S)-N(R3)-C〇-C3 烷基-Y、-N(R3)-C(O)-C0-C3 烷基-c4 -C6環烷基-、-N(R3 )-C⑸-CG -C3烷基-C4 -C6環烷基-、 -N(R3)-Cq-C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-C4-C6 雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基 -ORa、-N(R3 )-C〇 -C3 烷基-C〇 -C3 雜烷基-Y、-N(R3 )-C(O)-O-C0 -C3 烷基-Y、-r^RO-CXSHD-CQ-C^ 烷基-Y、-N(R3)-S(0)2-C〇-C3 烷 基-Y、-N(R3)-C(O)-N(R3)-C0-C3 烷基-Y、-NKRq-CXSyr^Rq-Co-q 烷基 -Y 、 -N(R3)-C(0)-CG-C3 烷基 -CQ-C3 雜 環基、 -N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環基、-N(R3 )-C(0)-C〇 -C3 烷基 -C〇 -C3 雜環基-Y、-N(R3 )-C(S)-C0 -C3 烷基-C〇 -C3 雜環基-Y 及 ~N(R3 )-S(0)2 -N(R3 )-C〇-C3 烷基·Y ; -c〇-c6烷基-c(o)-c〇-c3烷基-，其中當-c〇-c6烷基為烷基 時，其係視情況被取代基取代，取代基選自包括 -n(r3)-c(o)-c〇-c3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、 134026-2 •130- 200916447 -C(0)-N(R3)(R3a)、-C⑸_N(R3)(R3a)、-C(〇)_N(R3)_C〇_C3 烷基 -Y、-C⑶-N(R3)-Q)，C3 烷基-Y、-N(R3)-C(0)-Cq-C3 烷基-c4-c6 環烷基-、-N(R3 )-C(S)-CG -C3 烷基-C4 -C6 環烷基-、-N(R3 )-CQ -C3 烷基-Y、-N(R3)(R3a)、-N(R3)-Q-C3 烷基-C4-C6 雜環基、 -N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基-ORa-、 召(113><：()-(：3雜烷基-丫、-：^(113)-<：(〇)-〇-0：()-(：3烷基-丫、-风113)-〇^)-〇-(：0-(：3烷基-丫、->^3)-3(〇)2-0：。-(：3烷基-丫、-：^(尺3)-〇；〇)-N(R3)-C〇-C3 烷基-Y、-N(R3)-C⑸-N(R3)-CG-C3 烷基-Y、 -N(R3 )-C(0)-C〇 -C3 烷基-CQ -C3 雜環基、-N(R3 )-C(S)-C〇 -C3 烷基 -C〇-C3 雜環基、-N(R3)-C(0)-C〇-C3 烷基-C〇-C3 雜環基-Y、 -N(R3)-C(S)-C〇-C3 烷基-C〇-C3 雜環基-Y 及-NCRi-SPh-NKRy-Co -C3 烧基 - Y ; -c〇-c6烷基-C(S)-C〇-C3烷基-，其中當-C0-C6烷基為Ci -c3烷基 時，其係視情況被取代基取代，取代基選自包括-N(R3 )-C(0)-CQ-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-丫、-(：(0)-N(R3)(R3a)、-C(S)-N(R3)(R3a)、-C(0)-N(R3)-C〇-C3 烷基-Y、 -C(S)-N(R3 )-C〇 -C3 烷基-Y、-N(R3 )-C(O)-C0 -C3 烷基-C4 -C6 環烷 基-、-N(R3)-C(S)-C〇-C3 烷基-C4-C6 環烷基-、-N(R3)-C〇-C3 烷 基-Y、-N(R3)(R3a)、-N(R3)-Q-C3 烷基-C4-C6 雜環基、 -N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基-ORa-、 -N(R3)-C〇-C3 雜烷基-Y、-N(R3)-C(0)-0-C〇-C3 烷基-Y、-N(R3)-〇^)-0-(：()-(：3烷基-丫、-风113)-8(0)2-〇)-(：3烷基-丫、-风113)-(：(0)-N(R3)-C〇-C3 烷基-Y、-N(R3)-C(S)-N(R3)-C〇-C3 烧基-Y、 -N(R3 )-C(0)-C〇 -C3 烷基-C〇 -C3 雜環基、-N(R3 )-C(S)-C〇 -C3 烷基 134026-2 • 131 - 200916447 -C0-C3 雜環基、-N(R3 )-(：(〇)-(：〇-C3 烷基-C〇-C3 雜環基-Υ、 -N(R3)-C⑸-C〇-C3 烷基-C〇-C3 雜環基 _γ 及 C〇-C3 烷基-Υ ; -C〇 -Q烷基-，其中當-C〇 -C6烷基為q -C6烷基時，其係視情況 被取代基取代’取代基選自包括_N(R3 )-C(0)-CG -C3烷基 -Y、-N(R3 )-C(0)-C。-C3 烧基-雜環基及 _N(R3 )_c(〇)_c。；烷基 _ 環烷基； -C0 -C6 烧基-C(0)-N(R3 )-C0 -C3 院基-，其中當 _c〇 _c3 烧基為 q -C3 烷基時，其係視情況被取代基取代，取代基選自包括 -C(0)-N(R3)-C〇-C3 烷基-Y、-c(0)-雜環基、_c(〇)-N(R3)(R3a)、 芳基-芳基、芳基-雜芳基、-雜芳基-芳基、雜芳基_雜芳基、 雜芳基、雜環基-雜芳基及雜環基； -C〇 -C6烷基-雜烷基-c0 -C6烷基-C(0)-N(R3 )-C〇 -C3烷基-，其中當 -C0-C3烷基為C〗-C3烷基時，其係視情況被取代基取代， 取代基選自包括-C(O)-N(R3)-C0-C3烷基-Y ' -c(0)-雜環基、 -C(0)-N(R3)(Rh)、芳基-芳基、芳基_雜芳基、-雜芳基芳 基、雜芳基-雜芳基、雜芳基、雜環基-雜芳基及雜環基； -0) -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當 _C〇 _c6 烷基為 & _C6 烷基時’其係視情況被取代基取代，取代基選自包括 -N(R7)(R7a)、_N(R3)(R3a)、_N(r3)_c(〇)_c〇_C3 烷基 _γ、 C(0)-0-Cg-C3 烷基-γ ' -NXRM-CXCO-N^M-Q-q 烷基 _Y 及 -N(R3)-S(O)2-C0-C3 烷基-Υ ; -c0-c：6烷基-雜芳基_c〇_C3烷基_，其中當_c〇_C3烷基為Ci_c3烷 基時，其係視情況被取代基取代’取代基選自包括 134026-2 •132- 200916447 烷基-N(R3)-C(0)-C〇-C3 烷基-N(R3)(R3a)、-N(R3)-C(0)-C〇-C3 烷 基-Y、-n(r3)-c(o)-o-c〇-c3 烷基-Y、-n(r3)-c(o)-n(r3)-c〇-c3 烷基-Υ 及-N(R3 )-S(0)2 -CG -C3 烷基-Υ ; -C0-C6烷基-芳基-C〇-C3烷基-，其中當-C〇-C3烷基為CVC3烷基 時，其係視情況被取代基取代，取代基選自包括-N(R3)-C(0)-C〇-C3 烷基-Y 、-n(r3)-c(o)-c〇-c3 烷基-Y 、 -N(R3 )-C(0)-0-C〇 -C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-C〇 -C3 烷基-Y 及-N(R3 )-S(0)2 -CG -C3 烷基-Y ; -C〇-C6烷基-芳基-雜芳基-C〇-C3烷基-，其中當-C〇-C3烷基為 C! -C3烷基時，其係視情況被取代基取代，取代基選自包 括-N(R3)-C(O)-C0-C3 烷基-Y、-N(R3)-C(〇)-C〇-C3 烷基-Y、 -N(R3 )-C(O)-O-C0 -C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-C〇 -C3 烷基-Y 及-N(R3 )-S(0)2 -C〇 -C3 烷基-Y ; -C〇 -Cg烧基-雜方基-雜方基-C〇 -C3院基-’其中當-C〇 -C3院基為 Ci -c3烷基時，其係視情況被取代基取代，取代基選自包 括-N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-Y、 -N(R3 )-C(0)-0-C〇 -C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-CG -C3 烷基-Y 及-N(R3 )-S(0)2 -CQ -C3 烷基-Y ; -C〇-C6烷基-雜芳基-C0-C3烷基-，其中當-C0-C3烷基為CVC3烷 基時，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(0)-CQ-C3 烷基-Y、 -N(R3)-C(O)-O-C0-C3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及-N(R3 )-S(0)2 -C〇 -C3 烷基-Y ; -C〇-C6 烷基-O-C(O)-N(R3)-C0-C3 烷基-，其中當-C〇-C3 烷基為 134026-2 -133 - 200916447 c! -C3烷基時，其係視情況被基團取代，取代基選自 -C(0)-0Ra、-C(S)-ORa、_C(0)-N(R3)% -C3 烧基' _C(S)-N(R3 )- q -C3 烷基、-C(0)-N(R3 )(R3 a)-、_C(S)-N(R3)(R3a)---C(0)-N(R3)- C〇-C3 烧基-芳基、_c(S)-N(R3)-C0-C3 烷基-芳基、-C(0)-N(R3)-c0-C3烧基-雜芳基、_c⑸_N(R3)_c〇_C3烷基-雜芳基、 -C(0)-N(R3 )-CQ -C3 烧基-環烧基、-C(S)-N(R3 )-C〇 -C3 烧基-環烧 基、-C(O)-雜環基、-C(S)-雜環基、-C(0)-N(R3 )-C0 -C3 烷基-Y、 -C(S)-N(R3)-C〇-C3 烷基-Υ、-C(0)-N(R3)-雜環基、-C(S)-N(R3)-雜環基、-C(O)-N(R3)-C0-C3 烷基-雜環烷基及-C(S)-N(R3)-C〇 -C3炫基-雜環烧基； -C0-C6 烷基-O-C(S)-N(R3)-C0-C3 烷基-，其中當-c0-c3 烷基為 Q -C3烷基時，其係視情況被基團取代，取代基選自 -C(0)-0Ra、-C(S)-ORa、-C(0)-N(R3 )-(^-C3 烷基、-C(s)-N(R3)- (：1-(：3烷基、-(：(0)屮(1^)(1133)-、-(：(5)-风113)(1^)-、-(：(0)-叫尺3)-C0-C3 烷基-芳基、-C(S)-N(R3)-Q)-C3 烷基-芳基、-C(0)-N(R3)-C〇-C3烷基-雜芳基、-C⑸-N(R3)-C〇-C3烷基-雜芳基、 -C(0)-N(R3)-CG-C3 烷基-環烷基、-C(S)-N(R3)-C〇-C3 烷基-環烷 基、-C(O)-雜環基、-C⑸-雜環基、-C(0)-N(R3 )-C〇 -C3 烷基-Y、 -C(S)-N(R3)-C〇-C3 烷基-Y、-C(0)-N(R3)-雜環基、-C ⑸-N(R3)-雜環基、-C(0)-N(R3)-CQ-C3 烷基-雜環烷基及-C(S)-N(R3)-C〇 -C3统基-雜環烧基；及 -C3烷基-N(R3 -C7烷基·，其中q -C3烷基係視情況 被-C(0)N(R3 -C3烷基-A1 a取代，且C! -C7烷基係視情況被 取代基取代，取代基選自包括烷基 134026-2 -134- 200916447 -Alb、-N^KXOKVq 烷基-Alb、_n(R3)_s(〇)2_Ci_c3 烷基 -A1 b、-N(R3 )-S(0)2 -N(R3 )4 -C3 烷基-a1 b、-N(R3 )-C(0)-N(R3 )- C! -C3 烷基-A1 b 及-N(R3 )-S(0)2 -N(R3 -C3 烷基-A1 b ;Rh is hydrazine or AQ alkyl group, wherein the alkyl group is optionally substituted; R3 is -H; R4 is hydrazine or F; 134026-2 -127- 200916447 Z is optionally substituted _C1 -cs alkyl- L is -C0 -C6 alkyl-N(R3)C(O)-C0-C3 alkyl-, wherein when the C〇-C3 炫 is a Q-C3 alkyl group, the q-C3 The case is substituted by -N(R3)C(〇)-C〇-C3 alkyl-Y, -N(R3)(R3a) or -N(R3)-Y; and each Y is independently selected from the group consisting of alkyl groups, Aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl and W-B1-N(R3)-(:(0)-(^-C7 alkyl-, wherein aryl and heteroaryl The base is optionally substituted by one, two or three (or one or two, or one) substituents selected from the group consisting of halo, alkoxy, and optionally substituted C-C6 alkyl. , alkoxycarbonyl-, -OH, -CN, -C(0)-0H, optionally substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl, optionally Substituted -Oq-C6-homo-aryl, optionally substituted _(:(0)-0-(:]-c6 alkyl, -nh2, optionally substituted-aryl-heterocyclyl And a fused heterocyclic ring substituted as appropriate, and C]-C7 alkyl is optionally substituted by _NR3_B3, and the amine of B3 is linked to the acid of B to form a peptide bond, and wherein Y is β-Β1-N(R3)-CCCO-Ci-G; In the case of alkyl-, then z and L are covalent bonds; wherein any of the BB and B3 lines are linked together by a peptide bond, and the BB and B3 are independently selected from the group consisting of D-Pro and L-ile. And D-Phe-4-CF3. In another embodiment according to the present invention, 'optionally selected from the group consisting of an optionally substituted aryl group as the case, ', τ generation' Substituting the plant, ^Tu Shiqing's brother-substituted by -0_ci _匸6 alkyl-aryl, as the case may be, the base, optionally substituted _ aryl _ heterocyclic group and replaced by the situation The substituent of the fused heterocyclic ring itself is substituted by a substituent on the 134026-2 -128.200916447, arylheteroaryl or heterocyclic group moiety, and the substituent is selected from the group consisting of -0. -C]_C6 alkyl-alkoxy, _CF3, _〇_aryl, alkoxy, -NH-QCO-C]-C6 alkyl, dentate, Ci_c thiol, _〇 (complex substituted And /-0-alkyl-N(alkyl) 2. In another embodiment according to the invention Wherein each Y is independently selected from the group consisting of alkyl, aryl, arylaryl, heteroaryl, aryl-heteroaryl, heteroaryl-aryl, cycloalkyl, heterocyclyl and heterocyclyl- a heteroaryl group, each of which is optionally substituted; the L system is selected from the group consisting of -0)-C6 alkyl-N(R3)-C0-c3 alkyl-, wherein when _C〇_c6 alkyl is _Ci When _c6 is alkyl, it is optionally substituted with a substituent selected from the group consisting of _Ci_c3 alkyl-RA, -C]-C:3 alkyl-N(R3)(R3a), -C. -C3 alkyl-C(0)0Ra and C〇-C3 alkyl-C(0)-N(R3)(R3 a); -C〇-C6 alkyl-N(R3)-C(O)- C0-C3 alkyl-, wherein when -C〇-C6 alkyl is q-C6 alkyl, it is optionally substituted with a substituent selected from the group consisting of _Ci-C3 alkyl-0Ra, -C3 alkane -NR3 R3 3, _cG C3 alkyl-C(0)0Ra and C〇-C3 alkyl-C(0)-N(R3)(R3 a); -C0 -C6 alkyl-N(R3)- C(O)-C0-C3 alkyl-, wherein -C〇-C3 alkyl is C!-C3 alkyl, which is optionally substituted with a substituent selected from the group consisting of -N(R3)-(^ (^-(^-(^alkyl-丫...called 圮:^(5)-仏-^alkyl-丫, -^.:^^3)-C〇-C3 alkyl-Y, -C(S) -N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C(S )-CG-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C〇-C3 Alkyl-C4-C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3K:2-C3 alkyl 134026-2 -129- 200916447 -ORa, -N(R3)-C〇-C3 alkyl-C〇-C3 heteroalkyl-hydrazine, -N(R3)-C(O)-O-C0-C3 alkyl-Y, -N(R3)- C(S)-0-CG-C3 alkyl-Y, yl-Y, -N(R3)-C(0)-N(R3)-C〇-C3 alkyl-Y, -NCRq-CeVNCR^-Co-C^ alkyl-Y, -NKRq-CCOKVC^alkyl-C〇-C3 heterocyclic group, -N(R3)-C(S)-C〇-C3 alkyl-C 〇-C3 heterocyclic group, -N(R3)-C(0)-C〇-C3 alkyl-C〇-C3 heterocyclic group-Y, -N(R3)-C(S)-C〇-C3 Alkyl-C〇-C3 heterocyclyl-Y and -N(R3)-S(0)2 -N(R3)-C〇-C3 alkyl-Y; -C〇-C6 alkyl-N(R3 -C(S)-C〇-C3 alkyl-, wherein -C〇-C3 alkyl is q-C3 alkyl, which is optionally substituted with a substituent selected from the group consisting of -N(R3)- C(0)-CQ-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -C(0)-N(R3)-c〇-c3 alkyl -Y, -C(S)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(O)-C0-C3 alkyl-c4-C6 cycloalkyl-, -N (R3)-C(5)-CG-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-Cq-C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C 〇-C3 alkyl-C4-C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl-ORa, -N( R3 )-C〇-C3 alkyl-C〇-C3 heteroalkyl-Y, -N(R3)-C(O)-O-C0-C3 alkyl-Y, -r^RO-CXSHD-CQ- C^ alkyl-Y, -N(R3)-S(0)2-C〇-C3 alkyl-Y, -N(R3)-C(O)-N(R3)-C0-C3 alkyl- Y, -NKRq-CXSyr^Rq-Co-q alkyl-Y, -N(R3)-C(0)-CG -C3 alkyl-CQ-C3 heterocyclic group, -N(R3)-C(S)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-C(0)-C 〇-C3 alkyl-C〇-C3 heterocyclyl-Y, -N(R3)-C(S)-C0-C3 alkyl-C〇-C3 heterocyclyl-Y and ~N(R3)-S (0)2-N(R3)-C〇-C3 alkyl·Y; -c〇-c6 alkyl-c(o)-c〇-c3 alkyl-, wherein -c〇-c6 alkyl is In the case of an alkyl group, it is optionally substituted by a substituent selected from the group consisting of -n(r3)-c(o)-c〇-c3 alkyl-Y, -N(R3)-C(S)-C 〇-C3 alkyl-Y, 134026-2 •130- 200916447 -C(0)-N(R3)(R3a), -C(5)_N(R3)(R3a), -C(〇)_N(R3)_C〇_ C3 alkyl-Y, -C(3)-N(R3)-Q), C3 alkyl-Y, -N(R3)-C(0)-Cq-C3 alkyl-c4-c6 cycloalkyl-, -N (R3)-C(S)-CG-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-CQ-C3 alkyl-Y, -N(R3)(R3a), -N(R3 -Q-C3 alkyl-C4-C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl-ORa-, Call (113 ><:()-(:3 heteroalkyl-丫, -:^(113)-<:(〇)-〇-0:()-(:3 alkyl-丫,-wind 113)-〇^)-〇-(:0-(:3 alkyl-丫, ->^3)-3(〇) 2-0:. -(:3 alkyl-丫, -:^(尺3)-〇;〇)-N(R3)-C〇-C3 alkyl-Y,-N(R3)-C(5)-N(R3)-CG -C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-CQ-C3 heterocyclic group, -N(R3)-C(S)-C〇-C3 alkyl- C〇-C3 heterocyclic group, -N(R3)-C(0)-C〇-C3 alkyl-C〇-C3 heterocyclic group-Y, -N(R3)-C(S)-C〇- C3 alkyl-C〇-C3 heterocyclyl-Y and -NCRi-SPh-NKRy-Co-C3 alkyl-Y; -c〇-c6 alkyl-C(S)-C〇-C3 alkyl-, Wherein, when the -C0-C6 alkyl group is a Ci-c3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)-CQ-C3 alkyl-Y,- N(R3)-C(S)-C〇-C3 alkyl-丫, -(:(0)-N(R3)(R3a), -C(S)-N(R3)(R3a), -C (0)-N(R3)-C〇-C3 alkyl-Y, -C(S)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(O)-C0 -C3 alkyl-C4 -C6 cycloalkyl-, -N(R3)-C(S)-C〇-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkane -Y, -N(R3)(R3a), -N(R3)-Q-C3 alkyl-C4-C6 heterocyclic, -N(R3)-C2-C3 alkyl-N(R3)(R3a ), -N(R3)-C2-C3 alkyl-ORa-, -N(R3)-C〇-C3 heteroalkyl-Y, -N(R3)-C(0)-0-C〇-C3 Alkyl-Y, -N(R3)-〇^)-0-(:()-(:3 alkyl-丫, -风113)-8(0)2-〇)-( 3 alkyl-hydrazine, -wind 113)-(:(0)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(S)-N(R3)-C〇- C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-C(S)-C〇-C3 alkyl 134026 -2 • 131 - 200916447 -C0-C3 Heterocyclyl, -N(R3)-(:(〇)-(:〇-C3 alkyl-C〇-C3 heterocyclyl-oxime, -N(R3)- C(5)-C〇-C3 alkyl-C〇-C3 heterocyclyl-γ and C〇-C3 alkyl-Υ ; -C〇-Q alkyl-, wherein -C〇-C6 alkyl is q-C6 In the case of an alkyl group, it is optionally substituted with a substituent. The substituent is selected from the group consisting of _N(R3)-C(0)-CG-C3 alkyl-Y, -N(R3)-C(0)-C. -C3 alkyl-heterocyclic group and _N(R3)_c(〇)_c. ; alkyl-cycloalkyl; -C0-C6 alkyl-C(0)-N(R3)-C0-C3, wherein, when the _c〇_c3 alkyl group is a q-C3 alkyl group, Substituted by a substituent, the substituent is selected from the group consisting of -C(0)-N(R3)-C〇-C3 alkyl-Y, -c(0)-heterocyclyl, _c(〇)-N ( R3) (R3a), aryl-aryl, aryl-heteroaryl, -heteroaryl-aryl, heteroaryl-heteroaryl, heteroaryl, heterocyclyl-heteroaryl and heterocyclic -C〇-C6 alkyl-heteroalkyl-c0-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when -C0-C3 alkyl is C-C3 In the case of an alkyl group, it is optionally substituted by a substituent selected from the group consisting of -C(O)-N(R3)-C0-C3 alkyl-Y '-c(0)-heterocyclic group, -C( 0)-N(R3)(Rh), aryl-aryl, aryl-heteroaryl, -heteroarylaryl,heteroaryl-heteroaryl,heteroaryl,heterocyclyl-heteroaryl And a heterocyclic group; -0) -C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when _C〇_c6 alkyl is & _C6 alkyl Substituted by a substituent, the substituent is selected from the group consisting of -N(R7)(R7a), _N(R3)(R3a), _N(r3)_c(〇)_c〇_C3 alkyl_γ, C(0) -0-Cg-C3 alkyl-γ ' -NXRM-CXCO-N^MQq alkane _Y and -N(R3)-S(O)2-C0-C3 alkyl-Υ; -c0-c: 6-alkyl-heteroaryl_c〇_C3 alkyl_, wherein _c〇_C3 When the alkyl group is a Ci_c3 alkyl group, it is optionally substituted with a substituent. The substituent is selected from the group consisting of 134026-2 • 132- 200916447 alkyl-N(R3)-C(0)-C〇-C3 alkyl-N. (R3)(R3a), -N(R3)-C(0)-C〇-C3 alkyl-Y, -n(r3)-c(o)-oc〇-c3 alkyl-Y, -n( R3)-c(o)-n(r3)-c〇-c3 alkyl-Υ and -N(R3)-S(0)2 -CG-C3 alkyl-oxime; -C0-C6 alkyl-aryl a base-C〇-C3 alkyl-, wherein when the -C〇-C3 alkyl group is a CVC3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)- C〇-C3 alkyl-Y, -n(r3)-c(o)-c〇-c3 alkyl-Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y , -N(R3)-C(0)-N(R3)-C〇-C3 alkyl-Y and -N(R3)-S(0)2-CG-C3 alkyl-Y; -C〇- C6 alkyl-aryl-heteroaryl-C〇-C3 alkyl-, wherein when -C〇-C3 alkyl is C!-C3 alkyl, it is optionally substituted by a substituent selected from the group consisting of Including -N(R3)-C(O)-C0-C3 alkyl-Y, -N(R3)-C(〇)-C〇-C3 alkyl-Y, -N(R3)-C(O) -O-C0 -C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C〇-C3 alkyl-Y and -N(R 3)-S(0)2 -C〇-C3 alkyl-Y; -C〇-Cg alkyl-heteroaryl-hetero-based-C〇-C3 yard--When the -C〇-C3 institute When the group is a Ci-c3 alkyl group, it is optionally substituted by a substituent selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3)-C. (0)-C〇-C3 alkyl-Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y, -N(R3)-C(0)-N(R3) -CG-C3 alkyl-Y and -N(R3)-S(0)2-CQ-C3 alkyl-Y; -C〇-C6 alkyl-heteroaryl-C0-C3 alkyl-, wherein When the C0-C3 alkyl group is a CVC3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3). )-C(0)-CQ-C3 alkyl-Y, -N(R3)-C(O)-O-C0-C3 alkyl-Y, -N(R3)-C(0)-N(R3 )-C〇-C3 alkyl-Y and -N(R3)-S(0)2 -C〇-C3 alkyl-Y; -C〇-C6 alkyl-OC(O)-N(R3)- C0-C3 alkyl-, wherein when -C〇-C3 alkyl is 134026-2 -133 - 200916447 c! -C3 alkyl, it is optionally substituted by a group selected from -C(0) -0Ra, -C(S)-ORa, _C(0)-N(R3)% -C3 alkyl group _C(S)-N(R3)-q-C3 alkyl group, -C(0)-N( R3)(R3 a)-, _C(S)-N(R3)(R3a)---C(0)-N(R3)-C〇-C3 alkyl-aryl, _c(S)-N( R3)-C0-C 3 alkyl-aryl, -C(0)-N(R3)-c0-C3 alkyl-heteroaryl, _c(5)_N(R3)_c〇_C3 alkyl-heteroaryl, -C(0)-N (R3)-CQ-C3 alkyl-cycloalkyl, -C(S)-N(R3)-C〇-C3 alkyl-cycloalkyl, -C(O)-heterocyclyl, -C(S )-heterocyclyl, -C(0)-N(R3)-C0-C3 alkyl-Y, -C(S)-N(R3)-C〇-C3 alkyl-Υ, -C(0) -N(R3)-heterocyclyl, -C(S)-N(R3)-heterocyclyl, -C(O)-N(R3)-C0-C3 alkyl-heterocycloalkyl and -C( S)-N(R3)-C〇-C3 leuko-heterocyclic alkyl; -C0-C6 alkyl-OC(S)-N(R3)-C0-C3 alkyl-, wherein -c0-c3 When the alkyl group is a Q-C3 alkyl group, it is optionally substituted by a group selected from -C(0)-0Ra, -C(S)-ORa, -C(0)-N(R3)- (^-C3 alkyl, -C(s)-N(R3)- (:1-(:3 alkyl, -(:(0)屮(1^)(1133)-, -(:(5) - wind 113) (1^)-, -(:(0)-called ruler 3)-C0-C3 alkyl-aryl, -C(S)-N(R3)-Q)-C3 alkyl-aryl , -C(0)-N(R3)-C〇-C3 alkyl-heteroaryl, -C(5)-N(R3)-C〇-C3 alkyl-heteroaryl, -C(0)-N (R3)-CG-C3 alkyl-cycloalkyl, -C(S)-N(R3)-C〇-C3 alkyl-cycloalkyl, -C(O)-heterocyclyl, -C(5)-hetero Cyclic group, -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(S)-N(R3)-C〇-C3 alkyl-Y , -C(0)-N(R3)-heterocyclyl, -C(5)-N(R3)-heterocyclyl, -C(0)-N(R3)-CQ-C3 alkyl-heterocycloalkyl And -C(S)-N(R3)-C〇-C3 alkyl-heterocyclic alkyl; and -C3 alkyl-N (R3 -C7 alkyl, wherein q-C3 alkyl is optionally taken - C(0)N(R3-C3 alkyl-A1a substituted, and the C!-C7 alkyl group is optionally substituted with a substituent selected from the group consisting of alkyl 134026-2 -134- 200916447 -Alb, -N ^KXOKVq alkyl-Alb, _n(R3)_s(〇)2_Ci_c3 alkyl-A1 b, -N(R3)-S(0)2 -N(R3)4-C3 alkyl-a1 b,-N( R3)-C(0)-N(R3)-C!-C3 alkyl-A1 b and -N(R3)-S(0)2-N(R3-C3 alkyl-A1b;

Z係選自包括 視情況經取代之 ^~'(CH2)i.7)Z series is selected from the group consisting of ^~'(CH2)i.7)

_/(CH2)〇-3_/(CH2)〇-3

R3 A,R3 A,

、乂’（CH2)〇3， ^t(ch2)〈3,乂’(CH2)〇3, ^t(ch2)<3

人 A，十,People A, ten,

,A, A

134026-2 135- 200916447134026-2 135- 200916447

其中各A係獨立為氮、-CH=或-C(R4)=，其中可以有0、1、2 或3個氮；且Wherein each A is independently nitrogen, -CH= or -C(R4)=, wherein there may be 0, 1, 2 or 3 nitrogens;

Rc Ra Rc /A 4-W^ ^Rh C H c D為 A 或 A 。 於本發明之另一項具體實施例中，Rc Ra Rc /A 4-W^ ^Rh C H c D is A or A. In another embodiment of the invention,

D為 S W為氮；D is S W is nitrogen;

Rc 為-H ; X為S ;Rc is -H; X is S;

Rh為-Q-C6烷基或-Ci-Q烷基-苯基，其中該烷基與笨基係 視情況獨立經取代； Z為視情況經取之-c3-c8烷基-(例如-c4烷基-); 134026-2 -136- 200916447 L 為-NOD-QCO-q 烧基-’其中 Cl 烷基係被 _N(H)_c(〇)_〇_Ci 烧基-苯基或-N(H)-c(o)-aCl_c6烷基取代；且 Y為芳基-雜芳基-或雜芳基_，其每一個係視情況經取代。 在某些較佳具體實施例中，γ為苯基_p塞唑基、嘍唑或咪唑。 在某些其他具體實施例中，Z為_(：4烷基·。 於本發明之另一項具體實施例中，Rh is -Q-C6 alkyl or -Ci-Q alkyl-phenyl, wherein the alkyl group and the stupid group are optionally substituted independently; Z is optionally taken as -c3-c8 alkyl- (for example - C4 alkyl-); 134026-2 -136- 200916447 L is -NOD-QCO-q alkyl-' wherein the Cl alkyl group is _N(H)_c(〇)_〇_Ci alkyl-phenyl or -N(H)-c(o)-aCl_c6 alkyl substituted; and Y is aryl-heteroaryl- or heteroaryl-, each of which is optionally substituted. In certain preferred embodiments, γ is phenyl-p-pyrazole, carbazole or imidazole. In certain other specific embodiments, Z is _(: 4 alkyl. In another embodiment of the invention,

Rc 4—/Rh D為 S ; W為氮；Rc 4—/Rh D is S; W is nitrogen;

Rc 為-Η ; X為S ;Rc is -Η; X is S;

Rh為-CVQ烷基或必弋烷基-苯基，#中該烷基與苯基係 視情況獨立經取代； Z為視情況經取之-Cg-C：8烷基_(例如_c4烷基; L為-Cl炫基-’被選自包括刪_c(〇)_〇_Ci %烧基-苯基、 -nw-c^-o-cvc：6烷基、_NH-C(〇)_雜環基烷基及 -NH-C(0)-Cl-C6烷基-S(VCi_C6烷基之取代基取代；且 Y為雜芳基-，其係視情況經取代。在某些其他具體㈣ 例中，Y為視情況經取代之苯并㈣。在某些其他具體實 施例中，Υ為被-Ν02或娜)棚2取代之笨并味唾。在某些其 他具體實施例中，Ζ為_c4烷基_。 於本發明之另一項具體實施例中，Rh is -CVQ alkyl or benzyl-phenyl, in which the alkyl and phenyl are independently substituted; Z is optionally taken - Cg-C: 8 alkyl _ (eg _c4) Alkyl; L is -Cl ndyl-' is selected from the group consisting of _c(〇)_〇_Ci% alkyl-phenyl, -nw-c^-o-cvc:6 alkyl, _NH-C ( 〇)_heterocyclylalkyl and -NH-C(0)-Cl-C6 alkyl-S (substituent of the VCi-C6 alkyl group; and Y is a heteroaryl group, which is optionally substituted. In some other specific (four) examples, Y is optionally substituted benzo (IV). In some other specific embodiments, Υ is replaced by Ν 或 02 or 娜 棚 2, and in some other specific implementations. In the example, Ζ is _c4 alkyl _. In another embodiment of the invention,

Rc Ra 4-&lt;c&gt;、Rb D為 S ； 134026-2 *137· 200916447 w為氮；Rc Ra 4-&lt;c&gt;, Rb D is S; 134026-2 *137· 200916447 w is nitrogen;

Rc 為-Η ; X為S; M為氮； Η ;Rc is -Η; X is S; M is nitrogen;

Rb為苯基烷基； Z為視情況經取之-C3 -Cs燒基_ (例如烧基_); L 為-NCHyCCCO-Ci 烷基-，其中 Ci 烷基係被 _n(h)_c(〇)_〇_Ci _C6 烷基-苯基取代；且 Y為芳基•雜^基-’其係視情況經取代。在某些其他具體 實施例中’ Y為視情況經取代之苯基_魂n坐基_。 於本發明之另一項具體實施例中， DC 〇aRb is phenylalkyl; Z is optionally taken as -C3 -Cs alkyl (e.g., alkyl); L is -NCHyCCCO-Ci alkyl-, wherein Ci alkyl is _n(h)_c (〇)_〇_Ci _C6 alkyl-phenyl substituted; and Y is aryl • hetero-yl-' which is optionally substituted. In some other specific embodiments, Y is a phenyl group that is optionally substituted. In another embodiment of the invention, DC 〇a

D為 x ； W為氮；D is x; W is nitrogen;

Rc 為-Η ; X為S ; Μ為氮； 尺3為Η ;Rc is -Η; X is S; niobium is nitrogen; ruler 3 is niobium;

Rb為苯基或^-仏烷基； Z為視情況經取之-C3 -C8烧基—（例如烷基-); L 為烷基-，被-NOHKXOHD-Ci-Q烷基-苯基、-N(H)-C(0)-〇-Ci -C6烷基及-NH-CCOVq -C3烷基-S02 -C3烷基取代；且Rb is phenyl or ^-decylalkyl; Z is optionally taken as -C3 -C8 alkyl - (eg alkyl-); L is alkyl-, is -NOHKXOHD-Ci-Q alkyl-phenyl , -N(H)-C(0)-〇-Ci-C6 alkyl and -NH-CCOVq-C3 alkyl-S02-C3 alkyl substituted;

Y為視情況經取代之苯并σ米。坐。在某些具體實施例中，Z 134026-2 -138 - 200916447 為-C4烧基-。在某此盆仏《 —/、他具體實施例中，γ係被-C(〇)-NH2取 代在某t其他具體實施例中，γ係進一步選自視情況經 取代之芳基-雜芳基，例如次蕃基_三唾。 帛I體Λ施例中’本發明係、提供^⑽化合物： Y-L-D (ΠΙ) 其中 D係選自包括 •ΝΗ g 與 •NH RhY is a benzo σ meter which is optionally substituted. sit. In certain embodiments, Z 134026-2 -138 - 200916447 is -C4 alkyl-. In some embodiments of the basin, the gamma is replaced by -C(〇)-NH2. In other embodiments, the gamma is further selected from an optionally substituted aryl-heteroaryl. Base, for example, the second base _ three saliva. In the present invention, the present invention provides a compound of the formula (10): Y-L-D (ΠΙ) wherein D is selected from the group consisting of • ΝΗ g and • NH Rh

Rb 妒與妒係獨立選自包括（16烷基、_Q 1〇芳基及_Ci_c6烷 基-C〗_ 芳基； L係選自包括-C0-6次烷基_、_c〇3次烷基_N(H)_C(〇)_C〇4次 烧基視情況被0-3個R4取代； Y係選自包括視情況經取代之&lt;6_1()芳基與視情況經取 代之-5-10員雜芳基； V. R4係選自包括-N(H)-C(0)-R3與-N(H)-C(0)-0-R3 ;且 R3係選自包括視情況經取代之-Cm烷基、-Cl_6雜烷基、 各川員雜環基及-C7-16烷基芳基。 於根據式（III)之化合物之一項具體實施例中 如，\入 Y、b D為 （ 。 於根據式（III)之化合物之另一項具體實施例中， 134026-2 -139- 200916447The Rb 妒 and the lanthanide are independently selected from the group consisting of (16 alkyl, _Q 1 aryl and _Ci_c6 alkyl-C _ aryl; L is selected from the group consisting of -C0-6 alkyl _, _c 〇 3 decane The base_N(H)_C(〇)_C〇4 calcination base is optionally substituted by 0-3 R4; the Y series is selected from the group consisting of the &lt;6_1() aryl group substituted as appropriate and optionally substituted 5-10 member heteroaryl; V. R4 is selected from the group consisting of -N(H)-C(0)-R3 and -N(H)-C(0)-0-R3; and R3 is selected from the group consisting of Substituted -Cm alkyl, -Cl_6 heteroalkyl, each homocyclic heterocyclyl and -C7-16 alkylaryl. In a specific embodiment of the compound according to formula (III), eg Y, b D are (in another embodiment of the compound according to formula (III), 134026-2 -139- 200916447

於根據本發明之另一項具體實施例中，選自包括視情況 經取代之芳基與視情況經取代之雜芳基之取代基係本身進 一步視情況被取代基取代，取代基選自包括-O-Ci -c6烷基-烷氧基、-CF3、-0-芳基、烷氧基、-NH-CXCOA -C6烷基、ii素、 C! -C6烷基、-0-(_基取代之烷基）及-0_烷基-N(烷基）2。 於根據本發明之另一項具體實施例中，γ係進一步選自 雜環基。 於根據本發明之另一項具體實施例中， L為-C〇 -C6烧基-C(0)-N(R3 )-C0 -C3烧基-，其中當c0 -C3烧基為 q -C：3烷基時’此q -C3烷基係視情況被芳基、雜芳基、_ 雜芳基-芳基、-芳基-雜芳基、_芳基-芳基或雜芳基_雜芳 基取代’其中各雜芳基或芳基部份基團係視情況經取 代；且 Y為^基或雜芳基’其每一個係視情況經取代。 於根據本發明之另一項具體實施例中， L 為-C0-C6 烷基-O-Co-q 烷基-C(0)-N(R3 )-C0-C3 烷基 _ ,其中當 Co-q烷基為Cl_C3烷基時，此Ci_C3烷基係視情況被-雜芳 基-方基、-雜芳基-雜芳基、雜芳基、-雜芳基雜環基取代， 其中各雜芳基與芳基部份基團係視情況經取代；且 Y為視情況經取代之芳基。 於根據本發明之另一項具體實施例中，當C0_C3烷基為 134026-2 •140- 200916447 q -c：3烷基時，Cl _c：3烷基係視情況被_雜芳基_芳基、_雜芳基 -雜芳基、雜芳基、-雜芳基_雜環基取代’其中各雜芳基與 芳基部份基團係進一步視情況被1至3個視情況經取代之 芳基、烧氧基、-N(烧基h、_素、烧基、經稠合之雜環基、 -CF3、視情況經取代之雜環基、_〇_Ci 烷基_N(烷基h、 -O-C! -C6烷基-NH2及-NH-芳基取代。 於根據本發明之另一項具體實施例中， .L為-Q必烷基_C(0)_N(R3 )_c〇 A烷基_，其中當c〇 _C3烷基為 q -C：3烷基時，此Cl _C3烷基係視情況被_c(〇)_N(R3 ) 烷 基-雜芳基、-CXCO-Na^-CVC3烷基-芳基取代，其中各雜芳 基或芳基部份基團係視情況經取代；且 Y為η、視情況經取代之芳基或視情況經取代之雜環基。 於根據本發明之另—項具體實施例中，γ為視情況經取 代之雜芳基。 、於㈣本發明之另—項具體實施射，Υ為視情況經取 (:代之方基或視情況經取代之雜芳基，其中各雜芳基或芳基 π伤基團係視情況被i或2個獨立經選擇之鹵素、烧基或烧 氧基取代。 於根據本發明之另一項具體實施例中， 為，Q C6燒基_0_c〇 %烷基_c(〇)_n(r3 )_c〇 a烧基_，其中當 飞、院^為q -C3院基時，此Ci &amp;烷基係視情況被 ()(R )C〇&lt;：3 烷基-雜環基或-C(O)-N(R3)-C0-C3 烷基-芳 基取代，其中久灿i 各雜％基或方基部份基團係視情況經取 代；且 134026-2 -141 - 200916447 γ為視情況經取代之芳基或視情況經取代之雜芳基。 於根據本發明之另一項具體實施例中，γ為視情況經取 代之芳基。 於根據本發明之另一項具體實施例中，_c(〇)_n(r3)_c〇 _C3 烷基-雜環基為-C(0)-N(R3 &gt;C(rC3烷基_雜芳基。 於根據本發明之另一項具體實施例中，Y_L_為苯基 -CH2-0-C(0)-NH-。 於根據本發明之另—項具體實施例中， L 為-C〇 -C6 烷基-O_c〇 _Ci 烷基 _c(〇)_n(r3 )_c〇 _c3 烷基-，其中當 C0-C3烧基為Cl_Cs烷基時’此C1_C3烷基係視情況被 -C(O)-N(R3)-C0-C3 烷基-雜芳基或 _C(〇)_N(R3)_C〇_C3 烷基 _芳 基取代’其中各雜芳基或芳基部份基團係視情況被1至3 個獨立取代基取代’取代基選自包括鹵素、-OH、-NH2、 烧基、-C(0)-0H、-C(〇)-〇-烷基、-C(0)-NH-視情況經取代之 芳基' -C(0)-NH-視情況經取代之雜芳基、_c(〇)_NH_烷基_〇_ 烧基' -C(0)-NH-院基-雜環基、-院基-視情況經取代之芳 基、燒氧基、視情況經取代之芳基、視情況經取代之雜 芳基。 於根據本發明之另一項具體實施例中，其中選自包括 -C(0)-NH-視情況經取代之芳基、_c(〇)_NH-視情況經取代之雜 芳基、-烧基-視情況經取代之芳基、視情況經取代之芳基及 視情況經取代之雜芳基之取代基係視情況被1或2個獨立 經選擇之取代基取代，取代基選自包括南素、烷氧基 '烷 基、-〇-芳基、-NH-C(O)-烷基、酮基、-CN、雜環基、-〇-_基 134026-2 -142- 200916447 取代之烧基、-CF3及-〇-烧基-Ο-烧基。 於根據本發明之另一項具體實施例中，L為苯基 -CH2 -O-CCCO-NH-C! -C3 烷基-’其中 q -C3 烷基係被-C(0)-NH-嘧 唑基取代，其中嘧唑基係視情況經取代。 於根據本發明之另一項具體實施例中， L為苯基-CHrO-QCO-NH-Ci-C^烧基-，其中（^-匚3院基係被 -C(0)-NH-碟唑基取代’其中嘍唑基係視情況被！或2個獨 立經選擇之取代基取代，取代基選自包括視情況經取代 之芳基、烷基、-C(0)-0-烷基、-C(〇)-〇H、-C(O)-丽-視情況 經取代之芳基、-C(0)-NH-視情況經取代之雜芳基、 -C(0)-NH-烧基-0-烧基、-C(O)-丽-烧基_雜環基、稠合之視 情況經取代之環烷基、稠合之視情況經取代之雜環基及 稠合之視情況經取代之芳基。 於根據本發明之另一項具體實施例中， L 為-C〇 -Cg 烧基-N(R )-C(0)-N(R3 )-C〇 -C3 烧基-，其中當 c〇-C3 院 基為C! -C3烧基時’此Q -C；3烧基係視情況被_c(〇)_n(R3 )· c0 -C3烧基-雜芳基-芳基、_C(0)_N(R3 )_c〇 烷基_雜芳基或 -C(0)-N(R3)-C〇-C3烧基-芳基取代，其中各雜芳基或芳基部 份基團係視情況經取代；且 Y為視情況經取代之芳基、視情況經取代之雜環基或視情 況經取代之環烷基。 於根據本發明之另一項具體實施例中，γ為視情況經取 代之雜芳基。 於根據本發明之另一項具體實施例中， 134026-2 -143- 200916447 L 為-C0 -C6 烷基-〇_C〇 _c3 烷基 _c(〇)_n(r3 &gt;c〇 _C3 烷基 _，其中當 Q-C3烷基為Cl_(：3烷基時，此烷基係視情況被 -QCO-NO^-CVC3 炫基-雜芳基、_C(〇)_N(R3)_C〇_C3 烷基-芳 基、-C(O)-N(R3)-C0-C3 烷基-雜芳基 _芳基、_C(0)_N(R3)_C〇_C3 烷基-雜芳基-雜芳基、_C(0)_N(R3 )_c〇尤3烷基·芳基_芳基及 -C(〇&gt;N(R3 )-CG 烷基-芳基-雜芳基取代，其中各雜芳基或 芳基部份基團係視情況經取代；且 Y為Η。 於根據本發明之另一項具體實施例中，w係進一步選自 0。 f赁據亡發明之另一項具體實施例中， /N'Rb 構 ¥ ，例如In another embodiment according to the present invention, the substituent selected from the group consisting of an optionally substituted aryl group and an optionally substituted heteroaryl group is itself further optionally substituted with a substituent selected from the group consisting of -O-Ci-c6 alkyl-alkoxy, -CF3,-0-aryl, alkoxy, -NH-CXCOA-C6 alkyl, ii, C!-C6 alkyl, -0-(_ Alkyl substituted alkyl) and -0-alkyl-N(alkyl)2. In another embodiment of the invention, the gamma system is further selected from a heterocyclic group. In another embodiment of the invention, L is -C〇-C6 alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when c0-C3 is q- When C: 3 alkyl group, 'this q-C3 alkyl group is optionally aryl, heteroaryl, _heteroaryl-aryl, -aryl-heteroaryl, aryl-aryl or heteroaryl _Heteroaryl substituted 'wherein each heteroaryl or aryl moiety is substituted as appropriate; and Y is yl or heteroaryl', each of which is optionally substituted. In another particular embodiment of the invention, L is -C0-C6 alkyl-O-Co-q alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when Co When the -q alkyl group is a Cl_C3 alkyl group, the Ci_C3 alkyl group is optionally substituted by a -heteroaryl-aryl group, a -heteroaryl-heteroaryl group, a heteroaryl group or a -heteroarylheterocyclyl group, wherein each The heteroaryl and aryl moiety are optionally substituted; and Y is an optionally substituted aryl. In another embodiment of the present invention, when the C0_C3 alkyl group is 134026-2 • 140-200916447 q-c:3 alkyl, the Cl_c:3 alkyl group is optionally subjected to _heteroaryl-aryl , _heteroaryl-heteroaryl, heteroaryl, -heteroaryl-heterocyclyl substituted, wherein each heteroaryl and aryl moiety is further substituted by 1 to 3 as appropriate Aryl, alkoxy, -N (alkyl, ketone, alkyl, fused heterocyclic, -CF3, optionally substituted heterocyclic, _〇_Ci alkyl-N ( Alkyl h, -OC!-C6 alkyl-NH2 and -NH-aryl are substituted. In another embodiment according to the invention, .L is -Q-alkyl-C(0)_N (R3) )_c〇Aalkyl_, wherein when c〇_C3 alkyl is q-C:3 alkyl, this Cl_C3 alkyl group is optionally taken as _c(〇)_N(R3)alkyl-heteroaryl -CXCO-Na^-CVC3 alkyl-aryl substituted wherein each heteroaryl or aryl moiety is optionally substituted; and Y is η, optionally substituted aryl or optionally substituted In another embodiment according to the present invention, γ is an optionally substituted heteroaryl group. In addition, the specific implementation of the project is carried out according to the situation. (: Substituted or optionally substituted heteroaryl, wherein each heteroaryl or aryl π injury group is i or 2 depending on the situation. Independently selected halogen, alkyl or alkoxy substituted. In another embodiment according to the invention, Q C6 alkyl _ _ c 〇 % alkyl _c (〇) _n (r3 ) _ c 〇 a burnt base_, wherein when the fly, the hospital is q-C3, the Ci &amp; alkyl is optionally treated with ()(R)C〇&lt;:3 alkyl-heterocyclyl or -C( O)-N(R3)-C0-C3 alkyl-aryl substituted, wherein the hexanyl or aryl moiety is substituted as appropriate; and 134026-2 -141 - 200916447 γ A substituted aryl or optionally substituted heteroaryl. In another embodiment according to the invention, γ is an optionally substituted aryl group. Another embodiment in accordance with the invention Wherein _c(〇)_n(r3)_c〇_C3 alkyl-heterocyclic group is -C(0)-N(R3 &gt;C(rC3alkyl-heteroaryl). According to another aspect of the invention In a specific embodiment, Y_L_ is phenyl-CH2-0-C(0)-NH-. In the examples, L is -C〇-C6 alkyl-O_c〇_Ci alkyl_c(〇)_n(r3)_c〇_c3 alkyl-, wherein when the C0-C3 alkyl group is a Cl_Cs alkyl group' This C1_C3 alkyl group is optionally substituted by -C(O)-N(R3)-C0-C3 alkyl-heteroaryl or _C(〇)_N(R3)_C〇_C3 alkyl-aryl. Each heteroaryl or aryl moiety is optionally substituted with 1 to 3 independent substituents. The substituent is selected from the group consisting of halogen, -OH, -NH2, alkyl, -C(0)-0H, -C. (〇)-〇-alkyl, -C(0)-NH- optionally substituted aryl '-C(0)-NH- optionally substituted heteroaryl, _c(〇)_NH_alkyl _〇_alkyl group -C(0)-NH-homo-heterocyclyl, -homo--substituted aryl, alkoxy, optionally substituted aryl, optionally substituted Heteroaryl. In another embodiment according to the present invention, which is selected from the group consisting of -C(0)-NH- optionally substituted aryl, _c(〇)_NH-optionally substituted heteroaryl,-burning Substituent substituted aryl, optionally substituted aryl and optionally substituted heteroaryl substituents are optionally substituted with 1 or 2 independently selected substituents, including substituents selected from N, alkoxy 'alkyl, - fluorene-aryl, -NH-C(O)-alkyl, keto, -CN, heterocyclyl, -〇-yl 134026-2 -142- 200916447 The base, -CF3 and -〇-alkyl-oxime-alkyl. In another embodiment of the invention, L is phenyl-CH2-O-CCCO-NH-C!-C3 alkyl-' wherein the q-C3 alkyl group is -C(0)-NH- Pyrazolyl substituted, wherein the pyrazolyl group is optionally substituted. In another embodiment of the invention, L is phenyl-CHrO-QCO-NH-Ci-C^alkyl-, wherein (^-匚3 is based on -C(0)-NH- The oxazolyl substituent is wherein the carbazolyl group is optionally substituted with two independently selected substituents selected from the group consisting of optionally substituted aryl, alkyl, -C(0)-0-alkane , -C(〇)-〇H, -C(O)-Li- optionally substituted aryl, -C(0)-NH- optionally substituted heteroaryl, -C(0)- NH-alkyl-O-alkyl, -C(O)-Li-alkyl-heterocyclyl, cyclized substituted cycloalkyl, fused, optionally substituted heterocyclic and thick A substituted aryl group as appropriate. In another embodiment according to the invention, L is -C〇-Cg alkyl-N(R)-C(0)-N(R3)-C〇 -C3 alkyl group-, wherein when c〇-C3 is based on C!-C3, the Q-C; 3 alkyl group is optionally _c(〇)_n(R3)· c0 -C3 -heteroaryl-aryl, _C(0)_N(R3)_c〇alkyl-heteroaryl or -C(0)-N(R3)-C〇-C3 alkyl-aryl substituted, each of which is hetero An aryl or aryl moiety is optionally substituted; and Y is an optionally substituted aryl group, Optionally substituted heterocyclic group or optionally substituted cycloalkyl. In another embodiment according to the invention, γ is optionally substituted heteroaryl. Another item according to the invention In a specific embodiment, 134026-2 -143- 200916447 L is -C0 -C6 alkyl-〇_C〇_c3 alkyl_c(〇)_n(r3 &gt;c〇_C3 alkyl_, wherein when Q -C3 alkyl is Cl_(:3 alkyl, this alkyl group is optionally -QCO-NO^-CVC3 leu-heteroaryl, _C(〇)_N(R3)_C〇_C3 alkyl-aryl , -C(O)-N(R3)-C0-C3 alkyl-heteroaryl-aryl, _C(0)_N(R3)_C〇_C3 alkyl-heteroaryl-heteroaryl, _C (0)_N(R3)_c〇3 alkyl aryl-aryl and -C(〇&gt;N(R3)-CG alkyl-aryl-heteroaryl substitution, wherein each heteroaryl or aryl The radical moiety is optionally substituted; and Y is Η. In another embodiment of the invention, the w is further selected from 0. In another embodiment of the invention, /N'Rb construct ¥, for example

II XII X

Ra ,Μ'Ra, Μ'

Rb 為 II s HN I C$2 攀 另 之 明 發 本 據 根 於 h R \Rc-W、 I ιΛ/γν Η 中 例 施 實 體 具 項Rb is II s HN I C$2. The other is based on the examples in h R \Rc-W, I ιΛ/γν Η

CMX 構 結 為 &gt;&quot;s 很媒本發明第一方面之化合物之一些實例係列示於 中、。二等實例僅只是用以舉例說明本發明第—方面之 份化合物而已，並非限制本發明之範圍： 【實施方式】 合成圖式與實驗程序 :發明化合物可根據關於下文所示實例之反應圖式 般熟諸此藝者所已知之方法製成。此等圖式係用 134026-2 -144- 200916447 例說明一些可用以製造本發明化合物之程序。熟諳此藝者 將明瞭的是，可使用其他一般合成程序。本發明化合物可 製自市購可得之起始成份。可根據熟諳此藝者所習知之程 序，對起始成份施行任何種類之取代，以獲得本發明化合 物。 圖式1CMX is constructed as &gt;&quot;s. Some examples of compounds of the first aspect of the invention are shown in . The second-class examples are merely illustrative of the compounds of the first aspect of the invention, and are not intended to limit the scope of the invention: [Embodiment] Synthesis Schemes and Experimental Procedures: Inventive Compounds According to Reaction Schemes for Examples Illustrated Below It is made by methods known to those skilled in the art. These figures illustrate some of the procedures that can be used to make the compounds of the invention using 134026-2 -144- 200916447. Those skilled in the art will appreciate that other general synthetic procedures can be used. The compounds of the present invention can be prepared from commercially available starting ingredients. Any kind of substitution of the starting ingredients can be carried out according to procedures well known to those skilled in the art to obtain the compounds of the present invention. Figure 1

NHBoc NHCbzNHBoc NHCbz

ρ〇α3,吡啶 I~~程序A〇α3,pyridine I~~ program A

NHBocNHBoc

Y CSC!2i Et3N NH2 CH2CI2 NHCbz 3 :實例1Y CSC! 2i Et3N NH2 CH2CI2 NHCbz 3 : Example 1

程序C NHCbz 2 實例1 ⑸-1-酌基·1·(4·苯基?塞°坐-2-基胺基）-6-硫脉基己-2_基胺基甲酸 苄酯⑶ 11- ττϊΓ» 1 · /0、 r\ / -νΛ- λ-L s/,it 4+ »1^. 4+ \ /^ / trh - — As*. 、人1， -I-+ -M- 、 一r -·-，·&gt; 、τ y 4Procedure C NHCbz 2 Example 1 (5)-1- Discrete Base·1·(4·Phenyl-Phenyl-2-ylamino)-6-thiocarbenyl-2-ylaminocarbamate (3) 11- ττϊΓ» 1 · /0, r\ / -νΛ- λ-L s/,it 4+ »1^. 4+ \ /^ / trh - — As*. , person 1, -I-+ -M- , a r -·-,·&gt; , τ y 4

歹.鄉i .〈卞礼叛&amp;妝丞尸〇八乐二-)礼琅巷•妝悉j 0 K 苯基嘧唑-2-基）醯胺（1) 於吡啶（20毫升）中之Z-Lys(Boc)-OH (1.9克，5.0毫莫耳）内， 添加2-胺基-4-苯基嘧唑（1.32克，7.5毫莫耳）。使混合物冷卻 至〇°C，然後逐滴添加氯化磷醯（0.50毫升，5.5毫莫耳）。將 混合才勿在0 C下授掉30分鐘’接者在室溫下16小日夺°以水使 混合物淬滅，並以醋酸乙酯萃取，且將有機萃液以鹽水洗 務，脫水乾燥（MgS04)，過濾，及蒸發。使殘留物藉石夕膠管 柱層析，以己烧中之醋酸乙S旨（20至40%)純化，而得1 (2.25 134026-2 -145 - 200916447 克，84%)，為白色固體。LRMS(ESI):(計算值）538.2;(實測 值）539.3 (MH)+. 步驟2 : (S)-6-胺基-1-酮基-1-(4-笨基p塞唾_2_基胺基）己院_2_基胺 基甲酸芊酯（2) 於二氯甲烷（16毫升）中之化合物1 (2.15克，3.99毫莫耳） 内，添加二氣醋酸（4宅升）。將混合物於室溫下授拌2小時。 蒸發溶劑，並將醋酸乙酯添加至殘留物中。添加飽和Na2c〇3 水溶液，且將混合物以醋酸乙酯萃取，並使有機萃液脫水 乾燥（MgS〇4)，過濾，及蒸發。將粗製無色油2以本身使用 於下一步驟。LRMS (ESI):(計算值）438.2;(實測值）439.；! (MH)+. 步驟3 :⑸-1-酮基小(4-苯基嘍唑_2_基胺基）_6_硫脲基己_2_基胺 基曱酸苄酯⑶歹.乡i. <卞礼叛&amp; 丞 丞 〇 〇 - - - ) ) ) ) ) • • • • • • • • • • • • • • • • • • • • • 妆 妆 妆 妆 妆 妆 妆 妆 妆 妆 妆2-Amino-4-phenylpyrazole (1.32 g, 7.5 mmol) was added to Z-Lys(Boc)-OH (1.9 g, 5.0 mmol). The mixture was allowed to cool to 〇 ° C, then chlorophosphonium chloride (0.50 mL, 5.5 mmol) was added dropwise. Do not give the mixture for 30 minutes at 0 C. 'The receiver is quenched with water at room temperature for 16 hours. The mixture is quenched with water and extracted with ethyl acetate. The organic extract is washed with brine and dried. (MgS04), filtration, and evaporation. The residue was purified by column chromatography eluting with EtOAc EtOAc (EtOAc: EtOAc: LRMS (ESI): (calculated) 538.2; (found) 539.3 (MH) +. Step 2: (S)-6-amino-1-keto-1-(4-phenylpyrazine _ 胺 ) 己 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 ). The mixture was stirred at room temperature for 2 hours. The solvent was evaporated and ethyl acetate was added to the residue. A saturated aqueous solution of Na.sub.2Cl.sub.3 was added, and the mixture was extracted with ethyl acetate, and the organic extract was dried (MgSO.sub.4), filtered, and evaporated. The crude colorless oil 2 was used as it is in the next step. LRMS (ESI): (calculated) 438.2; (found) 439.; (MH)+. Step 3: (5)-1-keto-small (4-phenylcarbazol-2-ylamino)_6_ Thiourea-2-hexylamino phthalate (3)

於二氯甲烷（1.0毫升）中之化合物2 (88毫克，0.20毫莫耳） 内，在〇°C下添加三乙胺（42微升，〇3〇毫莫耳），接著為硫 代光氣（23微升，〇.3〇毫莫耳）。將混合物在〇〇c下攪拌】小時。 逐滴添加氨在甲醇中之溶液（〇 2毫升7N溶液，14毫莫耳）。 將混合物於室溫下攪拌2天。以飽和溶液使混合物淬 滅，並以醋酸乙酯萃取。使有機萃液脫水乾燥（MgS〇4)，過 濾，及蒸發，並使殘留物藉矽膠管柱層析，以己烷中之醋 酸乙酯（60至100%)純化，而得3 (2〇毫克，2〇%)，為白色固體。 (dmso-d6) (5 (ppm) ln： 12.39 (s, 1H), 7.88 (d, 1=7.4 Hz, 2H), 7.70 (d, J=6.8 Hz, 1H), 7.62 (s, 1H), 7.54 (bs, 1H), 7.42 (t, J=7.8 Hz, 2H), 7.38-7.11 (m, 6H), 6.86 (bs, 1H), 5.02 (d, J=2.5 Hz, 2H), 4.26 (q, J=4.9 Hz, 1H), 3.33 (m, 2H), 2.97 (m, 1H), 1.78-1.52 (m, 2H), 1.52-1.23 (m, 4H). LRMS 134026-2 -146- 200916447 (ESI):(計算值）497.2 ;(實測值）498.2 (ΜΗ)+·Add compound 3 (88 mg, 0.20 mmol) in dichloromethane (1.0 mL), add triethylamine (42 μL, 〇 3 〇 millimolar) at 〇 ° C, followed by thio light Gas (23 microliters, 〇.3 〇 millimoles). The mixture was stirred under 〇〇c for an hour. A solution of ammonia in methanol (〇 2 mL of 7N solution, 14 mmol) was added dropwise. The mixture was stirred at room temperature for 2 days. The mixture was quenched with a saturated solution and extracted with ethyl acetate. The organic extract is dehydrated and dried (MgS 4), filtered, and evaporated, and the residue is purified by EtOAc EtOAc EtOAc EtOAc Mg, 2% by weight), as a white solid. (dmso-d6) (5 (ppm) ln: 12.39 (s, 1H), 7.88 (d, 1 = 7.4 Hz, 2H), 7.70 (d, J = 6.8 Hz, 1H), 7.62 (s, 1H), 7.54 (bs, 1H), 7.42 (t, J=7.8 Hz, 2H), 7.38-7.11 (m, 6H), 6.86 (bs, 1H), 5.02 (d, J=2.5 Hz, 2H), 4.26 (q , J=4.9 Hz, 1H), 3.33 (m, 2H), 2.97 (m, 1H), 1.78-1.52 (m, 2H), 1.52-1.23 (m, 4H). LRMS 134026-2 -146- 200916447 ( ESI): (calculated value) 497.2; (measured value) 498.2 (ΜΗ)+·

圖式2 氣化乙醯 Et3N, THF 程序DFigure 2 Gasification of acetonitrile Et3N, THF Procedure D

程序Ε gjpau氏試劑Procedure Ε gjpau reagent

V NHCbz :實例2 實例2 ⑸-6-乙烧硫醯胺基-1-酮基·ι·(4-苯基屢„坐：基胺基）己燒_2-基 胺基曱酸苄酯（5) 步驟1 : (S)-6-乙醯胺基-1-酮基-1-(4-苯基嘧唑_2_基胺基）己烷_2 基胺基甲酸苄酯⑷ 於四氫呋喃（2毫升）中之胺2 (88毫克，〇.2〇毫莫耳）内，在 〇°C下添加三乙胺（84微升，0.60毫莫耳），接著為氯化乙醯（15 微升，0.20毫莫耳），並將混合物在(TC下攪拌丨小時。添加 水’且將混合物以醋酸乙酯萃取，並使有機萃液脫水乾燥 (MgS〇4)’過濾’及蒸發’且使殘留物藉石夕膠管柱層析，以 己烷中之醋酸乙酯（60至100%)純化，而得4 (45毫克，々％), 為白色固體。LRMS (ESI):(計算值）480.2;(實測值）481.2 (MH)+. 步驟2 :⑻_6_乙院硫醒胺基+酮基小…苯基噻唑·2_基胺基） 己烷-2-基胺基曱酸芊酯（5) 於四氫呋喃（0.7毫升）中之乙醯胺4 (35毫克，〇〇7毫莫耳） 内，在〇°C下添加2,4-雙（4-苯氧基苯基H，3_二硫_2斗二磷四圜 134026-2 •147· 200916447 -2,4-二硫化物（96毫克，0.18毫莫耳，Belleau氏試劑），並將混 合物於室溫下攪拌2小時。添加飽和Na2C03水溶液，且將混 合物以醋酸乙酯萃取，並將有機萃液洗滌，且脫水乾燥 (MgS04)，過濾，及蒸發，並使殘留物藉矽膠管柱層析，以 己烷中之醋酸乙酯（10至60%)純化，而得5 (24毫克，66%)， 為白色固體。（dmso-d6) 5 (ppm) 12.40 (s，1H)，9.95 (bs，1H)，7.90 (d, J=7.0 Hz, 2H), 7.71 (d, J=7.4 Hz, 1H), 7.63 (s, 1H), 7.43 (t, 3=1.2 Hz, 2H), 7.41-7.15 (m, 6H), 5.07-4.99 (m, 2H), 4.28 (q, J=4.9 Hz, 1H), 3.46 (q, J=6.7 Hz, 2H), 2.36 (s, 3H), 1.88-1.49 (m, 4H), 1.48-1.30 (m, 2H). LRMS (ESI):(計算值）496.2 ;(實測值）497.3 (MH)+. 圖式3V NHCbz : Example 2 Example 2 (5)-6-Ethylene thiolamino-1-keto- ι·(4-phenyl octopus: ylamino) hexyl-2-ylamino decanoate (5) Step 1: (S)-6-Ethylamino-1-keto-1-(4-phenylpyrazole-2-ylamino)hexane-2-ylcarbamate (4) Triethylamine (84 μL, 0.60 mmol) was added at 〇 ° C in an amine 2 (88 mg, 〇. 2 〇 mmol) in tetrahydrofuran (2 mL) followed by acetonitrile ( 15 μl, 0.20 mmol, and the mixture was stirred at TC for hr., water was added and the mixture was extracted with ethyl acetate and the organic extract was dried (MgS 〇 4) 'filtered' and evaporated. The residue was purified by chromatography on silica gel eluting with ethyl acetate (60 to 100%) to afford 4 (45 mg, 5%) as a white solid. LRMS (ESI): Calculated value) 480.2; (measured value) 481.2 (MH) +. Step 2: (8) _6_ 乙院 醒 胺 amine + keto small ... phenyl thiazole · 2 - ylamino) hexane-2-ylamino hydrazine Acid oxime ester (5) in acetamidine 4 (35 mg, 〇〇7 mmol) in tetrahydrofuran (0.7 ml), add 2 at 〇 ° C, 4-Bis(4-phenoxyphenyl H,3_disulfide-2-doudophosphonium tetrachloride 134026-2 •147· 200916447 -2,4-disulfide (96 mg, 0.18 mmol, Belleau's Reagent), and the mixture was stirred at room temperature for 2 hours. A saturated aqueous solution of Na 2 CO 3 was added, and the mixture was extracted with ethyl acetate, and the organic extract was washed and dried (MgS04), filtered, and evaporated. Purify by column chromatography on EtOAc EtOAc (EtOAc) (EtOAc (EtOAc) s,1H),9.95 (bs,1H), 7.90 (d, J=7.0 Hz, 2H), 7.71 (d, J=7.4 Hz, 1H), 7.63 (s, 1H), 7.43 (t, 3=1.2 Hz, 2H), 7.41-7.15 (m, 6H), 5.07-4.99 (m, 2H), 4.28 (q, J=4.9 Hz, 1H), 3.46 (q, J=6.7 Hz, 2H), 2.36 (s , 3H), 1.88-1.49 (m, 4H), 1.48-1.30 (m, 2H). LRMS (ESI): (calculated) 496.2 ; (measured value) 497.3 (MH)+.

TFA V CH2CI2TFA V CH2CI2

實例3 ⑸-6-乙烷硫醯胺基小酮基-1-(苯基胺基）己烷-2-基胺基曱酸 芊酯⑻ 步驟1 : (S)=2-(T氧羰基胺基）-6-(第三-丁氧羰基胺基）己酸 N-(苯基）醯胺⑹ 於 DMF (2.5 毫升）中之 Z-Lys(Boc)-OH (190 毫克，0.50 毫莫耳） 内，添加苯胺（55微升，0.60毫莫耳）、EDC (125毫克，0.65 134026-2 -148 - 200916447 $莫耳）及HOBT (100毫克，〇65毫莫耳），並將混合物於室 孤下攪拌16小％。添加飽和Na2C〇3水溶液，且將混合物以 醋酸乙醋萃取。使有機萃液脫水乾燥（MgS〇4)，過渡，及蒸 發，並使殘留物藉矽膠管柱層析，以己烷中之醋酸乙酯（1〇 至_純化，而得6 (193毫克，85%)，為自色固體。題5 (ESI).(什算值）455.2 ;(實測值）478 3 (M+Na)+. 步驟2 : (S)-6-胺基小酮基小(苯基胺基）己烷_2•基胺基甲酸苄 酯⑺ 標題化合物7 (145毫克，96%)係藉由按照一般程序B，使 用6 (193窆克’ 0.42毫莫耳）作為起始物質而得^ LRMS (紐工）： (計算值）355.2 ;(實測值）356 3 (MH)+. 步驟3 : (S)-6-乙烷硫醯胺基小酮基小(苯基胺基）己烷冬基胺 基曱酸苄酯（8) 於四氫呋喃（1_0毫升）中之胺7 (73毫克，〇 21毫莫耳）内， 在0 C下添加三乙胺（57微升，〇41毫莫耳），接著為二硫基 醋酸乙酯（35微升，〇,31毫莫耳），並將混合物於室溫下攪拌 16小時。添加飽和叫⑺3水溶液，且將混合物以醋酸乙酯 萃取，並使有機萃液脫水乾燥（MgS〇4)，過濾，及蒸發，且 使殘留物藉矽膠管柱層析，以己烷中之醋酸乙酯（4〇至8〇%) 純化’而得8 (63毫克’ 74%)，為白色固體。 (dmso-d6) δ (ppm) 1 Η： 10.02 (s, 1Η), 9.96 (bs, 1H), 7.60-7.56 (m, 3H), 7.37-7.18 (m, 7H), 7.04 (t, J=7.4 Hz, 1H), 5.03 (s, 2H), 4.12 (q, J=4.7 Hz, 1H), 3.44 (q, J=7.2 Hz, 2H), 2.35 (s, 3H), 1.73-1.49 (m, 4H), 1.49-1.27 (s, 2H). LRMS (ESI):(計算值）413.2 ;(實測值）414.3 (MH)+. 134026-2 -149- 200916447Example 3 (5)-6-Ethylthioguanamine-based small keto-1-(phenylamino)hexane-2-ylamino decanoate (8) Step 1: (S) = 2-(T-oxycarbonyl) Amino)-6-(tris-butoxycarbonylamino)hexanoic acid N-(phenyl)decylamine (6) Z-Lys(Boc)-OH in DMF (2.5 ml) (190 mg, 0.50 mmol) In the ear), add aniline (55 μl, 0.60 mmol), EDC (125 mg, 0.65 134026-2 -148 - 200916447 $m) and HOBT (100 mg, 〇65 mmol) and mix the mixture Stir 16 small % in the room. A saturated aqueous solution of Na 2 C 3 was added, and the mixture was extracted with ethyl acetate. The organic extract was dehydrated and dried (MgS 〇 4), transferred, and evaporated, and the residue was purified by chromatography on EtOAc EtOAc EtOAc EtOAc 85%), as a color solid. Title 5 (ESI). (calcd value) 455.2; (measured value) 478 3 (M+Na)+. Step 2: (S)-6-aminoketone small ketone Benzyl (phenylamino)hexane-2-ylcarbamate (7) The title compound 7 (145 mg, 96%) was obtained by using 6 (193 g of ' 0.42 mmol) according to General Procedure B. LRMS (New): (calculated) 355.2; (measured value) 356 3 (MH)+. Step 3: (S)-6-ethanethioguanamine small ketone small (phenyl Benzylamino) hexane-glycolyl benzyl decanoate (8) in amine 7 (73 mg, 〇21 mmol) in tetrahydrofuran (1_0 ml), triethylamine (57 μl) at 0 C , 〇41 mmol, followed by ethyl dithioacetate (35 μL, hydrazine, 31 mmol), and the mixture was stirred at room temperature for 16 hours. Adding a saturated aqueous solution of (7) 3 and adding the mixture Extracted with ethyl acetate and dehydrated the organic extract (MgS〇4), Filtration and evaporation, and the residue was purified eluting with EtOAc EtOAc EtOAc (EtOAc (EtOAc) Dmso-d6) δ (ppm) 1 Η: 10.02 (s, 1Η), 9.96 (bs, 1H), 7.60-7.56 (m, 3H), 7.37-7.18 (m, 7H), 7.04 (t, J=7.4 Hz, 1H), 5.03 (s, 2H), 4.12 (q, J=4.7 Hz, 1H), 3.44 (q, J=7.2 Hz, 2H), 2.35 (s, 3H), 1.73-1.49 (m, 4H ), 1.49-1.27 (s, 2H). LRMS (ESI): (calculated) 413.2 ; (measured) 414.3 (MH)+. 134026-2 -149- 200916447

圖式4 s^nh2 -NFigure 4 s^nh2 -N

19 :實例12 實例11 (S)-6·乙烧硫酿胺基-l._基4-(4-苯基p塞唾.2·基胺基）己烧·2-基 胺基曱酸第三-丁酯（18) 步驟1:⑸-6-(((9H-苐-9-基）甲氧基）幾基胺基）_2_(第三_丁氧幾基 胺基）己酸N-(4-苯基嘧唑-2-基）醯胺（16) 標題化合物16 (728毫克，61%)係藉由按照一般程序a，以 白色固體獲得，惟使用Boc-Lys(Fmoc)-OH (900毫克，1.92毫莫 耳）作為起始物質。LRMS (ESI).(計算值）626.3;(實測值）627.4 (MH)+. 步驟2 : (S)-6-胺基-1-銅基-1-(4-苯基p塞β坐_2_基胺基）己炫ι _2_基胺 134026-2 -150- 200916447 基甲酸第三-丁酯（17) 於一氯曱烧（4.6宅升）中之化合物；[6 (728毫克，1 16毫莫 耳）内，添加六氫吡啶（1.15毫升，12毫莫耳），並將混合物 於室溫下攪拌1小時。蒸發溶劑，且使殘留物藉矽膠管柱層 析’以二氣甲烧中之曱醇（〇至10%)純化，而得17 (11〇毫克， 23%)，為白色固體。LRMS (ESI):(計算值）4〇4.2;(實測值）4〇5 3 (MH)+. 步驟3 : (S)-6-乙烷硫醯胺基小酮基小(4_苯基噻唑_2基胺基） 己烷-2-基胺基甲酸第三-丁酯（18) 標題化合物18 (34毫克，54%)係藉由按照一般程序G，以 白色固體獲得，惟使用17 (55毫克，0.14毫莫耳）作為起始物 質。（dmso-d6) (5 (ppm) 1H: 12.34 (s，1H)，9.96 (s，1H)，7.90 (d, J=7.0 Hz, 2H), 7.63 (s, 1H), 7.43 (t, J=7.4 Hz, 2H), 7.32 (t, J=7.4 Hz, 1H), 7.22 (d, J=7.4 Hz, 1H), 4.20 (q, J=4.7 Hz, 1H), 3.50-3.40 (m, 2H), 2.36 (s, 3H), 1.72-1.46 (m, 4H), 1.45-1.22 (m，2H)，1.38 (s, 9H). LRMS (ESI):(計算 值）462.2 ;(實測值）463.3 (mh)+ . 實例12 ⑸·1,基-1-(4•苯基嘍唑_2-基胺基)-6-硫脲基己-2-基胺基甲酸 第三-丁酯（19) 步驟1 : (S)-l-酮基-1_(4-苯基嘧唑-2-基胺基）-6-硫脲基己-2-基胺 基曱酸第三-丁酯（19)19: Example 12 Example 11 (S)-6·Ethylene-sulphur-sweetyl-l.-yl 4-(4-phenyl-p-sodium.2-ylamino)hexanyl-2-ylamino decanoic acid Third-butyl ester (18) Step 1: (5)-6-(((9H-苐-9-yl)methoxy)alkylamino)_2_(third-butoxyamino)hexanoic acid N -(4-Phenylpyrazol-2-yl)decylamine (16) The title compound 16 (728 mg, 61%) was obtained as a white solid, according to the general procedure a, using Boc-Lys (Fmoc)- OH (900 mg, 1.92 mmol) was used as the starting material. LRMS (ESI). (calculated) 626.3; (found) 627.4 (MH) +. Step 2: (S)-6-Amino-1-copperyl-1-(4-phenyl-p-beta) 2 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Within 1 16 mmol, hexahydropyridine (1.15 mL, 12 mmol) was added and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated, and the residue was purified eluting with EtOAc EtOAc (EtOAc) LRMS (ESI): (calculated) 4〇4.2; (measured) 4〇5 3 (MH)+. Step 3: (S)-6-ethanethioguanamine ketone small (4_phenyl) Thiazol-2-ylamino) hexane-2-ylaminocarbamic acid tert-butyl ester (18) The title compound 18 (34 mg, 54%) was obtained as a white solid (55 mg, 0.14 mmol) as the starting material. (dmso-d6) (5 (ppm) 1H: 12.34 (s, 1H), 9.96 (s, 1H), 7.90 (d, J = 7.0 Hz, 2H), 7.63 (s, 1H), 7.43 (t, J =7.4 Hz, 2H), 7.32 (t, J=7.4 Hz, 1H), 7.22 (d, J=7.4 Hz, 1H), 4.20 (q, J=4.7 Hz, 1H), 3.50-3.40 (m, 2H ), 2.36 (s, 3H), 1.72-1.46 (m, 4H), 1.45-1.22 (m, 2H), 1.38 (s, 9H). LRMS (ESI): (calculated) 462.2 ; (measured value) 463.3 (mh)+. Example 12 (5)·1,-1-(4-phenylindazol-2-ylamino)-6-thioureidohexan-2-ylcarbamic acid tert-butyl ester (19 Step 1: (S)-l-keto-1(4-phenylpyrazol-2-ylamino)-6-thioureidohexan-2-ylaminodecanoic acid tert-butyl ester (19 )

標題化合物19 (24毫克，38%)係藉由按照程序C，以白色 固體獲得，惟使用17 (55毫克，0.14毫莫耳）作為起始物質。 (dmso-d6) δ (ppm) ln ： 7.88 (d, J=7.0 Hz, 2H), 7.59 (s, 1H), 7.42 (t, J=7A 134026-2 • 151 - 200916447The title compound 19 (24 mg, 38%) was obtained as a white solid by procedure C, using 17 (55 mg, 0.14 mmol) as starting material. (dmso-d6) δ (ppm) ln : 7.88 (d, J=7.0 Hz, 2H), 7.59 (s, 1H), 7.42 (t, J=7A 134026-2 • 151 - 200916447

Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.17 (d, J=7.0 Hz, 1H), 6.84 (m, 1H), 4.20-4.14 (m, 1H), 3.38-3.27 (m, 2H), 3.02-2.94 (m, 1H), 1.70-1.53 (m, 2H)，1.52-1.22 (m，4H)，1.36 (s, 9H). LRMS (ESI):(計算值）463.2;(實 測值）464.3 (ΜΗ)+· 表1中所舉例之化合物係以所指示之起始物質開始，並 按照所予之製備順序，利用表4中所列示之一般程序製成。 表1 化合物 實例 起始物質 結構 特徵鑒定 製備 順序Hz, 2H), 7.32 (t, J=7.2 Hz, 1H), 7.17 (d, J=7.0 Hz, 1H), 6.84 (m, 1H), 4.20-4.14 (m, 1H), 3.38-3.27 (m , 2H), 3.02-2.94 (m, 1H), 1.70-1.53 (m, 2H), 1.52-1.22 (m, 4H), 1.36 (s, 9H). LRMS (ESI): (calculated) 463.2; Found 464.1 (ΜΗ)+· The compounds exemplified in Table 1 were prepared starting from the indicated starting materials and prepared according to the general procedure shown in Table 4 in the order of preparation. Table 1 Compounds Examples Starting materials Structure Characterization Preparation Order

NHBoc NHCbzNHBoc NHCbz

r NHCbz S (S)-6-乙烧硫酿_胺基-1-嗣基 基胺基)己烷-2-基胺基甲酸芊酯 (CD3OD) d(ppm) : 7·44 (d，J=3_7 Ηζ， 1H)，7.38-7.16 (m，5H)，7.13 (d, J=3.7 Hz, lH)，5.10(q， J=12Hz，2H)， 4.34 (q, J=4.1 Hz, 1H), 3.57 (t，J=7.0Hz， 2H), 2.42 (s, 3H), 1.9M.60 (m，4H)，1.58-1.39 (m，2H). LRMS ： (計算值)420.1 (實測值)421.2 (MH)+r NHCbz S (S)-6-ethyl sulphur saponin_amino-1-mercaptoamino) hexane-2-ylaminocarbazate (CD3OD) d (ppm): 7·44 (d, J=3_7 Ηζ, 1H), 7.38-7.16 (m,5H), 7.13 (d, J=3.7 Hz, lH), 5.10(q, J=12Hz, 2H), 4.34 (q, J=4.1 Hz, 1H ), 3.57 (t, J=7.0Hz, 2H), 2.42 (s, 3H), 1.9M.60 (m, 4H), 1.58-1.39 (m, 2H). LRMS : (calculated) 420.1 (measured value) )421.2 (MH)+

F，B， G 134026-2 152- 200916447 實例 化合物 起始物質 結構 特徵鑒定 製備 順序F, B, G 134026-2 152- 200916447 Examples Compounds Starting materials Structure Characterization Preparation Order

NH 巳 oc NHCbzNH 巳 oc NHCbz

r NHCbz S (S)-1-(聯本-3-基胺基)-6-乙烧硫龜胺基 -1-酮基己-2-基胺基甲酸苄酯 (CD3OD) d(ppm) '· 7.84 (s，1Η)，7·60 (d，J=7.6 Ηζ， 2H), 7.54 (d, J=7.0Hz，1Η)， 7.43 (t，J=7.4 Hz，2H)，7.39-7.13 (m, 8H), 5.11 (d, J=19 Hz, 2H), 4.26 (dd，J=9.0, 5.5 Hz, 1H), 3.58 (t, J=7.2 Hz, 2H), 2.41 (s, 3H), 1.92-1.65 (m，4H), 1.55- 1.44 (m，2H). LRMS ： (計算值）489.2 (實測值）490.3 (MH)+r NHCbz S (S)-1-(biben-3-ylamino)-6-ethylthiocarbamate-1-ketohexyl-2-ylcarbamate benzyl ester (CD3OD) d (ppm) '· 7.84 (s, 1Η), 7·60 (d, J=7.6 Ηζ, 2H), 7.54 (d, J=7.0Hz, 1Η), 7.43 (t, J=7.4 Hz, 2H), 7.39-7.13 (m, 8H), 5.11 (d, J=19 Hz, 2H), 4.26 (dd, J=9.0, 5.5 Hz, 1H), 3.58 (t, J=7.2 Hz, 2H), 2.41 (s, 3H) , 1.92-1.65 (m, 4H), 1.55- 1.44 (m, 2H). LRMS : (calculated) 489.2 (measured value) 490.3 (MH)+

F,B， G 6 11 11F, B, G 6 11 11

HO .NHBoc NHCbzHO .NHBoc NHCbz

r N ' NHCbz S (S)-6-乙烧硫酿胺基-1-嗣基 基胺基)己烷-2-基胺基甲酸芊酯 (CD3OD) d(ppm) 8.77 (d, J=4.1 Hz, 1H)，8.65 (d， J=7.6Hz，1H)， 8.30 (d, J=8.4 Hz, 1H), 7.64 (d, J=8.2 Hz, i τ T\ 产i /-产1 r· r\ 丄n)，/.：) /-/.j：) (m, 2H), 7.40 (d, J=6.3 Hz, 1H), 7.28-6.87 (m, 4H),5.23-5.10 (m, 2H), 4.36 (q, J=4.7 Hz, 1H), 3.59 (t, J=7.0 Hz, 2H), 2.42 (s, 3H), 2.10-1.97 (m, 1H), 1.87-1.77 (m, 1H), 1.71-1.67 (m, 2H), 1.61- 1.47 (m, 2H). LRMS ： (計算值）464.2 (實測值）465.3 (MH)+r N 'NHCbz S (S)-6-Ethylene sulphate-ylamino-1-ylamino) hexane-2-ylaminocarbazate (CD3OD) d (ppm) 8.77 (d, J= 4.1 Hz, 1H), 8.65 (d, J=7.6Hz, 1H), 8.30 (d, J=8.4 Hz, 1H), 7.64 (d, J=8.2 Hz, i τ T\ yield i /- yield 1 r · r\ 丄n), /.:) /-/.j:) (m, 2H), 7.40 (d, J=6.3 Hz, 1H), 7.28-6.87 (m, 4H), 5.23-5.10 (m , 2H), 4.36 (q, J=4.7 Hz, 1H), 3.59 (t, J=7.0 Hz, 2H), 2.42 (s, 3H), 2.10-1.97 (m, 1H), 1.87-1.77 (m, 1H), 1.71-1.67 (m, 2H), 1.61- 1.47 (m, 2H). LRMS : (calculated) 464.2 (measured value) 465.3 (MH)+

F,B, G 6- 02 340 -153 - 200916447 化合物112_13 實^7 8 起始物質 結構 特徵鑒定 製備 順序F,B, G 6- 02 340 -153 - 200916447 Compound 112_13 实^7 8 Starting material Structure Characterization Preparation Order

NHBoc NHCbz +NHBoc NHCbz +

NHCbz (S)-6-乙烷硫醯胺基-1-酮基-1-(4-(吡啶 -4-基)嘧唑-2-基胺基)己烷-2-基胺基曱 酸苄酯 (CD3OD) d(ppm) : 8.55 (d, J=6.1 Hz, 2H), 7.93 (d, J=6.1 Hz, 2H), 7.80 (s, 1H), 7.39-7.11 (m, 5H),5.11 (q, J=9.8 Hz, 2H), 4.36 (dd, J= 9.2, 5.3 Hz, lH)，3.58(t， J=7.0 Hz，2H)， 2.42 (s，3H)， 1.92-1.68 (m, 4H)，1.57-1.47 (m, 2H). LRMS ： (計算值)497.2 (實測值）498.3 (MH)+NHCbz (S)-6-ethanethioguanidino-1-keto-1-(4-(pyridin-4-yl)pyrazol-2-ylamino)hexane-2-ylamino decanoic acid Benzyl ester (CD3OD) d (ppm): 8.55 (d, J = 6.1 Hz, 2H), 7.93 (d, J = 6.1 Hz, 2H), 7.80 (s, 1H), 7.39-7.11 (m, 5H), 5.11 (q, J=9.8 Hz, 2H), 4.36 (dd, J= 9.2, 5.3 Hz, lH), 3.58 (t, J=7.0 Hz, 2H), 2.42 (s, 3H), 1.92-1.68 (m , 4H), 1.57-1.47 (m, 2H). LRMS : (calculated) 497.2 (measured value) 498.3 (MH)+

F,B, GF, B, G

NHBoc NHCbzNHBoc NHCbz

r NHCbz S (S)-l-(4-(3,4-二氟苯基)p塞唑-2-基胺基)-6-乙烷硫醯胺基-1-酮基己-2-基胺基甲 酸芊酯 (CD3OD) d(ppm):7.84-7.79 (m, 1H), 7.72-7.69 (m, 1H), 7.43 (s, 1H)，7.39-7.12 (m，6H),5.11 (q，J二 10 Hz， 2H), 4.35 (q, J=3.9 Hz, 1H), 3.58(t，J=7.0 Hz, 2H), 2.42 (s, 3H), 1.92-1.66 (m, 4H), 1.57-1.44 (m, 2H). LRMS ： (計算值）532.1 (實測值）533.2 (MH)+r NHCbz S (S)-l-(4-(3,4-difluorophenyl)p-axazol-2-ylamino)-6-ethanethioguanidino-1-ketohexan-2- Ethyl carbazate (CD3OD) d (ppm): 7.84-7.79 (m, 1H), 7.72-7.69 (m, 1H), 7.43 (s, 1H), 7.39-7.12 (m, 6H), 5.11 ( q, J 2 10 Hz, 2H), 4.35 (q, J=3.9 Hz, 1H), 3.58 (t, J=7.0 Hz, 2H), 2.42 (s, 3H), 1.92-1.66 (m, 4H), 1.57-1.44 (m, 2H). LRMS : (calculated) 532.1 (measured value) 533.2 (MH)+

F,B, G 134026-2 154- 200916447 化合物IΜ 實例 9F, B, G 134026-2 154- 200916447 Compound IΜ Example 9

起始物質 結構 特徵鑒定 製備 順序 h〇A^^^NHBoc NHCbz ο 丫 ΝΗ2 Η NHCbz S (S)-1 -酮基-1 -〇奎啉-8-基胺基)-6-硫脲基 己-2-基胺基曱酸苄酯 (dmso-d6) d(ppm) : 8.83 (d, J=2.7 Hz, 1H), 8.59 (d, J=7_6Hz，1H)， 8.41 (dd, J=8.2, 1.7 Hz, 1H), 8.11 (d，J=7.0 Hz，1H)，7.68 (dd, J=8.4, 1.5 Hz, 1H), 7.65- 7.61 (m，2H)’ 7.58 (t，J=7.8 Hz, 1H), 7.39-7.31 (m,2H), 7.30-7.10 (m, 3H)，6.84 (bs， lH)，5.14(d， J=12Hz, 1H), 5.03 (d, J=12 Hz，lH)，4.23-4.17 (m, 1H), 3.38-3.27 (m， 2H), 3.03-2.95 (m, 1H), 1.92- 1.62 (m，2H)， 1.57-1.33 (m, 4H). LRMS : (計算值）465.2 (實測值）466.3 (MH)+ F，B， C 155- 134026-2 200916447Determination of the structure of the starting material. Preparation sequence h〇A^^^NHBoc NHCbz ο 丫ΝΗ2 Η NHCbz S (S)-1 -keto-1 -nonylquinolin-8-ylamino)-6-thiourea Benzyl-2-ylamino decanoate (dmso-d6) d (ppm): 8.83 (d, J = 2.7 Hz, 1H), 8.59 (d, J = 7_6 Hz, 1H), 8.41 (dd, J = 8.2 , 1.7 Hz, 1H), 8.11 (d, J=7.0 Hz, 1H), 7.68 (dd, J=8.4, 1.5 Hz, 1H), 7.65- 7.61 (m, 2H)' 7.58 (t, J=7.8 Hz , 1H), 7.39-7.31 (m, 2H), 7.30-7.10 (m, 3H), 6.84 (bs, lH), 5.14 (d, J=12Hz, 1H), 5.03 (d, J=12 Hz, lH ), 4.23-4.17 (m, 1H), 3.38-3.27 (m, 2H), 3.03-2.95 (m, 1H), 1.92-1.62 (m, 2H), 1.57-1.33 (m, 4H). LRMS : ( Calculated value) 465.2 (measured value) 466.3 (MH) + F, B, C 155- 134026-2 200916447

實 例 化 合 物 起始物質 結構 特徵鑒定 製備 順序 10 15 MU ： NHCbz + n nh2 F &lt;fl i H NHCbz S (S)-l-(4-(3,4-二氟笨基 &gt;塞唑-2-基胺基)-1 -酮基-6-硫脲基己-2-基胺基甲酸芊酯 (dmso-d6) d(ppm) ·· 7.91-7.85 (m, 1H), 7.77-7.70 (m, 1H), 7.68 (s, 1H), 7.48 (q, J=10 Hz, 1H), 7.38- 7.28 (m, 5H), 7.19-7.09 (m, 1H), 6.84 (bs, 1H), 5.01 (d, J=2.9 Hz, 2H), 4.24 (q, J=5.1 Hz, 1H), 3.38- 3.29 (m, 2H), 2.97 (bs, 1H), 1.75-1.57 (m,2H), 1.51-1.22 (m,4H). LRMS ： (計算值）533.1 (實測值）534.2 (MH)+ F,B, C 根據本發明之其他化合物係顯示於表2中 表2 化合物 結構 特徵鑒定 14 20 H )SIH S (S)-l-(苯并[d]嘍唑-2-基胺基)-6-乙烷硫 醯胺基-1-酮基己-2-基胺基甲酸芊酯 (dmso-d6) d(ppm) 1H ： 9.96 (s, 1H), 7.98 (d, J=7.6 Hz, 1H), 7.78-7.73 (m, 2H), 7.44 (t, J=7.2 Hz, 1H), 7.39-7.10 (m, 6H), 5.04 (s, 2H), 4.34-4.27 (m, 1H), 3.44 (t, J=6.8 Hz, 2H), 2.35 (s, 3H), 1.78-1.49 (m, 4H), 1.48-1.29 (m, 2H). LRMS (ESI):(計算值）470.1 (實 測值）471.3 (MH)+ — 15 21 H NH S (S)-6-乙烷硫醯胺基-1-酮基-1-(吡啶-3-基胺基)己烧-2-基胺基曱酸苄酯 (dmso-d6) d(ppm) 1H ： 10.27 (s, 1H), 9.96 (s, 1H), 8.75 (d, J=2.3 Hz, 1H), 8.27 (dd, J=4.7, 1.4 Hz, 1H), 8.04 (dt, J=8.6, 2.3 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.39-7.10 (m, 6H), 5.03 (d, J=1.8 Hz, 2H), 4.14 (q, J=5.5 Hz, 1H), 3.45 (q, J=6.8 Hz, 2H), 2.35 (s, 3H), 1.69-1.34 (m，6H). LRMS (ESI):(計算值） 414.2(實測值）415.3 (MH)+ \34026-2 -156- 200916447 實例 一^— 16 化合物 結構 特徵鑒定 22 Η NH S CK、 (S)-6-乙烷硫醯胺基-1 -(5-曱基異噚唑 -3-基胺基)-1-酮基己-2-基胺基甲酸芊 is (dmso-d6) d(ppm) 1H : 11.01 (s，iH) 9.96(s, 1H), 7.61 (d, J=7.6Hz, 1H) ’ 7.39-7.29 (m, 4H), 7.23 (s, 1H), 6 61 (s, 1H), 5.02 (s, 2H), 4.15 (q, j=4.5 Hz, 1H), 3.44 (q, J=7.2 Hz, 2H) 2 37 (s, 3H), 2.36 (s, 3H), 1.70-1.44 (m' 4H), 1.44-1.27 (m, 2H). LRMS ’ (ESI):(計算值）418.2 (實測值)419 3 (MH)+ __一 17 23 Η Η &gt; I (S)-l-(lH-咪唑-2-基胺基)-6-乙烧硫醯 胺基-1-酮基己-2-基胺基甲酸芊酯 (dmso-d6) d(ppm) 1H : 11.53 (s, 1H) 11.18(5, 1H), 9.96 (s, 1H),7.59 (d ’ J=6.4 Hz, 1H), 7.39-7.21 (m, 5H),' 6.77 (s, 1H), 6.66 (s, 1H), 5.02 (s, 2H), 4.16 (q, J=5.3 Hz, 1H), 3.44 (q, J=6.9 Hz, 2H), 2.36 (s, 3H), 1.76-1.48 (ra, 4H), 1.48-1.25 (m, 2H). LRMS (ESI):(計算值）403.2 (實測值）404.2 (MH)+ ---一 18 __---- 19 24 π NH S (S)-6-乙烷硫醯胺基-1-(甲胺基)-1-酮基 己-2-基胺基甲酸苄酯 (dmso-d6) d(ppm) 1H : 9.95 (s, 1H), 7.83 (q, J=4.5 Hz, 1H), 7.39-7.28 (m, 6H), 5.01 (d, J=7.0 Hz, 2H), 3.89 (q, J=4.9 Hz, 1H), 3.42 (q, J=7.2 Hz, 2H), 2.57 (d, J=4.7 Hz, 3H), 2.36 (s, 3H), 1.63-1.46 (m, 4H), 1.40-1.18 (m, 2H). 25 /〇r^人r^V /0 M NH S (S)-l-(2,2-二甲氧基乙胺基)-6-乙烷硫 醯胺基-1-酮基己-2-基胺基甲酸芊酯 (dmso-d6) d(ppm) 1H ： 9.94 (s, 1H), 7.96 (t, J=5.9 Hz, 1H), 7.39-7.28 ’ (mm, 6H), 5.01 (s, 2H), 4.32 (t, J=5.5 Hz, 1H), 3.96 (q, J=5.3 Hz, 1H), 3.42 (q; J=5.1 H/; 2H), 3.25 (s, 6H), 3.25-3.06 (m, 2H), 2.36 (s, 3H), 1.63-1.45 (m, 4H), 1.42-1.22 (m, 2H). LRMS (ESI):(計算值）425.2 (實測值)426.3 (MH)+ ---^ 2〇 26 (_S)-6-乙烧硫酿胺基小酮基小(4-本基 嘧唑-2-基胺基)己烷-2-基胺基甲酸(9H-第-9-基)甲酯 (dmso-d6) d(ppm) 1H ： 12.42 (s, 1H), 9.98 (s, 1H), 7.90 (d, J=7.2 Hz, 4H) ’ 7.79 (d, J=7.6 Hz, 1H), 7.75-7.72 (m, 2H), 7.64 (s, 1H), 7.45-7.39 (m, 4H), 7.35-7.30 (m, 3H), 4.33-4.22 (m, 4H), 3.58-3.43 (m, 2H), 2.37 (s, 3H), 1.80-1.52 (m, 4H). 1.52-1.32 (m, 2ΗΊ. LRMS (ESI):(計算值）584.2 (實測 值）585.4 (MH)+ 1____一 13402^-2 -157· 200916447 實例 化合物 結構 特徵鑒定 21 27 H “ S (S)-2-胺基-6-乙院硫醯胺基-N-(4-苯基 噻唑-2-基)己醯胺 (dmso-d6) d(ppm) 1H * 9.96 (bs, 1H), 7.90 (d，J=8.4 Hz, 2H)，7.61 (s，1H)， 7.42 (t，J=7.4 Hz，2H)，7.32 (t, J=7.2 Hz，1H)，3.48-3.42 (m，3H)，2.36 (s, 3H), 1.70-1.30 (m, 6H). LRMS 〇ESI):(計算值）362.1 (實測值）363.2 (MH)h- 22 28 H NH S Qr1^ (S)，6-乙坑硫酿胺基-2-(3-苯基丙酿胺 基)-N-(4-笨基4唑-2-基)己醯胺 (dmso-d6) d(ppm) 1H ： 12.37 (s, 1H), 9.95 (s, 1H), 8.21 (d, J=7.0 Hz, 1H), 7.89 (d, J=7.0 Hz, 2H), 7.62 (s, 1H), 7.42 (t, J=7.4 Hz, 2H), 7.31 (t, J=7.2 Hz, 1H), 7.26-7.12 (ra, 5H), 4.47 (q, J=4.1 Hz, 1H), 2.80 (t, J=7.4 Hz, 2H), 2.50-2.40 (m, 2H), 2.35 (s, 3H), 1.78-1.43 (m, 2H), 1.39-1.20 (m, 2H). LRMS (ESI):(計算值)494.2 (實測 值）495.3 (MH)+ 23 29 H s (S)-6-乙烷硫醯胺基-2-(苯基甲基績醯 胺基)-N-(4-苯基嘧唑-2-基)己醯胺 (dmso-d6) d(ppm) 1H ： 12.34 (s, 1H), 9.95 (s, 1H), 7.89 (d, J=7.〇 Hz, 2H), 7.71 (d, J=8.0 Hz, 1H), 7.65 (s, 1H), 7.42 (t, J=7.2 Hz, 2H), 7.37-7.29 (m, 6H), 4.31 (s, 2H), 4.07 (q, J=6.5 Hz, 1H), 3.45-3.35 (m, 2H), 2.34 (s, 3H), 1.76-1.43 (m, 4H), 1.42-1.21 (m, 2H). LRMS (ESI):(計算值)5】6.1 (實測 值）517·2(ΜΗ)+ 24 30 C又 H HN^O S 1 ⑸-6-乙烧破醯胺基-1-酮基-H違0坐-2-基胺基)己烧-2-基胺基甲酸乙酯 (dmso-d6)d(ppm) 1H : 12.20(s, 1H), 9.96 (s, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.47 (d, J=3.5 Hz, 1H), 7.21 (d, J=3.5 Hz, 1H), 4.21 (q, J=4.7 Hz, 1H), 3.98 (q, J=7.0 Hz, 2H), 3.44 (q, J=6.3 Hz, 2H), 2.36 (s, 3H), 1.72-1.49 (m, 4H), 1.48-1.27 (m, 2H), 1‘16 (t，j=7.〇 Hz， 3H). LRMS (ESI):(計算值）358 2 (實 測值）359.2 (MH)+ 25 31 C又 H HNv^O S (S)-2-乙醯胺基-6-乙烧硫醯胺基-N_(P塞 唑-2-基_)己醯胺 (dmso-d6) d(ppm) 1H : 9.96 (s，1H), 8.22 (d，J=7.2 Hz，1H)，7.47 (d，J=3.5 Hz, 1H),7.21 (d,J=3.7 Hz, 1H), 4.46-4.40 (m, 1H), 3.44 (q, J=5.’9 Hz, 2H), 2.36 (s, 3H), 1.86 (s, 3H), 1.77-1.50 (m, 4H), 1.50-1.22 (m, 2H). LRMS (ESI):(計算值）328」（實測 值）329.2 (MH)+ 134026-2 -158- 200916447 實例 化合物 結構 特徵鑒定 26 32 H HNv^O S 0 N 1 (S)-N-(6-乙烷硫醯胺基-1-酮基-1-(嘧唑 -2-基胺基)己烷-2-基)-1-甲基六氮吡啶 -4-羧醯胺 (dmso-d6) d(ppm) 1H 12.20 (s, 1H), 9.97 (s, 1H), 8.02 (m, 1H), 7.44 (d, J=3.5 Hz, 1H), 7.14 (s, 1H), 4.40 (d, J=4.5 Hz, 1H), 3.43 (q, J=8.0 Hz, 2H), 2.75 (d, J=ll Hz, 2H), 2.36 (s, 3H), 2.22-2.10 (m, 1H), 2.12 (s, 3H), 1.80 (t，J=12 Hz, 2H)，1.76-1.43 (m，7H)， 1.42-1.21 (m，3H). LRMS (ESI) ··(計 算值）411.2 (實測值)412.3 (MH)+ 27 33 H HN^O S \ NH P MeO (S)-6-乙烷硫醯胺基-2-(2-(5-曱氧基-2-曱基-1H-4哚-3-基）乙醯胺基)-N-0塞唑 -2-基）己醯胺 (dmso-d6) d(ppm) 1H : 12.22 (s，1H)， 10.59 (s，1H)，9.94 (s，1H)，8.30 (d， J=7.4 Hz, 1H), 7.46 (d, J=3.5 Hz, 1H), 7.21 (d，J=3.7 Hz，1H)，7.08 (d，J=8.8 Hz, 1H), 7.01 (d, J=2.3 Hz, 1H), 6.58 (dd, J=8.6, 2.3 Hz, 1H), 4.45 (q, J=4.3 Hz，1H)，3.73 (s，3H)，3.54-3.35 (m， 4H)，2.35 (s，3H)，2.30 (s，3H)， 1.78-1.60 (m, 2H), 1.52 (qi, J=7.4 Hz, 2H), 1.43-1.21 (m, 2H). LRMS (ESI):(計算值)487.2 (實測值)488.3 (MH)+ 圖式5EXAMPLES Compounds Starting Materials Structural Characterization Preparation Sequence 10 15 MU : NHCbz + n nh2 F &lt; fl i H NHCbz S (S)-l-(4-(3,4-Difluoro Styrene &gt; -ylamino)-1 -keto-6-thioureidohexan-2-ylaminocarbazate (dmso-d6) d (ppm) ·· 7.91-7.85 (m, 1H), 7.77-7.70 ( m, 1H), 7.68 (s, 1H), 7.48 (q, J=10 Hz, 1H), 7.38- 7.28 (m, 5H), 7.19-7.09 (m, 1H), 6.84 (bs, 1H), 5.01 (d, J=2.9 Hz, 2H), 4.24 (q, J=5.1 Hz, 1H), 3.38- 3.29 (m, 2H), 2.97 (bs, 1H), 1.75-1.57 (m, 2H), 1.51- 1.22 (m,4H). LRMS : (calculated) 533.1 (actual value) 534.2 (MH) + F, B, C Other compounds according to the invention are shown in Table 2 Table 2 Structural Characterization of the Compound 14 20 H ) SIH S (S)-l-(benzo[d]oxazol-2-ylamino)-6-ethanethioguanidino-1-ketohexan-2-ylaminocarbazate (dmso- D6) d(ppm) 1H : 9.96 (s, 1H), 7.98 (d, J=7.6 Hz, 1H), 7.78-7.73 (m, 2H), 7.44 (t, J=7.2 Hz, 1H), 7.39- 7.10 (m, 6H), 5.04 (s, 2H), 4.34-4.27 (m, 1H), 3.44 (t, J=6.8 Hz, 2H), 2.35 (s, 3H), 1.78-1.49 (m, 4H) , 1.48-1.29 (m, 2H). LRMS (ESI): (calculated value 470.1 (measured value) 471.3 (MH) + — 15 21 H NH S (S)-6-ethanethioguanidin-1-one-1-(pyridin-3-ylamino)hexan-2- Benzyl decyl decanoate (dmso-d6) d (ppm) 1H : 10.27 (s, 1H), 9.96 (s, 1H), 8.75 (d, J = 2.3 Hz, 1H), 8.27 (dd, J= 4.7, 1.4 Hz, 1H), 8.04 (dt, J=8.6, 2.3 Hz, 1H), 7.65 (d, J=7.8 Hz, 1H), 7.39-7.10 (m, 6H), 5.03 (d, J=1.8 Hz, 2H), 4.14 (q, J=5.5 Hz, 1H), 3.45 (q, J=6.8 Hz, 2H), 2.35 (s, 3H), 1.69-1.34 (m,6H). LRMS (ESI): (calculated value) 414.2 (measured value) 415.3 (MH)+ \34026-2 -156- 200916447 Example 1^-16 Structural characterization of compound 22 Η NH S CK, (S)-6-ethanethioguanamine- 1-(5-Mercapthyl isoxazol-3-ylamino)-1-ketohexan-2-ylaminocarbazate 芊is (dmso-d6) d (ppm) 1H : 11.01 (s, iH) 9.96 (s, 1H), 7.61 (d, J=7.6Hz, 1H) ' 7.39-7.29 (m, 4H), 7.23 (s, 1H), 6 61 (s, 1H), 5.02 (s, 2H), 4.15 (q, j=4.5 Hz, 1H), 3.44 (q, J=7.2 Hz, 2H) 2 37 (s, 3H), 2.36 (s, 3H), 1.70-1.44 (m' 4H), 1.44-1.27 ( m, 2H). LRMS ' (ESI): (calculated) 418.2 (measured value) 419 3 (MH) + __ a 17 23 Η Η &gt; I (S)-l-(lH-imidazol-2-ylamino)-6-ethylsulfanylamino-1-ketohexan-2-ylaminocarbazate (dmso-d6) d (ppm) 1H : 11.53 (s, 1H) 11.18(5, 1H), 9.96 (s, 1H), 7.59 (d ' J=6.4 Hz, 1H), 7.39-7.21 (m, 5H), ' 6.77 (s, 1H) , 6.66 (s, 1H), 5.02 (s, 2H), 4.16 (q, J=5.3 Hz, 1H), 3.44 (q, J=6.9 Hz, 2H), 2.36 (s, 3H), 1.76-1.48 ( Ra, 4H), 1.48-1.25 (m, 2H). LRMS (ESI): (calculated) 403.2 (measured value) 404.2 (MH)+ ---18 __---- 19 24 π NH S (S -6-Ethylthioamido-1-(methylamino)-1-ketohexan-2-ylcarbamate benzyl ester (dmso-d6) d (ppm) 1H: 9.95 (s, 1H) , 7.83 (q, J=4.5 Hz, 1H), 7.39-7.28 (m, 6H), 5.01 (d, J=7.0 Hz, 2H), 3.89 (q, J=4.9 Hz, 1H), 3.42 (q, J=7.2 Hz, 2H), 2.57 (d, J=4.7 Hz, 3H), 2.36 (s, 3H), 1.63-1.46 (m, 4H), 1.40-1.18 (m, 2H). 25 /〇r^ Human r^V /0 M NH S (S)-l-(2,2-dimethoxyethylamino)-6-ethanethioguanidino-1-ketohexyl-2-ylaminocarboxylic acid Ester (dmso-d6) d (ppm) 1H: 9.94 (s, 1H), 7.96 (t, J = 5.9 Hz, 1H), 7.39-7.28 ' (mm, 6H), 5.01 (s, 2H), 4.32 (t, J=5.5 Hz, 1H), 3.96 (q, J=5.3 Hz, 1H), 3. 42 (q; J=5.1 H/; 2H), 3.25 (s, 6H), 3.25-3.06 (m, 2H), 2.36 (s, 3H), 1.63-1.45 (m, 4H), 1.42-1.22 (m , 2H). LRMS (ESI): (calculated) 425.2 (measured value) 426.3 (MH) + ---^ 2〇26 (_S)-6-ethyl sulphur sulphonyl ketone ketone small (4-ben (5H-9-yl)methyl formate (dHso-d6) d (ppm) 1H : 12.42 (s, 1H), 9.98 ( s, 1H), 7.90 (d, J=7.2 Hz, 4H) ' 7.79 (d, J=7.6 Hz, 1H), 7.75-7.72 (m, 2H), 7.64 (s, 1H), 7.45-7.39 (m , 4H), 7.35-7.30 (m, 3H), 4.33-4.22 (m, 4H), 3.58-3.43 (m, 2H), 2.37 (s, 3H), 1.80-1.52 (m, 4H). 1.52-1.32 (m, 2ΗΊ. LRMS (ESI): (calculated) 584.2 (measured value) 585.4 (MH) + 1____ 13400^-2 -157· 200916447 Example compound structural characterization 21 27 H “ S (S)-2 -Amino-6-Binosa thioguanamine-N-(4-phenylthiazol-2-yl)hexylamine (dmso-d6) d (ppm) 1H * 9.96 (bs, 1H), 7.90 (d , J = 8.4 Hz, 2H), 7.61 (s, 1H), 7.42 (t, J = 7.4 Hz, 2H), 7.32 (t, J = 7.2 Hz, 1H), 3.48-3.42 (m, 3H), 2.36 (s, 3H), 1.70-1.30 (m, 6H). LRMS 〇ESI): (calculated value) 362.1 (measured value) 363.2 (MH)h- 22 28 H NH S Qr1^ (S), 6-ethyl thiosulfanyl-2-(3-phenylpropenylamino)-N-(4-phenyl 4-azole-2 -yl) hexylamine (dmso-d6) d (ppm) 1H : 12.37 (s, 1H), 9.95 (s, 1H), 8.21 (d, J = 7.0 Hz, 1H), 7.89 (d, J = 7.0 Hz, 2H), 7.62 (s, 1H), 7.42 (t, J=7.4 Hz, 2H), 7.31 (t, J=7.2 Hz, 1H), 7.26-7.12 (ra, 5H), 4.47 (q, J =4.1 Hz, 1H), 2.80 (t, J=7.4 Hz, 2H), 2.50-2.40 (m, 2H), 2.35 (s, 3H), 1.78-1.43 (m, 2H), 1.39-1.20 (m, 2H). LRMS (ESI): (calculated) 494.2 (measured value) 495.3 (MH) + 23 29 H s (S)-6-ethanethioguanamine-2-(phenylmethyl benzylamino) -N-(4-phenylpyrazol-2-yl)hexylamine (dmso-d6) d (ppm) 1H: 12.34 (s, 1H), 9.95 (s, 1H), 7.89 (d, J= 7.〇Hz, 2H), 7.71 (d, J=8.0 Hz, 1H), 7.65 (s, 1H), 7.42 (t, J=7.2 Hz, 2H), 7.37-7.29 (m, 6H), 4.31 ( s, 2H), 4.07 (q, J=6.5 Hz, 1H), 3.45-3.35 (m, 2H), 2.34 (s, 3H), 1.76-1.43 (m, 4H), 1.42-1.21 (m, 2H) . LRMS (ESI): (calculated value) 5] 6.1 (measured value) 517·2 (ΜΗ) + 24 30 C and H HN^OS 1 (5)-6-Ethylene-deactivated amino-1-keto-H 0-ylamino)hexan-2-ylamino Ethyl ester (dmso-d6)d (ppm) 1H : 12.20 (s, 1H), 9.96 (s, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 3.5 Hz, 1H) , 7.21 (d, J=3.5 Hz, 1H), 4.21 (q, J=4.7 Hz, 1H), 3.98 (q, J=7.0 Hz, 2H), 3.44 (q, J=6.3 Hz, 2H), 2.36 (s, 3H), 1.72-1.49 (m, 4H), 1.48-1.27 (m, 2H), 1'16 (t, j=7.〇Hz, 3H). LRMS (ESI): (calculated) 358 2 (measured value) 359.2 (MH) + 25 31 C and H HNv^OS (S)-2-acetamido-6-ethyl thioanthramine-N_(P-propazol-2-yl-) Indoleamine (dmso-d6) d (ppm) 1H: 9.96 (s, 1H), 8.22 (d, J = 7.2 Hz, 1H), 7.47 (d, J = 3.5 Hz, 1H), 7.21 (d, J = 3.7 Hz, 1H), 4.46-4.40 (m, 1H), 3.44 (q, J=5.'9 Hz, 2H), 2.36 (s, 3H), 1.86 (s, 3H), 1.77-1.50 (m, 4H), 1.50-1.22 (m, 2H). LRMS (ESI): (calc.) 328 (found) 329.2 (MH)+ 134026-2 -158- 200916447 Example Compound Structural Characterization 26 32 H HNv^OS 0 N 1 (S)-N-(6-ethanethioguanidino-1-one-1-(pyrazol-2-ylamino)hexane-2-yl)-1-methylhexanitro Pyridin-4-carboxamide (dmso-d6) d (ppm) 1H 12.20 (s, 1H), 9.97 (s, 1H), 8.02 (m, 1H), 7.44 (d, J = 3.5 Hz, 1H), 7.14 ( s, 1H), 4.40 (d, J=4.5 Hz, 1H), 3.43 (q, J=8.0 Hz, 2H), 2.75 (d, J=ll Hz, 2H), 2.36 (s, 3H), 2.22- 2.10 (m, 1H), 2.12 (s, 3H), 1.80 (t, J=12 Hz, 2H), 1.76-1.43 (m, 7H), 1.42-1.21 (m, 3H). LRMS (ESI) ·· (calculated) 411.2 (measured value) 412.3 (MH) + 27 33 H HN^OS \ NH P MeO (S)-6-ethanethioguanamine-2-(2-(5-decyloxy-2) -mercapto-1H-4ind-3-yl)acetamido)-N-0-pyrazol-2-yl)hexylamine (dmso-d6) d (ppm) 1H: 12.22 (s, 1H), 10.59 (s,1H), 9.94 (s,1H), 8.30 (d, J=7.4 Hz, 1H), 7.46 (d, J=3.5 Hz, 1H), 7.21 (d, J=3.7 Hz, 1H), 7.08 (d, J=8.8 Hz, 1H), 7.01 (d, J=2.3 Hz, 1H), 6.58 (dd, J=8.6, 2.3 Hz, 1H), 4.45 (q, J=4.3 Hz, 1H), 3.73 (s, 3H), 3.54-3.35 (m, 4H), 2.35 (s, 3H), 2.30 (s, 3H), 1.78-1.60 (m, 2H), 1.52 (qi, J = 7.4 Hz, 2H) , 1.43-1.21 (m, 2H). LRMS (ESI): (calculated) 487.2 (measured value) 488.3 (MH) + Figure 5

NHCbz .CH2N2.Et20 .HBr NHCbz 34 K2C03tTHF/H20 程序j | 1 1 程序j_ 1NHCbz .CH2N2.Et20 .HBr NHCbz 34 K2C03tTHF/H20 Procedure j | 1 1 Procedure j_ 1

1. TFA, DC Μ1. TFA, DC Μ

I~WM~I二硫基醋酸乙酯 NB3THF 2. 二硫基醋酸乙酯 NEt3,THF PhI~WM~I dithioacetate ethyl ester NB3THF 2. Dithioacetate ethyl ester NEt3, THF Ph

NHCbz rNHCbz r

NHCbz 37:實例28NHCbz 37: Example 28

39:實例29 159- 134026-2 200916447 實例28 (S)-5-乙烷硫醯胺基-1-(2-(苯基胺基 &gt;塞唑-4-基）戊基胺基甲酸 苄酯（37) 步驟1 : (S)-7-溴基-6-酮基-5-(爷氧羰基胺基）庚基胺基甲酸第 三-丁酯（34) 於〇°C下’將氯甲酸乙酯（0.505毫升，5.26毫莫耳）添加至 Z-Lys(Boc)-OH (2克，5.26毫莫耳）與三乙胺（0.806毫升，5.78毫 莫耳）在THF (10.51毫升）中之溶液内，然後，使反應物慢慢 溫熱至室溫’並搜拌1小時。使混合物冷卻至，且添加 重氮甲烧（2.5M ’ 10.51毫升’ 26.3毫莫耳）在_中之溶液，及 將所形成之黃色溶液在Ot：下攪拌3小時。以水稀釋反應物， 並以EtOAc萃取（3x)。使有機萃液脫水乾燥（Na2S〇4)，過濾， 及療發，並使所形成之重氮基酮再溶於醚（1〇.5毫升）中，且 冷卻至0°C。分次添加48%HBr在水中之溶液（〇571毫升，1〇5 毫莫耳），歷經1小時，並於反應完成後，以飽和 其泮滅，且以EtOAc萃取。使有機層以Ν%5〇4脫水乾燥，過 濾，及蒸發。使殘留物藉矽膠層析，以己烷中之Et〇Ac (20-40%)純化，而得α溴基酮34 (1 78克，74%),為白色固體。 LRMS 卿）：（計算值）457.3 (實測值）479 1，481 2 (驗)+ 步驟2 :⑸-5-(第三-丁氧幾基胺基）·Η2 (苯基胺基）碟〇坐冰幻 戍基胺基甲酸苄酯（35) 一將34 (0.200克’ 0.437毫莫耳）與苯基硫脲(73 2毫克，讀 毛莫耳）在乙醇（1.74毫升）中之溶液，於室溫下授拌16小時。 蒸發溶劑，並使殘留物藉石夕膠層析…烧中之職 134026-2 -160- 200916447 (20-50%)純化’而得35 (0.106克，47%)，為白色固體。LRMs (ESI):(計算值）510.6 (實測值）511 4 (MH)+ 步驟3 : (S)-5-胺基-1-(2-(苯基胺基 &gt;塞唑-4-基）戊基胺基曱酸节 酯（36) 按照一般程序B，而得粗製36 (86.0毫克，100%)，為黃色 泡沐物。LRMS (ESI):(計算值）41〇.5 (實測值）411.3 (MH)+ 步驟4 :⑸-5-乙烷硫醯胺基+(2-(苯基胺基 &gt;塞唑_4_基）戊基胺 基甲酸芊酯（37) 於〇°C下，將三乙胺（58.4微升，0.419毫莫耳）與二硫基醋 酸乙酯（36.1微升，0.314毫莫耳）添加至36 (86.0毫克，0.209毫 莫耳）在THF (838微升）中之溶液内，並將反應物攪拌16小 時。以水中之10% HC1稀釋混合物，且以EtOAc萃取（3x)，並 使有機萃液脫水乾燥（Na2S04)，過濾，及蒸發，且使殘留物 藉矽膠層析，以己烷中之EtOAc (40-80%)純化，而得37 (24.5 毫克，25%)，為白色固體。（CD3OD) (5 (ppm) 1H : 7.53 (d, J=84 Hz, 2H), 7.36-7.32 (m, 3H), 7.30-7.25 (m, 3H). 6.97-6.93 (m, 1H), 6.45 (s, 1H), 5.13-5.05 (m, 2H), 4.65-4.61 (m, 1H), 3.56 (t, J=7.2 Hz, 2H), 2.43 (s, 3H), 2.00-1.94 (m, 1H), 1.81-1.74 (m, 1H), 1.73-1.64 (m, 2H), 1.47-1.37 (m，2H). LRMS (ESI):(計算值）468.6 (實測值）469.3 (MH)+. 實例29 ⑸-5-乙院硫酿胺基-1-(2-苯基-1H-蜂啥-4_基）戊基胺基甲酸苄 酯（39) 步驟1: (S)-5-(第三-丁氧羰基胺基）ι·(2_苯基-1H-咪唑-4-基）戊基 胺基曱酸苄酯（38) 134026-2 • 161 - 200916447 將苯并醯亞胺醯胺鹽酸鹽（〇.188毫克，uo毫莫耳）添加至 34 (0.550克，1.20毫莫耳）在THF (4.0毫升）中之溶液内，接著 為碳酸鉀（0.332克，2.40毫莫耳）在水（〇 5〇〇毫升）中之溶液， 並將反應物加熱至60°C，且攪拌16小時。於冷卻後，將反 應物以水稀釋，並以EtOAc萃取，且使有機層以Na2S〇4脫水 乾燥’過濾，及蒸發，並使殘留物藉矽膠層析，以已炫中 之EtOAc (30-80%)純化，而得38 (0.107克，18%)，為白色固體。 LRMS (ESI):(計算值）478.5 (實測值）479.4 (MH)+ 步驟2 : (S)-5-乙烧硫醯胺基-1-(2-苯基-1H-咪峻-4-基）戊基胺基 曱酸苄酯（39) 按一般程序B中所述，將化合物38 (0.107克，0.224毫莫耳） 以TFA/DCM之25%溶液（1毫升）處理，並獲得粗製胺，為普 色泡沫物（51毫克，60%)。LRMS (ESI):(計算值）378.4 (實測 值）379.3 (MH)+. 按一般程序K中所述，於THF (0.539毫升）中之胺（51毫克， 0.135毫莫耳）内，在〇°C下添加三乙胺（37.6微升，0.270毫莫 耳）與二硫基醋酸乙酯（23.1微升，0.202毫莫耳）。在藉梦膠 層析’以己烷中之EtOAc (40-80%)純化後，獲得所要之化合 物 39 ’ 為白色固體（15 毫克，25%)。（CD30D) 5 (ppm) 1H : 7 82 (d, J=7.2 Hz, 2H), 7.45-7.41 (m, 2H), 7.39-7.27 (m, 6H), 6.98 (s, 1H), 5.13-5.05 (m, 2H), 4.75-4.72 (m, 1H), 3.57-3.53 (m, 2H), 1.96-1.92 (m, 1H), 1.84-1.80 (m, 1H), 1.70-1.64 (m, 2H), 1.48-1.40 (m, 2H). LRMS (ESI):(計算值）436.5 (實測值）437.3 (MH)+ 134026-2 •162- 200916447 圖式639: Example 29 159-134026-2 200916447 Example 28 (S)-5-Ethylthioguanidino-1-(2-(phenylamino)pyrazole-4-yl)pentylaminocarbamate Ester (37) Step 1: (S)-7-Bromo-6-keto-5-(anthoxycarbonylamino)heptylcarbamic acid tert-butyl ester (34) at 〇 ° C Ethyl chloroformate (0.505 ml, 5.26 mmol) was added to Z-Lys(Boc)-OH (2 g, 5.26 mmol) and triethylamine (0.806 mL, 5.78 mmol) in THF (10.51 ml) In the solution, then, the reaction was slowly warmed to room temperature' and mixed for 1 hour. The mixture was allowed to cool until the addition of diazo-methyl (2.5 M ' 10.51 ml ' 26.3 mmol) in _ The solution was stirred and the yellow solution formed was stirred for 3 h at EtOAc. The mixture was diluted with water and extracted with EtOAc (3×). The organic extract was dried (Na2S 〇4), filtered, and treated And the formed diazonal ketone was redissolved in ether (1. 5 ml) and cooled to 0 ° C. A solution of 48% HBr in water was added in portions (〇571 ml, 1〇5 mmol) Ear), after 1 hour, and after the reaction is completed, to saturate it And extracted with EtOAc. The organic layer was dried with EtOAc EtOAc EtOAc EtOAc EtOAc Bromocarbone 34 (1 78 g, 74%) as a white solid. LRMS (): (calc.) 457.3 (measured) 479 1,481 2 (test) + step 2: (5)-5- (third - Butoxyxylamino)·Η2 (phenylamino) disc 〇 冰 戍 戍 胺 ( (35) One will be 34 (0.200 g '0.437 mmol) with phenyl thiourea (73 2 A solution of milligrams, read the molars in ethanol (1.74 ml), was stirred at room temperature for 16 hours. The solvent was evaporated, and the residue was purified eluting with EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc LRMs (ESI): (calculated) 510.6 (found) 511 4 (MH) + Step 3: (S)-5-amino-1-(2-(phenylamino)&gt; Amyl decyl decanoate (36) According to the general procedure B, crude 36 (86.0 mg, 100%) was obtained as a yellow foam. LRMS (ESI): (calculated) 41 〇.5 (measured) Value) 411.3 (MH) + Step 4: (5)-5-Ethylthioguanidinyl + (2-(phenylamino)&gt;------- 4-yl)-pentylaminocarboxylate (37) Triethylamine (58.4 μl, 0.419 mmol) and ethyl dithioacetate (36.1 μL, 0.314 mmol) were added to 36 (86.0 mg, 0.209 mmol) in THF at ° C. The mixture was stirred for 16 hours. The mixture was diluted with EtOAc (EtOAc) (EtOAc) (EtOAc) The residue was purified by EtOAc (EtOAc) elut elut elut elut elut elut elut elut d, J=84 Hz, 2H), 7.36-7.32 (m, 3H), 7.30-7.25 (m, 3H). 6.97-6.93 (m, 1H), 6.45 (s, 1H), 5.13-5.05 (m , 2,,,,, 1.73-1.64 (m, 2H), 1.47-1.37 (m, 2H). LRMS (ESI): (calculated) 468.6 (measured value) 469.3 (MH)+. Example 29 (5)-5-B. Benzyl 1-(2-phenyl-1H-bee-4-yl)pentylaminocarboxylate (39) Step 1: (S)-5-(T-Butoxycarbonylamino) ι·( 2_Phenyl-1H-imidazol-4-yl)pentylamino benzyl decanoate (38) 134026-2 • 161 - 200916447 benzoindoleimine hydrochloride (〇.188 mg, uo 毫Mole) was added to a solution of 34 (0.550 g, 1.20 mmol) in THF (4.0 mL), followed by potassium carbonate (0.332 g, 2.40 mmol) in water (5 mL) The solution was heated to 60 ° C and stirred for 16 hours. After chilling, the reaction was diluted with EtOAc (EtOAc) eluting eluting eluting 80%) was purified to give 38 (0.107 g, 18%) as white solid. LRMS (ESI): (calculated) 478.5 (found) 479.4 (MH) + Step 2: (S)-5-ethyl thioanthramine-1-(2-phenyl-1H-mi Benzylaminopentanoic acid benzyl ester (39) Compound 38 (0.107 g, 0.224 mmol) was treated with a 25% solution of TFA/DCM (1 mL) as described in General Procedure B and obtained crude. The amine was a plain color foam (51 mg, 60%). LRMS (ESI): (calcd.) 378.4 (found): 379.3 (MH) +. ??? Triethylamine (37.6 μl, 0.270 mmol) and ethyl dithioacetate (23.1 μL, 0.202 mmol) were added at °C. After purification by EtOAc (40-80%) eluting EtOAc (EtOAc) (CD30D) 5 (ppm) 1H : 7 82 (d, J=7.2 Hz, 2H), 7.45-7.41 (m, 2H), 7.39-7.27 (m, 6H), 6.98 (s, 1H), 5.13-5.05 (m, 2H), 4.75-4.72 (m, 1H), 3.57-3.53 (m, 2H), 1.96-1.92 (m, 1H), 1.84-1.80 (m, 1H), 1.70-1.64 (m, 2H) , 1.48-1.40 (m, 2H). LRMS (ESI): (calculated) 436.5 (measured value) 437.3 (MH) + 134026-2 • 162- 200916447 Figure 6

43:實例30 實例30 ⑻-5-乙烷硫醯胺基-1-(5-苯基·1Η•味唾·2_基）戊基胺基甲酸苄 酯(43) 步驟1 :⑸-2-(辛氧羰基胺基）各乙烷硫醯胺基己酸甲酯（40) 按一般程序G中所述，於〇°C下，將（S)-6-胺基-2-(罕氧羰基 胺基）己酸曱酯.HC1 (2.5克，7.56毫莫耳）在THF (30.2毫升）中 之溶液，以Et3 N (3.16毫升，22.67毫莫耳）與二硫基醋酸乙酯 (0:910毫升，7.94毫莫耳）處理。在藉矽膠層析，以己烧中之 KOAc (20%至60%)純化後，獲得化合物40，為無色油(2.8克， 定量）。LRMS (ESI):(計算值）352.5 (實測值）353.2 (MH)+ 步驟2 : (S)-2-(苄氧幾基胺基）-6-乙燒硫酸胺基己酸(41) 於酯 40 (2.66 克，7.56 毫莫耳）在 THF (7 5 毫升）、Me〇H (7 5〇 毫升）及水（7_50 *升）中之經攪拌溶液内，在〇。〇下添加Li〇H 單水合物（1.269克，30.2毫莫耳）。將所形成之溶液在室溫下 攪拌1小時，然後，將其處理至乾涸，添加1Μ Ηα至pH〜3， 並以萃取混合物’且使有機萃液以娜〇4脫水乾燥， 134026-2 -163· 200916447 過濾，及濃縮，留下白色固體，將其以本身使用於下一步 驟。LRMS (ESI):(計算值）338.4 (實測值）339.2 (MH)+ 步驟3 : (S)-6-乙烷硫醯胺基-1-酮基-1-(2-酮基-2-苯基乙胺基） 己烷-2-基胺基甲酸芊酯（42) 於41 (254毫克，0.75毫莫耳）在DMF (3.75毫升）中之經攪拌 溶液内，添加α-胺基-苯乙酮鹽酸鹽（154毫克，0.90毫莫耳）、 Et3N (125微升，0.90毫莫耳）、EDC (187毫克，0.975毫莫耳）， 接著為HOBT (149毫克，0.975毫莫耳），並將混合物在室溫下 攪拌16小時。添加飽和Na2C03，並以EtOAc萃取混合物，且 將萃液以鹽水洗滌，以MgS04脫水乾燥，過濾，及濃縮，並 使殘留物藉層析，以己烷中之EtOAc (10%至100% EtOAc)純 化，而得42，為白色油性固體（186毫克，54.4%產率）。LRMS (ESI):(計算值）455.6 (實測值）456.3 (MH)+ ; 478.3 (MNa)+. 步驟4 : (S)-5-乙烷硫醯胺基-1-(5-苯基-1H-咪唑-2-基）戊基胺基 甲酸芊酯（43) 於42 (186毫克，0.408毫莫耳）在AcOH (2.041毫升）中之經攪 拌溶液内，添加醋酸銨（787毫克，10.21毫莫耳），並將混合 物在100°C下攪拌16小時。添加飽和Na2C03溶液，並以EtOAc 萃取混合物，且使萃液以MgS04脫水乾燥，過濾，及濃縮， 並使殘留物藉預備之HPLC純化（Aquasil C18，5-95% MeOH/ H20)，而得 43，為白色固體（29 毫克，16.3%)。（dmso-d6) d(ppm) 1H ： 11.84 (s, 1H), 9.96 (s, 1H), 7.73-7.71 (m, 2H), 7.66 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.36-7.15 (m, 7H), 7.16 (t, J=7.2 Hz, 1H), 5.04 (d, J=8.2 Hz, 2H), 4.64 (q, J=6.3 Hz, 1H), 3.44 (q, J=6.3 Hz, 2H), 2.36 (s, 3H), 1.97-1.72 134026-2 -164- 200916447 (m，2H)，1.56 (五重峰，J=6.5 Hz, 2H), 1.42-1.22 (m, 2H). LRMS (ESI):(計算值）436.2 (實測值）437.3 (MH)+ 圖式743: Example 30 Example 30 (8)-5-Ethylthioguanidino-1-(5-phenyl·1Η•味撒·2_yl)benzyl amyl amide (43) Step 1: (5)-2 -(Oxyloxycarbonylamino)methyl thioglycolyl hexanoate (40) (S)-6-Amino-2-(H), as described in General Procedure G, at 〇 °C Oxycarbonylamino) decanoic acid hexyl ester. HCl (2.5 g, 7.56 mmol) in THF (30.2 mL), Et3N (3.16 mL, 22.67 mmol) and ethyl dithioacetate ( 0: 910 ml, 7.94 mmoles). The compound 40 was obtained as a colorless oil (2.8 g, quantitative) after purification from EtOAc (20% to 60%). LRMS (ESI): (calculated) 352.5 (found) 353.2 (MH) + Step 2: (S)-2-(benzyloxyamino)-6-ethylsulfonic acid aminohexanoic acid (41) Ester 40 (2.66 g, 7.56 mmol) in a stirred solution of THF (75 mL), Me 〇H (75 mL) and water (7-50 liters). Li〇H monohydrate (1.269 g, 30.2 mmol) was added under the arm. The resulting solution was stirred at room temperature for 1 hour, then, it was treated to dryness, 1 Μ Ηα was added to pH 〜3, and the mixture was extracted, and the organic extract was dehydrated and dried with Nat 4, 134026-2 - 163· 200916447 Filtration, and concentration, leaving a white solid which was used in the next step. LRMS (ESI): (calculated) 338.4 (found) 339.2 (MH) + Step 3: (S)-6-Ethylthioguanidin-1-one-1-(2-keto-2- Phenylethylamino) hexane-2-ylaminocarbazate (42) In a stirred solution of 41 (254 mg, 0.75 mmol) in DMF (3.75 mL) Acetophenone hydrochloride (154 mg, 0.90 mmol), Et3N (125 μl, 0.90 mmol), EDC (187 mg, 0.975 mmol), followed by HOBT (149 mg, 0.975 mmol) The mixture was stirred at room temperature for 16 hours. The mixture was extracted with EtOAc (EtOAc) (EtOAc) Purification gave 42 as a white oily solid (186 mg, 54.4% yield). LRMS (ESI): (calcd.) 455.6 (found) 456.3 (MH)+; 478.3 (MNa)+. Step 4: (S)-5-Ethylthiolamino-1-(5-phenyl- Addition of ammonium acetate (787 mg, 10.21) to a stirred solution of 42 (186 mg, 0.408 mmol) in AcOH (2.041 mL). Milligrams) and the mixture was stirred at 100 ° C for 16 hours. A saturated Na.sub.2C.sub.3 solution was added, and the mixture was extracted with EtOAc. EtOAc EtOAc (EtOAcjjjjjjjjj , as a white solid (29 mg, 16.3%). (dmso-d6) d(ppm) 1H : 11.84 (s, 1H), 9.96 (s, 1H), 7.73-7.71 (m, 2H), 7.66 (d, J=8.4 Hz, 1H), 7.46 (s, 1H), 7.36-7.15 (m, 7H), 7.16 (t, J=7.2 Hz, 1H), 5.04 (d, J=8.2 Hz, 2H), 4.64 (q, J=6.3 Hz, 1H), 3.44 ( q, J=6.3 Hz, 2H), 2.36 (s, 3H), 1.97-1.72 134026-2 -164- 200916447 (m,2H), 1.56 (five peaks, J=6.5 Hz, 2H), 1.42-1.22 (m, 2H). LRMS (ESI): (calculated) 436.2 (measured value) 437.3 (MH) + Figure 7

實例35 (S)-l-(4,5-二苯基-1H-咪唑-2-基）-5-乙烷硫醯胺基戊基胺基甲 酸苄酯（49) 步驟1: (2S)-2-(苄氧羰基胺基）-6-乙烷硫醯胺基己酸2-酮基-1,2-二苯基乙酯（48) 於41 (104毫克，0.307毫莫耳）在DMF (1.537毫升）中之經攪 拌溶液内，添加安息香（78毫克，0.369毫莫耳）、DMAP (7.51 毫克，0.061毫莫耳）、EDC (77毫克，0.400毫莫耳），接著為 HOBT (61.2毫克，0.4〇0毫莫耳）。將混合物在室溫下攪拌16 小時，然後添加H20，並將混合物以EtOAc萃取，以鹽水洗 蘇，以MgS04脫水乾燥，過渡，及濃縮，且使殘留物藉層析， 以己烷中之EtOAc (20%至60%)純化，提供48，為白色固體（80 毫克，48.9% 產率）。LRMS (ESI):(計算值）532.7 (實測值）533.3 (MH)+ ； 555.3 (MNa)+ 步驟2: (S)-1-(4,5-二苯基-1H-咪唑-2-基）-5-乙烷硫醯胺基戊基胺 基曱酸苄酯（49) 於48 (80毫克，0.150毫莫耳）在甲苯（1.001毫升）中之經攪拌 134026-2 165· 200916447 溶液内，在室溫下添加醋酸銨（116毫克，1.502毫莫耳），並 將混合物在100°C下攪拌4小時。藉由層析，以己烷中之EtOAc (20%至80%) —般處理及純化，獲得被未反應之48污染之 49。藉預備之HPLC進一步純化（5-95% Me0H/H20)，獲得49， 為白色固體（5 毫克，6.5%)(dmso-d6) d(ppm) 1H : 12.19 (s，1H)，9.96 (s, 1H), 7.64 (d, J=8.6 Hz, 1H), 7.44-7.19 (m, 15H), 5.04 (q, J=5.9 Hz, 2H), 4.68 (q, J=6.3 Hz, 1H), 3.45 (q, J=6.7 Hz, 2H), 2.35 (s, 3H), 1.98-1.74 (m, 2H), 1.57 (qi，J=6.7 Hz, 2H)，1.48-1.25 (m, 2H). LRMS (ESI):(計算值） 512.2 (實測值）513.4 (MH)+ 圖式8Example 35 (S)-l-(4,5-Diphenyl-1H-imidazol-2-yl)-5-ethanethiobenzylaminopentylcarbamate (49) Step 1: (2S) 2-(Benzyloxycarbonylamino)-6-ethanethioguanidinohexanoic acid 2-keto-1,2-diphenylethyl ester (48) at 41 (104 mg, 0.307 mmol) In a stirred solution of DMF (1.537 ml), add benzoin (78 mg, 0.369 mmol), DMAP (7.51 mg, 0.061 mmol), EDC (77 mg, 0.400 mmol), followed by HOBT ( 61.2 mg, 0.4〇0 mmol). The mixture was stirred at room temperature for 16 h, then H20 was added and EtOAc was evaporated. EtOAc EtOAc. Purification (20% to 60%) afforded 48 as a white solid (yield: 80 mg, 48.9% yield). LRMS (ESI): (calc.) 532.7 (found) 533.3 (MH)+; 555.3 (MNa)+ Step 2: (S)-1-(4,5-diphenyl-1H-imidazol-2-yl Benzyl-5-ethanethioguanamine amylamine decanoate (49) in 48 (80 mg, 0.150 mmol) in toluene (1.001 mL) stirred in 134026-2 165 · 200916447 solution Ammonium acetate (116 mg, 1.502 mmol) was added at room temperature, and the mixture was stirred at 100 ° C for 4 hours. By chromatography and purification with EtOAc (20% to 80%) in hexanes, 49 was obtained from unreacted 48. Further purification by preparative HPLC (5-95% Me0H/H20) gave 49 as a white solid (5 mg, 6.5%) (dmso-d6) d (ppm) 1H: 12.19 (s, 1H), 9.96 (s , 1H), 7.64 (d, J=8.6 Hz, 1H), 7.44-7.19 (m, 15H), 5.04 (q, J=5.9 Hz, 2H), 4.68 (q, J=6.3 Hz, 1H), 3.45 (q, J=6.7 Hz, 2H), 2.35 (s, 3H), 1.98-1.74 (m, 2H), 1.57 (qi, J=6.7 Hz, 2H), 1.48-1.25 (m, 2H). LRMS ( ESI): (calculated value) 512.2 (measured value) 513.4 (MH) + Figure 8

CbzCbz

Dess-Martin -N、n 過碘烷 Boc ---- 52 CH2CI2Dess-Martin -N, n periodane Boc ---- 52 CH2CI2

,%〇c 叫,Me〇H 程序S Cbz' ，NH 53 f3c, %〇c called, Me〇H program S Cbz' , NH 53 f3c

BrBr

BH3 ,thf 程序RBH3, thf program R

Boc CbzxBoc Cbzx

Br NH3，MeOH f3c I 程序τ 乙二醛三聚二水合物 「程序U 一]Br NH3, MeOH f3c I program τ glyoxal trimeric dihydrate "program U one]

Br n H HN- /NU- 57 Na2S〇3，BU4NSO4 二氧陸園，h2o γ \八〜n、b〇c HNsBr n H HN- /NU- 57 Na2S〇3, BU4NSO4 Dioxere, h2o γ \8~n, b〇c HNs

Cbz 54 程序w 1.TFA,CH2CI2 2, HN\Cbz 54 program w 1.TFA, CH2CI2 2, HN\

Cbz 55:實例38Cbz 55: Example 38

V KCbz 58 1.TFA,CH2C12V KCbz 58 1.TFA, CH2C12

2. Et3N S 〜THF2. Et3N S ~ THF

Cbz 59:實例39 134026-2 -166 - 200916447 實例38 ⑸-5-乙烷硫醯胺基-1-(5·(三氟曱基）-1Η·咪唑·2-基）戊基胺基甲 酸芊酯（55) 步驟1 : (S)-6-(第三-丁氧羰基胺基）-1-羥基己-2-基胺基曱酸苄 酯（52) 於 Z-Lys(Boc)-OH (5 克，13.14 毫莫耳）在 THF (26.3 毫升）中之 經攪拌溶液内，在0°C下逐滴添加BH3.THF (1M ,在THF中， 28.9毫升，28.9毫莫耳）。將所形成之溶液在〇。〇下攪拌3〇分 鐘’然後在室溫下2小時。使反應物冷卻至〇°c，以MeOH使 反應淬滅，並處理至乾涸，且使殘留物藉層析，以己烧中 之EtOAc (20%至60% EtOAc)純化，獲得52，為無色油。LRMS (ESI):(計算值）366.5 (實測值）389.4 (MNa)+ 步驟2 : (S)-6-(第三-丁氧羰基胺基）4_酮基_己烷_2_基胺基甲酸 苄酯（53) 於52 (3.5克，9.55毫莫耳）在0^(^(38.2毫升）中之經攪拌 溶液内，在室溫下添加Dess-Martin過碘烷（5.06克，11.94毫莫 耳），並將所形成之溶液在室溫下攪拌〗小時。添加飽和 NaeO3溶液，且將CH/l2萃液以飽和NaHC〇3溶液，接著以鹽 水洗滌，以MgS〇4脫水乾燥，過濾，及濃縮。獲得粗製醛幻， 為無色油性固體，並以本身使用於下一步驟（3176克，9ι%卜 步驟3 : (S)-5-(第三-丁氧羰基胺基H_(5_(三氟甲基）·1Η_咪唑-基）戊基胺基曱酸芊酯（54) 於U-二溴基-3,3,3-三氟丙酮（163毫克，〇 6〇4毫莫耳）在 MeOH (2.195毫升）中之經攪拌溶液内’在室溫下添加氨溶液 134026-2 •167· 200916447 (7N，在MeOH中，0.392毫升，2.74毫莫耳），接著為53 (〇 549 毫升’ 0.549毫莫耳’在甲醇中之1M溶液）。將所形成之溶 液在彳政波中’於100 C下擾拌5分鐘。蒸發MeOH，並添加餘 和NaHC〇3溶液，且將混合物以Et0Ac萃取。於正常處理後， 使殘留物藉層析’以己烷中之EtOAc (20%至60%)純化，而得 咪唑54，為白色固體。LRMS (ESI):(計算值）470.5 (實測值） 471.3 (MH)+ 步驟4: (S)-5-乙烷硫醯胺基-i_(5-(三氟曱基）_1H_咪唑冬基）戊基 胺基甲酸苄酯（55) 按一般程序B中所述，於室溫下，將THF (0.737毫升）中之 化合物54 (52毫克，0.111毫莫耳）以TFA (0.213毫升，2.76毫莫 耳）處理。獲得粗製胺，為淡黃色油，並以本身使用於下一 步驟。LRMS (ESI):(計算值）370.4 (實測值）371.3 (MH)+Cbz 59: Example 39 134026-2 -166 - 200916447 Example 38 (5)-5-Ethylthioguanidino-1-(5·(trifluoromethyl)-1Η·imidazole·2-yl)pentylaminocarboxylic acid Oxime ester (55) Step 1: (S)-6-(T-Butoxycarbonylamino)-1-hydroxyhexanylamino phthalic acid benzyl ester (52) in Z-Lys(Boc)- OH (5 g, 13.14 mmol) in THF (26.3 mL), EtOAc (EtOAc,EtOAc. The resulting solution was placed in a crucible. Stir under the arm for 3 〇 minutes and then at room temperature for 2 hours. The reaction was cooled to EtOAc (EtOAc) EtOAc (EtOAc m. oil. LRMS (ESI): (calculated) 366.5 (found) 389.4 (MNa) + Step 2: (S)-6-(T-butoxycarbonylamino) 4-keto-hexane-2-amine Benzyl carbamate (53) was added to a stirred solution of 52 (3.5 g, 9.55 mmol) in EtOAc (38.2 mL). Mol), and the resulting solution was stirred at room temperature for one hour. A saturated NaeO3 solution was added, and the CH/l2 extract was washed with saturated NaHC 3 solution, followed by brine, and dried with MgS 4 . Filtration, and concentration. Obtained crude aldehydes as a colorless oily solid, and used in the next step (3176 g, 9% by weight) Step 3: (S)-5-(T-butoxycarbonylamino H_( 5_(Trifluoromethyl)·1Η-imidazolyl-yl)pentylamino decanoate (54) in U-dibromo-3,3,3-trifluoroacetone (163 mg, 〇6〇4 毫Mol) in a stirred solution of MeOH (2.195 ml) - at room temperature, add ammonia solution 134026-2 • 167. 200916447 (7N in MeOH, 0.392 mL, 2.74 mmol), followed by 53 ( 〇 549 ml '0.549 mmol' in methanol 1M solution). The resulting solution was scrambled for 5 minutes at 100 C in a limpid wave. Evaporate MeOH, add the remaining NaHC〇3 solution, and extract the mixture with Et0Ac. After normal treatment, make a residue. Purification by chromatography EtOAc (20% to 60%) eluted elut elut elut elut elut elut elut elut elut elut : (S)-5-ethanethioguanamine-i-(5-(trifluoromethyl)_1H-imidazolidyl) amyl carbamic acid benzyl ester (55) as described in General Procedure B, in the chamber Compound 54 (52 mg, 0.111 mmol) in THF (0.737 mL) was obtained eluted elute elute elut One step. LRMS (ESI): (calculated) 370.4 (measured value) 371.3 (MH)+

按關於一般程序G所述，於THF (1.11毫升）中之得自上文 之胺（41.1毫克’ am毫莫耳）内，在室溫下添加Et3N (30.9微 升’ 0.222毫莫耳）’接著為二硫基醋酸乙酯（14.〇i微升，0.122 毫莫耳）’並在以己烷中之EtOAc (20%至100%)層析後，獲得 化合物 55，為白色固體。（dmso-d6) &lt;5 (ppm) 1H: 12.49 (s，1H)，9.93 (s, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.62 (d, J=1.2 Hz, 1H), 7.34-7.27 (m, 5H), 5.02 (q, J=9.8 Hz, 2H), 4.61 (q, J=5.7 Hz, 1H), 3.43-3.39 (m, 2H), 2.34 (s, 3H),1.91-1.65 (m, 2H), 1.59-1.48 (m, 2H), 1.40-1.19 (m, 2H). LRMS (ESI):(計算值）428.1 (實測值）429,2 (MHH 實例39 (S)-l-(S-漠基-1H-咪唑-2-基）-5-乙烷硫醯胺基戊基胺基曱酸苄 134026-2 -168- 200916447 酯（59) 步驟1 : (S)-5-(第三-丁氧羰基胺基）-1-(1Η-咪唑-2-基）戍基胺基 曱酸苄酯（56) 於53 (1克，2.74毫莫耳）在MeOH (7毫升）中之經攪拌溶液 内，在室溫下添加乙二醛三聚體二水合物（0.288克，1.372毫 莫耳），接著逐滴添加氨溶液（7N，在MeOH中，1.960毫升， 13.72毫莫耳），並將所形成之溶液在室溫下攪拌16小時。蒸 發溶劑，且使殘留物藉層析（0%至15% MeOH在DCM中）純 化，而得56 (585毫克，53%)，為白色固體。LRMS (ESI):(計 算值）4〇2.5 (實測值）403Λ (MH)+ 步驟2 : (S)-5-(第三-丁氧羰基胺基）-l_(4,5-二溴基-1H-咪唑-2-基） 戊基胺基甲酸苄酯（57) 於56 (143毫克，0.355毫莫耳）在DMF (1.776毫升）中之經攪 拌溶液内，在〇°C下添加NBS (56.9毫克，0.320毫莫耳），並使 所形成之溶液溫熱至室溫，且攪拌16小時，使混合物冷卻 至0°C，並添加更多NBS (56.9毫克，0.320毫莫耳），且在0°C 下30分鐘後，反應已完成。添加飽和NaHC03溶液，並將混 合物以EtOAc萃取，以MgS04脫水乾燥，過濾，及濃縮，且 使殘留物藉層析，以己烧中之EtOAc (20%至60%)純化，而得 57 (90 毫克，45.2%)，為白色固體。LRMS (ESI):(計算值）560.3 (實測值）561.2 (MH)+ 步驟3 : (S)-5-(第三-丁氧羰基胺基）-1-(4-溴基-1H-咪唑-2-基）戊 基胺基甲酸苄酯（58) 於57 (150毫克，0.268毫莫耳）在二氧陸圜（2.142毫升）與H20 134026-2 -169- 200916447 ⑴.536毫升）t之經授拌溶液内，在室溫下添加亞硫酸納（挪 耄克，2.68毫莫耳）與氫硫酸四丁基銨（182毫克，μ%毫莫 耳）。將所形成之溶液在10(rc下攪拌2天，但主要為起始物 質’故將混合物在微波中，於鳩。c下加熱5分鐘；在赋 下2分鐘；接著在軟下15分鐘，以供反應逹到完成。添 加水，且將混合物以Et〇Ac萃取，以MgS〇4脫水乾燥，過濾， 及濃縮，並使殘留物藉層析，以己烷中之Et〇Ac (1〇%至6〇%) 純化’而知58 (39耄克’ 30.3%)，為白色固體。LRMS卿）： (計算值）482.1 (實測值）483.3 (MH)+ 步驟4 · (S)-l-(5-漠基-1H-咪唑-2-基）-5-乙烷硫醯胺基戊基胺基 曱酸苄酯（59) 按一般程序B中所述，於室溫下，將THF (〇·81毫升）中之 化合物58 (39毫克，0.081毫莫耳）以TFA (0.156毫升，2.03毫莫 耳）處理。以定量產率獲得粗製胺，為淡黃色固體，並以本 身使用於下一步驟。 按關於一般程序G所述，於THF (0.81毫升）中之得自上文 之胺（30.9毫克，〇·〇81毫莫耳）内，在室溫下添加Et3N (23微 升’ 0.16毫莫耳），接著為二硫基醋酸乙酯（1〇 2微升，〇 〇89 毫莫耳）’在以己烷中之EtOAc (10%至100%)層析後，獲得化 合物 59 (9 毫克，25.3%)，為白色固體。（dmso-d6) δ (ppm) 1H : 12.17 (s, 1H), 9.93 (s, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.38-7,28 (m, 5H), 7.11 (d, J=2.2 Hz, 1H), 5.03 (q, J=13 Hz, 2H), 4.54 (q, J=5.9 Hz, 1H), 3.40 (q, J=5.7 Hz, 2H), 2.34 (s, 3H), 1.87-1.63 (m, 2H), 1.57-1.45 (m, 2H), 1-37-1.18 (m，2H). LRMS (ESI):(計算值）438.1 ; 440.1 (實測值） 134026-2 -170· 200916447 439.2 ； 441.2 (MH)+ 圖式9 HO γ\ &quot; 'Cbz D 3 BocAdd Et3N (30.9 μl '0.222 mmol) at room temperature in THF (1.11 mL) from the above amine (41.1 mg 'am) This was followed by chromatography of EtOAc (20% to 100%) elute elute (dmso-d6) &lt;5 (ppm) 1H: 12.49 (s,1H), 9.93 (s, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.62 (d, J=1.2 Hz, 1H) , 7.34-7.27 (m, 5H), 5.02 (q, J=9.8 Hz, 2H), 4.61 (q, J=5.7 Hz, 1H), 3.43-3.39 (m, 2H), 2.34 (s, 3H), 1.91-1.65 (m, 2H), 1.59-1.48 (m, 2H), 1.40-1.19 (m, 2H). LRMS (ESI): (calculated) 428.1 (measured value) 429, 2 (MHH example 39 (S )-l-(S-Molyl-1H-imidazol-2-yl)-5-ethanethioguanamine pentylamino phthalic acid benzyl 134026-2 -168- 200916447 Ester (59) Step 1: (S -5-(T-Butoxycarbonylamino)-1-(1Η-imidazol-2-yl)nonylamino benzyl decanoate (56) at 53 (1 g, 2.74 mmol) in MeOH Glyceraldehyde trimer dihydrate (0.288 g, 1.372 mmol) was added to the stirred solution in (7 ml), followed by dropwise addition of ammonia solution (7N in MeOH, 1.960 ml) , 13.72 mmol, and the resulting solution was stirred at room temperature for 16 h. The solvent was evaporated and the residue was purified eluting elute , 53%), as a white solid. LRMS (ESI): (calculated) 4 〇 2.5 (measured 403Λ(MH)+ Step 2: (S)-5-(T-butoxycarbonylamino)-l-(4,5-dibromo-1H-imidazol-2-yl)benzyl amyl carboxylate Add the NBS (56.9 mg, 0.320 mmol) to a stirred solution of 56 (143 mg, 0.355 mmol) in DMF (1.776 mL). The solution was warmed to room temperature and stirred for 16 hours, the mixture was cooled to 0 ° C, and more NBS (56.9 mg, 0.320 mmol) was added, and after 30 minutes at 0 ° C, the reaction was completed. The NaHC03 solution was saturated, and the mixture was dried with EtOAc EtOAc EtOAc EtOAcjjjjjjjjj , 45.2%), as a white solid. LRMS (ESI): (calc.) 560.3 (found): 561.2 (MH) + Step 3: (S)-5-(T-butoxycarbonylamino)-1- Benzyl (4-bromo-1H-imidazol-2-yl)pentylaminocarboxylate (58) at 57 (150 mg, 0.268 mmol) in dioxane (2.142 mL) with H20 134026-2 169- 200916447 (1).536 ml) t in the mixing solution at room temperature Was added sodium sulfite (Norway Mao g, 2.68 mmol) and tetrabutylammonium hydrogen sulfate (182 mg, μ% Mo ear mmol). The resulting solution was stirred at 10 (rc for 2 days, but primarily starting material) so the mixture was heated in a microwave for 5 minutes at 鸠.c; for 2 minutes; then under soft for 15 minutes. After the reaction was completed, water was added, and the mixture was extracted with Et EtOAc, dried over MgSO 4 , filtered, and concentrated, %至6〇%) Purified 'King 58 (39 gram '30.3%) as a white solid. LRMS qing): (calculated) 482.1 (measured value) 483.3 (MH) + step 4 · (S)-l -(5-Mosyl-1H-imidazol-2-yl)-5-ethanethioguanamine amylamine benzyl decanoate (59) THF as described in General Procedure B at rt Compound 58 (39 mg, 0.081 mmol) in (yield: 81 mL) was treated with TFA (0.156 mL, 2.03 mmol). The crude amine was obtained as a light yellow solid in quantitative yield and used in the next step. Add Et3N (23 μl ' 0.16 mmol) at room temperature in THF (0.81 mL) from the above amine (30.9 mg, 〇·〇 81 mmol) as described in General Procedure G Ears, followed by ethyl dithioacetate (1 〇 2 μL, 〇〇89 mmol), after chromatography in EtOAc (10% to 100%) , 25.3%), as a white solid. (dmso-d6) δ (ppm) 1H : 12.17 (s, 1H), 9.93 (s, 1H), 7.67 (d, J=8.2 Hz, 1H), 7.38-7,28 (m, 5H), 7.11 ( d, J=2.2 Hz, 1H), 5.03 (q, J=13 Hz, 2H), 4.54 (q, J=5.9 Hz, 1H), 3.40 (q, J=5.7 Hz, 2H), 2.34 (s, 3H), 1.87-1.63 (m, 2H), 1.57-1.45 (m, 2H), 1-37-1.18 (m, 2H). LRMS (ESI): (calc.) 438.1 ; 440.1 (measured value) 134026- 2 -170· 200916447 439.2 ; 441.2 (MH)+ Figure 9 HO γ\ &quot; 'Cbz D 3 Boc

Cbz 5分鐘Cbz 5 minutes

MeOH H7i 10%Pd/C .MeOH H7i 10% Pd/C.

HN、 61 BocHN, 61 Boc

程序X NH, 62:實例40Procedure X NH, 62: Example 40

實例40 (S)-l-(5-(lH-&lt;哚-3-基）-1Η-咪唑-2-基）-5-(3-甲基硫脲基）戊基胺 基甲酸第三-丁酯（62) 步驟1 : (S)-5-(5-(lH-吲哚-3-基）-1Η-咪唑-2-基）-5-(第三-丁氧羰基 胺基）戊基胺基甲酸苄酯（60) 按一般程序P中所述，於Boc-Lys(Z)-OH (481毫克，1.265毫 莫耳）在DMF (3.834毫升）中之經授拌溶液内，添加2-經基 叫|哚-3-基）乙酮（266毫克，1.518毫莫耳）、DMAP (30.9毫 克，0.253毫莫耳）、EDC (315毫克，1.645毫莫耳），接著為HOBT (252毫克，1.645毫莫耳），在藉由層析，以EtOAc (10%至80%) 己烷純化後，獲得酯，為白色固體（284毫克，41.7%)。LRMS (ESI):(計算值）537.6 (實測值）560.4 (MNa)+. 於CH3CN (2.641毫升）中之酯（284毫克，0.528毫莫耳）内， 在室溫下添加醋酸銨（407毫克，5.28毫莫耳），並將溶液在 微波中，於160°C下攪拌5分鐘。在一般處理後，使殘留物 藉層析，以己烷中之EtOAc (20%至80%)純化，而得60 (147毫 克，53.8%)，為米黃色固體。LRMS (ESI):(計算值）517.6 (實 134026-2 -171 - 200916447 -5-胺基戊基胺基曱 測值）518.4 (ΜΗ)+· 步驟 2: (S)-l-(5-(lH-吲哚 酸第三-丁酯（61) -3-基HH-咪唑-2-基） 於MeOH (1.9毫升）中之60 (147毫克，0.284亳莫耳）内，在 室溫下添加Pd/C (10% Degussa型，30.2毫克，0 〇28毫莫耳）， 並將所形成之懸浮液在室溫及1大氣壓之氫氣下攪拌2小 時。於石夕藻土上過濾觸媒’及使濾液濃縮，而得61 (1〇4毫 克，95%)，為米黃色固體。LRMS (ESI):(計算值）383 5 (實 測值）384.5 (MH)+. 步驟3 : (S)-l-(5-(lH-吲哚-3-基）-1Η-咪唑-2-基）-5-(3-曱基硫服基） 戊基胺基曱酸第三-丁酯（62) 於〇°C下’將三光氣（〇·〇36毫升’ 0.469毫莫耳）添加至61 (12〇 毫克，0.313毫莫耳）在THF (1.565毫升）與EtsN (0.065毫升， 0.469毫莫耳）中之溶液内。將混合物攪拌1小時，然後添加 EtOH中之甲胺33% (0.390毫升，3.13毫莫耳），並使反應物溫 熱至室溫，且授拌2小時。在一般處理後，使殘留物藉層析， 以DCM中之MeOH (5%至15%)純化，及使此物質藉預備之 HPLC 進一步純化（Luna C18 管柱，20-100% MeOH/H2〇)，而得 62 (35毫克，24.5%)，為米黃色固體。 (dmso-d6) d(ppm) 1H : 11.08 (s，1H)，8.12 (s，1H)，7.85 (d，J=7.6 Hz 1H), 7.56 (d, J=1.6 Hz, 1H), 7.40 (bs, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.3〇 (bs 1H), 7.19 (s, 1H), 7.09 (t, J=7.8 Hz, 1H), 7.03 (t, J=7.8 Hz, 2H), 4.6〇 (q J=6.5 Hz, 1H), 3.29 (m, 2H), 2.76 (bs, 3H), 1.87-1.65 (m, 2H), 1.47 (qi J=7.2 Hz，2H)，1.38 (s，9H)，1.42-1.19 (m, 2H). LRMS (ESI):(計算值） 134026-2 -172- 200916447 456.2 (實測值）457.0 (MH)+ 圖式10Example 40 (S)-l-(5-(lH-&lt;哚-3-yl)-1Η-imidazol-2-yl)-5-(3-methylthioureido)pentylaminocarboxylic acid -Butyl ester (62) Step 1: (S)-5-(5-(lH-indol-3-yl)-1Η-imidazol-2-yl)-5-(tris-butoxycarbonylamino) Benzyl amyl carboxylate (60) as described in General Procedure P, in Boc-Lys(Z)-OH (481 mg, 1.265 mmol) in DMF (3.834 mL) Add 2-carbyl group [哚-3-yl) ethyl ketone (266 mg, 1.518 mmol), DMAP (30.9 mg, 0.253 mmol), EDC (315 mg, 1.645 mmol), followed by HOBT (252 mg, 1.645 mmol), EtOAc (EtOAc) LRMS (ESI): (calc.) 537.6 (found): 560.4 (M.sup.). s. , 5.28 millimoles), and the solution was stirred in a microwave at 160 ° C for 5 minutes. After </RTI> </RTI> <RTI ID=0.0> LRMS (ESI): (calculated) 517.6 (Real 134026-2 -171 - 200916447 -5-Aminopentylamino group 曱) 518.4 (ΜΗ)+· Step 2: (S)-l-(5- (lH-decanoic acid tert-butyl ester (61)-3-yl HH-imidazol-2-yl) in 60 (147 mg, 0.284 mmol) in MeOH (1.9 mL) at room temperature Add Pd/C (10% Degussa type, 30.2 mg, 0 〇 28 mmol), and stir the resulting suspension for 2 hours at room temperature under 1 atmosphere of hydrogen. Filter the catalyst on Shixiazao soil. ' And the filtrate was concentrated to give 61 (1,4 mg, 95%) as a beige solid. LRMS (ESI): (calc.) 383 5 (found) 384.5 (MH)+. Step 3: (S )-l-(5-(lH-indol-3-yl)-1Η-imidazol-2-yl)-5-(3-indolylthio-yl)-pentylaminopyruic acid tert-butyl ester 62) Add phosgene (〇·〇36 ml '0.469 mmol) to 61 (12 mg, 0.313 mmol) in THF (1.565 ml) and EtsN (0.065 ml, 0.469 m) at 〇 °C In the solution in the molar. The mixture was stirred for 1 hour, then methylamine 33% (0.390 ml, 3.13 mmol) in EtOH was added and the reaction was Heat to room temperature and allow for 2 hours of mixing. After the usual workup, the residue was purified by chromatography eluting with MeOH (5% to 15%) in DCM and further purified by preparative HPLC (Luna C18) Column, 20-100% MeOH/H2 〇), which gave 62 (35 mg, 24.5%) as a beige solid. (dmso-d6) d (ppm) 1H: 11.08 (s, 1H), 8.12 (s ,1H), 7.85 (d, J=7.6 Hz 1H), 7.56 (d, J=1.6 Hz, 1H), 7.40 (bs, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.3〇 (bs 1H), 7.19 (s, 1H), 7.09 (t, J=7.8 Hz, 1H), 7.03 (t, J=7.8 Hz, 2H), 4.6〇 (q J=6.5 Hz, 1H), 3.29 (m, 2H), 2.76 (bs, 3H), 1.87-1.65 (m, 2H), 1.47 (qi J=7.2 Hz, 2H), 1.38 (s, 9H), 1.42-1.19 (m, 2H). LRMS (ESI) : (calculated value) 134026-2 -172- 200916447 456.2 (measured value) 457.0 (MH) + schema 10

實例44 (S)-l-(lH-苯并[d]咪唑-2-基）-5-(3-甲基硫脲基）戊基胺基甲酸苄 酯（69) 步驟1 : (S)-6-(第三-丁氧羰基胺基）-1-(2-胺基苯基胺基）-1-酮基 己-2-基胺基甲酸芊酯（66) 按照一般程序F，於CbZ-Lys(Boc)-OH (1克，2.63毫莫耳）在 DMF (10.51毫升）中之經攪拌溶液内，添加鄰-苯二胺（0.341 克，3.15毫莫耳）、EDC (ϋ·655克，3.42毫莫耳），接著為HOBT (0.523克，3.42毫莫耳）。在藉由層析，以己烷中之EtOAc (20% 至80%)純化後，獲得化合物66，為黃色固體（461毫克， 37.3%)。LRMS (ESI):(計算值）470.6 (實測值）471.4 (MH)+ 步驟2 : (S)-5-(第三-丁氧羰基胺基）-1-(1Η-苯并[d]咪唑-2-基）戊 基胺基曱酸辛酉旨（67) 將66 (461毫克，0.980毫莫耳）在AcOH (3.919毫升）中之溶 液，於65t下攪拌1小時，然後將其處理至乾涸，添加飽和 Na2 C03溶液，並將混合物以EtOAc萃取，以MgS04脫水乾燥， 134026-2 -173 - 200916447 過濾，及濃縮。獲得粗製67 (322毫克，72.6%)，為米黃色固 體。LRMS (ESI):(計算值）452.6 (實測值）453.4 (MH)+ 步驟3 :⑸-5-胺基小(1Η_苯并[d]咪唑_2_基）戊基胺基甲酸芊酯 (68) 按一般程序B中所述，於67 (322毫克，0.712毫莫耳）在 CH2C12(2.372毫升）中之經攪拌溶液内，在室溫下添加τρΑ (1.096 φ升，i4.23毫莫耳）。獲得粗製68 (25〇毫克，定量）， 為米汽色固體。LRMS (ESI):(計算值）352.4 (實測值）353.3 (MH)+ 步驟4 ·· (S)-l-(lH-苯并[d]咪唑-2-基)-5-(3-曱基硫脲基）戊基胺基 甲酸芊酯（69) 於68 (83毫克，0.236毫莫耳）在THF (1_570毫升）中之經攪拌 溶液内，在Ot下添加Et3N(0.082毫升，0.589毫莫耳），接著 為異硫氰酸曱酯（0.018毫升，〇·259毫莫耳），並將所形成之 /谷液在至溫下授拌1小時。添加飽和Na2 c〇3溶液，且以Et〇Ac 萃取混合物’並使萃液以MgS〇4脫水乾燥，過濾，及濃縮， 且使殘留物藉層析，以己烷中之Et0Ac (2〇%至1〇〇%)純化’ 而得 69 (37 毫克 ’ 36.9%) ’ 為白色固體。（dmso_d6) d(ppm) m : 12.21 (s, 1H), 7.82 (d, J=8.2 Hz, 1H), 7.53 (d, J=6.7 Hz, 1H), 7.44-7.29 (m, 7H), 7.15-7.08 (m, 2H), 5.03 (q, J=15 Hz, 2H), 4.77 (q, J=5.7 Hz, 1H), 3勝3.18 (m，2H)，2.76 (bs，3H)，2.02-1.76 (m, 2H)，1.48 (五重峰，J=6.7 Hz，2H)，141-1.22 (m，2H). LRMS (ESI):(計算值）425.2 (實測值） 4263 (MH)+ 134026-2 -174- 200916447 圖式11Example 44 (S)-l-(lH-Benzo[d]imidazol-2-yl)-5-(3-methylthioureido)pentylaminocarboxylate (69) Step 1: (S) -6-(Thrs-butoxycarbonylamino)-1-(2-aminophenylamino)-1-ketohexan-2-ylaminocarbazate (66) according to the general procedure F, CbZ-Lys(Boc)-OH (1 g, 2.63 mmol) in a stirred solution of DMF (10.51 ml), o-phenylenediamine (0.341 g, 3.15 mmol), EDC (ϋ· 655 g, 3.42 mmol, followed by HOBT (0.523 g, 3.42 mmol). After purification by EtOAc (20% to EtOAc) LRMS (ESI): (calc.) 470.6 (found) 471.4 (MH) + Step 2: (S)-5-(tris-butoxycarbonylamino)-1-(1Η-benzo[d]imidazole 2-yl)pentylamino decanoic acid oxime (67) A solution of 66 (461 mg, 0.980 mmol) in AcOH (3.919 ml) was stirred at 65t for 1 hour and then treated to dryness. Saturated Na.sub.2 C.sub.3 solution was added, and the mixture was extracted with EtOAc, dried over EtOAc EtOAc EtOAc. Crude 67 (322 mg, 72.6%) was obtained as a beige solid. LRMS (ESI): (calculated) 452.6 (found) 453.4 (MH) + Step 3: (5)-5-amine-amine (1Η-benzo[d]imidazolium-2-yl)pentylaminocarbazate (68) Add τρΑ (1.096 φ liter, i4.23 毫) at room temperature in a stirred solution of 67 (322 mg, 0.712 mmol) in CH2C12 (2.372 mL) as described in General Procedure B. Moore). Obtained crude 68 (25 mg, quantitative) as a beige solid. LRMS (ESI): (calculated) 352.4 (found) 353.3 (MH) + Step 4 ··(S)-l-(lH-benzo[d]imidazol-2-yl)-5-(3-曱Ethyl thiourea) decylaminocarbazate (69) In a stirred solution of 68 (83 mg, 0.236 mmol) in THF (1 - 570 mL), Et3N (0.082 mL, 0.589 Moor) followed by decyl isothiocyanate (0.018 mL, 〇 259 mmol) and the formed / gluten solution was stirred for 1 hour at ambient temperature. A saturated Na 2 c 〇 3 solution was added, and the mixture was extracted with Et 〇 Ac and the extract was dehydrated and dried with MgSO 4 , filtered, and concentrated, and the residue was subjected to chromatography to give Et0Ac in hexane (2%) Up to 1%)) purified to give 69 (37 mg '36.9%)' as a white solid. (dmso_d6) d(ppm) m : 12.21 (s, 1H), 7.82 (d, J=8.2 Hz, 1H), 7.53 (d, J=6.7 Hz, 1H), 7.44-7.29 (m, 7H), 7.15 -7.08 (m, 2H), 5.03 (q, J=15 Hz, 2H), 4.77 (q, J=5.7 Hz, 1H), 3 wins 3.18 (m, 2H), 2.76 (bs, 3H), 2.02- 1.76 (m, 2H), 1.48 (five peaks, J = 6.7 Hz, 2H), 141-1.22 (m, 2H). LRMS (ESI): (calculated) 425.2 (measured) 4263 (MH) + 134026 -2 -174- 200916447 Figure 11

實例45 (S)-N_(5-乙烷硫醯胺基-1-(6-(4-氟苯基）-1Η-苯并[d]哺唑-2-基）戊 基）-2,2,2-三氟乙醯胺（73) 步驟1 : (S)-2-(第三-丁氧羰基胺基）-6-乙烷硫醯胺基己酸(70) 按一般程序K中所述，於Boc-Lys-OH (3.39克，13.78毫莫耳） 在二氧陸圜（7.87毫升）與H2 0 (31.5毫升）中之經攪拌溶液内， 在室溫下添加K2C03 (4.76克，34.5毫莫耳），並使混合物冷卻 至0°C，且逐滴添加二硫基醋酸乙酯（1·739毫升，15.16毫莫 耳）。獲得粗製70 ’為黃色油’及以本身使用於下一步驟。 LRMS (ESI):(計算值）304.4 (實測值）305.3 (ΜΗ)+ 步驟2. (S)-l-(4-胺基-4’-氟基聯苯-3-基胺基）各乙院硫醯胺基_ι_ 酮基己-2-基胺基甲酸第三_丁酯（71) 134026-2 -175» 200916447 按一般程序N中所述，於70 (4.19克，13.78毫莫耳）在DMF (55.1毫升）中之經攪拌溶液内，添加4，_氟基聯苯基_3,4_二胺 (3.34 克，16.54 毫莫耳）、DMAP (0.337 克，2.76 毫莫耳）、EDC (3.43 克’ 17.91毫莫耳）’接著為h〇bt (2.74克，17.91毫莫耳）。在 藉由層析’以己烷中之EtO Ac (20%至100%)純化後，獲得化 合物71，為淡黃色固體（5 315克，79%)。LRMS (ESI):(計算 值）488.6 (實測值）489.4 (MH)+ 步驟3 : (S)-N-(5-胺基-5-(6-(4-氟苯基HH-苯并[d]咪唑-2-基）戊基） 乙烷硫醯胺（72) 按一般程序X中所述，將AcOH (27.2毫升）中之醯胺71 (5.315克，10.88毫莫耳）在60。。下加熱1小時。獲得笨并咪 唑，為淡褐色固體（4.442克，87%)。LRMS (ESI):(計算值）470.6 (實測值）471.4 (MH)+。按一般程序B中所述，將DCM (23.43 毫升）中之笨并咪唑（4.41克’ 9.37毫莫耳）以TFA (10.83毫升， 141毫莫耳）處理。使所形成之胺藉層析，以dcm中之MeOH (0%至10%)進一步純化，而得72 (3 9克，定量），為淡黃色固 體。LRMS (ESI):(計算值）370.5 (實測值）371.3 (MH)+ 步驟4 : (S)-N-(5-乙烷硫醯胺基小(6_(4_氟苯基）-1Η-笨并[d]咪唑 -2-基）戊基）-2,2,2-三氟乙醯胺（73) 於〇°C下，將三氟醋酸酐（0.056毫升，〇·4毫莫耳）逐滴添加 至72 (148毫克，〇.4毫莫耳）與(0.139毫升，1.0毫莫耳） 在THF (1.6毫升）中之溶液内，並將所形成之溶液在室溫下 攪拌16小時。添加飽和NaHC03溶液，並以EtOAc萃取混合 物’且使萃液以MgS〇4脫水乾燥，過濾，及濃縮，並使殘留 134026-2 -176· 200916447 物藉層析，以己烷中之EtOAc (20%至100%)純化，而得73 (53 毫克，28.4%)，為黃色固體。（dmso-d6) d(ppm) 1H : 12.48 (d，J=10.5 Hz, 1H), 10.02 (dd, J=8.0, 3.1 Hz, 1H), 9.96 (s, 1H), 7.82-7.51 (m, 3H), 7.46-7.40 (m, 1H), 7.29-7.23 (m, 2H), 5.12 (q, J=7.0 Hz, 1H), 3.45 (qi, J=5.5 Hz, 2H), 2.35 (s, 3H), 2.21-2.10 (s, 1H), 2.03-1.91 (m, 1H), 1.59 (qi, J=7.4 Hz，2H)，1.43-1.28 (m, 2H). LRMS (ESI):(計算值）466.5 (實測 值）467.3 (MH)+ 實例46 (S)-5-乙烷硫醯胺基-1-(6-(4-氟苯基）-1Η-苯并[d]咪唑-2-基）戊基 胺基曱酸吡啶-2-基甲酯（74) 步驟1 : (S)-5-乙烷硫醯胺基-1-(6-(4-氟苯基）-1Η-苯并[d]咪唑-2-基）戊基胺基曱酸吡啶-2-基甲酯（74) 於2-吡啶基甲醇（0.053毫升，0.55毫莫耳）在DCM (1.25毫升） 與乙腈（1.25毫升）中之經攪拌溶液内，在0°C下添加2,6-二甲 基吡啶（0.070毫升，0.6毫莫耳），接著為碳酸Ν,Ν’-二琥珀醯 亞胺醯酯（141毫克，0.550毫莫耳），並將所形成之溶液在室 溫下攪拌16小時。添加胺72 (185毫克，0.5毫莫耳），且將混 合物於室溫下攪拌2小時，然後添加飽和NaHC03溶液，並 以EtOAc萃取混合物，且使萃液以MgS04脫水乾燥，過濾， 及濃縮，並使殘留物藉層析，以DCM中之MeOH (0%至10%) 純化，及使此物質藉預備之HPLC進一步純化（Aquasil C18管 柱，10-100% Me0H/H20)，而得 74 (40 毫克，15.8%)，為白色 固體。 (dmso-d6) d(ppm) 1H ： 12.32 (d, J=10 Hz, 1H), 9.96 (s, 1H), 8.52 (d, 134026-2 -177- 200916447 J=4.5 Hz, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.82-7.49 (m, 5H), 7.41 (d, J=7.6 Hz, 2H), 7.32-7.24 (m, 3H), 5.10 (q, J=13 Hz, 2H), 4.80 (q, J=5.7 Hz, 1H), 3.44 (q, J=6.5 Hz, 2H), 2.35 (s, 3H), 2.08-1.80 (m, 2H), 1.58 (qi, J=7.1 Hz, 2H), 1.48-1.27 (m，2H). LRMS (ESI):(計算值）505.6 (實測值）506.3 (MH)+ 實例47 ⑻-N-(5-(3-辛基脲基)-5-(6-(4-氟苯基)-1Η-苯并[d]咪唑-2_基）戊基） 乙烷硫醯胺（75) 步驟1 . (S)-N-(5-(3-爷基ϋ尿基）-5-(6-(4-氟苯基）-1Η-苯并[d]w米唾-2-基）戊基）乙烷硫醯胺（75) 於72 (148毫克，0.4毫莫耳）在THF (1.6微升）中之經攪拌溶 液内，在0°C下添加Et3N (139微升，1.0毫莫耳），接著逐滴 添加異氰酸苄酯（49.8微升，0.400毫莫耳），並將所形成之溶 液在室溫下授拌16小時。在一般處理後，使殘留物藉層析， 以己烷中之EtOAc (20%至100%)純化，及使所形成之物質藉 預備之 HPLC 進一步純化（Luna C18 管柱，10-100% Me0H/H20)， 而得75 (9毫克，4.5%)，為白色固體。 (dmso-d6) d(ppm) 1H ： 9.94 (s, 1H), 7.70-7.65 (m, 3H), 7.62-7.51 (m, 1H), 7.40 (dd, J=8.2, 1.6 Hz, 1H), 7.30-7.17 (m, 7H), 6.60-6.53 (m, 2H), 4.95 (q, J=6.5 Hz, 1H), 4.27-4.14 (m, 2H), 3.41 (q, J=5.9 Hz, 2H), 2.33 (s, 3H), 1.97-1.77 (m, 2H), 1.56 (qi, J=7.8 Hz, 2H), 1.38-1.23 (m, 2H). LRMS (ESI):(計算值）503.2 (實測值）504.4 (MH)+ 134026-2 -178- 200916447Example 45 (S)-N_(5-ethanethioguanidino-1-(6-(4-fluorophenyl)-1 fluorene-benzo[d]oxazol-2-yl)pentyl)-2, 2,2-Trifluoroacetamide (73) Step 1: (S)-2-(Thr-Butoxycarbonylamino)-6-ethanethioguanidinohexanoic acid (70) according to the general procedure K Add K2C03 (4.76 g) to Boc-Lys-OH (3.39 g, 13.78 mmol) in a stirred solution of dioxane (7.87 ml) and H2 0 (31.5 ml) at room temperature. , 34.5 mmol, and the mixture was cooled to 0 ° C, and ethyl dithioacetate (1·739 mL, 15.16 mmol) was added dropwise. Obtained crude 70 'as yellow oil' and used as such in the next step. LRMS (ESI): (calculated) 304.4 (found) 305.3 (ΜΗ)+ Step 2. (S)-l-(4-Amino-4'-fluorobiphenyl-3-ylamino) B醯 醯 醯 _ _ _ _ 酮 第三 第三 第三 ( ( ( ( ( ( ( ( ( ( ( 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 134 In a stirred solution of DMF (55.1 ml), 4,-fluorophenylbiphenyl-3,4-diamine (3.34 g, 16.54 mmol), DMAP (0.337 g, 2.76 mmol) was added. , EDC (3.43 grams ' 17.91 millimoles)' followed by h〇bt (2.74 grams, 17.91 millimoles). After purification by chromatography <RTI ID=0.0>: </RTI> EtOAc (20% to 100%) hexanes, Compound 71 was obtained as pale yellow solid (5 315 g, 79%). LRMS (ESI): (calculated) 488.6 (found) 489.4 (MH) + Step 3: (S)-N-(5-Amino-5-(6-(4-fluorophenylHH-benzo[ d]imidazol-2-yl)pentyl) ethionamide (72) The decylamine 71 (5.315 g, 10.88 mmol) in AcOH (27.2 mL) was taken at 60 as described in General Procedure X. The next heating was carried out for 1 hour. Obtained as a methylene solid (4.442 g, 87%). LRMS (ESI): (calc.) 470.6 (found) 471.4 (MH)+. The stupid imidazole (4.41 g ' 9.37 mmol) in DCM (23.43 mL) was treated with TFA (10.83 mL, 141 mmol). The amine formed was chromatographed with MeOH in dcm (0) (% to 10%) further purified to give 72 (39 g, quantitative) as pale yellow solid. LRMS (ESI): (calc.) 370.5 (found) 371.3 (MH) + Step 4: (S)- N-(5-ethanethioguanamine small (6-(4-fluorophenyl)-1Η- benzo[d]imidazol-2-yl)pentyl)-2,2,2-trifluoroacetamide (73) Trifluoroacetic anhydride (0.056 ml, 〇·4 mmol) was added dropwise to 72 (148 mg, 〇.4 mmol) and (0.139 ml, 1.0 mmol) at 〇 °C. The solution was stirred at room temperature for 16 hours. The saturated NaHC03 solution was added and the mixture was extracted with EtOAc and the extract was dried over MgSO 4 and filtered. And concentrating, and the residue was purified by EtOAc EtOAc EtOAc (EtOAc (EtOAc) -d6) d(ppm) 1H : 12.48 (d, J=10.5 Hz, 1H), 10.02 (dd, J=8.0, 3.1 Hz, 1H), 9.96 (s, 1H), 7.82-7.51 (m, 3H) , 7.46-7.40 (m, 1H), 7.29-7.23 (m, 2H), 5.12 (q, J=7.0 Hz, 1H), 3.45 (qi, J=5.5 Hz, 2H), 2.35 (s, 3H), 2.21-2.10 (s, 1H), 2.03-1.91 (m, 1H), 1.59 (qi, J=7.4 Hz, 2H), 1.43-1.28 (m, 2H). LRMS (ESI): (calculated) 466.5 ( Found 46) (MH) + Example 46 (S)-5-Ethylthioguanidino-1-(6-(4-fluorophenyl)-1 fluorene-benzo[d]imidazol-2-yl)pentane Pyridyl-2-ylmethyl decyl phthalate (74) Step 1: (S)-5-Ethylthioguanidino-1-(6-(4-fluorophenyl)-1 fluorene-benzo[d] Imidazol-2-yl)pentylaminopyridinium pyridin-2-ylmethyl ester (74) in 2-pyridylmethanol (0.053 m , 0.55 mmol; 2,6-lutidine (0.070 ml, 0.6 mmol) was added at 0 ° C in a stirred solution of DCM (1.25 mL) and acetonitrile (1.25 mL). This was cesium carbonate, Ν'-disuccinimide (141 mg, 0.550 mmol), and the resulting solution was stirred at room temperature for 16 hours. Amine 72 (185 mg, 0.5 mmol) was added, and the mixture was stirred at room temperature for 2 hr then a saturated NaHC03 solution was added and the mixture was extracted with EtOAc. The residue was purified by EtOAc (EtOAc (EtOAc:EtOAc) (40 mg, 15.8%) as a white solid. (dmso-d6) d(ppm) 1H : 12.32 (d, J=10 Hz, 1H), 9.96 (s, 1H), 8.52 (d, 134026-2 -177- 200916447 J=4.5 Hz, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.82-7.49 (m, 5H), 7.41 (d, J=7.6 Hz, 2H), 7.32-7.24 (m, 3H), 5.10 (q, J=13 Hz, (H, 2H), 3.80 Hz, 2H), 1.48-1.27 (m, 2H). LRMS (ESI): (calc.) 505.6 (found) 506.3 (MH) + Example 47 (8)-N-(5-(3-octylureido) -5-(6-(4-fluorophenyl)-1 fluorene-benzo[d]imidazol-2-yl)pentyl) ethionamide (75) Step 1. (S)-N-(5- (3-Glycosyl)--5-(6-(4-fluorophenyl)-1Η-benzo[d]w-sial-2-yl)pentyl)ethanethioguanamine (75) 72 (148 mg, 0.4 mmol) of Et3N (139 μl, 1.0 mmol) at 0 ° C in a stirred solution of THF (1.6 μl), followed by dropwise addition of benzyl isocyanate Ester (49.8 microliters, 0.400 millimoles) and the resulting solution was stirred at room temperature for 16 hours. After the usual workup, the residue was purified by chromatography eluting with EtOAc (20% to 100%) in hexanes, and further purified by preparative HPLC (Luna C18 column, 10-100% Me0H /H20), which gave 75 (9 mg, 4.5%) as a white solid. (dmso-d6) d(ppm) 1H : 9.94 (s, 1H), 7.70-7.65 (m, 3H), 7.62-7.51 (m, 1H), 7.40 (dd, J=8.2, 1.6 Hz, 1H), 7.30-7.17 (m, 7H), 6.60-6.53 (m, 2H), 4.95 (q, J=6.5 Hz, 1H), 4.27-4.14 (m, 2H), 3.41 (q, J=5.9 Hz, 2H) , 2.33 (s, 3H), 1.97-1.77 (m, 2H), 1.56 (qi, J=7.8 Hz, 2H), 1.38-1.23 (m, 2H). LRMS (ESI): (calculated) 503.2 (measured) Value) 504.4 (MH)+ 134026-2 -178- 200916447

圖式12Figure 12

UFA, CH2CI2 日 3n,thfUFA, CH2CI2 day 3n, thf

π Υ 實例48 ⑻-1-(7-氣基_1Η-苯并[d]咪唑-2-基）-5-乙烷硫醯胺基戊基胺基 甲酸苄酯（77) 步驟1 : 5-(苄氧羰基胺基）-5-(7-氣基-1H-苯并[d]咪唑-2-基）戊基 胺基曱酸第三-丁酯（76) 於3-氯苯-l，2-二胺（263毫克，1.844毫莫耳）在p比咬（9.2毫升） 中之經攪拌溶液内，在室溫下添加z_Lys(B〇c)_〇H (7〇2毫克， L844毫莫耳）與亞磷酸三笨基酯(〇.582毫升，2.21毫莫耳）， 並將所形成之溶液在微波中，於200°C下攪拌10分鐘。使反 應物濃縮，添加飽和NaHC〇3，並以EtOAc萃取混合物，且使 萃液以MgS〇4脫水乾燥’過濾’反濃縮，並使殘留物藉層析， 以己烷中之EtOAc (10%至50%)純化，而得76 (140毫克，15.6%)， 為白色固體。LRMS (ESI):(計算值）486.2 (實測值）487.3 (MH)+. 步驟2 : (S)-l-(7-氣基-1H-苯并[d]咪唑-2_基）-5_乙烷硫醯胺基戊 基胺基甲酸芊酯（77) 按一般程序B中所述，將76 (110毫克，〇.226毫莫耳）在DCM (1.506毫升）中之溶液，以TFA(0.522毫升，6J8毫莫耳）處理。 獲得粗製胺（60毫克，68.7%)，為褐色固體。LRMS(ESI):(計 算值）386.2 (實測值）387.3 (MH)+. 134026-2 -179- 200916447 按一般程序G中所述，將THF (1.551毫升）中之胺（60毫克， 0.155毫莫耳）以Et3N (0.043毫升，0.310毫莫耳）與二硫基醋酸 乙酯（0.020毫升，0.171毫莫耳）處理，並使粗製物質藉層析， 以己烷中之EtOAc (20%至100%)純化，接著藉預備之HPLC進 一步純化（Aquasil 管柱 C18，10-100% Me0H/H20)，而得77 (11 毫克，15.9%)，為白色固體。 (dmso-d6) d(ppm) 1H ： 12.63 (s, 1H), 9.97 (s, 1H), 7.95 (d, J=7.6 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.37-7.06 (m, 7H), 5.05 (q, J=13 Hz, 2H), 4.80 (q, J=4.9 Hz, 1H), 3.45 (q, J=6.1 Hz, 2H), 2.36 (s, 3H), 2.03-1.78 (m, 2H), 1.65-1.50 (m，2H), 1.50-1.23 (m, 2H). LRMS (ESI):(計算值）444.1 (實 測值）445.2 (MH)+π Υ Example 48 (8)-1-(7-Gasyl_1Η-benzo[d]imidazol-2-yl)-5-ethanethioammonium amylaminocarbamate (77) Step 1: 5 -(Benzyloxycarbonylamino)-5-(7-alkyl-1H-benzo[d]imidazol-2-yl)pentylamino decanoic acid tert-butyl ester (76) in 3-chlorobenzene- l,2-diamine (263 mg, 1.844 mmol) in a stirred solution of p to bite (9.2 ml), add z_Lys(B〇c)_〇H (7〇2 mg, at room temperature) L844 millimolar) and triphenyl phosphite (〇.582 ml, 2.21 mmol), and the resulting solution was stirred in a microwave at 200 ° C for 10 minutes. The reaction was concentrated, EtOAc (10% EtOAc (EtOAc) Purification to 50% (76 mg, 15.6%) as a white solid. LRMS (ESI): (calculated) 486.2 (found) 487.3 (MH) +. Step 2: (S)-l-(7-carbyl-1H-benzo[d]imidazole-2-yl)-5 _ Ethyl thioguanamine pentylaminocarbazate (77) A solution of 76 (110 mg, 〇.226 mmol) in DCM (1.506 mL) as described in General Procedure B, with TFA (0.522 ml, 6J8 mmol) treatment. The crude amine (60 mg, 68.7%) was obtained as a brown solid. LRMS (ESI): (calcd.) 386.2 (found) 387.3 (MH) +. 134026-2 -179 - 200916447 THF (1.55 ml) of amine (60 mg, 0.155 m) as described in General Procedure G Treatment of Et3N (0.043 mL, 0.310 mmol) with ethyl dithioacetate (0.020 mL, 0.171 mmol) and EtOAc (20% Purification by 100%) followed by further purification (Aquasil column C18, 10-100% Me0H/H20) to afford 77 (11 mg, 15.9%) as white solid. (dmso-d6) d(ppm) 1H : 12.63 (s, 1H), 9.97 (s, 1H), 7.95 (d, J=7.6 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.37 -7.06 (m, 7H), 5.05 (q, J=13 Hz, 2H), 4.80 (q, J=4.9 Hz, 1H), 3.45 (q, J=6.1 Hz, 2H), 2.36 (s, 3H) , 2.03-1.78 (m, 2H), 1.65-1.50 (m, 2H), 1.50-1.23 (m, 2H). LRMS (ESI): (calculated) 444.1 (measured value) 445.2 (MH)+

圖式13,QCNH2 丫 nh2 hobt, edc -0N-0 DMF 2. AcOH,60°C,4hFigure 13, QCNH2 丫 nh2 hobt, edc -0N-0 DMF 2. AcOH, 60 ° C, 4 h

rr

r 實例49 ⑸-1-(7-胺基-1H-苯并[d]咪唑-2-基)-5-乙烷硫醯胺基戊基胺基 甲酸苄酯（79) 步驟1 : (S)-5-乙烷硫醯胺基-1-(7-硝基-1H-苯并[d]咪唑-2-基）戊 134026-2 -180- 200916447 基胺基曱酸芊酯（78) 按一般程序N中所述，使41 (2.500毫升，2.5毫莫耳）在DMF (7.5毫升）、3-硝基-鄰-苯二胺（459毫克，3.00毫莫耳）、DMAP (61.1毫克，0.500毫莫耳）、EDC (623毫克，3.25毫莫耳）及HOBT (498毫克，3.25毫莫耳）中之溶液反應。藉由層析，以己烷 中之EtOAc (20%至80%)純化，獲得醯胺中間物（447毫克， 37.8%.)，為黃色固體。LRMS (ESI):(計算值）473.6 (實測值） 474.3 (MH)+. 按一般程序Y中所述，將得自上文之醯胺（513毫克，1.083 毫莫耳）在AcOH (3.611毫升）中，於60°C下加熱4小時，並在 藉由層析，以己烷中之EtOAc (20%至100%)純化後，獲得78 (321毫克，65%)，為黃色固體。LRMS (ESI):(計算值）455.5 (實 測值）456.3 (MH)+· 步驟2 : (S)-l-(7-胺基-1H-苯并[d]咪唑-2-基）-5-乙烷硫醯胺基戊 基胺基曱酸苄酯（79) 於78 (321毫克，0.705毫莫耳）在MeOH (5.637毫升）與AcOH (1.409毫升）中之經攪拌溶液内，在室溫下添加鋅粉（276毫 克，4.23毫莫耳），並將所形成之懸浮液在室溫下攪拌1小 時。於矽藻土上過濾混合物，且將此物質處理至乾涸，及 添加飽和NaHC03，並以EtOAc萃取混合物，且使萃液以MgS〇4 脫水乾燥，過濾，及濃縮。使殘留物藉層析，以DCM中之 MeOH (0%至10%)純化，而得79 (217毫克，72.4%)，為灰白色 固體。（dmso-d6) d(ppm) 1H : 11.87 (s, 1H)，9.94 (s，1H)，7.71 (d，J=8.2 Hz, 1H), 7.36-7.10 (m, 5H), 6.81 (t, J=7.8 Hz, 1H), 6.61 (d, J=8.0 Hz, 1H), 134026-2 -181 - 200916447 6.28 (d, J=7.6 Hz, 1H), 5.18-4.97 (m, 4H), 4.73 (q, J=5.7 Hz, 1H), 3.43 (q, J=6.3 Hz, 2H), 2.34 (s, 3H), 2.04-1.77 (m, 2H), 1.62-1.45 (m, 2H), I. 43-1.25 (m, 2H). LRMS (ESI):(計算值）425.2 (實測值）426.3 (MH)+ 實例50 ⑻-5·乙烷硫醯胺基-1-(7-(4-氟基苯甲醯胺基）-lH-苯并[d]咪唑 -2-基）戊基胺基甲酸宇醋（80) 步驟1 : (S)-5-乙烷硫醯胺基-1-(7-(4-氟基苯甲醯胺基）-1Η-苯并 [d]咪唑-2-基）戊基胺基曱酸苄酯（80) 按一般程序D中所述，於〇°C下，將79 (100毫克，0.235毫 莫耳）、THF (1.567毫升）及EyN (0.082毫升，0.587毫莫耳）之 溶液’以氯化4-氟苯曱醯（0.028毫升，〇_235毫莫耳）處理。在 藉由層析’以己烷中之EtOAc (20%至100%)純化後，獲得化 合物 80 (45 4:克 ’ 35%) ’ 為米黃色固體。（dmso-d6) d(ppm) 1H : II. 85 (s, 1H), 10.32 (s, 1H), 9.94 (s, 1H), 8.11-8.05 (m, 2H), 7.86 (t, J=9.〇 Hz, 1H), 7.42-7.26 (m, 8H), 7.15-7.11 (m, 2H), 5.08-4.97 (m, 2H), 4.85-4.76 (m, 1H), 3.42 (q, J=5.9 Hz, 2H), 2.33 (s, 3H), 2.02-1.77 (m, 2H), I.63. 1.50 (m, 2H)，1.50-1.25 (m, 2H). LRMS (ESI):(計算值）547.2 (實測 值）548.4 (MH)+ 134026-2 -182- 200916447 圖式14r Example 49 (5)-1-(7-Amino-1H-benzo[d]imidazol-2-yl)-5-ethanethioammonium amylaminocarbamate (79) Step 1: (S) -5-ethanethioguanamine-1-(7-nitro-1H-benzo[d]imidazol-2-yl)penta 134026-2 -180- 200916447 guanyl decyl decanoate (78) 41 (2.500 mL, 2.5 mmol) in DMF (7.5 mL), 3-nitro-o-phenylenediamine (459 mg, 3.00 mmol), DMAP (61.1 mg) as described in General Procedure N , 0.500 mmol, EDC (623 mg, 3.25 mmol) and HOBT (498 mg, 3.25 mmol) solution. Purification by EtOAc (20% to 80%) LRMS (ESI): (calcd.) 473.6 (found) 474.3 (MH) +. s. s. s. The mixture was heated at 60 ° C for 4 hours and purified by EtOAc (20% toEtOAc) LRMS (ESI): (calc.) 455.5 (found) 456.3 (MH) + · Step 2: (S)-l-(7-Amino-1H-benzo[d]imidazol-2-yl)-5 - Ethyl thioamidoamine amyl phthalic acid benzyl ester (79) in a stirred solution of 78 (321 mg, 0.705 mmol) in MeOH (5.637 mL) and AcOH (1.409 mL) Zinc powder (276 mg, 4.23 mmol) was added at a temperature, and the resulting suspension was stirred at room temperature for 1 hour. The mixture was filtered over celite, and this material was taken to dryness, and saturated NaHC03 was added, and the mixture was extracted with EtOAc, and the mixture was dried over <RTIgt; The residue was purified by EtOAc EtOAc (EtOAc:EtOAc (dmso-d6) d(ppm) 1H : 11.87 (s, 1H), 9.94 (s, 1H), 7.71 (d, J = 8.2 Hz, 1H), 7.36-7.10 (m, 5H), 6.81 (t, J=7.8 Hz, 1H), 6.61 (d, J=8.0 Hz, 1H), 134026-2 -181 - 200916447 6.28 (d, J=7.6 Hz, 1H), 5.18-4.97 (m, 4H), 4.73 ( q, J=5.7 Hz, 1H), 3.43 (q, J=6.3 Hz, 2H), 2.34 (s, 3H), 2.04-1.77 (m, 2H), 1.62-1.45 (m, 2H), I. 43 -1.25 (m, 2H). LRMS (ESI): (calc.) 425.2 (found) 426.3 (MH) + Example 50 (8) -5 - ethanethioguanamine-1-(7-(4-fluoro) Benzylamino)-lH-benzo[d]imidazol-2-yl)pentylaminocarboxylic acid vinegar (80) Step 1: (S)-5-Ethylthioanthryl-1-(7) -(4-Fluorobenzoguanamine)-1Η-benzo[d]imidazol-2-yl)pentylamino decanoate (80) as described in General Procedure D, at 〇 ° C , a solution of 79 (100 mg, 0.235 mmol), THF (1.567 ml) and EyN (0.082 ml, 0.587 mmol) as 4-fluorophenylhydrazine chloride (0.028 ml, 〇 235 235 mmol) Ear) processing. After purification by chromatography <RTIgt; EtOAc</RTI> (20% to 100%) (dmso-d6) d(ppm) 1H : II. 85 (s, 1H), 10.32 (s, 1H), 9.94 (s, 1H), 8.11-8.05 (m, 2H), 7.86 (t, J=9 .〇Hz, 1H), 7.42-7.26 (m, 8H), 7.15-7.11 (m, 2H), 5.08-4.97 (m, 2H), 4.85-4.76 (m, 1H), 3.42 (q, J=5.9 Hz, 2H), 2.33 (s, 3H), 2.02-1.77 (m, 2H), I.63. 1.50 (m, 2H), 1.50-1.25 (m, 2H). LRMS (ESI): (calculated) 547.2 (measured value) 548.4 (MH)+ 134026-2 -182- 200916447 Figure 14

Ph々人〜CF3CH2C02H,DCC,Ph々人~CF3CH2C02H, DCC,

153:實例 122153: Example 122

THF, 〇°C-^r.t.THF, 〇°C-^r.t.

152:實例 121 實例121 ⑸-1·酮基-1-(4-苯基嘧唑-2-基胺基）-6-(3,3,3-三氟丙烷硫醯胺 基）己烷-2-基胺基甲酸苄酯（152) 步驟1: (S)-l-酮基-1-(4-笨基P塞峻-2-基胺基）-6-(3,3,3-三氟丙醯胺 基）己烷-2-基胺基甲酸苄酯（151) 於2 (100毫克’ 0.228毫莫耳）在DCM (4.6毫升）中之溶液内， 在室溫下添加DCC (47.0毫克，0.228毫莫耳），接著為DMAP (2.79 ^:克’ 0.023宅莫耳）與3,3,3-三氟丙酸（35·0毫克，0.274毫 莫耳）。在攪拌16小時後，添加水，並將混合物以EtOAc萃 取，且使萃液以Na2 S04脫水乾燥，於真空下濃縮，及以層 析，使用己烷中之EtOAc (10至80%)純化，而得151 (69_0毫克， 55.2% 產率）。LRMS (ESI):(計算值）548.6 (實測值）549.3 (MH)+ 步驟2.⑸-1-嗣基-1-(4-本基p塞°坐-2-基胺基）-6-(3,3,3-三說丙烧硫 醯胺基）己烷-2-基胺基甲酸芊酯（152) 按一般程序E中所述’於〇°C下，將151 (69.0毫克，0.126 134026-2 -183- 200916447 宅莫耳）在丁1^(1毫升）中之溶液，以2,4-雙（4-苯氧基苯基）-1，3-一硫-2,4-二填四圜-2,4-二硫化物（166毫克，〇·314毫莫耳）處 理。在以己烷中之EtOAc(10至80%)層析後，獲得化合物152 (31.3耄克’ 44%產率），為白色泡床物。（cd3〇D) d(ppm) 1H : 7.89 (dd, J=8.4, 1.4 Hz, 2H) ； 7.41-7.12 (m, 9H) ； 5.14 (d, J=12.3 Hz, 1H)； 5.09 (d, 1=12.5 Hz, 1H) ； 4.37-4.34 (m, 1H) ； 3.60 (t, J=7.2 Hz, 2H) ； 3.54 (d, J=10.2 Hz, 1H) ； 3.49 (d, J=10.4 Hz, 1H) ； 1.91-1.70 (m, 4H) ； 1.51-1.48 (m，2H). LRMS (ESI):(計算值）564.2 (實測值）565.3 (MH)+ 實例122 (S)-6·⑽碳硫醯胺基)·ι_綱基小(4.苯基。塞e坐_2_基胺基）己烧_2_ 基胺基甲酸苄酯（153) 步驟1 : (S)-6-(肼碳硫醯胺基）-1_酮基_ι_(4-苯基嘧唑-2-基胺基） 己烷-2-基胺基甲酸苄酯（153) 於1，Γ-硫代羰基二咪唑（122毫克，0.684毫莫耳）在DMF (1 毫升）中之溶液内，在〇。(：下添加2 (300毫克，0.684毫莫耳）， 並將混合物在〇。(：下攪拌30分鐘，接著在室溫下1小時。然 後添加胼單水合物（68.5毫克，1.368毫莫耳），且將混合物擾 拌30分鐘’接著添加EtOAc與飽和NaHC03溶液，及分離有機 層’並以Na2S〇4脫水乾燥’且在真空下濃縮，及藉由層析， 使用己烷中之EtOAc (50至100%)純化，而得153 (18〇毫克， 51.3% 產率）’為白色泡沫物。（CD3〇D) d(ppm) 1H: 7 89 (dd，J=7 9, 1.4 Hz, 2H) ； 7.40-7.12 (m, 9H) ； 5.13 (d, 1=12.5 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 4.37-4.34 (m, 1H) ； 3.56 (t, J=7.0 Hz, 2H) ； 1.99-1.84 (m, 1H)； 1.81-1.75 (m, 1H) ； 1.65-1.60 (m, 2H) ； 1.53-1.43 (m, 2H). LRMS (ESI)： 134026-2 -184- 200916447 (計算值）512.2 (實測值）513.3 (MH)+ 實例123 ⑸-6-(甲基硫卡硫基胺基)小酮基4.(4.苯基嘍唑_2_基胺基）己 烷-2-基胺基甲酸芊酯（154) 步驟1: (S)-6-(甲基硫卡硫基胺基）小酮基小(4_笨基嘧唑_2_基胺 基）己烷-2-基胺基甲酸芊酯（154) 於2 (75宅克’ 0.Π1宅莫耳）在DCM (1.7毫升）中之溶液内， 在0 C下添加Et；3 N (26.2微升，0.188¾莫耳）與CS2 (11 34微升， 0.188宅莫耳）’並將溶液在〇°c下攪拌1小時，然後添加Mel (11.76微升，0.188 4莫耳），且使溫度溫熱至室溫，及將混 合物擾拌16小時。添加飽和ΝΗ4 α溶液，並將混合物以Et〇Ac 萃取，以Naz SO4脫水乾燥，濃縮，及藉由層析，以己烧中 之EtOAc (5至50%)純化，而得154 (50毫克，0.095毫莫耳，55.3% 產率）’為白色泡沐物。（CD30D) d(ppm) 1H : 7.90 (dd，J=8.4，1.4152: Example 121 Example 121 (5)-1·keto-1-(4-phenylpyrazol-2-ylamino)-6-(3,3,3-trifluoropropanethioguanamine)hexane- Benzyl 2-ylaminocarbamate (152) Step 1: (S)-l-keto-1-(4-styl P-Shen-2-ylamino)-6-(3,3,3- Benzyl trifluoropropylamino) hexane-2-ylcarbamate (151) was added to a solution of 2 (100 mg '0.228 mmol) in DCM (4.6 mL). 47.0 mg, 0.228 mmol, followed by DMAP (2.79 ^: g ' 0.023 house moles) and 3,3,3-trifluoropropionic acid (35 · 0 mg, 0.274 mmol). After stirring for 16 h, water was added and EtOAc EtOAc (EtOAc m. And 151 (69_0 mg, 55.2% yield). LRMS (ESI): (calc.) 548.6 (found) 549.3 (MH) + Step 2. (5)-1-decyl-1-(4-propenyl p-s-s-yl-2-ylamino)-6- (3,3,3-three said propyl thioguanamine) hexane-2-ylaminocarbazate (152) 151 (69.0 mg, as described in General Procedure E) at 〇 °C 0.126 134026-2 -183- 200916447 House Moore) in D1 (1 ml) with 2,4-bis(4-phenoxyphenyl)-1,3-monosulfide-2,4 - Two-filled tetrahydro-2,4-disulfide (166 mg, 〇·314 mmol). After chromatography in EtOAc (10 to 80%) eluting hexanes, Compound 152 (31.3 g. (cd3〇D) d(ppm) 1H : 7.89 (dd, J=8.4, 1.4 Hz, 2H); 7.41-7.12 (m, 9H); 5.14 (d, J=12.3 Hz, 1H); 5.09 (d, 1 = 12.5 Hz, 1H); 4.37-4.34 (m, 1H); 3.60 (t, J = 7.2 Hz, 2H); 3.54 (d, J = 10.2 Hz, 1H); 3.49 (d, J = 10.4 Hz, 1H) ; 1.91-1.70 (m, 4H) ; 1.51-1.48 (m, 2H). LRMS (ESI): (calculated) 564.2 (measured value) 565.3 (MH) + Example 122 (S)-6·(10) Carbon Thioguanamine)·ι_cylinder is small (4. phenyl. ese sitting _2_ylamino) hexane _2 benzyl carbamate (153) Step 1: (S)-6-(肼Carbothiolamino)-1-keto-_ι_(4-phenylpyrazol-2-ylamino)benzyl hexane-2-ylcarbamate (153) at 1, fluorene-thiocarbonyl A solution of diimidazole (122 mg, 0.684 mmol) in DMF (1 mL) in hydrazine. (: Add 2 (300 mg, 0.684 mmol), and mix the mixture in 〇. (: stir for 30 minutes, then at room temperature for 1 hour. Then add hydrazine monohydrate (68.5 mg, 1.368 mmol) And the mixture was stirred for 30 minutes' followed by the addition of EtOAc and sat. NaHCO3, and the organic layer was separated and dried <RTI ID=0.0> 50 to 100%) purified to give 153 (18 mg, 51.3% yield) as a white foam. (CD3 〇D) d (ppm) 1H: 7 89 (dd, J=7 9, 1.4 Hz, 2H) ; 7.40-7.12 (m, 9H) ; 5.13 (d, 1 = 12.5 Hz, 1H); 5.08 (d, J = 12.5 Hz, 1H); 4.37-4.34 (m, 1H) ; 3.56 (t, J =7.0 Hz, 2H) ; 1.99-1.84 (m, 1H); 1.81-1.75 (m, 1H) ; 1.65-1.60 (m, 2H) ; 1.53-1.43 (m, 2H). LRMS (ESI): 134026- 2 -184- 200916447 (calculated) 512.2 (measured value) 513.3 (MH) + Example 123 (5)-6-(methylthiocarbamoylamino) ketone group 4. (4. Phenylcarbazole_2_ Ethylamino) hexane-2-ylaminocarbazate (154) Step 1: (S)-6-(methylthiocarbamoylamino) ketone group small (4_ stupid Ethyl pyridyl-2-ylamino)hexane-2-ylaminocarbamate (154) in a solution of 2 (75 克 '0. Π1 house Moer) in DCM (1.7 mL) Add Et; 3 N (26.2 μl, 0.1883⁄4 m) and CS2 (11 34 μl, 0.188 house Moule) at 0 C and stir the solution for 1 hour at 〇 °c, then add Mel (11.76 μm) l, 0.188 4 moles, and allowed to warm to room temperature, and the mixture was stirred for 16 hours. Add saturated ΝΗ4 α solution, and extract the mixture with Et〇Ac, dehydrated with Naz SO4, concentrated, and borrowed Purified by chromatography, EtOAc (5 to 50%) eluted eluted eluted EtOAc : 7.90 (dd, J=8.4, 1.4

Hz, 2H), 7.41-7.13 (m, 9H) ； 5.14 (d, J=12.3 Hz, 1H) ； 5.08 (d, J=12.3 Hz, 1H) ； 4.36-4.33 (m, 1H) ； 3.68 (t, J=6.8 Hz, 2H) ； 2.53 (s, 3H) ； 1.88-1.67 (m，4H) ; 1.50-1.46 (m，2H). LRMS (ESI):(計算值）528 !(實測值） 529.3 (MH)+Hz, 2H), 7.41-7.13 (m, 9H); 5.14 (d, J = 12.3 Hz, 1H); 5.08 (d, J = 12.3 Hz, 1H); 4.36-4.33 (m, 1H); 3.68 (t , J=6.8 Hz, 2H) ; 2.53 (s, 3H) ; 1.88-1.67 (m, 4H) ; 1.50-1.46 (m, 2H). LRMS (ESI): (calculated) 528 ! (measured value) 529.3 (MH)+

圖式15 K2CO3, MeOH,0°C 程序IIScheme 15 K2CO3, MeOH, 0 °C Procedure II

實例124 ⑸-6·(2-羥基乙烷硫醯胺基）_1-酮基小(4笨基p塞嗤·2·基胺基）己 134026-2 -185- 200916447 烷-2-基胺基曱酸苄酯（155) 步驟1 : (S)-6-(2-羥基乙烷硫醯胺基）-1-酮基-1-(4-笨基嘧唑-2-基胺基）己烷-2-基胺基甲酸苄酯（155) 於149 (125.1毫克，0.226毫莫耳）在MeOH (2255微升）中之溶 液内，在0°C下添加K2C03 (94毫克，0.677毫莫耳），並將混 合物攪拌30分鐘，然後攪拌，添加EtOAc與飽和NaCl溶液， 且使有機萃液以Na2S04脫水乾燥，及濃縮，並使殘留物藉 層析，以己烷中之EtOAc (10至100%)純化，獲得155 (87.1毫克， 75% 產率），為白色固體。（CD30D) d(ppm) 1H : 7.89 (dd，J=8.4, 1.4 Hz, 2H) ； 7.40-7.13 (m, 9H) ； 5.13 (d, J=12.3 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 4.27 (s, 2H) ； 3.70 (t, J=7.4 Hz, 2H) ； 1.90-1.71 (m, 4H) ； 1.51-1.47 (m, 2H). LRMS (ESI):(計算值）512.2 (實測值）513.3 (MH)+Example 124 (5)-6·(2-Hydroxyethanethioguanidino)1-keto group small (4 phenyl group p 嗤 嗤 2 ylamino) 134026-2 -185- 200916447 alk-2-ylamine Benzyl phthalate (155) Step 1: (S)-6-(2-Hydroxyethanethioguanidino)-1-keto-1-(4-pyridylpyrazol-2-ylamino) Benzyl hexane-2-ylcarbamate (155) in a solution of 149 (125.1 mg, 0.226 mmol) in MeOH (2255 mL), EtOAc (EtOAc) The mixture was stirred for 30 minutes, then stirred, EtOAc and EtOAc EtOAc (EtOAc) Purification to 100%) gave 155 (87.1 mg, 75% yield) as a white solid. (CD30D) d(ppm) 1H : 7.89 (dd, J=8.4, 1.4 Hz, 2H); 7.40-7.13 (m, 9H); 5.13 (d, J=12.3 Hz, 1H); 5.08 (d, J= 12.5 Hz, 1H); 4.27 (s, 2H); 3.70 (t, J=7.4 Hz, 2H); 1.90-1.71 (m, 4H); 1.51-1.47 (m, 2H). LRMS (ESI): (calculation Value) 512.2 (measured value) 513.3 (MH)+

HN. DCM 0°C-^rt Cbz 圖式16HN. DCM 0°C-^rt Cbz Figure 16

DAST, K2C03 DCM,-78°C^r.t.DAST, K2C03 DCM, -78°C^r.t.

程序JJProgram JJ

NHBoc HN\ Cbz 157 1.TFA/ DCMNHBoc HN\ Cbz 157 1.TFA/ DCM

2.Me-CS-SEt, Et3NfTHF2.Me-CS-SEt, Et3NfTHF

158;實例 125 實例125 (lS)-5-乙烷硫醯胺基·1·(4·苯基_4,5_二氫哼唑·2·基）戊基胺基甲 酸苄酯（158) 步驟1 : (S)-6-第三-丁氧羰基胺基-l-((R)-2-羥基-1-苯基乙胺 134026-2 -186- 200916447 基）-1-酮基己-2-基胺基曱酸苄酯（156) 按一般程序FF中所述，於Z-Lys(Boc)-OH (500毫克，1.314毫 莫耳）之經攪拌溶液中，在0°C下添加（S)-(+)-2-苯基甘胺醇 (198毫克，1.446毫莫耳）與DCC (298毫克，1.446毫莫耳）。在 以己烷中之EtOAc (40至100%)層析後，獲得化合物156 (173.4 毫克，26.4%產率），為白色固體。LRMS (ESI):(計算值）499.6 (實測值）522.4 (MNa)+ 步驟2 : (lS)-5-第三-丁氧羰基胺基-1-(4-苯基-4,5-二氫哼唑-2-基）戊基胺基甲酸苄酯（157) 於156 (171毫克，0.342毫莫耳）在DCM (3.4毫升）中之溶液 内，在-78°C下逐滴添加DAST (47.5微升，0.359毫莫耳），並 將混合物在該溫度下攪拌2小時，然後以一份添加K2C03 (95 毫克，0.685毫莫耳），且將混合物在-78°C下攪拌15分鐘，接 著在室溫下20分鐘，傾倒於飽和NaHC03溶液上，並以DCM 萃取。使萃液以Na2S04脫水乾燥，濃縮，及以層析純化， 而得 157 (47 毫克，28.5% 產率）。LRMS (ESI):(計算值）481.6 (實 測值）482.4 (MH)+ 步驟3 : (lS)-5-乙烷硫醯胺基-1-(4-苯基-4,5-二氫崎唑-2-基）戊基 胺基甲酸苄酯（158) 按一般程序B中所述，將化合物157 (47毫克，0.098毫莫耳） 以TFA在DCE中之25%溶液（2毫升）處理，而得粗製胺，定量 產率。LRMS (ESI):(計算值）381.5 (實測值）382.3 (MH)+。按 一般程序G中所述，於0°C下，將THF中之此胺（65毫克，0.170 毫莫耳）以Et3N (47.5微升，0.341毫莫耳）與二硫基醋酸乙酯 134026-2 -187· 200916447 (29.3微升，0.256毫莫耳）處理，而得158 (5·6毫克，7·5%產率）， 為帶黃色膠質。 (CD30D) d(ppm) 1H : 7.36-7.28 (m，1〇Η); 5·22-5.20 (m，1H); 5.12 (s， 2H) ; 4.74 (t，J=7.0 Hz，1H) ; 4.44 (br, 1H) ; 4·16-4.12 (m，1H) ; 3.60 (br， 2H) ； 2.45 (s, 3H) ； 1.91-1.81 (m, 2H) ； 1-80Ί-61 (m, 2H) ； 1.60-1.40 2H). LRMS (ESI):(計算值）439.2 (實測值）440.3 (MH)+ 圖式l7158; Example 125 Example 125 (lS)-5-Ethylthioanthryl·1·(4-Phenyl-4,5-dihydrooxazole·2·yl)benzyl amyl carboxylate (158) Step 1: (S)-6-T-Butoxycarbonylamino-l-((R)-2-hydroxy-1-phenylethylamine 134026-2 -186- 200916447)-1-ketohexyl Benzyl-2-ylamino decanoate (156) in a stirred solution of Z-Lys(Boc)-OH (500 mg, 1.314 mmol) at 0 ° C as described in General Procedure FF (S)-(+)-2-Phenylglycolamine (198 mg, 1.446 mmol) was added with DCC (298 mg, 1.446 mmol). After chromatography in EtOAc (40 to 100%) elute LRMS (ESI): (calcd.) 499.6 (found) 522.4 (MNa)+ Step 2: (lS)-5-tris-butoxycarbonylamino-1-(4-phenyl-4,5-di Benzyl hydrocarbazol-2-yl)pentylaminocarboxylate (157) was added dropwise at -78 °C in a solution of 156 (171 mg, 0.342 mmol) in DCM (3.4 mL) (47.5 μl, 0.359 mmol), and the mixture was stirred at this temperature for 2 hours, then K2C03 (95 mg, 0.685 mmol) was added in one portion, and the mixture was stirred at -78 ° C for 15 min. Then, it was poured into a saturated NaHC03 solution at room temperature for 20 minutes, and extracted with DCM. The extract was dried (Na2SO4), dried and concentrated to purified LRMS (ESI): (calculated) 481.6 (found) 482.4 (MH) + Step 3: (lS)-5-ethanethioguanidino-1-(4-phenyl-4,5-dihydrosaki Benzazol-2-yl)pentylaminocarbamate (158) Compound 157 (47 mg, 0.098 mmol) was treated as a 25% solution (2 mL) of TFA in DCE as described in General Procedure B The crude amine was obtained in quantitative yield. LRMS (ESI): (calculated) 381.5 (found) 382.3 (MH)+. This amine (65 mg, 0.170 mmol) in THF was taken as Et3N (47.5 μL, 0.341 mmol) and ethyl dithioacetate 134026 at 0 ° C as described in General Procedure G. 2 -187· 200916447 (29.3 μl, 0.256 mmol) was treated with 158 (5.6 mg, 7.5% yield) with yellow gum. (CD30D) d (ppm) 1H: 7.36-7.28 (m, 1〇Η); 5·22-5.20 (m, 1H); 5.12 (s, 2H); 4.74 (t, J = 7.0 Hz, 1H); 4.44 (br, 1H) ; 4·16-4.12 (m,1H) ; 3.60 (br, 2H) ; 2.45 (s, 3H) ; 1.91-1.81 (m, 2H) ; 1-80Ί-61 (m, 2H ; 1.60-1.40 2H). LRMS (ESI): (calculated) 439.2 (measured value) 440.3 (MH) + Figure l7

162:實例126 實例126 (S)-5-(3-甲基硫脲基）.1.(5-苯基·ih.hi三唑各基）戊基胺恭〒 酸芊酯（162) 步驟1: (S)-6-第三-丁氡羰基胺基+肼基小酮基己冬基胺基平 酸苄酯（159) 於Z-Lys(Boc)-OH (2克，5.26毫莫耳）在DCM (52.6毫并）中之 134026-2 -188- 200916447 經攪拌溶液内，添加HOBT (0.805克，5.26毫莫耳）與1-(3-二曱 胺基丙基）-3-乙基碳化二亞胺鹽酸鹽（EDCI) (1.008克，5.26毫 莫耳）。使混合物冷卻至0°C，並快速添加肼單水合物（1.020 毫升，21.03毫莫耳）。於添加後，將混合物在0°C下攪拌1 小時，且在室溫下16小時，接著使混合物濃縮，添加水與 EtOAc，及分離有機層，並以Na2S04脫水乾燥，濃縮，及藉 由層析，使用DCM中之MeOH (0至10%)純化，而得159 (1.6519 克，80%產率），為白色固體。LRMS (ESI):(計算值）394·5 (實 測值）417.3 (MNa)+ 步驟2 :⑸-5-第三-丁氧羰基胺基-H5-苯基-1H-1,2,4-三唑-3-基） 戊基胺基甲酸苄酯（160) 於159 (200毫克，0.507毫莫耳）在THF (5070微升）中之混合 物内，添加苯并醯亞胺酸甲酯鹽酸鹽（91毫克，0.532毫莫 耳），接著為Et3N (74.2微升，0.532毫莫耳），並將溶液於回 流下加熱16小時。使混合物濃縮，且藉由層析，使用己烷 中之EtOAc (40至100%)純化，而得160 (266毫克，定量產率）， 為透明油。LRMS (ESI):(計算值）479.6 (實測值）480.4 (MH)+ 步驟3 : (S)-5-胺基-1-(5-苯基-1Η-1,2,4-三唑-3-基）戊基胺基甲酸 苄酯（161) 按一般程序B中所述，將化合物160 (266毫克，0.555毫莫 耳）以255 TFA在DCE中之溶液（5毫升）處理，而得161 (117毫 克，42.7% 產率）。LRMS (ESI):(計算值）379.5 (實測值）380.3 (MH)+ 步驟4 : (S)-5-(3-曱基硫脲基）-1-(5-苯基-1H-1，2,4-三唑-3-基）戊基 134026-2 -189- 200916447 胺基曱酸苄酯（162) 按一般程序C中所述，於〇°C下，將161 (200毫克，0.405毫 莫耳）與Et3N (226微升，1.621毫莫耳）在DCM (1.61毫升）中之 溶液，以硫代光氣（46.6微升’ 0.608毫莫耳），接著以曱胺（381 毫克，4.05毫莫耳’ 33%重量，在乙醇中）處理，而得162 (41 毫克 ’ 22.4% 產率），為白色固體。（CD30D) d(ppm) 1H : 7.97 (br， 2H) ； 7.47 (br, 3H) ； 7.38-7.20 (m, 5H) ； 5.14 (d, J=12.3 Hz, 1H) ； 5.08 (d, J=12.7 Hz, 1H) ； 4.89-4.87 (m, 1H) ； 3.43-3.32 (m, 2H) ； 2.90 (br, 3H)； 2.16-1.91 (m, 2H) ； 1.65-1.62 (m, 2H) ； 1.46-1.40 (m, 2H). LRMS (ESI) · (計算值）452.2 (實測值）453.3 (MH)+ 實例127 (S)-l-(5-苯基-1H-1，2,4-三》坐-3·基)-5-硫I尿基戊基胺基甲酸爷酯 (163) 按一般程序C中所述’於0°c下，將DCM (1.6毫升）中之胺 161 (200毫克，〇·4〇5毫莫耳）與Et3N (226微升，1.621毫莫耳） 以硫代光氣（46.6微升’ 0.608毫莫耳），接著以氨（7N，在MeOH 中’ 5乃微升，4.05毫莫耳）處理，而得164 (30毫克，16.9%產 率）’為米黃色固體。（CD30D) d(ppm) 1H : 7.97-7.96 (m，2H); 7.48-7.46 (m, 3H) ； 7.37-7.20 (m, 5H) ； 5.13 (d, J=12.3 Hz, 1H) ； 5.07 (d, J=12.5 Hz, 1H) ； 4.87-4.85 (m, 1H) ； 3.47 (br, 1.35H) ； 3.11 (br, 0.65H)； 1.96-1.92 (m, 2H) ； 1.61-1.60 (m, 2H) ； 1.50-1.39 (m, 2H). LRMS (ESI)： (計算值）438.2 (實測值）439.3 (MH)+ 實例128 ⑸·5_乙烷硫醯胺基小(5-苯基.出·^·三唑·3·基）戊基胺基甲 134026-2 -190· 200916447 酸苄酯（164) 按一般程序G中所述，於0°C下，將THF中之胺161 (100毫 克，0.203毫莫耳）與Et3N (85微升，0.608毫莫耳）以二硫基醋 酸乙酯（34.9微升，0.304毫莫耳）處理，在以己烷中之EtOAc (40 至100%)層析後，獲得164 (21毫克，23.7%產率），為透明膠 質。（CDC13) 5 (ppm) 1H: 7.93-7.91 (m，2H); 7.41-7.37 (m，3H); 7.30-7.27 (m, 5H)； 5.12 (d, J=12.1 Hz, 1H)； 5.02-4.99 (m, 2H) ； 3.59-3.57 (m, 2H)； 2.44 (s, 3H) ； 2.07-1.89 (m, 2H) ； 1.68-1.63 (m, 2H) ； 1.46-1.40 (m, 2H). LRMS (ESI):(計算值）437.2 (實測值）438.3 (MH)+162: Example 126 Example 126 (S)-5-(3-methylthioureido).1. (5-phenyl·ih.hi triazole) pentylamine 〒 芊 ( (162) Step 1: (S)-6-Third-butyrylcarbonylamino + fluorenyl ketohexylhexylaminomethyl benzylate (159) in Z-Lys(Boc)-OH (2 g, 5.26 mmol) Ear) 134026-2 -188- 200916447 in DCM (52.6 mA), added HOBT (0.805 g, 5.26 mmol) and 1-(3-dioguanylpropyl)-3- in a stirred solution Ethylcarbodiimide hydrochloride (EDCI) (1.008 g, 5.26 mmol). The mixture was cooled to 0 ° C and hydrazine monohydrate (1.020 mL, 21.03 mmol) was added quickly. After the addition, the mixture was stirred at 0 ° C for 1 hour and at room temperature for 16 hours, then the mixture was concentrated, water and EtOAc was added, and the organic layer was separated and dried over Na 2 EtOAc. Purified by MeOH (0 to 10%) eluted elute LRMS (ESI): (calculated) 394·5 (found) 417.3 (MNa)+ Step 2: (5)-5-tris-butoxycarbonylamino-H5-phenyl-1H-1,2,4- Benzyl-3-yl)methyl amyl amide (160) In a mixture of 159 (200 mg, 0.507 mmol) in THF (5070 μl), methyl benzoquinone Acid salt (91 mg, 0.532 mmol) followed by Et3N (74.2 <RTIgt; The mixture was concentrated and purified by EtOAc EtOAc (EtOAc) LRMS (ESI): (calc.) 479.6 (found): 480.4 (MH) + Step 3: (S)-5-amino-1-(5-phenyl-1Η-1,2,4-triazole- Benzyl 3-yl)pentylaminocarboxylate (161) Compound 160 (266 mg, 0.555 mmol) was treated as a solution of 255 TFA in DCE (5 mL). 161 (117 mg, 42.7% yield). LRMS (ESI): (calculated) 379.5 (found) 380.3 (MH) + Step 4: (S)-5-(3-mercaptothioureido)-1-(5-phenyl-1H-1, 2,4-Triazol-3-yl)pentyl 134026-2 -189- 200916447 Benzyl decanoate (162) 161 (200 mg, 0.405) at 〇 ° C as described in General Procedure C a solution of Et3N (226 μl, 1.621 mmol) in DCM (1.61 mL) with thiophosgene (46.6 μl '0.608 mmol) followed by decylamine (381 mg, </ RTI> </ RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; (CD30D) d(ppm) 1H : 7.97 (br, 2H) ; 7.47 (br, 3H) ; 7.38-7.20 (m, 5H) ; 5.14 (d, J = 12.3 Hz, 1H) ; 5.08 (d, J= 12.7 Hz, 1H); 4.89-4.87 (m, 1H); 3.43-3.32 (m, 2H); 2.90 (br, 3H); 2.16-1.91 (m, 2H); 1.65-1.62 (m, 2H); -1.40 (m, 2H). LRMS (ESI) · (calculated) 452.2 (measured value) 453.3 (MH) + Example 127 (S)-l-(5-phenyl-1H-1,2,4-three "Sit-3-yl"-5-thiol-ureido-amylaminocarbamate (163) Amine 161 (200 in DCM (1.6 mL) at 0 ° C as described in General Procedure C Mg, 〇·4〇5 mmol) with Et3N (226 μl, 1.621 mmol) with thiophosgene (46.6 μl '0.608 mmol) followed by ammonia (7N in MeOH '5 It was slightly liter, 4.05 mmol, and 164 (30 mg, 16.9% yield) was obtained as a beige solid. (CD30D) d(ppm) 1H : 7.97-7.96 (m, 2H); 7.48-7.46 (m, 3H); 7.37-7.20 (m, 5H); 5.13 (d, J = 12.3 Hz, 1H); 5.07 ( d, J = 12.5 Hz, 1H); 4.87-4.85 (m, 1H); 3.47 (br, 1.35H); 3.11 (br, 0.65H); 1.96-1.92 (m, 2H); 1.61-1.60 (m, 2H) ; 1.50-1.39 (m, 2H). LRMS (ESI): (calc.) 438.2 (measured value) 439.3 (MH) + Example 128 (5)·5_ethanethioguanamine small (5-phenyl. ····Triazole·3·yl)pentylaminomethyl 134026-2 -190· 200916447 Benzyl acrylate (164) The amine 161 in THF was 100 mg, 0.203 mmol, and Et3N (85 μL, 0.608 mmol) treated with ethyl dithioacetate (34.9 μL, 0.304 mmol) in EtOAc (40 to 100) %) After chromatography, 164 (21 mg, 23.7% yield) was obtained as a clear gum. (CDC13) 5 (ppm) 1H: 7.93-7.91 (m, 2H); 7.41-7.37 (m, 3H); 7.30-7.27 (m, 5H); 5.12 (d, J = 12.1 Hz, 1H); 4.99 (m, 2H) ; 3.59-3.57 (m, 2H); 2.44 (s, 3H) ; 2.07-1.89 (m, 2H) ; 1.68-1.63 (m, 2H) ; 1.46-1.40 (m, 2H). LRMS (ESI): (calculated) 437.2 (measured) 438.3 (MH)+

NHBoc Cbz 159 圖式18NHBoc Cbz 159 Figure 18

NaOH, EtOHNaOH, EtOH

NHBoc 二曱苯 110°C 0 至 60GC Cbz 程序MM 165 程序NNNHBoc diphenyl benzene 110 ° C 0 to 60 GC Cbz program MM 165 program NN

NHBoc 167:實例 129NHBoc 167: Example 129

1. TFA/ DCM 2. EtS-SC-Me, Et3N, THF1. TFA/ DCM 2. EtS-SC-Me, Et3N, THF

r 實例129 ⑸-5-乙烷硫醯胺基-1_(5·甲基-1H-1，2,4-三唑-3-基）戊基胺基曱 酸苄酯（167) 步驟1 : (S)-6-第三-丁氧羰基胺基-1-(2-(1-亞胺基乙基）胼基）-i-酮基己-2-基胺基甲酸苄酯（165) 於0°C下，將乙醯亞胺酸乙酯鹽酸鹽（128毫克，1.035毫莫 耳）添加至氫氧化鈉（41.4毫克，1.035毫莫耳）在乙醇（4.7毫 134026-2 200916447 升）中之溶液内。在攪拌15分鐘後，濾出此懸浮液，並將濾 液置於密封管中，且逐滴添加159 (371.3毫克，〇·941毫莫耳） 在乙醇（4.7毫升）中之溶液。將混合物在6〇。〇下加熱16小 時，濃縮，及藉層析純化，而得165。LRMS (ESI):(計算值） 435.5 (實測值）436·3 (MH)+ 步驟2 : (S)-5-第三-丁氧羰基胺基-1-(5-甲基-1H-1，2,4-三唑各基） 戊基胺基甲酸苄酯（166) 將化合物165 (410毫克，〇·941毫莫耳）於密封管中，在二 甲苯（9.4毫升）中’於ll〇°C下加熱數小時。然後使其濃縮， 並藉由層析，使用己烷中之EtO Ac (50%-100%)，接著以段〇 Ac 中之 MeOH (0-10%)純化’而得 166 (373.3 毫克，95% 產率）。LRMS (ESI):(計算值）417.5 (實測值）418.4 (MH)+ 步驟3 : (S)-5-乙烧硫醯胺基-1-(5-曱基-1H-1，2,4-三°坐-3-基）戊基 胺基曱酸苄酯（167) 按一般程序B中所述’將化合物166 (373毫克，0.893毫莫 耳）以DCE中之25% TFA (4毫升）處理，並將粗製胺以本身使 用於下一步驟。按一般程序G中所述，於〇。〇下，將THF中 之胺（145毫克，0.336毫莫耳）與EtsN (187微升，1.344毫莫耳） 以二硫基醋酸乙自旨（57.8微升，0.504毫莫耳）處理，在以DCM 中之MeOH (0至15%)層析後’獲得167 (39.7毫克，0.106毫莫 耳 ’ 31.5% 產率），為白色固體。（CD3〇D) ό' (ppm) 1H : 7.37-7.29 (m, 5H) ； 5.12 (d, J=12.5 Hz, 1H) ； 5.05 (d, J=12.5 Hz, 1H) ； 4.77 (t, J=7.6 Hz, 1H) ； 3.55 (t, J=7.4 Hz, 2H) ； 2.43 (s, 3H) ； 2.39 (s, 3H) ； 2.01-1.83 (m，2H) ; 1.70-1.63 (m，2H) ; 1·43-1·29 (m，2H). LRMS (ESI):(計算 134026-2 -192- 200916447 值）375.2 (實測值）376.3 (MH)+ 圖式19r Example 129 (5)-5-Ethylthioguanidino-1_(5·methyl-1H-1,2,4-triazol-3-yl)pentylamino decanoate (167) Step 1: (S)-6-Benzyl-butoxycarbonylamino-1-(2-(1-iminoethyl)indolyl)-i-ketohexan-2-ylcarbamate (165) Ethyl acetimidate hydrochloride (128 mg, 1.035 mmol) was added to sodium hydroxide (41.4 mg, 1.035 mmol) in ethanol (4.7 s 134026-2 200916447 liters) at 0 °C. In the solution. After stirring for 15 minutes, the suspension was filtered, and the filtrate was placed in a sealed tube, and a solution of 159 (371.3 mg, 941·941 mmol) in ethanol (4.7 ml) was added dropwise. The mixture was placed at 6 Torr. The mixture was heated under heating for 16 hours, concentrated, and purified by chromatography to yield 165. LRMS (ESI): (calculated) 435.5 (found) 436·3 (MH)+ Step 2: (S)-5-tris-butoxycarbonylamino-1-(5-methyl-1H-1 , 2,4-triazoleyl) benzyl amyl amide (166) Compound 165 (410 mg, 〇·941 mmol) in a sealed tube in xylene (9.4 mL) Heat at 〇 ° C for several hours. It was then concentrated and purified by chromatography using EtOAc (50% - 100%) eluting EtOAc EtOAc (0-10%) % Yield). LRMS (ESI): (calculated) 417.5 (found) 418.4 (MH) + Step 3: (S)-5-ethyl thioanthramine-1-(5-mercapto-1H-1,2,4 - Benzyl-3-yl)pentylamino benzyl decanoate (167) As described in General Procedure B, 'Compound 166 (373 mg, 0.893 mmol) to 25% TFA in DCE (4 mL) The treatment is carried out and the crude amine is used as such in the next step. As described in General Procedure G, Yu Yu. Under the arm, the amine in THF (145 mg, 0.336 mmol) and EtsN (187 μL, 1.344 mmol) were treated with dithioacetic acid (57.8 μL, 0.504 mmol). Chromatography of MeOH (0 to 15%) in DCM afforded 167 (39.7 mg, 0.106 <RTIgt; (CD3〇D) ό' (ppm) 1H : 7.37-7.29 (m, 5H) ; 5.12 (d, J=12.5 Hz, 1H); 5.05 (d, J=12.5 Hz, 1H) ; 4.77 (t, J 7.6 Hz, 1H) ; 1·43-1·29 (m, 2H). LRMS (ESI): (calculated 134026-2 -192- 200916447 value) 375.2 (measured value) 376.3 (MH) + Figure 19

實例147 ⑻-5_(3-曱基硫脲基)-1-(5-(莕-2-基)-1Η-峨唑-3-基）戊基胺基甲酸 苄酯（187) 步驟1 _ (S)-8-弟二-丁氧搂基胺基-1-(奈-2-基）-1,3-二嗣基辛-4-基胺基甲酸芊酯（185) 於 Z-Lys(Boc)-OH (1.5 克，3.94 毫莫耳）在 THF (19.7 毫升）中之 經攪拌溶液内，在室溫下添加1-氯-Ν,Ν,2-三曱基-1-丙烯基胺 (0.574毫升，4.34毫莫耳），並將混合物攪拌1小時。於另一 個圓底燒瓶中，將THF中之2’-曱莕酮（1342毫克，7.89毫莫耳） 添加至LDA之剛製成-78°C溶液（藉由於〇°C下，THF中之二異 丙基胺（1.124毫升，7.89毫莫耳）添加至n-BuLi (3.15毫升，7.89 毫莫耳）中而製成）中，且將溶液攪拌30分鐘，接著，將其 添加至上文製成之氣化醯中，並將反應混合物於-78°C下攪 拌30分鐘。添加飽和NH4C1溶液，及將此物質以EtOAc萃取， 134026-2 -193 - 200916447 並使有機萃液以Na2 S04脫水乾燥，濃縮，及藉由層析，使 用己烷中之EtOAc (5至50%)純化，而得185 (825.4毫克，39.3% 產率），為帶黃色油。LRMS (ESI):(計算值）532.6 (實測值）531.0 (M-H)+ 步驟2 : (S)-5-第三-丁氧羰基胺基-1-(5-(莕-2-基）-1Η-吡唑-3-基） 戊基胺基曱酸苄酯（186) 將185 (100毫克，0.188毫莫耳）、AcOH (9.4毫升）及肼單水 合物（27.3微升，0.563毫莫耳）之混合物在密封管中，於90°C 下加熱2小時。於冷卻後，使混合物在減壓下濃縮，添加 EtOAc與飽和NaHC03溶液，及分離有機層，並以Na2S04脫水 乾燥，濃縮，及藉由層析，使用己烷中之EtOAc (20至80%) 純化，而得186 (71.8毫克，72.3%產率）。LRMS (ESI):(計算 值）528.6 (實測值）529.5 (MH)+ 步驟3: (S)-5-(3-甲基硫脲基）-1-(5-(莕-2-基）-1Η-吡唑-3-基）戊基胺 基曱酸苄酯（187) 按一般程序B中所述，將化合物186 (71.8毫克，0.136毫莫 耳）以DCE中之25% TFA (2毫升）處理，而得胺，定量產率。 按一般程序G中所述，將THF (906微升）中之粗製胺（73.7 毫克，0.136毫莫耳）與Et3N (56.8微升，0.408毫莫耳）以異硫 氰酸曱酯（11.92毫克，0.163毫莫耳）處理，在以己烷中之EtOAc (50至100%)層析後，獲得187 (38.2毫克，56.1%產率），為白 色固體（CD30D) d(ppm) 1H: 8.18 (s，1H); 7.89-7.83 (m, 4H); 7.550-7.44 (m, 2H) ； 7.37-7.25 (m, 5H) ； 6.67 (s, 1H) ； 5.13 (d, J=12.5 Hz, 1H) ； 5.08 (d, J=12.3 Hz, 1H) ； 4.85-4.81 (m, 1H) ； 3.42 (br, 2H) ； 2.89 (br, 3H)； 134026-2 -194- 200916447 1.99-1.84 (m, 2H) ； 1.65-1.59 (m, 2H) ； 1.49-1.36 (m, 2H). LRMS (ESI)： (計算值）501.2 (實測值）502.4 (MH)+ 表3中所舉例之其他化合物係以所指示之起始物質開 始，並按照所予之製備順序，利用表4中所列示之一般程序 製成。 134026-2 195- 200916447 製備順序 〇 Ν，0 i N，0 特徵鑒定 (dmso-d6) d(ppm) 1H ： 9.96 (s, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.38-7.21 (m, 5H), 6.89 (s, 2H), 5.02 (q, J=13 Hz, 2H), 4.61 (q, J=6.1 Hz, 1H), 3.40 (t, J=7.2 Hz, 2H), 2.36 (s, 3H), 1.92-1.65 (m, 2H), 1.53 (qi, J=7.0 Hz, 2H), 1.40-1.19 (m，2H). LRMS (ESI):(計算值） 360.2 (實測值）361.2 (MH)+ (dmso-d6) d(ppm) 1Η：9.95 (s, 1Η), 7.62 (bd, J=8.0 Hz, 2H), 7.55-7.15 (m, 6H), 6.89 (d, J=8.4 Hz，2H)，5.02 (d，J=9.0 Hz，2H)，4.61 (q, J=6.3 Hz, 1H), 3.73 (s, 3H), 3.40 (m, 2H), 2.34 (s, 3H), 1.95-1.68 (m, 2H), 1.54 (qi, J=7.2 Hz，2H)，1.43-1.18 (m，2H)_ LRMS (ESI):(計算值)466.2 (實涓丨J值)467.4 (MH)+ (dmso-d6) d(ppm) 1H ： 11.97 (s, 1H), 9.95 (s, 1H), 7.67-7.66 (m, 3H), 7.50-7.46 (m, 3H), 7.35-7.28 (m, 5H), 5.02 (d, J=8.8 Hz, 2H), 4.62 (q, J=5.9 Hz, 1H), 3.33 (m, 2H), 2.34 (s, 3H), 1.98-1.68 (m, 2H), 1.54 (qi, J=6.5 Hz, 2H), 1.42-1.21 (m, 2H). LRMS (ESI):(計算 值）514.1 (實測值）515.3, 517.3 (MH)+ 結構 H H&amp;丫 0 S 〇、Bn (S)-5-乙烷硫醯胺基咪唑-2-基） 戊基胺基甲酸苄酯 HN^O S 〇、Bn (S)-5-乙烷硫醯胺基-1-(5-(4-甲氧苯 基)-.1Η-咪唑-2-基)戊基胺基甲酸芊酯 H HlQ丫。 s 〇、Bn (S)-1 -(5-(4-溴苯基)-1H-咪唑-2-基)-5-乙 烷硫醯胺基戊基胺基甲酸苄酯 起始物質 〆〇 /Η S pH 巳 η 〇 25 + NH4OAc/AcOH °° S ' 1 ^ 工 化合物 5 S (Ν m r〇 ΓΟ 196- 134026-2 200916447 製備順序 Ν,Ο 〇 0； 特徵鑒定 (CD30D) d(ppm) 1H ： 8.27 (s, 1H), 8.16 (s, 1H), 7.87-7.78 (m, 4H), 7.49-7.41 (m, 3H), 7.36-7.02 (m, 5H), 5.13 (t, J=12 Hz, 2H), 4.85-4.82 (m, 1H), 3.57 (t, J=6.9 Hz, 2H), 2.41 (s, 3H), 2.08-1.88 (m, 2H), 1.70 (qi, J=7.4 Hz, 2H), 1.57-1.32 (m, 2H). LRMS (ESI):(計算值）486.2(實測值）487.3 (MH)+ (CD30D) d(ppm) 1H ： 8.22 (s, 1H), 7.66 (d, J-8.4 Hz, 2H), 7.38-7.02 (m, 8H), 5.11 (t, J=12 Hz, 2H), 4.84-4.74 (m, 1H), 3.56 (t, J=6.9 Hz, 2H), 2.41 (s, 3H), 2.03-1.85 (m, 2H)，1.67 (qi, J=7.1 Hz, 2H), 1.55-1.30 (m, 2H). LRMS (ESI):(計算值）470.2 (實測值） 471.3 (MH)+ 結構 Ly H h^〇 I T 〇、Bn (SK)-乙烷硫醯胺基-1-(5-(苯-2-基)-lH-咪唑-2-基)戊基胺基甲酸芊酯 \ i IZ\ 砟餵 / fl λ II U Ϊ3 II 起始物質 1 ^ 〇=&lt;〇 Ο 工 CQ 1： · 5 工 CQ 化合物 5 -197 · 134026-2 200916447Example 147 (8)-5-(3-Mercaptothioureido)-1-(5-(indol-2-yl)-1Η-indazol-3-yl)pentylaminocarbamate (187) Step 1 _ (S)-8-di-butyl-butoxy-amino-l-(in-2-yl)-1,3-didecyloctyl-4-ylaminocarbazate (185) in Z-Lys (Boc)-OH (1.5 g, 3.94 mmol) in a stirred solution of THF (19.7 mL), 1-chloro-indole, hydrazine, 2-trimercapto-1-propenyl at room temperature Amine (0.574 mL, 4.34 mmol) and the mixture was stirred 1 hr. In another round bottom flask, 2'-fluorenone (1342 mg, 7.89 mmol) in THF was added to the solution of LDA at -78 ° C (by 〇 ° C, in THF) Diisopropylamine (1.124 ml, 7.89 mmol) was added to n-BuLi (3.15 mL, 7.89 mmol), and the solution was stirred for 30 minutes, then added to the above The mixture was gasified and the reaction mixture was stirred at -78 ° C for 30 minutes. A saturated NH4C1 solution was added and the material was extracted with EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc Purified to give 185 (825.4 mg, 39.3% yield) as a yellow oil. LRMS (ESI): (calc.) 532.6 (found) 531.0 (MH) + Step 2: (S)-5-tris-butoxycarbonylamino-1-(5-(indol-2-yl)- 1Η-pyrazol-3-yl) benzyl amyl decanoate (186) 185 (100 mg, 0.188 mmol), AcOH (9.4 mL) and hydrazine monohydrate (27.3 μL, 0.563 mmol) The mixture of the ears was heated in a sealed tube at 90 ° C for 2 hours. After cooling, the mixture was concentrated under reduced EtOAc. EtOAc (EtOAc)EtOAc. Purification gave 186 (71.8 mg, 72.3% yield). LRMS (ESI): (calculated) 528.6 (found) 529.5 (MH) + Step 3: (S)-5-(3-methylthioureido)-1-(5-(indol-2-yl) -1 Η-pyrazol-3-yl)pentylamino decanoic acid benzyl ester (187) Compound 186 (71.8 mg, 0.136 mmol) as 25% TFA in DCE as described in General Procedure B (2) ML) treatment, yielding amine, quantitative yield. The crude amine (73.7 mg, 0.136 mmol) in THF (906 μL) and Et3N (56.8 μL, 0.408 mmol) as decyl isothiocyanate (11.92 mg) as described in General Procedure G </ RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; (s, 1H); 7.89-7.83 (m, 4H); 7.550-7.44 (m, 2H); 7.37-7.25 (m, 5H); 6.67 (s, 1H); 5.13 (d, J=12.5 Hz, 1H 5.08 (d, J = 12.3 Hz, 1H); 4.85-4.81 (m, 1H); 3.42 (br, 2H); 2.89 (br, 3H); 134026-2 -194- 200916447 1.99-1.84 (m, 2H) ; 1.65-1.59 (m, 2H) ; 1.49-1.36 (m, 2H). LRMS (ESI): (calculated) 501.2 (measured value) 502.4 (MH)+ Other compounds exemplified in Table 3 are The indicated starting materials were started and made according to the general procedure shown in Table 4 in the order of preparation. 134026-2 195- 200916447 Preparation sequence 〇Ν, 0 i N,0 Characterization (dmso-d6) d(ppm) 1H : 9.96 (s, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.38- 7.21 (m, 5H), 6.89 (s, 2H), 5.02 (q, J=13 Hz, 2H), 4.61 (q, J=6.1 Hz, 1H), 3.40 (t, J=7.2 Hz, 2H), 2.36 (s, 3H), 1.92-1.65 (m, 2H), 1.53 (qi, J=7.0 Hz, 2H), 1.40-1.19 (m, 2H). LRMS (ESI): (calculated) 360.2 (measured value) 361.2 (MH)+ (dmso-d6) d(ppm) 1Η:9.95 (s, 1Η), 7.62 (bd, J=8.0 Hz, 2H), 7.55-7.15 (m, 6H), 6.89 (d, J =8.4 Hz, 2H), 5.02 (d, J=9.0 Hz, 2H), 4.61 (q, J=6.3 Hz, 1H), 3.73 (s, 3H), 3.40 (m, 2H), 2.34 (s, 3H) ), 1.95-1.68 (m, 2H), 1.54 (qi, J=7.2 Hz, 2H), 1.43-1.18 (m, 2H)_ LRMS (ESI): (calculated) 466.2 (actual J value) 467.4 (MH)+ (dmso-d6) d(ppm) 1H : 11.97 (s, 1H), 9.95 (s, 1H), 7.67-7.66 (m, 3H), 7.50-7.46 (m, 3H), 7.35-7.28 (m, 5H), 5.02 (d, J=8.8 Hz, 2H), 4.62 (q, J=5.9 Hz, 1H), 3.33 (m, 2H), 2.34 (s, 3H), 1.98-1.68 (m, 2H), 1.54 (qi, J=6.5 Hz, 2H), 1.42-1.21 (m, 2H). LRMS (ESI): (calc.) 514.1 (measured) 515.3, 517.3 (M H)+ Structure H H&amp;丫0 S 〇, Bn (S)-5-ethanethioguanidinoimidazol-2-yl) benzyl amyl amide HN^OS 〇, Bn (S)-5- Ethyl thioguanamine-1-(5-(4-methoxyphenyl)-.1Η-imidazol-2-yl)pentylaminocarbazate H HlQ丫. s 〇, Bn (S)-1 -(5-(4-bromophenyl)-1H-imidazol-2-yl)-5-ethane thiononylaminopentylcarbamate starting material 〆〇 /Η S pH 巳η 〇25 + NH4OAc/AcOH °° S ' 1 ^ Compound 5 S (Ν mr〇ΓΟ 196- 134026-2 200916447 Preparation sequence Ο, Ο 〇0; Characterization (CD30D) d (ppm) 1H : 8.27 (s, 1H), 8.16 (s, 1H), 7.87-7.78 (m, 4H), 7.49-7.41 (m, 3H), 7.36-7.02 (m, 5H), 5.13 (t, J=12 Hz, 2H), 4.85-4.82 (m, 1H), 3.57 (t, J=6.9 Hz, 2H), 2.41 (s, 3H), 2.08-1.88 (m, 2H), 1.70 (qi, J=7.4 Hz , 2H), 1.57-1.32 (m, 2H). LRMS (ESI): (calculated) 486.2 (measured value) 487.3 (MH) + (CD30D) d (ppm) 1H : 8.22 (s, 1H), 7.66 ( d, J-8.4 Hz, 2H), 7.38-7.02 (m, 8H), 5.11 (t, J=12 Hz, 2H), 4.84-4.74 (m, 1H), 3.56 (t, J=6.9 Hz, 2H ), 2.41 (s, 3H), 2.03-1.85 (m, 2H), 1.67 (qi, J=7.1 Hz, 2H), 1.55-1.30 (m, 2H). LRMS (ESI): (calculated) 470.2 ( Found 471.1 (MH)+ Structure Ly H h^〇IT 〇, Bn (SK)-Ethylthioguanidino-1-(5-(phenyl-2-yl)-lH-imidazol-2-yl) Ethyl amyl amide \ i IZ\ 砟 feed / fl λ II U 3 II starting material 1 billion ^ = &lt; square Ο working CQ 1: · 5 · work CQ Compound 5-197 200916447 134026-2

V 製備順序| K,P,Q Β,Ν 特徵鑒定 (dmso-d6) d(ppm) 1H: 11.91 (s, 1H), 9.94 (s， 1H), 8.73 (s, 1H), 7.93 (d, J=TA Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.59-7.54 (m, 2H), 7.39 (t, J=6.8 Hz, 1H), 7.15 (d, J=8.8 Hz, 1H), 4.63 (q, J=6.5 Hz, 1H), 4.11 (s, 3H), 3.51-3.40 (m, 2H), 2.34 (s, 3H), 1.97-1.68 (m, 2H), 1.56 (qi, J=7.2 Hz, 2H), 1.38 (s, 9H), 1.40-1.21 (m, 2H). LRMS (ESI):(計算 值）483.2 (實測值）484.4 (MH)+ i__— (dmso-d6) d(ppm) 1H ： 12.03 (s, 1H), 9.95 (s, 1H), 8.72 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 7.92 (d, J=7.6 Hz, 1H), 7.74 (d, J=8.6 Hz, 1H), 7.59-7.55 (m, 2H), 7.39 (t, J=7.4 Hz, 1H), 4.95 (q, J-7.1 Hz, 1H), 4.11 (s, 3H), 3.58-3.39 (m, 4H), 3.33-3.18 (m, 3H), 2.34 (s, 3H), 2.24 (s, 3H), 2.02-1.91 (m, 1H), 1.85-1.69 (m, 1H), 1.57 (qi, J=7.4 Hz, 2H), 1.41-1.22 (m, 2H). LRMS (ESI):(計算值） 480.2 (實測值）481.4 (MH)+ 結構 OMe HN 丫。 S 〇七 (S)-:5-乙烷硫醯胺基-1-(5-(2-甲氧基喳 啉-3-基)-1 Η-咪唑-2-基)戊基胺基甲酸 第三-丁酯 ^ A ^ 〇 j：兩 ri: its ^Y° U IIT 起始物質 ...... .i 1 ΗΟ 人〆Ν Η2 Ο丫 Ι^ΙΗ 十 + N 〇Me OMe 州丫0 S 1 51 〇、/ + 〇，z〇H Λ 化合物 ro \〇 S -198- 134026-2 200916447 m 1¾ PQ Ο α： Ν 齣 靼 (dmso-d6) d(ppm) 1H ： 11.96 (s, 1H), 9.94 (s, 1H), 8.72 (s, 1H), 8.13 (d, J=8.2 Hz, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H)，7.57 (s, 1H), 7.57 (t，J=6.9 Hz, 1H), 7.39 (t, J=7.2 Hz, 1H), 4.93 (q, J=5.9 Hz, 1H), 4.10 (s, 3H), 3.43 (qi, J=4.5 Hz, 2H), 2.85-2.73 (m, 2H), 2.34 (s, 3H), 2.21-2.15 (m, 1H), 2.13 (s, 3H), 2.02-1.53 (m, 10H), 1.42-1.21 (m, 2H). LRMS (ESI):(計算值） 508.3 (實測值）509.2 (MH)+ (dmso-d6) d(ppm) 1Η ： 11.90 (s, 1H), 8.73 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.59-7.54 (m, 2H), 7.49-7.30 (m, 3H), 7.14 (d, J=8.4 Hz, 1H), 4.62 (q, J=6.5 Hz, 1H), 4.11 (s, 3H), 3.40-3.32 (m, 2H), 2.77 (bs, 3H), 1.98-1.65 (m, 2H), 1.58-1.20 (m, 4H), 1.38 (s，9H). LRMS (ESI):(計算 值）498.2 (實測值）499.4 (MH)+ 破 i 工Ζ 丨、入 〉 ν ^ (Η&gt;_Ρ 魏丄-了輿 Ψ ^-HT a k -ζ)-ς)-1 -(s) /、〇 S 0 人 NH Θ1ΛΙΟ 工2 身。' R&gt;- ό&quot; ΘΙΛΙΟ N 八 H〇^0〇 + 〇/\ HN人O &lt;0 ；〇 ¥ 3 -199- 134026-2 200916447 製備順序 P, Q, B, C P,Q,B,C 特徵鑒定 (dmso-d6) d(ppm) 1H： 11.89 (s, 1H), 7.74 (d, J=7.4 Hz, 2H), 7.71-7.49 (m, 3H), 7.37-7.13 (m, 9H), 6.88 (s, 1H), 5.05 (d, J=4.9 Hz, 2H), 4.64 (q, J-6.8 Hz, 1H), 3.42-3.35 (m, 1H), 3.09-3.01 (m, 1H), 1.98-1.69 (m, 2H), 1.56-1.19 (m, 4H). LRMS (ESI):(計算值）437.2 (實測值)438.3 (MH)+ ! (dmso-d6) d(ppm) 1H： 11.89 (s, 1H), 7.74 (d, J=7.2 Hz, 2H), 7.71-7.62 (m, 1H), 7.49-7.13 (m, 11H), 5.05 (d, J=5.1 Hz, 2H), 4.64 (q, J=6.3 Hz, 1H), 3.42-3.12 (m, 2H), 2.79 (bs, 3H), 1.98-1.70 (m, 2H), 1.58-1.41 (m, 2H), 1.40-1.19 (m, 2H). LRMS (ESI):(計算值） 451.2(實測值)452.3 (MH)+ 結構 丫 叫 H - HN. S Cbz (S)-l-(5-苯基-1H-咪唑-2-基)-5-硫脲基 戊基胺基甲酸芊酯 Η II HN、Cbz s (S)-5-(3-甲基硫脲基)-1-(5-苯基-1H-咪 唑-2-基)戊基胺基甲酸芊酯 起始物質 〇 CD \ V 〇 〇 8 h HO 人N、Boc ^IMH 1 Cbz + 1 〇 1 r^vA^〇H + ^NH2 〇〇 r-i 00 1〇 (N vn -200 - 134026-2 200916447 k 製備順序 [ΧΓ 丨N，Y 1 1 1 ! 特徵鑒定 (dmso-d6) d(ppm) 1H： 12.23 (s, 1H), 9.97 (s, 1H), 7.84 (q, J=8.2 Hz, 1H), 7.55 (d, J=6.8 Hz, 1H), 7.44 (d, J=6.9 Hz, 1H), 7.37-7.29 (m, 4H), 7.17-7.10 (m, 3H), 5.10-4.99 (m, 2H), 4.79 (q, J=5.5 Hz, 1H), 3.44 (q, J=5.9 Hz, 2H), 2.36 (s, 3H), 2.03-1.95 (m, 1H), 1.87-1.78 (m, 1H), 1.57 (qi, J=6.5 Hz, 2H), 1.46-1.25 (m, 2H). LRMS (ESI):(計算值） 410.2 (實測值）411.3 (MH)+ (dmso-d6) d(ppm) 1H： 12.12 (s, 1H), 9.95 (s, 1H), 7.52 (dd, J=6.7, 1.8 Hz, 1H), 7.43 (dd, J=6.3, 1.6 Hz, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.14-7.07 (m, 2H), 4.71 (q, J=5.9 Hz, 1H), 3.42 (q, J=6.3 Hz, 2H), 2.34 (s, 3H), 2.00-1.72 (m, 2H), 1.55 (qi, J=7.2 Hz’ 2H)， 1.37 (s, 9H), 1.40-1.22 (m, 2H). LRMS (ESI):(計算值）376.2 (實測值）377.3 (MH)+ 結構 \ 璩 XZv i ) 〈P S Efr- ymz 孕_ / 工吒绪 人/Z工 书 ίτ 工s \ W IZ 9 \ l〇 «3 &gt; # )8|S ( 戶玄l )&quot;iZ V _ 工5錯 人/Z工 K书 〇Γ -¾ 起始物質 xz \ X X °K '总 〇 〇 ) i i …5 Vi 0K X8 〇 CD 工 化合物 CO 00 5 cn &gt;〇 -201 - 134026-2 200916447 製備順序 B，N N, Y 特徵鑒定 (CD3CN) d(ppm) 1H ： 7.58-7.53 (m, 2H), 7.25-7.20 (m, 2H), 5.14 (dd, J=8.6, 5.9 Hz, 1H), 4.28-4.20 (m, 2H), 4.12-4.06 (m, 2H), 3.65 (qi, J=7.0 Hz, 1H), 3.53 (t, J=7.0 Hz, 2H), 2.81 (s, 3H), 2.41 (s, 3H), 2.10-1.88 (m, 2H), 1.65 (qi, J=7.2 Hz, 2H), 1.45-1.34 (m, 2H). LRMS (ESI):(計算值）373.2 (實測值) 374.3 (MH)+ (dmso-d6) d(ppm) 1H ： 12.31 (d, J=12 Hz, 1H), 9.95 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.81 (s, 1H), 7.65 (s, 1H), 7.57-7.43 (m, 3H), 7.36-7.10 (m, 6H), 5.10-4.98 (m, 2H), 4.78 (q, J=5.5 Hz, 1H), 3.43 (q, J=5.7 Hz, 2H), 2.35 (s, 3H), 2.07-1.77 (m, 2H), 1.63-1.49 (m, 2H), 1.49-1.26 (m, 2H). LRMS (ESI)： (計算值）492.2 (實測值）493.3 (MH)+ 結構 \ t0 , /= CO A ^ 工 z ii® ) ^ 5 / fi f 〈VO—&amp; 乂 工 工砩 S v H HN、Cbz S (S)-5-乙烷硫醯胺基-1-(6-0塞吩-2-基)-1H-苯并[d]咪唑-2-基)戊基胺基甲 酸芊酯 起始物質 Ql η ΗΝ. S 巳OC 84 HOy^O Λ IN 1 〇 〇 工 化合物 QO 5 m -202- 134026-2 200916447 製備順序| N, Y j 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.31 (d, J=8.0 Hz, 1H), 9.95 (s, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.78 (s, 1H), 7.68 (t, J=7.2 Hz, 2H), 7.62 (s, 1H), 7.51-7.09 (m, 8H), 5.10-4.98 (m, 2H), 4.80 (q, J=5.7 Hz, 1H), 3.44 (q, J=5.7 Hz, 2H), 2.35 (s, 3H), 2.05-1.79 (m, 2H), 1.63-1.49 (m, 2H), 1.47-1.28 (m, 2H). LRMS (ESI):(計算值）504.2 (實測值） 505.4 (MH)+ 結構 h &quot;H&quot;'Cbz S (S)-5-乙烷硫醯胺基-1-(6-(4-氟苯基)-1H-苯并[d]咪唑-2-基)戊基胺基甲酸芊 酯 起始物質 °κ 、公 〇 ο 工 化合物 5 •203 · 134026-2 200916447 製備順序 N, Y N, Y 特徵鑒定 (dmso-d6) d(ppm) 1H ： 9.96 (s, 1H), 8.59 (d, J=6.1 Hz, 2H), 7.89 (d, J=8.2 Hz, 1H), 7.72 (d, J=6.3 Hz, 2H), 7.64-7.55 (m, 2H), 7.40-7.05 (m, 5H), 5.10-4.99 (m，2H), 4.82 (q, J=5.7 Hz, 1H), 3.44 (q, J=5.9 Hz, 2H), 2.35 (s, 3H), 2.07-1.80 (m, 2H), 1.58 (qi, J=6.7 Hz, 2H), 1.47-1.29 (m, 2H). LRMS (ESI):(計算值)487.2(實測值）488.3 (MH)+ 1 (dmso-d6) d(ppm) 1H · 12.04 (s, 1H), 9.94 (s, 1H), 9.50 (s, 1H), 7.75 (d, J=8.2 Hz, 1H), 7.36-7.13 (m, 5H), 7.00-6.83 (m, 2H), 6.46 (d，J=6.9 Hz，1H)，5Ό8-4.97 (m，2H)， 4.76-4.73 (m, 1H), 3.48-3.41 (m, 2H), 2.34 (s, 3H), 2.02-1.77 (m, 2H), 1.63-1.47 (m, 2H)，1.42-1.21 (m，2H). LRMS (ESI):(計算 值）426.2 (實測值）427.3 (ΜΗ)十 結構 H H - j| HN、Cbz s (8)..5-乙院琉酿胺基-1-(6-('1比咬-4-基)-1H-笨并[d]咪唑-2-基)戊基胺基甲 酸芊酯 H〇 [^人广 Η ** J* HN、Cbz s (S)-5-乙烷硫醯胺基-1-(7-羥基-1H-苯并 [d]咪唑-2-基)戊基胺基甲酸苄酯 起始物質 。=&lt; 、公 〇 〇 工 1 〇K S ά 〇 o 工 X 化合物 i 〇〇 00 ON 00 5 00 On 134026-2 -204 - 200916447 Μ. 娴 (dmso-d6) d(ppm) 1H ： 12.60-12.57 (m, 1H), 9.94 (s, 1H), 8.15 (s, 1H), 7.91 (t, J=8.2 Hz, 1H), 7.79 (t, J=8.8 Hz, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.36-7.11 (m, 5H), 5.09-4.98 (m, 2H), 4.80 (q, J=5.7 Hz, 1H), 4.30 (q, J=7.0 Hz, 2H), 3.43 (q, J=5.3 Hz, 2H), 2.34 (s, 3H), 2.04-1.79 (m, 2H), 1.56 (qi, J=7.2 Hz, 2H), 1.43-1.25 (m, 2H), 1.32 (t, J=7.0 Hz, 3H). LRMS (ESI):(計算值）482.2 (實測值) 483.4 (MH)+ 1 (dmso-d6) d(ppm) 1H ： 12.53-12.48 (m, 1H), 9.94 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.59 (d, J=10 Hz, 1H), 7.46 (d, J=9.0 Hz, 1H), 7.36-7.11 (m, 5H), 5.09-4.97 (m, 2H), 4.76 (q, J=5.7 Hz, 1H), 3.42 (q, J=5.5 Hz, 2H), 2.34 (s, 3H), 2.02-1.76 (m, 2H), 1.55 (qi, J=7.4 Hz, 2H), L43-1.25 (m, 2H). LRMS (ESI)： (計算值）462.1 (實測值）463.3 (MH)+ x2\ IS 赫 if V II 0八0八^ % 1¾ V li 工2 g硇 ) ^ / ^ \ N H ^ l 3 \ ' ^ ^ / x滅瘤 / zx 4 域 ^ t〇 X? s l._ 〇 \ A T ^ LL ^ ^ tf 客 竣 〇Ko '5 X xh&quot; 1 〇K ^ A o o X 荽 g S 3 -205 - 134026-2 200916447 製備順序 N，Y 1_ Q 特徵鑒定 (dmso-d6) d(ppm) 1H ： 9.93 (s, 1H), 8.98 (s, 1H), 8.84 (s, 1H), 7.94 (s, 1H), 7.36-7.14 (m, 5H), 5.08-4.97 (m, 2H), 4.82 (q, J=5.3 Hz, 1H), 3.43 (q, J=5.7 Hz, 2H), 2.34 (s, 3H), 2.03-1.78 (m, 2H), 1.56 (qi, J=7.4 Hz, 2H), 1.47-1.28 (m, 2H). LRMS (ESI) ··(計算值） 412.2 (實測值）413.3 (MH)+ ί 1_ (dmso-d6) d(ppm) 1H ： 12.40 (d, J=9.2 Hz, 1H), 9.97 (s, 1H), 8.37 (dd, J=8.2, 2.5 Hz, 1H), 7.81-7.51 (m, 4H), 7.45-7.23 (m, 5H), 7.19 (t, J=7.4 Hz, 1H), 7.12 (d, J=8.6 Hz, 2H), 4.83 (q, J=5.9 Hz, 1H), 3.47 (q, J=6.1 Hz, 2H), 2.35 (s, 3H), 2.13-2.02 (m, 1H), 1.99-1.87 (m, 1H), 1.61 (qi, J=6.5 Hz, 2H), 1.53-1.37 (m，2H). LRMS (ESI):(計算值） 490.2 (實測值）491.4 (MH)+ 結構 N=\ ΗΝ. S Cbz (S)-5-乙烷硫醯胺基-1-(9Η-嘌呤-8-基） 戊基胺基甲酸苄酯 j V HN 丫〇 s Ph〆0 (S)-5-乙烧硫醯胺基-1-(6-(4-氟苯 基)-1Η-苯并[d]咪唑-2-基)戊基胺基甲 酸苯酯 起始物質 1 〇 ο X X2 j CVJ Ο V&quot;1 + 9 Li_ 化合物 5 s s -206 - 134026-2 200916447 製備順序 特徵鑒定 (dmso-d6) d(ppm) 1H · 12.44 (d, J=12 Hz, 1H), 9.93 (s, 1H), 9.13 (d, J=8.6 Hz, 1H), 8.70 (d, J=4.1 Hz, 1H), 8.08-7.99 (m, 2H), 7.82-7.50 (m, 5H), 7.44-7.38 (m, 1H), 7.29-7.23 (m, 2H), 5.34 (q, J=8.0 Hz, 1H), 3.41 (q, J=5.9 Hz, 2H), 2.31 (s, 3H), 2.19-1.98 (m, 2H), 1.58 (qi, J=7.2 Hz, 2H), 1.43-1.25 (m, 2H). LRMS (ESI):(計算值）475.2 (實測值）476.3 (MH)+ 1_ (dmso-d6) d(ppm) 1H ： 9.95 (s, 1H), 8.40-8.32 (m, 1H), 8.20-8.16 (m, 2H), 7.69-7.64 (m, 3H), 7.54 (d, J=8.4 Hz, 1H), 7.40 (dd, J=8.4, 1.7 Hz, 1H), 7.26 (t, J=8.8 Hz, 2H), 5.05 (q, J=5.7 Hz, 1H), 3.43 (q, J=7.2 Hz, 2H), 2.93-2.80 (m, 2H), 2.34 (s, 3H), 2.27-2.18 (m, 4H), 2.08-1.90 (m, 3H), 1.90-1.57 (m, 7H), 1.42-1.23 (m, 2H). LRMS (ESI)： (計算值）495.2 (實測值）496.4 (MH)+ 結構 H H — II HN^.0 S u (S)-N-(5-乙烷硫醯胺基-1 -(6-(4-氟苯 基)-1H-苯并[d]咪唑-2-基)戊基)甲基吡 啶醯胺 HN^O S ό (S)-N-(5-乙烷硫醯胺基-1 -(6-(4-氟苯 基)-1Η-苯并[d]咪唑-2-基)戊基)-1-甲基 六氫吡啶-4-羧醯胺 起始物質 工 ο V 9 LL 《工。 LL 化合物1 實例 -207 - 134026-2 200916447V Preparation sequence | K, P, Q Β, Ν Characterization (dmso-d6) d (ppm) 1H: 11.91 (s, 1H), 9.94 (s, 1H), 8.73 (s, 1H), 7.93 (d, J=TA Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.59-7.54 (m, 2H), 7.39 (t, J=6.8 Hz, 1H), 7.15 (d, J=8.8 Hz, 1H), 4.63 (q, J=6.5 Hz, 1H), 4.11 (s, 3H), 3.51-3.40 (m, 2H), 2.34 (s, 3H), 1.97-1.68 (m, 2H), 1.56 (qi , J=7.2 Hz, 2H), 1.38 (s, 9H), 1.40-1.21 (m, 2H). LRMS (ESI): (calculated) 483.2 (measured value) 484.4 (MH)+ i__— (dmso-d6 ) d(ppm) 1H : 12.03 (s, 1H), 9.95 (s, 1H), 8.72 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 7.92 (d, J=7.6 Hz, 1H ), 7.74 (d, J=8.6 Hz, 1H), 7.59-7.55 (m, 2H), 7.39 (t, J=7.4 Hz, 1H), 4.95 (q, J-7.1 Hz, 1H), 4.11 (s , 3H), 3.58-3.39 (m, 4H), 3.33-3.18 (m, 3H), 2.34 (s, 3H), 2.24 (s, 3H), 2.02-1.91 (m, 1H), 1.85-1.69 (m , 1H), 1.57 (qi, J=7.4 Hz, 2H), 1.41-1.22 (m, 2H). LRMS (ESI): (calc.) 480.2 (measured) 481.4 (MH) + structure OMe HN 丫. S 〇7(S)-: 5-ethanethioguanidino-1-(5-(2-methoxyindol-3-yl)-1 Η-imidazol-2-yl)pentylaminocarboxylic acid Third-butyl ester ^ A ^ 〇j: two ri: its ^Y° U IIT starting material... .i 1 ΗΟ人〆Ν Η2 Ο丫Ι^ΙΗ 十+ N 〇Me OMe State 丫0 S 1 51 〇, / + 〇, z〇H Λ compound ro \〇S -198- 134026-2 200916447 m 13⁄4 PQ Ο α: Ν 靼 (dmso-d6) d(ppm) 1H : 11.96 (s, 1H), 9.94 (s, 1H), 8.72 (s, 1H), 8.13 (d, J=8.2 Hz, 1H), 7.92 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.57 (t, J=6.9 Hz, 1H), 7.39 (t, J=7.2 Hz, 1H), 4.93 (q, J=5.9 Hz, 1H), 4.10 (s, 3H), 3.43 (qi, J=4.5 Hz, 2H), 2.85-2.73 (m, 2H), 2.34 (s, 3H), 2.21-2.15 (m, 1H), 2.13 (s, 3H), 2.02-1.53 (m, 10H), 1.42-1.21 (m, 2H). LRMS (ESI): (calculated) 508.3 (measured value) 509.2 (MH) + (dmso-d6) d (ppm) 1Η : 11.90 (s, 1H ), 8.73 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.59-7.54 (m, 2H), 7.49-7.30 (m, 3H) , 7.14 (d, J=8.4 Hz, 1H), 4.62 (q, J=6.5 Hz, 1H), 4.11 (s, 3H), 3.40-3.32 (m, 2H), 2.77 (bs, 3H), 1.98-1.65 (m, 2H), 1.58-1.20 (m, 4H), 1.38 (s, 9H). LRMS (ESI): (calculated) 498.2 (measured value) 499.4 (MH) + 破 i工Ζ 丨,入〉 ν ^ (Η&gt;_Ρ 魏丄-舆Ψ舆Ψ ^-HT ak -ζ)-ς)-1 -(s) /,〇S 0 person NH Θ1ΛΙΟ 2 body. ' R&gt;- ό&quot; ΘΙΛΙΟ N 八H〇^0〇+ 〇/\ HN人O &lt;0 ;〇¥ 3 -199- 134026-2 200916447 Preparation order P, Q, B, CP, Q, B, C Characterization (dmso-d6) d(ppm) 1H: 11.89 (s, 1H), 7.74 (d, J=7.4 Hz, 2H), 7.71-7.49 (m, 3H), 7.37-7.13 (m, 9H), 6.88 (s, 1H), 5.05 (d, J=4.9 Hz, 2H), 4.64 (q, J-6.8 Hz, 1H), 3.42-3.35 (m, 1H), 3.09-3.01 (m, 1H), 1.98 -1.69 (m, 2H), 1.56-1.19 (m, 4H). LRMS (ESI): (calculated) 437.2 (measured value) 438.3 (MH)+ ! (dmso-d6) d(ppm) 1H: 11.89 ( s, 1H), 7.74 (d, J=7.2 Hz, 2H), 7.71-7.62 (m, 1H), 7.49-7.13 (m, 11H), 5.05 (d, J=5.1 Hz, 2H), 4.64 (q , J=6.3 Hz, 1H), 3.42-3.12 (m, 2H), 2.79 (bs, 3H), 1.98-1.70 (m, 2H), 1.58-1.41 (m, 2H), 1.40-1.19 (m, 2H LRMS (ESI): (calculated) 451.2 (measured value) 452.3 (MH) + structure nickname H - HN. S Cbz (S)-l-(5-phenyl-1H-imidazol-2-yl) -5-thioureidoylpentylaminocarbazate Η II HN, Cbz s (S)-5-(3-methylthioureido)-1-(5-phenyl-1H-imidazol-2-yl ) decylaminocarbazate starting material 〇CD \ V 〇〇8 h HO human N, Boc ^IMH 1 Cbz + 1 〇1 r^vA^〇H + ^NH2 〇〇ri 00 1〇(N vn -200 - 134026-2 200916447 k Preparation sequence [ΧΓ 丨N, Y 1 1 1 ! Characterization (dmso-d6) d( Ppm) 1H: 12.23 (s, 1H), 9.97 (s, 1H), 7.84 (q, J=8.2 Hz, 1H), 7.55 (d, J=6.8 Hz, 1H), 7.44 (d, J=6.9 Hz , 1H), 7.37-7.29 (m, 4H), 7.17-7.10 (m, 3H), 5.10-4.99 (m, 2H), 4.79 (q, J=5.5 Hz, 1H), 3.44 (q, J=5.9 Hz, 2H), 2.36 (s, 3H), 2.03-1.95 (m, 1H), 1.87-1.78 (m, 1H), 1.57 (qi, J=6.5 Hz, 2H), 1.46-1.25 (m, 2H) LRMS (ESI): (calculated) 410.2 (measured value) 411.3 (MH) + (dmso-d6) d (ppm) 1H: 12.12 (s, 1H), 9.95 (s, 1H), 7.52 (dd, J =6.7, 1.8 Hz, 1H), 7.43 (dd, J=6.3, 1.6 Hz, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.14-7.07 (m, 2H), 4.71 (q, J= 5.9 Hz, 1H), 3.42 (q, J=6.3 Hz, 2H), 2.34 (s, 3H), 2.00-1.72 (m, 2H), 1.55 (qi, J=7.2 Hz' 2H), 1.37 (s, 9H), 1.40-1.22 (m, 2H). LRMS (ESI): (calculated) 376.2 (measured value) 377.3 (MH) + structure \ 璩XZv i ) <PS Efr- ymz pregnancy _ / 吒 吒 / Z工书 ίτ工s \ W IZ 9 \ l〇«3 &gt;# )8|S (户玄 l ) &quot;iZ V _工5错人/Z工K书〇Γ -3⁄4 Starting material xz \ XX °K 'Total 〇〇) ii ...5 Vi 0K X8 〇CD Compound CO 00 5 cn &gt;〇-201 - 134026-2 200916447 Preparation sequence B, NN, Y Characterization (CD3CN) d(ppm) 1H : 7.58-7.53 (m, 2H), 7.25-7.20 (m, 2H), 5.14 (dd, J=8.6, 5.9 Hz, 1H), 4.28-4.20 (m, 2H), 4.12-4.06 (m, 2H), 3.65 (qi, J=7.0 Hz, 1H), 3.53 (t, J=7.0 Hz, 2H), 2.81 (s , 3H), 2.41 (s, 3H), 2.10-1.88 (m, 2H), 1.65 (qi, J=7.2 Hz, 2H), 1.45-1.34 (m, 2H). LRMS (ESI): (calculated) 373.2 (measured value) 374.3 (MH)+ (dmso-d6) d(ppm) 1H : 12.31 (d, J=12 Hz, 1H), 9.95 (s, 1H), 7.86 (d, J=8.4 Hz, 1H ), 7.81 (s, 1H), 7.65 (s, 1H), 7.57-7.43 (m, 3H), 7.36-7.10 (m, 6H), 5.10-4.98 (m, 2H), 4.78 (q, J=5.5 Hz, 1H), 3.43 (q, J=5.7 Hz, 2H), 2.35 (s, 3H), 2.07-1.77 (m, 2H), 1.63-1.49 (m, 2H), 1.49-1.26 (m, 2H) LRMS (ESI): (calculated) 492.2 (measured value) 493.3 (MH) + structure \ t0 , /= CO A ^ work z ii® ) ^ 5 / fi f <VO-&amp; 乂工工砩 S v H HN, Cbz S (S)-5-ethanethioguanamine -1--1-(6-0-secen-2-yl)-1H-benzo[d]imidazol-2-yl)pentylaminocarbazate starting material Ql η ΗΝ. S 巳OC 84 HOy^O Λ IN 1 Completion compound QO 5 m -202- 134026-2 200916447 Preparation sequence | N, Y j Characterization (dmso-d6) d(ppm) 1H : 12.31 (d, J=8.0 Hz, 1H), 9.95 (s, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.78 (s, 1H), 7.68 (t, J=7.2 Hz, 2H), 7.62 (s, 1H), 7.51-7.09 (m, 8H), 5.10-4.98 (m, 2H), 4.80 (q, J=5.7 Hz, 1H), 3.44 (q, J=5.7 Hz, 2H), 2.35 (s, 3H), 2.05-1.79 (m, 2H ), 1.63-1.49 (m, 2H), 1.47-1.28 (m, 2H). LRMS (ESI): (calculated) 504.2 (measured value) 505.4 (MH)+ structure h &quot;H&quot;'Cbz S (S -5-5-ethanethioguanidino-1-(6-(4-fluorophenyl)-1H-benzo[d]imidazol-2-yl)pentylaminocarbazate starting material °κ,公〇ο工化合物5 •203 · 134026-2 200916447 Preparation sequence N, YN, Y Characterization (dmso-d6) d(ppm) 1H : 9.96 (s, 1H), 8.59 (d, J=6.1 Hz, 2H ), 7.89 (d, J=8.2 Hz, 1H), 7.72 (d, J=6.3 Hz, 2H), 7.64-7.55 (m, 2H), 7.40-7.05 (m, 5H), 5.10-4.99 (m, 2H), 4.82 (q, J=5.7 Hz , 1H), 3.44 (q, J=5.9 Hz, 2H), 2.35 (s, 3H), 2.07-1.80 (m, 2H), 1.58 (qi, J=6.7 Hz, 2H), 1.47-1.29 (m, 2H). LRMS (ESI): (calculated) 487.2 (measured value) 488.3 (MH) + 1 (dmso-d6) d (ppm) 1H · 12.04 (s, 1H), 9.94 (s, 1H), 9.50 ( s, 1H), 7.75 (d, J=8.2 Hz, 1H), 7.36-7.13 (m, 5H), 7.00-6.83 (m, 2H), 6.46 (d, J=6.9 Hz, 1H), 5Ό8-4.97 (m, 2H), 4.76-4.73 (m, 1H), 3.48-3.41 (m, 2H), 2.34 (s, 3H), 2.02-1.77 (m, 2H), 1.63-1.47 (m, 2H), 1.42 -1.21 (m,2H). LRMS (ESI): (calculated) 426.2 (measured value) 427.3 (ΜΗ) 十结构HH - j| HN, Cbz s (8)..5-B. 1-(6-('1 to -4-yl)-1H- benzo[d]imidazol-2-yl)pentylaminocarbazate H〇[^人广Η ** J* HN, Cbz s (S)-5-Ethylthioguanidino-1-(7-hydroxy-1H-benzo[d]imidazol-2-yl)pentylaminocarbamate starting material. =&lt; 、公〇〇1 〇KS ά 〇o gong X compound i 〇〇00 ON 00 5 00 On 134026-2 -204 - 200916447 Μ. 娴(dmso-d6) d(ppm) 1H : 12.60-12.57 (m, 1H), 9.94 (s, 1H), 8.15 (s, 1H), 7.91 (t, J=8.2 Hz, 1H), 7.79 (t, J=8.8 Hz, 1H), 7.52 (d, J= 8.6 Hz, 1H), 7.36-7.11 (m, 5H), 5.09-4.98 (m, 2H), 4.80 (q, J=5.7 Hz, 1H), 4.30 (q, J=7.0 Hz, 2H), 3.43 ( q, J=5.3 Hz, 2H), 2.34 (s, 3H), 2.04-1.79 (m, 2H), 1.56 (qi, J=7.2 Hz, 2H), 1.43-1.25 (m, 2H), 1.32 (t , J=7.0 Hz, 3H). LRMS (ESI): (calculated) 482.2 (measured value) 483.4 (MH) + 1 (dmso-d6) d (ppm) 1H : 12.53-12.48 (m, 1H), 9.94 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.59 (d, J=10 Hz, 1H), 7.46 (d, J=9.0 Hz, 1H), 7.36-7.11 (m, 5H) , 5.09-4.97 (m, 2H), 4.76 (q, J=5.7 Hz, 1H), 3.42 (q, J=5.5 Hz, 2H), 2.34 (s, 3H), 2.02-1.76 (m, 2H), 1.55 (qi, J=7.4 Hz, 2H), L43-1.25 (m, 2H). LRMS (ESI): (calculated) 462.1 (measured value) 463.3 (MH)+ x2\ IS 赫 if V II 0 八八^% 13⁄4 V li 2 g硇) ^ / ^ \ NH ^ l 3 \ ' ^ ^ / x annihilation / zx 4 domain ^ t〇X? sl ._ 〇\ AT ^ LL ^ ^ tf Customer Ko '5 X xh&quot; 1 〇K ^ A oo X 荽g S 3 -205 - 134026-2 200916447 Preparation sequence N,Y 1_ Q Characterization (dmso-d6 ) d(ppm) 1H : 9.93 (s, 1H), 8.98 (s, 1H), 8.84 (s, 1H), 7.94 (s, 1H), 7.36-7.14 (m, 5H), 5.08-4.97 (m, 2H), 4.82 (q, J=5.3 Hz, 1H), 3.43 (q, J=5.7 Hz, 2H), 2.34 (s, 3H), 2.03-1.78 (m, 2H), 1.56 (qi, J=7.4 Hz, 2H), 1.47-1.28 (m, 2H). LRMS (ESI) ··(calculated value) 412.2 (measured value) 413.3 (MH)+ ί 1_ (dmso-d6) d(ppm) 1H : 12.40 (d , J=9.2 Hz, 1H), 9.97 (s, 1H), 8.37 (dd, J=8.2, 2.5 Hz, 1H), 7.81-7.51 (m, 4H), 7.45-7.23 (m, 5H), 7.19 ( t, J=7.4 Hz, 1H), 7.12 (d, J=8.6 Hz, 2H), 4.83 (q, J=5.9 Hz, 1H), 3.47 (q, J=6.1 Hz, 2H), 2.35 (s, 3H), 2.13-2.02 (m, 1H), 1.99-1.87 (m, 1H), 1.61 (qi, J=6.5 Hz, 2H), 1.53-1.37 (m, 2H). LRMS (ESI): (calculated value 490.2 (measured value) 491.4 (MH) + structure N=\ ΗΝ. S Cbz (S)-5-ethanethioguanidino-1-(9Η-嘌呤-8-yl) benzyl amyl carboxylate j V HN 丫〇s Ph〆0 (S)-5-Ethylene thioanthramine-1-(6-(4-fluorobenzene) ) -1 - benzo[d]imidazol-2-yl)pentylaminocarboxylate phenyl starting material 1 〇ο X X2 j CVJ Ο V&quot;1 + 9 Li_ Compound 5 ss -206 - 134026-2 200916447 Preparation Sequential characterization (dmso-d6) d(ppm) 1H · 12.44 (d, J=12 Hz, 1H), 9.93 (s, 1H), 9.13 (d, J=8.6 Hz, 1H), 8.70 (d, J =4.1 Hz, 1H), 8.08-7.99 (m, 2H), 7.82-7.50 (m, 5H), 7.44-7.38 (m, 1H), 7.29-7.23 (m, 2H), 5.34 (q, J=8.0 Hz, 1H), 3.41 (q, J=5.9 Hz, 2H), 2.31 (s, 3H), 2.19-1.98 (m, 2H), 1.58 (qi, J=7.2 Hz, 2H), 1.43-1.25 (m , 2H). LRMS (ESI): (calculated) 475.2 (measured value) 476.3 (MH) + 1_ (dmso-d6) d (ppm) 1H : 9.95 (s, 1H), 8.40-8.32 (m, 1H) , 8.20-8.16 (m, 2H), 7.69-7.64 (m, 3H), 7.54 (d, J=8.4 Hz, 1H), 7.40 (dd, J=8.4, 1.7 Hz, 1H), 7.26 (t, J =8.8 Hz, 2H), 5.05 (q, J=5.7 Hz, 1H), 3.43 (q, J=7.2 Hz, 2H), 2.93-2.80 (m, 2H), 2.34 (s, 3H), 2.27-2.18 (m, 4H), 2.08-1.90 (m, 3H), 1.90-1.57 (m, 7H), 1.42-1.23 (m, 2H). LRMS (ESI): (calculated) 495.2 (measured value) 496.4 (MH )+ structure HH — II HN^.0 S u (S)-N-(5-ethanethioguanamine-1 (6-(4-Fluorophenyl)-1H-benzo[d]imidazol-2-yl)pentyl)methylpyridinium HN^OS ό (S)-N-(5-ethanethioguanamine -1-(6-(4-Fluorophenyl)-1 fluorene-benzo[d]imidazol-2-yl)pentyl)-1-methylhexahydropyridine-4-carboxamide as a starting material. V 9 LL "Work. LL Compound 1 Example -207 - 134026-2 200916447

製備順序 N, Y 1 N, Y 特徵鑒定 (dmso-d6) d(ppm) 1H： 12.13 (s, 1H), 9.94 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.35-7.06 (m, 6H), 7.03-6.98 (m, 1H), 6.91 (t, J=7.2 Hz, 1H), 5.07-4.97 (m, 2H), 4.83-4.73 (m, 1H), 3.48-3.39 (m, 2H), 2.48 (s, 3H), 2.34 (s, 3H), 2.02-1.78 (m, 2H), 1.63-1.47 (m, 2H), 1.45-1_23 (m，2H). LRMS (ESI):(計算值）424.2 (實測值）425.3 (MH)+ (dmso-d6) d(ppm) 1H ： 12.18 (s, 1H), 9.94 丨(m，1H), 7.79 (d，J=8.4 Hz，1H)，7.35-7.28 ! (m, 5H), 7Ό6-6.99 (m, 2H), 6.62 (d, J=6.0 Hz, 1H), 5.08-4.96 (m, 2H), 4.81-4.71 (m, 1H), 3.87 (s, 3H), 3.42 (qi, J=6.3 Hz, 2H), 2.34 (s, 3H), 1.99-1.76 (m, 2H), 1.62-1.48 (m, 2H), 1.43-1.20 (m, 2H). LRMS (ESI)： (計算值）440.2 (實測值）441.3 (MH)+ 結構 Rx h H — U HN、Cbz S (S)-5-乙烷硫醯胺基-1-(7-甲基-1H-苯并 [d]咪唑-2-基)戊基胺基甲酸芊酯 MeO H 人丫&quot; ‘Cbz S (S)-:5-乙烷硫醯胺基-1 -(7-甲氧基-1H-苯 并[d]咪唑-2-基)戊基胺基甲酸苄酯 起始物質 ^+ib °={、名 / 〇 〇 工 4：ι&quot; + ^ °K ^ 〇 〇 〇 1 化合物: σ\ 5 \D •208 -Preparation order N, Y 1 N, Y Characterization (dmso-d6) d (ppm) 1H: 12.13 (s, 1H), 9.94 (s, 1H), 7.82 (d, J=8.4 Hz, 1H), 7.35- 7.06 (m, 6H), 7.03-6.98 (m, 1H), 6.91 (t, J=7.2 Hz, 1H), 5.07-4.97 (m, 2H), 4.83-4.73 (m, 1H), 3.48-3.39 ( m, 2H), 2.48 (s, 3H), 2.34 (s, 3H), 2.02-1.78 (m, 2H), 1.63-1.47 (m, 2H), 1.45-1_23 (m, 2H). LRMS (ESI) : (calculated) 424.2 (measured value) 425.3 (MH) + (dmso-d6) d (ppm) 1H : 12.18 (s, 1H), 9.94 丨 (m, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.35-7.28 ! (m, 5H), 7Ό6-6.99 (m, 2H), 6.62 (d, J=6.0 Hz, 1H), 5.08-4.96 (m, 2H), 4.81-4.71 (m, 1H ), 3.87 (s, 3H), 3.42 (qi, J=6.3 Hz, 2H), 2.34 (s, 3H), 1.99-1.76 (m, 2H), 1.62-1.48 (m, 2H), 1.43-1.20 ( m, 2H). LRMS (ESI): (calc.) 440.2 (measured) 441.3 (MH) + structure Rx h H — U HN, Cbz S (S)-5-ethanethioguanamine-1-( Ethyl 7-methyl-1H-benzo[d]imidazol-2-yl)pentylaminocarbamate MeO H 丫&quot; 'Cbz S (S)-: 5-Ethylthioanthryl-1 (7-Methoxy-1H-benzo[d]imidazol-2-yl)pentylaminocarbamate starting material ^+ib °={, first name / 〇 4 4:ι&quot; + ^ °K ^ 〇 〇 〇 1 Compound: σ\ 5 \D •208 -

134026-2 200916447 製備順序 N，Y Ν, Υ 特徵鑒定 (dmso-d6) d(ppm) 1H ： 13.01 (s, 1H), 9.93 (s, 1H), 8.10 (d, J=8.2 Hz, 1H), 8.06 (d, J=7.8 Hz, 1H), 7.90 (d, J=8.2 Hz, 1H), 7.48-7.04 (m, 6H), 5.05-4.97 (m, 3H), 3.42 (q, J=6.7 Hz, 2H), 3.31 (s, 3H), 1.93-1.77 (m, 2H), 1.55 (qi, J=6.9 Hz, 2H), 1.46-1.20 (m, 2H). LRMS (ESI):(計算值）455.2 (實測值） 456.3 (MH)+ (dmso-d6) d(ppm) 1Η ； 12.38 (s, 1H), 9.94 (s, 1H), 8.15-7.42 (m, 4H), 7.38-7.03 (m, 9H), 5.04 (d, J=9.8 Hz, 2H), 4.80 (q, J=5.7 Hz, 1H), 3.43 (q, J=6.7 Hz, 2H), 2.34 (s, 3H), 2.05-1.78 (m, 2H), 1.65-1.22 (m, 4H). LRMS (ESI):(計算值）504.2 (實測值） 505.3 (MH)+ 結構 Rl H 〇2n HN、Cbz S (S)-5-乙烷硫醯胺基-1-(7-硝基-1H-苯并 [d]咪唑-2-基)戊基胺基甲酸苄酯 0 Η Η、 S F (S)-5-乙烧硫酿胺基-1-(7-(4-氣苯 基)-1Η-苯并[d]咪唑-2-基)戊基胺基甲 酸芊酯 起始物質 &gt; 1 〇K 、它 ί 〇 〇 CD 1 ^ ί 〇 ο °-工 化合物 οο OS 〇\ ★ -209- 134026-2 200916447 製備順序| N，Y 1 j 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.14 (s, 1H), 9.94 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.85 (d, J=7.8 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.34-7.03 (m, 6H), 5.05-4.93 (m, 3H), 4.41 (q, J=7.0 Hz, 2H), 3.42 (q, J=6.3 Hz, 2H), 2.33 (s, 3H), 1.91-1.76 (m, 2H), 1.61-1.48 (m, 2H), 1.46-1.20 (m, 2H), 1.36 (t, J=7.0 Hz, 3H). LRMS (ESI):(計算值）482.2 (實測值） 483.4 (MH)+ [(dmso-d6) d(ppm) 1H : 9.95 (m, 1H), 7.94 (m, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.72 (d, J=7.6 Hz, 1H), 7.34-7.06 (m, 6H), 5.04-4.92 (m, 3H), 3.41 (q, J=7.0 Hz, 2H), 2.33 (s, 3H), 1.82 (qi, J=7.2 Hz, 2H), 1.55 (qi, J=7.0 Hz, 2H), 1.44-1.20 (m, 2H). LRMS (ESI):(計算 值）454.2 (實測值）455.3 (MH)+ 結構 Λν—V ~ 0 HN、cbz s (S&gt; 2-(1-(芊氡羰基胺基)-5-乙烷硫醯胺 基戊基)-1 Η-苯并[d]咪唑-7-羧酸乙酯 1 ho^W-v 〇 HN、CbZ S (S)-2-(l-(芊氧羰基胺基)-5-乙烷硫醯胺 基戊基)-1 Η-苯并[d]咪唑-7-羧酸 起始物質 。=&lt; 、 〇={ / Ο 〇 ~〇-V Rx η pH 、° HN、cbz s 100 I 化合物 〇 1—H o «—H 5 Ο i Ή -210- 134026-2 200916447 製備順序| N，Y 1 ιΝ,Υ 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.43 (s, 1H), 9.93 (s, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.35-6.98 (m, 11H), 6.59 (d, J=7.8 Hz, 1H), 5.08-4.97 (m, 2H), 4.83-4.72 (m, 1H), 3.41 (q, J=5.9 Hz, 2H), 2.34 (s, 3H), 2.00-1.73 (m, 2H), 1.54 (qi, J=7.0 Hz, 2H), 1.42-1.21 (m, 2H). LRMS (ESI):(計算值）520.2 (實測值） 521.3 (MH)+ (dmso-d6) d(ppm) 1H ： 9.98 (s, 1H), 9.95 (s, 1H), 7.92 (d, J=8.2 Hz, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.36-7.10 (m, 6H), 5.12-4.99 (m, 2H), 4.86 (q, J=5.5 Hz, 1H), 3.45 (q, J=6.5 Hz, 2H), 2.35 (s, 3H), 2.13-2.03 (m, 1H), 1.95-1.80 (m, 1H), 1.59 (qi, J=7.0 Hz, 2H), 1.42 (s, 9H), 1.52-1.35 (m, 2H). LRMS (ESI):(計算值） 509.2 (實測值）510.4 (MH)+ 結構 HNW S f: (S)- 5-乙烷硫酿胺基-1 -(7-(4-氟基苯氧 基)-1Η-苯并[d]咪唑-2-基)戊基胺基甲 酸芊酯 hN^V^V 7、〇 HN、Cbz s (S)-1-(7-(第三-丁基胺甲醯基)-1H-苯并 [d]咣唑-2-基)-5-乙烷硫醯胺基戊基胺 基甲酸苄酯 起始物質 £ V + Φ Ο 〇 έ V。 1 V + Φ 化合物_ g S Η S rn -211 · 134026-2 200916447134026-2 200916447 Preparation sequence N,Y Ν, Υ Characterization (dmso-d6) d(ppm) 1H : 13.01 (s, 1H), 9.93 (s, 1H), 8.10 (d, J=8.2 Hz, 1H) , 8.06 (d, J=7.8 Hz, 1H), 7.90 (d, J=8.2 Hz, 1H), 7.48-7.04 (m, 6H), 5.05-4.97 (m, 3H), 3.42 (q, J=6.7 Hz, 2H), 3.31 (s, 3H), 1.93-1.77 (m, 2H), 1.55 (qi, J=6.9 Hz, 2H), 1.46-1.20 (m, 2H). LRMS (ESI): (calculated value ) 455.2 (measured value) 456.3 (MH) + (dmso-d6) d (ppm) 1Η ; 12.38 (s, 1H), 9.94 (s, 1H), 8.15-7.42 (m, 4H), 7.38-7.03 (m , 9H), 5.04 (d, J=9.8 Hz, 2H), 4.80 (q, J=5.7 Hz, 1H), 3.43 (q, J=6.7 Hz, 2H), 2.34 (s, 3H), 2.05-1.78 (m, 2H), 1.65-1.22 (m, 4H). LRMS (ESI): (calculated) 504.2 (measured value) 505.3 (MH)+ structure Rl H 〇2n HN, Cbz S (S)-5-B Benzylthio-1-amino-1-(7-nitro-1H-benzo[d]imidazol-2-yl)pentylaminocarboxylate 0 Η , SF (S)-5-ethyl sulphur Base-1-(7-(4-carbophenyl)-1Η-benzo[d]imidazol-2-yl)pentylaminocarbazate starting material &gt; 1 〇K , it ί 1 CD 1 ^ ί 〇ο °-工化合物οο OS 〇\ ★ -209- 134026-2 2009164 47 Preparation sequence | N,Y 1 j Characterization (dmso-d6) d(ppm) 1H : 12.14 (s, 1H), 9.94 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.85 ( d, J=7.8 Hz, 1H), 7.78 (d, J=7.8 Hz, 1H), 7.34-7.03 (m, 6H), 5.05-4.93 (m, 3H), 4.41 (q, J=7.0 Hz, 2H ), 3.42 (q, J=6.3 Hz, 2H), 2.33 (s, 3H), 1.91-1.76 (m, 2H), 1.61-1.48 (m, 2H), 1.46-1.20 (m, 2H), 1.36 ( t, J=7.0 Hz, 3H). LRMS (ESI): (calculated) 482.2 (measured value) 483.4 (MH) + [(dmso-d6) d (ppm) 1H: 9.95 (m, 1H), 7.94 ( m, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.72 (d, J=7.6 Hz, 1H), 7.34-7.06 (m, 6H), 5.04-4.92 (m, 3H), 3.41 (q , J=7.0 Hz, 2H), 2.33 (s, 3H), 1.82 (qi, J=7.2 Hz, 2H), 1.55 (qi, J=7.0 Hz, 2H), 1.44-1.20 (m, 2H). LRMS (ESI): (calculated) 454.2 (measured value) 455.3 (MH) + structure Λν—V ~ 0 HN, cbz s (S&gt; 2-(1-(芊氡carbonylamino)-5-ethane thiopurine Aminopentyl)-1 oxime-benzo[d]imidazole-7-carboxylic acid ethyl ester 1 ho^Wv 〇HN, CbZ S (S)-2-(l-(芊-oxycarbonylamino)-5- Ethyl thioguanamine pentyl)-1 fluorene-benzo[d]imidazole-7-carboxylic acid starting material. =&lt; 、 〇={ / Ο 〇~〇-V Rx η pH , ° HN, cbz s 100 I Compound 〇 1—H o «—H 5 Ο i Ή -210- 134026-2 200916447 Preparation sequence | N, Y 1 ιΝ,Υ Characterization (dmso-d6) d(ppm) 1H : 12.43 (s, 1H), 9.93 (s, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.35-6.98 (m, 11H), 6.59 (d, J=7.8 Hz, 1H), 5.08-4.97 (m, 2H), 4.83-4.72 (m, 1H), 3.41 (q, J=5.9 Hz, 2H), 2.34 (s, 3H) ), 2.00-1.73 (m, 2H), 1.54 (qi, J=7.0 Hz, 2H), 1.42-1.21 (m, 2H). LRMS (ESI): (calculated) 520.2 (measured value) 521.3 (MH) + (dmso-d6) d(ppm) 1H : 9.98 (s, 1H), 9.95 (s, 1H), 7.92 (d, J=8.2 Hz, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.36-7.10 (m, 6H), 5.12-4.99 (m, 2H), 4.86 (q, J=5.5 Hz, 1H), 3.45 (q, J=6.5 Hz , 2H), 2.35 (s, 3H), 2.13-2.03 (m, 1H), 1.95-1.80 (m, 1H), 1.59 (qi, J=7.0 Hz, 2H), 1.42 (s, 9H), 1.52- 1.35 (m, 2H). LRMS (ESI): (calculated) 509.2 (found) 510.4 (MH) + structure HNW S f: (S)- 5-ethanesulfanylamino-1 -(7-( 4-fluorophenoxy)-1Η-benzo[d]imidazol-2-yl)pentylaminocarbazate hN^V^V 7, HN, Cbz s (S)-1-(7-(Third-butylaminocarbamimidyl)-1H-benzo[d]oxazol-2-yl)-5-ethanethioguanamine pentyl Benzyl carbamide starting material £ V + Φ Ο 〇έ V. 1 V + Φ compound _ g S Η S rn -211 · 134026-2 200916447

製備順序| Ν,Υ |N,Y 特徵鑒定 (dmso-d6) d(ppm) 1H ： 13.00 (m, 1H), 9.94 (m, 1H), 8.40 (m, 1H), 8.08 (dd, J=8.8, 2.2 Hz, 1H), 7.98 (d, J=8.0 Hz, 1H), 7.67 (m, 1H), 7.38-6.98 (m, 5H), 5.10-4.98 (m, 2H), 4.82 (q, J=5.9 Hz, 1H), 3.43 (q, J=5.7 Hz, 2H), 2.34 (s, 3H), 2.03-1.79 (m, 2H), 1.56 (qi, J=5.9 Hz, 2H), 1.48-1.27 (m, 2H). LRMS (ESI):(計算值）455.2 (實測值） 456.3 (MH)+ (dmso-d6) d(ppm) 1H * 12.46 (m, 1H), 9.96 !(s, 1H), 7.90 (m, 1H), 7.51 (m, 1H), 7.37-7.08 (m, 7H), 5.03 (d, J=8.6 Hz, 2H), ! 4.93-4.77 (m, 1H), 3.43 (q, J=6.5 Hz, 2H), 3.09-2.66 (m, 6H), 2.35 (s, 3H), 2.01-1.79 (m, 2H), 1.57 (qi, J=6.8 Hz, 2H), 1.44-1.22 (m，2H). LRMS (ESI):(計算值）481.2 (實測 值）482.4 (MH)+ 結構 h H 二 K i HN、Cbz S (S)- 5-乙烷硫醯胺基-1 -(6-硝基-1H-苯并 [d]咪唑-2-基)戊基胺基甲酸芊酯 \ 5 ^ )=^ 5¾ &gt; £ ^ (it )饍饍 \ /U t _ A/zx ' A ti M /、 巴 f®- 起始物質 〇 O u 工 V=cn £ g。 广 化合物 S s 5 UO -212- 134026-2 200916447 i,v\ 製備順序 N，Y N, Y, B, Z 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.90 (s, 1H), 9.96 (s, 1H)，8.01 (d, J=8.0 Hz, 1H), 7.79 (d，J=8.2 Hz, 1H), 7.63 (d, J=6.7H, 1H), 7.36-7.01 (m, 6H), 5.04 (d, J=13 Hz, 2H), 4.81 (q, J=5.3 Hz, 1H), 3.43 (q, J=5.9 Hz, 2H), 2.34 (s, 3H), 2.01-1.79 (m, 2H), 1.62-1.49 (m, 2H), 1.49-1.25 (m, 2H). LRMS (ESI):(計算值） 435.2 (實測值）436.3 (MH)+ (dmso-d6) d(ppm) 1H： 13.01 (s, 1H), 8.10 (d, J=8.0 Hz, 1H), 8.06 (d, J=7.8 Hz, 1H), 7.89 (d, J=8.6 Hz, 1H), 7.39-7.04 (m, 8H), 5.04-4.95 (m, 3H), 3.41-3.19 (m, 2H), 2.76 (bs, 3H), 1.82 (qi, J=5.5 Hz, 2H), 1.53-1.19 (m, 4H).LRMS (ESI):(計算值）470.2 (實測值） 471.3 (MH)+ 結構 ) 杂潜 ) / '不你 ( (5zx ii 2 ^ o 〇2n 丫 丫 H^Cbz S (S)-5-(3-甲基硫脲基)-1-(7-确基-1H-苯 并[d]咪唑-2-基)戊基胺基甲酸苄酯 起始物質 )=ω f ^ + Φ 〇=&lt; 、公 Z 〇 o 工 8 w 工气 1 « ;+ φ 4 η 〇Ν °K js 〇 U 化合物 g 1—H 5 JO -213 - 134026-2 200916447 製備順序| N, Y, B, C N, Y 特徵鑒定 (dmso-d6) d(ppm) 1H： 13.04 (s, 1H), 8.12 (d, J=8.2 Hz, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.68-6.98 (m, 8H), 6.87 (bs, 1H), 5.08-4.90 (m, 3H), 3.27-2.92 (m, 2H), 1.92-1.78 (m, 2H), 1.57-1.21 (m,4H). LRMS (ESI):(計算值）456.2 (實測值） 457.3 (MH)+ (dmso-d6) d(ppm) 1H ： 12.76 (s, 1H), 9.93 (bs, 1H), 9.26 (d, J=3.1 Hz, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.80 (d, J=1.0 Hz, 1H), 7.79 (d, J=1.0 Hz, 1H), 7.64 (d, J=7.0 Hz, 1H), 7.35-7.09 (m, 6H), 5.09-5.01 (m, 2H), 4.84 (q, J=5.7 Hz, 1H), 3.43 (q, J=6.3 Hz, 2H), 2.34 (s, 3H), 2.04-1.77 (m, 2H), 1.65-1.48 (m, 2H), 1.48-1.20 (m, 2H). LRMS (ESI)： (計算值)453.2 (實測值）454.3 (MH)+ 結構 H 〇2Ν”Μ^^^ΝγΝΗ2 H^Cbz S (S)-l -(7-硝基-1H-苯并[d]咪唑-2-基)-5-硫脲基戊基胺基甲酸芊酯 h2^V^V ° HN、cbz s (S)-l-(7-胺甲醯基-1H-苯并[d]咪唑-2-基)-5-乙烷硫醯胺基戊基胺基甲酸芊酯 起始物質 〇 工f &quot; \ Ϊ °' g ° XZ X 1 5 + 〇^Z i 〇—^ Ν Ο ο X 化合物 g τ-Η 109 1 1 5 〇〇 α\ •214- 134026-2 200916447Preparation sequence | Ν,Υ |N,Y Characterization (dmso-d6) d(ppm) 1H : 13.00 (m, 1H), 9.94 (m, 1H), 8.40 (m, 1H), 8.08 (dd, J= 8.8, 2.2 Hz, 1H), 7.98 (d, J=8.0 Hz, 1H), 7.67 (m, 1H), 7.38-6.98 (m, 5H), 5.10-4.98 (m, 2H), 4.82 (q, J =5.9 Hz, 1H), 3.43 (q, J=5.7 Hz, 2H), 2.34 (s, 3H), 2.03-1.79 (m, 2H), 1.56 (qi, J=5.9 Hz, 2H), 1.48-1.27 (m, 2H). LRMS (ESI): (calculated) 455.2 (measured value) 456.3 (MH) + (dmso-d6) d (ppm) 1H * 12.46 (m, 1H), 9.96 !(s, 1H) , 7.90 (m, 1H), 7.51 (m, 1H), 7.37-7.08 (m, 7H), 5.03 (d, J=8.6 Hz, 2H), ! 4.93-4.77 (m, 1H), 3.43 (q, J=6.5 Hz, 2H), 3.09-2.66 (m, 6H), 2.35 (s, 3H), 2.01-1.79 (m, 2H), 1.57 (qi, J=6.8 Hz, 2H), 1.44-1.22 (m , 2H). LRMS (ESI): (calculated) 481.2 (measured value) 482.4 (MH) + structure h H di K i HN, Cbz S (S) 5- 5- thioanthryl-1 - (6 -nitro-1H-benzo[d]imidazol-2-yl)pentylaminocarbazate \ 5 ^ )=^ 53⁄4 &gt; £ ^ (it ) Diet \ /U t _ A/zx ' A Ti M /, Ba f® - starting material 〇O u work V=cn £ g. Wide compound S s 5 UO -212- 134026-2 200916447 i,v\ Preparation order N,YN, Y, B, Z Characterization (dmso-d6) d(ppm) 1H : 12.90 (s, 1H), 9.96 ( s, 1H), 8.01 (d, J=8.0 Hz, 1H), 7.79 (d, J=8.2 Hz, 1H), 7.63 (d, J=6.7H, 1H), 7.36-7.01 (m, 6H), 5.04 (d, J=13 Hz, 2H), 4.81 (q, J=5.3 Hz, 1H), 3.43 (q, J=5.9 Hz, 2H), 2.34 (s, 3H), 2.01-1.79 (m, 2H) ), 1.62-1.49 (m, 2H), 1.49-1.25 (m, 2H). LRMS (ESI): (calculated) 435.2 (measured value) 436.3 (MH) + (dmso-d6) d (ppm) 1H: 13.01 (s, 1H), 8.10 (d, J=8.0 Hz, 1H), 8.06 (d, J=7.8 Hz, 1H), 7.89 (d, J=8.6 Hz, 1H), 7.39-7.04 (m, 8H) ), 5.04-4.95 (m, 3H), 3.41-3.19 (m, 2H), 2.76 (bs, 3H), 1.82 (qi, J=5.5 Hz, 2H), 1.53-1.19 (m, 4H).LRMS ( ESI): (calculated value) 470.2 (measured value) 471.3 (MH)+ structure) Miscellaneous) / 'No you ((5zx ii 2 ^ o 〇2n 丫丫H^Cbz S (S)-5-(3- Methylthiourea)-1-(7-decyl-1H-benzo[d]imidazol-2-yl)pentylaminocarbamate starting material)=ω f ^ + Φ 〇=&lt; Gong Z 〇o 8W Engineering 1 « ;+ φ 4 η 〇Ν °K js 〇U Compound g 1—H 5 JO -213 - 134026-2 200916447 Preparation sequence | N, Y, B, CN, Y Characterization (dmso-d6) d(ppm) 1H: 13.04 (s, 1H), 8.12 (d, J=8.2 Hz, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.68-6.98 (m, 8H), 6.87 (bs, 1H), 5.08-4.90 (m, 3H) ), 3.27-2.92 (m, 2H), 1.92-1.78 (m, 2H), 1.57-1.21 (m, 4H). LRMS (ESI): (calculated) 456.2 (measured value) 457.3 (MH)+ (dmso -d6) d(ppm) 1H : 12.76 (s, 1H), 9.93 (bs, 1H), 9.26 (d, J=3.1 Hz, 1H), 7.99 (d, J=8.0 Hz, 1H), 7.80 (d , J=1.0 Hz, 1H), 7.79 (d, J=1.0 Hz, 1H), 7.64 (d, J=7.0 Hz, 1H), 7.35-7.09 (m, 6H), 5.09-5.01 (m, 2H) , 4.84 (q, J=5.7 Hz, 1H), 3.43 (q, J=6.3 Hz, 2H), 2.34 (s, 3H), 2.04-1.77 (m, 2H), 1.65-1.48 (m, 2H), 1.48-1.20 (m, 2H). LRMS (ESI): (calculated) 453.2 (measured value) 454.3 (MH)+ structure H 〇2Ν"Μ^^^ΝγΝΗ2 H^Cbz S (S)-l -(7 -nitro-1H-benzo[d]imidazol-2-yl)-5-thioureidopentylaminocarbazate h2^V^V ° HN, cbz s (S)-l-(7-amine Mercapto-1H-benzo[d]imidazol-2-yl)-5-ethane thioanthrylaminopentylaminocarbamate starting material completion f &q Uot; \ Ϊ °' g ° XZ X 1 5 + 〇^Z i 〇—^ Ν ο ο X Compound g τ-Η 109 1 1 5 〇〇 α\ •214- 134026-2 200916447

V 製備順序| N，Y i Ν, Υ, Η, G 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.93 (s, 1H), 9.94 (bs, 1H), 7.99 (d, J=7.8 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.38-7.05 (m, 6H), 5.08-4.99 (m, 2H), 4.84 (q, J=4.9 Hz, 1H), 3.50-3.32 (m, 5H), 2.34 (s, 3H), 2.05-1.76 (m, 2H), 1.63-1.48 (m, 2H), 1.48-1.24 (m, 2H). LRMS (ESI):(計算值） 488.2 (實測值）489.3 (MH)+ 1 (dmso-d6) d(ppm) 1Η ： 12.91 (s, 1H), 9.93 (bs, 1H), 8.10-8.04 (m, 2H), 7.41-7.34 (m, 2H), 4.90 (m, 1H), 3.42 (q, J=5.1 Hz, 2H), 2.33 (s, 3H), 1.80-1.72 (m, 2H), 1.54 (q, J=7.6 Hz, 2H), 1.35 (s, 9H), 1.48-1.15 (m, 2H)· LRMS (ESI):(計算值）421.2 (實測值） 422.3 (MH)+ 結構 00 HN、Cbz s (S)-5-乙烷硫醯胺基-1-(7-(甲磺醯 基)-1Η-苯并[d]咪唑-2-基)戊基胺基甲 酸芊酯 Rl H 02IS| N 人丫 H^Boc S (S)-5-乙烷硫醯胺基-1-(7-硝基-1H-苯并 [d]咪唑-2-基)戊基胺基甲酸第三-丁酯 起始物質 CM ^ 工2 i Z 4:广 tH。 〇K 、 〇 〇 工 〇 E ，u_ X X 工Z Z z 〇=( \ 〇 CQ X 化合物 ο μ Η 1—Η »—Η 5 § -215- 134026-2 200916447 f 製備順序 Ν, ΥΗ,Ζ D, Ν, Υ,Ε 特徵鑒定 (dmso-d6) d(ppm) 1H： 12.93 (s, 1H), 9.48 (s, 1H), 8.10 (d, J=7.8 Hz, 1H), 8.05 (d, J=7.4 Hz, 1H), 7.78 (s, 1H), 7.43-7.24 (m, 6H), 7.06 (t, J=7.2 Hz, 1H), 4.92 (q, J=6.3 Hz, 1H), 3.45-3.32 (m, 2H), 1.88-1.74 (m, 2H), 1.53 (qi, J=7.0 Hz, 2H), 1.35 (s, 9H), 1.45-1.19 (m, 2H). LRMS (ESI):(計算值）498.2 (實測值）499.4 (MH)+ (dmso-d6) d(ppm) 1H ： 12.91 (s, 1H), 10.17 (s, 1H), 8.10 (d, J=8.2 Hz, 1H), 8.06 (d, J=7.8 Hz, 1H), 7.40-7.34 (m, 2H), 7.28-7.06 (m, 5H), 4.92 (q, J=7.2 Hz, 1H), 3.82 (s, 3H), 3.48-3.39 (m, 2H), 1.86-1.73 (m, 2H), 1.56 ^ (qi, J=7.6 Hz, 2H), 1.36 (s, 9H), 1.40-1.18 (m, 2H). LRMS (ESI):(計算值）497.2 (實測 值）498.4 (MH)+ 結構 Η H 。/ HN'Boc S ^ (S)-1 -(7-硝基-1H-苯并[d]咪唑-2-基)-5-(3-苯基硫脲基)戊基胺基甲酸第 三-丁酯 _ Qx h 〇2n HN'Boc S ^ (S)-1 -(7-硝基-1H-苯并[d]咪唑-2-基)-5-(2-苯基乙烷硫醯胺基)戊基胺基 甲酸第三-丁酯 起始物質 〇 1 . £ 〇 CQ 工 j hcAI叫 1 /NH 3 Boc Vo + ^γΝΗ2 S 人 νη2 Ν〇2 化合物 CN 1—Η CO 5 CNI 〇〇 rn 00 134026-2 -216- 200916447 /k 製備順序i &lt; &lt; pS IJ-. 特徵鑒定 (dmso-d6) d(ppm) 1H: 13.05 (s，1H), 9.93 (s， 1H), 8.46 (d, J=7.2 Hz, 1H), 8.09 (d, J=7.8 ： Hz, 1H), 7.36 (t, J=8.0 Hz, 1H), 5.22 (q, J=5.5 Hz, 1H), 3.41 (q, J=6.8 Hz, 2H), 2.33 (s, 3H), 1.87 (s, 3H), 1.89-1.70 (m, 2H), 1.55 (qi, J=7.6 Hz, 2H), 1.43-1.19 (m, 2H). LRMS (ESI):(計算值）363.1 (實測值） 364.2 (MH)+ i__ (dmso-d6) d(ppm) 1H 9.94 (s, 1H), 8.39 (t, J=7.6 Hz，1H), 8.18 (s，1H)，8.08 (d，J二8_2 Hz, 1H)，8.03 (d，J=8_0 Hz，1H)，7.36 (t， J=8.2 Hz, 1H), 5.22 (q, J=6.9 Hz, 1H), 3.48-3.37 (m, 2H), 2.91-2.78 (m, 2H), 2.33 (s, 3H), 2.29-2.12 (m, 4H), 2.10-1.43 (m, 10H)，1.41-1.20 (m，2H)· LRMS (ESI):(計 算值）446.2 (實測值）447.3 (MH)+ 結構 Ql H H&amp;丫 0 S (S)-N-(5-乙烷硫醯胺基-1 -(7-硝基-1H-苯并[d]咪唑-2-基)戊基)乙醯胺 土 ¥ \ m )=co 工z 赏确 \ l&gt; ®- ( ? i / V-/ ^ ^ X | 4 1 zi ιό寺缕 rPY ^带墙 〇 % 5 ^ 起始物質 βχ Η HN. S Boc 111 ； 人又 QX η ΗΝ、 S Boc 111 + Ο^Ο Η 化合物 2 5 00 -217- 134026-2 200916447 製備順序i B，D B,D I PL, pi 特徵鑒定 (dmso-d6) d(ppm) 1H： 12.97 (s, 1H), 9.93 (s, 1H), 8.10 (d, J=8.0 Hz, 1H), 8.05 (d, J=7.8 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.36 (t, J=8.0 Hz, 1H), 4.95 (q, J=6.3 Hz, 1H), 3.96 (q, J=6.8 Hz, 2H), 3.42 (q, J=6.3 Hz, 2H), 2.33 (s, 3H), 1.81 (qi, J=8.8 Hz, 2H), 1.55 (qi, J=7.2 Hz, 2H), 1.46-1.22 (m, 2H), 1.14 (t, J=6.8 Hz, 3H). LRMS (ESI):(計算值） 393.1 (實測值）394.3 (MH)+ (CD30D) d(ppm) 1H : 8.17 (dd，J=8.2, 0.8 Hz, 1H)，8.01 (d，J=8.2 Hz，1H)，7.42 (t， :J二8.0 Hz，1H)，5.26 (dd，J=8.4, 6.5 Hz，1H)， ,3.57 (t, J=7.0 Hz, 2H), 2.57 (qi, J=6.8 Hz, 1H), 2.40 (s, 3H), 2.12-1.97 (m, 2H), 1.70 (qi,J=7.4 Hz, 2H), 1.57-1.35 (m, 2H), 1.16 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H). LRMS (ESI):(計算值）391.2 (實測值） 392.3 (MH)+ (CD30D) d(ppm) 1H ： 8.18 (d, 1H), 8.02 (d, J=7.8 Hz, 1H), 7.42 (t, J=8.0 Hz, 1H), 5.41 (t，J二8.0 Hz，1H)，4.06 (d，J=4.5 Hz，2H)， 3·56 (t，J=7.2 Hz，2H)，2.40 (s，3H)， 2.15-1.98 (m，2H)，1.70 (qi，J=7.4 Hz，2H)， 1.56-1.34 (m，2H). LRMS (ESI):(計算值） 379.1 (實測值）380.2 (MH)+ 結構 V HN 丫 0 S °Ί (S)- 5-乙烷硫醯胺基-1 -(7-硝基-1H-苯并 [d]咪唑-2-基)戊基胺基甲酸乙酯 Ql H 〇2N HN^O S (S)-N-(5-乙烷硫醯胺基-1 -(7-硝基-1H-苯并[d]咪唑-2-基)戍基)異丁醯胺 Rx H HNx^O S OH (S)-N-(5-乙烷硫醯胺基-1-(7-硝基-1H-苯并[d]咪唑-2-基)戊基)-2-羥基乙醯胺 起始物質 Ρχ Η 〇2N HN. S B〇C 111 〇Λ〇- _ …-J Ρχ Η HN、 S Boc 111 +· Rx η 〇2ν HN. S ! B〇C 111 + ηοΛ^〇η 化合物1 r-Η Η 00 H 5 00 00 00 134026-2 .218 - 200916447 製備順序 Q cd&quot; B’BB 特徵鑒定 (dmso-d6) d(ppm) 1H ： 13.17 (s, 1H), 9.93 (s, 1H), 8.91 (d, J=8.0 Hz, 1H), 8.11 (d, J=8.2 Hz, 1H), 8.07 (d, J=7.8 Hz, 1H), 7.38 (t, J=8.0 Hz, 1H), 5.27 (q, J=6.5 Hz, 1H), 3.73 (q, J=10 Hz, 2H), 3.41 (qi, J=4.5 Hz, 2H), 2.33 (s, 3H), 1.97-1.78 (m, 2H), 1.55 (qi, J=7.0 Hz, 2H), 1.41-1.25 (m, 2H). LRMS (ESI):(計算值）388.1 (實測值）389.2 (MH)+ 1___ . (dmso-d6) d(ppm) 1H： 12.97 (s, 1H), 9.93 (s, 11H), 8.10 (d, J=7.6 Hz, 1H), 8.05 (d, J=7.6 Hz, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.37 (t, J=8.0 Hz, 1H), 4.95 (q, J=6.5 Hz, 1H), 4.08-3.98 (m, 2H), 3.48-3.39 (m, 4H), 3.23 (s, 3H), 2.33 (s, 3H), 1.86-1.78 (m, 2H), 1.54 (qi, J=7.0 Hz, 2H), 1.46-1.21 (m, 2H). LRMS (ESI):(計算值）423.2 (實測值） 424.2 (MH)+ 結構 Rl H HN-^O S (S)-2-氧基-N-(5-乙烧硫酿胺基-1-(7-硝 基-m-苯并[d]咪唑-2-基)戊基)乙醯胺 Qx h 〇2n NH S 0 -Ό (S)-5-乙炫硫酿胺基-1-(7-石肖基-1H-苯弁 [d]咪唑-2-基)戊基胺基甲酸2-曱氧基乙 |酯 起始物質 Ρχ Η ΗΝ. S Boc 111 + i h〇A^cn Ρχ Η 〇2n HN、 S Boc 111 + 化合物 120 5 On 00 § 219- 134026-2 200916447 〆 r„s. 製備順序 ρί PL, 特徵鑒定 (dmso-d6) d(ppm) 1H: 13.02 (s，1H)，9.93 (s， 1H), 8.46 (bd, J=8.4 Hz, 1H), 8.11-8.04 (m, 2H), 7.37 (t, J=8.0 Hz, 1H), 5.32-5.19 (m, 1H), 3.55-3.47 (m, 2H), 3.41 (qi, J=5.1 Hz, 2H), 3.18 (m, 3H), 2.42 (t, J=6.7 Hz, 1H), 2.36 (t, J=6.1 Hz, 1H), 2.33 (s, 3H), 1.93-1.73 (m, 2H), 1.55 (qi, J=7.0 Hz, 2H), 1.42-1.19 (m, 2H). LRMS (ES：[):(計算值）407.2 (實測值）408.3 (MH)+ (dmso-d6) d(ppm) 1H* 13.18 (s, 1H), 9.92 (s, 1H), 9.00 (d, J=8.8 Hz, 1H), 8.12 (d, J=8.4 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.39 (t, J=8.0Hz，lH)，5.32(q，J=6.7Hz，lH)，4.23-4.11 (m, 2H), 3.41 (qi, J=4.1 Hz, 2H), 3.10 (s, 3H), 2.32 (s, 3H), 1.98-1.77 (ra, 2H), 1.56 (qi, J=7.2 Hz, 2H), 1.48-1.23 (m, 2H). LRMS (ESI):(計算值）441.1 (實測值） 442.2 (MH)+ 結構 RX H HN^O S OMe (S)-N-(5-乙烷硫醯胺基-1-(7-硝基-1H-苯乒[d]咪唑-2-基)戊基)-3-甲氧基丙醯 胺 Rx h 〇2N HN-^O S S02 1 (S&gt;-N-(5-乙烷硫醯胺基-1 -(7-硝基-1H-苯并[d]咪唑-2-基)戊基)-2-(甲磺醯基） 乙醯胺 起始物質 Rx Η 〇2N V HN. S Boc 111 HO 人 Ρχ Η 〇2n HN. S Boc川 + J 〇2 化合物 CNl S C\ - 220 - 134026-2 200916447 製備順序| N，Y，X，Z 1 Ν,Υ,Χ,Ζ 特徵鑒定 (dmso-d6) d(ppm) 1H： 12.67 (s, 1H), 9.28 (d, J=3.3 Hz, 1H), 7.78 (dd, J=7.6, 1.0 Hz, 1H), 7.70 (d, J=2.7 Hz, 1H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.52-7.15 (m, 4H), 4.76 (q, J=5.3 Hz, 1H), 3.41-3.20 (m, 2H), 2.76 (bs, 3H), 1.99-1.72 (m, 2H), 1.58-1.14 (m, 4H), 1.38 (s, 9H). LRMS (ESI):(計算值）434.2 (實測 .)435.1(MH)+ (dmso-d6) d(ppm) 1H '· 12.68 (s, 1H), 9.41 (bs, 1H), 9.29 (d, J=3.5 Hz, 1H), 7.79 (dd, J=7.6, 1.2 Hz, 1H), 7.73-7.70 (m, 2H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.55-7.45 (m, 1H), 7.37-7.23 (m, 5H), 7.18 (t, J=7.8 Hz, 1H), 4.77 (q, J=5.7 Hz, 1H), 3.43 (bs,2H), 2.00-1.74 (m, 2H), 1.62-1.47 (m, 2H), 1.38 (s, 9H), 1.45-U7 (m, 2H). LRMS (ESI):(計算 值）496.2 (實測值）497.1 (MH)+ 結構 ° H^B0C S (S)-l-(7-胺甲醯基-1H-苯并[d]咪唑-2-基)-5-(3-甲基硫脲基)戊基胺基甲酸第 三-丁酯 。亂B0C s u (S)-l-(7-胺甲醯基-1H-苯并[d]咪唑-2-基)-.5-(3-笨基磁脲基)戊基胺基甲酸第 三-丁酯 起始物質 N 〇 ^ £ / 5 i co 工 z Z f a 4+tk+ J ◦K、 x 〇 CD 工 N p X | C0 工 Z 2 f- U ivWO 〇 CQ 工 化合物| 5 -221 - 134026-2 200916447 製備順序| Q &gt;&lt; 2&quot; ω 特徵鑒定 . 1 (dmso-d6) d(ppm) 1H ： 12.67 (s, 1H), 10.17 (s, 1H), 9.28 (d, J=3.1 Hz, 1H), 7.79 (dd, J=7.6, 1.2 Hz, 1H), 7.75-7.70 (m, 1H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.46 (d, J=7.6 Hz, 1H), 7.29-7.16 (m, 6H), 4.76 (q, J=5.9 Hz, 1H), 3.83 (s, 2H), 3.52-3.39 (m, 2H), 1.99-1.69 (m, 2H), 1.66-1.49 (m, 2H), 1.43-1.13 (m, 2H), 1‘38 (s，9H). LRMS (ESI):(計算 值）495.2 (實測值）496.1 (MH)+ 結構 〇 HN、 S Boc (S)-l-(7-胺甲醯基-1H-苯并[d]咪唑-2-基)-5-(2-笨基乙烧硫酿胺基)戍基胺基 曱酸第三-丁酯 起始物質 β χ&quot; x ITS l+tk 七 /‘‘ •乙 C\J 1 、g 1 δ Ο ω 工 化合物 5 m Q\ -222 134026-2 200916447 製備順序| N, Y，B, F， X，G ! 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.80 (s, 1H), 9.95 (s, 1H), 9.27 (s, 1H), 8.44 (m, 1H), 7.78 (bd, J=6.7 Hz, 1H), 7.76-7.66 (m, 1H), 7.64 (bd, J=7.6 Hz, 1H), 7.25-7.19 (m, 1H), 5.18-5.02 (m, 1H), 3.43 (q, J=7.0 Hz, 2H), 2.93-2.85 (m, 2H), 2.34 (s, 3H), 2.30-2.15 (m, 1H), 2.23 (s, 3H), 2.08-1.92 (m, 3H), 1.90-1.47 (m, 7H), 1.47-1.25 (m, 2H). LRMS (ESI)： (計算值)444.2 (實測值)445.1 (MH)+ ! 結構 )=OT 砩祙 工z s- &gt;4 y\~/ 础。 K1 is 1 i 淫 i A 〇 7 ^ ^ z x Ψ' rf 起始物質 N 8 工〜| I’tk +κ&gt;- Ο ω 工 化合物 實例 -223 - 134026-2 200916447 製備順序| tx；&gt;&lt; 特徵鑒定 (dmso-d6) d(ppm) 1H： 12.83 (s, 1H), 9.20 (d, J=3.5 Hz, 1H), 9.00 (d, J=8.0 Hz, 1H), 7.80 (d, J=7.6 Hz, 1H), 7.73-7.70 (m, 1H), 7.65 (d, J=8.0 Hz, 1H), 7.43-7.18 (m, 2H), 7.28 (t, J=8.0 Hz, 1H), 5.10 (q, J=5.7 Hz, 1H), 4.23-4.10 (m, 2H), 3.38-3.19 (m, 2H), 3.10 (s, 3H), 2.77 (bs, 3H), 2.09-1.73 (m, 2H), 1.50 (qi, J=6.7 Hz, 2H), 1.43-1.19 (m, 2H). LRMS (ESI):(計算值）454.1 (實測值） 455.0 (MH)+ 結構 〇 HN-^O S 、S02 1 (S&gt;-2-(5-(3-甲基硫脲基)-1-(2-(甲磺醯 基)乙醯胺基)戊基)-1H-苯并[d]咪唑-7-羧醯胺 1 起始物質 N /° x 化合物i 5 σ\ -224 - 134026-2 200916447V Preparation sequence | N,Y i Ν, Υ, Η, G Characterization (dmso-d6) d(ppm) 1H : 12.93 (s, 1H), 9.94 (bs, 1H), 7.99 (d, J=7.8 Hz , 1H), 7.81 (d, J=7.8 Hz, 1H), 7.65 (d, J=7.6 Hz, 1H), 7.38-7.05 (m, 6H), 5.08-4.99 (m, 2H), 4.84 (q, J=4.9 Hz, 1H), 3.50-3.32 (m, 5H), 2.34 (s, 3H), 2.05-1.76 (m, 2H), 1.63-1.48 (m, 2H), 1.48-1.24 (m, 2H) LRMS (ESI): (calculated) 488.2 (measured value) 489.3 (MH) + 1 (dmso-d6) d (ppm) 1Η : 12.91 (s, 1H), 9.93 (bs, 1H), 8.10-8.04 ( m, 2H), 7.41-7.34 (m, 2H), 4.90 (m, 1H), 3.42 (q, J=5.1 Hz, 2H), 2.33 (s, 3H), 1.80-1.72 (m, 2H), 1.54 (q, J=7.6 Hz, 2H), 1.35 (s, 9H), 1.48-1.15 (m, 2H)· LRMS (ESI): (calculated) 421.2 (measured value) 422.3 (MH)+ structure 00 HN, Cbz s (S)-5-ethanethioguanidino-1-(7-(methylsulfonyl)-1Η-benzo[d]imidazol-2-yl)pentylaminocarbazate Rl H 02IS N 丫H^Boc S (S)-5-ethanethioguanidino-1-(7-nitro-1H-benzo[d]imidazol-2-yl)pentylaminocarboxylic acid third- Butyl ester starting material CM ^ 2 2 Z 4: wide tH. 〇K , 〇〇 〇 E , u_ XX ZZ z 〇 = ( \ 〇 CQ X compound ο μ Η 1 - Η » - Η 5 § -215- 134026-2 200916447 f Preparation order Ν, ΥΗ, Ζ D, Ν, Υ, Ε characterization (dmso-d6) d(ppm) 1H: 12.93 (s, 1H), 9.48 (s, 1H), 8.10 (d, J=7.8 Hz, 1H), 8.05 (d, J= 7.4 Hz, 1H), 7.78 (s, 1H), 7.43-7.24 (m, 6H), 7.06 (t, J=7.2 Hz, 1H), 4.92 (q, J=6.3 Hz, 1H), 3.45-3.32 ( m, 2H), 1.88-1.74 (m, 2H), 1.53 (qi, J=7.0 Hz, 2H), 1.35 (s, 9H), 1.45-1.19 (m, 2H). LRMS (ESI): (calculated value 498.2 (measured value) 499.4 (MH) + (dmso-d6) d (ppm) 1H : 12.91 (s, 1H), 10.17 (s, 1H), 8.10 (d, J = 8.2 Hz, 1H), 8.06 ( d, J=7.8 Hz, 1H), 7.40-7.34 (m, 2H), 7.28-7.06 (m, 5H), 4.92 (q, J=7.2 Hz, 1H), 3.82 (s, 3H), 3.48-3.39 (m, 2H), 1.86-1.73 (m, 2H), 1.56 ^ (qi, J=7.6 Hz, 2H), 1.36 (s, 9H), 1.40-1.18 (m, 2H). LRMS (ESI): ( Calculated value) 497.2 (measured value) 498.4 (MH) + structure Η H . / HN 'Boc S ^ (S)-1 -(7-nitro-1H-benzo[d]imidazol-2-yl)-5 -(3-phenylthioureido)pentylaminocarboxylic acid tert-butyl ester _ Qx h 〇2n HN'Boc S ^ ( S)-1 -(7-nitro-1H-benzo[d]imidazol-2-yl)-5-(2-phenylethanesulfonylamino)pentylaminocarboxylic acid tert-butyl ester Starting material 〇 1 . £ 〇CQ worker j hcAI is called 1 /NH 3 Boc Vo + ^γΝΗ2 S Human νη2 Ν〇2 Compound CN 1—Η CO 5 CNI 〇〇rn 00 134026-2 -216- 200916447 /k Preparation sequence i &lt;&lt; pS IJ-. Characterization (dmso-d6) d (ppm) 1H: 13.05 (s, 1H), 9.93 (s, 1H), 8.46 (d, J = 7.2 Hz, 1H), 8.09 ( d, J=7.8 : Hz, 1H), 7.36 (t, J=8.0 Hz, 1H), 5.22 (q, J=5.5 Hz, 1H), 3.41 (q, J=6.8 Hz, 2H), 2.33 (s , 3H), 1.87 (s, 3H), 1.89-1.70 (m, 2H), 1.55 (qi, J=7.6 Hz, 2H), 1.43-1.19 (m, 2H). LRMS (ESI): (calculated) 363.1 (measured value) 364.2 (MH)+ i__ (dmso-d6) d(ppm) 1H 9.94 (s, 1H), 8.39 (t, J=7.6 Hz, 1H), 8.18 (s,1H), 8.08 (d , J 2 8_2 Hz, 1H), 8.03 (d, J=8_0 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 5.22 (q, J=6.9 Hz, 1H), 3.48-3.37 (m , 2H), 2.91-2.78 (m, 2H), 2.33 (s, 3H), 2.29-2.12 (m, 4H), 2.10-1.43 (m, 10H), 1.41-1.20 (m, 2H)· LRMS (ESI ): (calculated value) 446.2 (measured value) 447.3 (MH) + structure Ql H H&amp;丫0 S (S)-N-(5-ethanethioguanamine-1 -(7-nitro-1H-benzo[d]imidazol-2-yl)pentyl)acetamide土¥ \ m )=co工z Reward \ l&gt; ®- ( ? i / V-/ ^ ^ X | 4 1 zi ιό寺缕rPY ^带墙〇% 5 ^ Starting substance βχ Η HN. S Boc 111 ; human QX η ΗΝ, S Boc 111 + Ο^Ο 化合物 Compound 2 5 00 -217- 134026-2 200916447 Preparation sequence i B, DB, DI PL, pi Characterization (dmso-d6) d (ppm) 1H : 12.97 (s, 1H), 9.93 (s, 1H), 8.10 (d, J=8.0 Hz, 1H), 8.05 (d, J=7.8 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H) , 7.36 (t, J=8.0 Hz, 1H), 4.95 (q, J=6.3 Hz, 1H), 3.96 (q, J=6.8 Hz, 2H), 3.42 (q, J=6.3 Hz, 2H), 2.33 (s, 3H), 1.81 (qi, J=8.8 Hz, 2H), 1.55 (qi, J=7.2 Hz, 2H), 1.46-1.22 (m, 2H), 1.14 (t, J=6.8 Hz, 3H) LRMS (ESI): (calculated) 393.1 (measured value) 394.3 (MH) + (CD30D) d (ppm) 1H : 8.17 (dd, J = 8.2, 0.8 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.42 (t, :J 2 8.0 Hz, 1H), 5.26 (dd, J=8.4, 6.5 Hz, 1H), , 3.57 (t, J=7.0 Hz, 2H), 2.57 (qi, J =6.8 Hz, 1H), 2.40 (s, 3H), 2.12-1.97 (m, 2H), 1.70 (qi, J=7 .4 Hz, 2H), 1.57-1.35 (m, 2H), 1.16 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H). LRMS (ESI): (calculated) 391.2 (Measured value) 392.3 (MH)+ (CD30D) d(ppm) 1H : 8.18 (d, 1H), 8.02 (d, J=7.8 Hz, 1H), 7.42 (t, J=8.0 Hz, 1H), 5.41 (t, J 8.0 Hz, 1H), 4.06 (d, J = 4.5 Hz, 2H), 3·56 (t, J = 7.2 Hz, 2H), 2.40 (s, 3H), 2.15-1.98 (m, 2H), 1.70 (qi, J=7.4 Hz, 2H), 1.56-1.34 (m, 2H). LRMS (ESI): (calculated) 379.1 (measured value) 380.2 (MH)+ structure V HN 丫0 S ° Ί (S)- 5-Ethylthioguanidino-1 -(7-nitro-1H-benzo[d]imidazol-2-yl)pentylaminocarboxylic acid ethyl ester Ql H 〇2N HN^OS ( S)-N-(5-ethanethioguanamine-1 -(7-nitro-1H-benzo[d]imidazol-2-yl)indolyl)isobutylamine Rx H HNx^OS OH ( S)-N-(5-Ethylthioguanidino-1-(7-nitro-1H-benzo[d]imidazol-2-yl)pentyl)-2-hydroxyacetamide starting materialΡχ Η N 2N HN. SB〇C 111 〇Λ〇- _ ...-J Ρχ Η HN, S Boc 111 +· Rx η 〇2ν HN. S ! B〇C 111 + ηοΛ^〇η Compound 1 r-Η Η 00 H 5 00 00 00 134026-2 .218 - 200916447 Preparation sequence Q cd&quot; B BB characterization (dmso-d6) d(ppm) 1H : 13.17 (s, 1H), 9.93 (s, 1H), 8.91 (d, J=8.0 Hz, 1H), 8.11 (d, J=8.2 Hz, 1H ), 8.07 (d, J=7.8 Hz, 1H), 7.38 (t, J=8.0 Hz, 1H), 5.27 (q, J=6.5 Hz, 1H), 3.73 (q, J=10 Hz, 2H), 3.41 (qi, J=4.5 Hz, 2H), 2.33 (s, 3H), 1.97-1.78 (m, 2H), 1.55 (qi, J=7.0 Hz, 2H), 1.41-1.25 (m, 2H). LRMS (ESI): (calculated) 388.1 (measured value) 389.2 (MH) + 1___ . (dmso-d6) d (ppm) 1H: 12.97 (s, 1H), 9.93 (s, 11H), 8.10 (d, J =7.6 Hz, 1H), 8.05 (d, J=7.6 Hz, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.37 (t, J=8.0 Hz, 1H), 4.95 (q, J=6.5 Hz, 1H), 4.08-3.98 (m, 2H), 3.48-3.39 (m, 4H), 3.23 (s, 3H), 2.33 (s, 3H), 1.86-1.78 (m, 2H), 1.54 (qi, J=7.0 Hz, 2H), 1.46-1.21 (m, 2H). LRMS (ESI): (calculated) 423.2 (measured value) 424.2 (MH)+ structure Rl H HN-^OS (S)-2-oxygen --N-(5-ethylsulfurylsulfanyl-1-(7-nitro-m-benzo[d]imidazol-2-yl)pentyl)acetamide Qx h 〇2n NH S 0 -Ό (S)-5-Ethylsulfonylamino-1-(7-succinyl-1H-benzoquinone[d]imidazol-2-yl)pentylaminocarbamic acid 2-decyloxyethyl ester starting material Η Η S Boc 111 + ih〇A^cn Ρχ 〇 〇2n HN, S Boc 111 + Compound 120 5 On 00 § 219- 134026-2 200916447 〆r„s. Preparation order ρί PL, Characterization (dmso-d6) d (ppm) 1H: 13.02 (s, 1H), 9.93 (s, 1H), 8.46 (bd, J=8.4 Hz, 1H), 8.11-8.04 (m, 2H), 7.37 (t, J=8.0 Hz, 1H ), 5.32-5.19 (m, 1H), 3.55-3.47 (m, 2H), 3.41 (qi, J=5.1 Hz, 2H), 3.18 (m, 3H), 2.42 (t, J=6.7 Hz, 1H) , 2.36 (t, J=6.1 Hz, 1H), 2.33 (s, 3H), 1.93-1.73 (m, 2H), 1.55 (qi, J=7.0 Hz, 2H), 1.42-1.19 (m, 2H). LRMS (ES:[): (calculated) 407.2 (measured value) 408.3 (MH) + (dmso-d6) d (ppm) 1H* 13.18 (s, 1H), 9.92 (s, 1H), 9.00 (d, J=8.8 Hz, 1H), 8.12 (d, J=8.4 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.39 (t, J=8.0Hz, lH), 5.32 (q, J= 6.7 Hz, lH), 4.23-4.11 (m, 2H), 3.41 (qi, J=4.1 Hz, 2H), 3.10 (s, 3H), 2.32 (s, 3H), 1.98-1.77 (ra, 2H), 1.56 (qi, J=7.2 Hz, 2H), 1.48-1.23 (m, 2H). LRMS (ESI): (calculated) 441.1 (measured value) 442.2 (MH)+ structure RX H HN^OS OMe (S) -N-(5-ethanethioguanamine-1-(7-nitro-1H-phenylphen[d]imidazol-2-yl)pentyl)- 3-methoxypropionamide Rx h 〇2N HN-^OS S02 1 (S&gt;-N-(5-ethanethioguanamine-1 -(7-nitro-1H-benzo[d]imidazole) -2-yl)pentyl)-2-(methylsulfonyl) acetamide starting material Rx Η N2N V HN. S Boc 111 HO Ρχ 〇 n 2n HN. S Boc川+ J 〇2 Compound CNl SC\ - 220 - 134026-2 200916447 Preparation sequence | N,Y,X,Z 1 Ν,Υ,Χ,Ζ characterization (dmso-d6) d(ppm) 1H: 12.67 (s, 1H), 9.28 (d , J=3.3 Hz, 1H), 7.78 (dd, J=7.6, 1.0 Hz, 1H), 7.70 (d, J=2.7 Hz, 1H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.52 -7.15 (m, 4H), 4.76 (q, J=5.3 Hz, 1H), 3.41-3.20 (m, 2H), 2.76 (bs, 3H), 1.99-1.72 (m, 2H), 1.58-1.14 (m , 4H), 1.38 (s, 9H). LRMS (ESI): (calculated) 434.2 (measured.) 435.1 (MH) + (dmso-d6) d (ppm) 1H '· 12.68 (s, 1H), 9.41 (bs, 1H), 9.29 (d, J=3.5 Hz, 1H), 7.79 (dd, J=7.6, 1.2 Hz, 1H), 7.73-7.70 (m, 2H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.55-7.45 (m, 1H), 7.37-7.23 (m, 5H), 7.18 (t, J=7.8 Hz, 1H), 4.77 (q, J=5.7 Hz, 1H), 3.43 (bs , 2H), 2.00-1.74 (m, 2H), 1.62-1.47 (m, 2H), 1.38 (s, 9H), 1.45-U7 (m, 2H). LRM S (ESI): (calculated) 496.2 (found) 497.1 (MH) + structure ° H^B0C S (S)-l-(7-Aminomethyl-1H-benzo[d]imidazole-2- Base -5-(3-methylthioureido)pentylaminocarboxylic acid tert-butyl ester. Chao B0C su (S)-l-(7-Aminocarbamido-1H-benzo[d]imidazol-2-yl)-.5-(3-indolylureaido)pentylaminocarboxylic acid -butyl ester starting material N 〇^ £ / 5 i co work z Z fa 4+tk+ J ◦K, x 〇CD work N p X | C0 work Z 2 f- U ivWO 〇CQ compound | 5 -221 - 134026-2 200916447 Preparation sequence | Q &gt;&lt;2&quot; ω Characterization. 1 (dmso-d6) d(ppm) 1H : 12.67 (s, 1H), 10.17 (s, 1H), 9.28 (d, J= 3.1 Hz, 1H), 7.79 (dd, J=7.6, 1.2 Hz, 1H), 7.75-7.70 (m, 1H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 7.46 (d, J=7.6 Hz, 1H), 7.29-7.16 (m, 6H), 4.76 (q, J=5.9 Hz, 1H), 3.83 (s, 2H), 3.52-3.39 (m, 2H), 1.99-1.69 (m, 2H) , 1.66-1.49 (m, 2H), 1.43-1.13 (m, 2H), 1'38 (s, 9H). LRMS (ESI): (calculated) 495.2 (measured value) 496.1 (MH)+ structure 〇HN , S Boc (S)-l-(7-Aminomethylindolyl-1H-benzo[d]imidazol-2-yl)-5-(2-indolylsulfurylsulfonylamino)nonylaminopurine Acid tri-butyl ester starting material β χ&quot; x ITS l+tk VII/'' • B C\J 1 , g 1 δ Ο ω Working compound 5 m Q\ -222 134026-2 200916447 Preparation sequence | N, Y, B, F X,G ! Characterization (dmso-d6) d(ppm) 1H : 12.80 (s, 1H), 9.95 (s, 1H), 9.27 (s, 1H), 8.44 (m, 1H), 7.78 (bd, J =6.7 Hz, 1H), 7.76-7.66 (m, 1H), 7.64 (bd, J=7.6 Hz, 1H), 7.25-7.19 (m, 1H), 5.18-5.02 (m, 1H), 3.43 (q, J=7.0 Hz, 2H), 2.93-2.85 (m, 2H), 2.34 (s, 3H), 2.30-2.15 (m, 1H), 2.23 (s, 3H), 2.08-1.92 (m, 3H), 1.90 -1.47 (m, 7H), 1.47-1.25 (m, 2H). LRMS (ESI): (calculated) 444.2 (measured value) 445.1 (MH)+ ! Structure)=OT Completion z s- &gt;4 y\~/ Foundation. K1 is 1 i 淫i A 〇7 ^ ^ zx Ψ' rf starting material N 8 work ~| I'tk +κ&gt;- Ο ω compound example -223 - 134026-2 200916447 Preparation order | tx;&gt;&lt Characterization (dmso-d6) d(ppm) 1H: 12.83 (s, 1H), 9.20 (d, J=3.5 Hz, 1H), 9.00 (d, J=8.0 Hz, 1H), 7.80 (d, J =7.6 Hz, 1H), 7.73-7.70 (m, 1H), 7.65 (d, J=8.0 Hz, 1H), 7.43-7.18 (m, 2H), 7.28 (t, J=8.0 Hz, 1H), 5.10 (q, J=5.7 Hz, 1H), 4.23-4.10 (m, 2H), 3.38-3.19 (m, 2H), 3.10 (s, 3H), 2.77 (bs, 3H), 2.09-1.73 (m, 2H ), 1.50 (qi, J=6.7 Hz, 2H), 1.43-1.19 (m, 2H). LRMS (ESI): (calculated) 454.1 (measured value) 455.0 (MH)+ structure 〇HN-^OS, S02 1 (S&gt;-2-(5-(3-methylthioureido)-1-(2-(methylsulfonyl)acetamido)pentyl)-1H-benzo[d]imidazole-7 - Carboxylamamine 1 Starting material N / ° x Compound i 5 σ\ -224 - 134026-2 200916447

製備順序 Z U：&gt;&lt; 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.84 (s, 1H), 9.41 (s, 1H)，9.21 (d，J=3.5 Hz，1H)，9.01 (d，J=7.8 Hz，lH)，7.81(dd,J=7.6，1.2Hz，lH)，7.73-7.64 (m, 3H), 7.34-7.19 (m, 5H), 7.06 (t, J=7.2 Hz, 1H), 5.12 (q, J=6.1 Hz, 1H), 4.23-4.06 (m, 2H), 3.48-3.34 (m, 2H), 3.10 (s, 3H), 2.09-1.74 (m, 2H), 1.63-1.19 (m, 4H). LRMS (ESI):(計算值）516.2 (實測值) 517.1 (MH)+ 結構 H2N 只 〇 HNs^O s 、S02 1 (S)-2-(5-(3-苯基硫脲基)-1-(2-( T磺醯 基）L醯胺基)戊基)-1Η-苯并[d]咪唑-7-羧醯胺 起始物質 N η /0 CM 〇c/ \J O f 〇=&lt;〇 '§ ^ ? o 化合物 實例 00 ON -225 - 134026-2 200916447 製備順序 tux Ν 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.83 (s, 1H), 9.91 (bs, 1H), 9.20 (d, J=3.1 Hz, 1H), 9.00 (d, J=8.0 Hz, 1H), 7.80 (dd, J=7.4, 1.0 Hz, 1H), 7.73-7.70 (m, 1H), 7.65 (dd, J=7.8, 1.1 Hz, 1H), 7.28 (t, J=7.8 Hz, 1H), 5.12 (q, J=5.7 Hz, 1H), 4.23-4.06 (m, 2H), 3.45-3.40 (m, 2H), 3.10 (s, 3H), 2.33 (s, 3H), 2.08-1.69 (m, 2H), 1.62-1.19 (m, 4H). LRMS (ESI):(計算 值）439.1 (實測值）440.0 (MH)+ 1_ _ … (dmso-d6) d(ppm) 1H ： 12.41 (s, 1H), 11.27 '(s, 1H), 10.88 (t, J=5.3 Hz, 1H), 7.88 (d, J=7.2Hz，4H)，7.74(d，J=7.6Hz，4H)，7.62-7.58 (m, 2H), 7.47 (t, J=8.0 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.35-7.12 (m, 6H), 5.01 (d, J=3.5 Hz，2H), 4.29 (q，J=5.1 Hz, 1H)，3.60 (q, J=5.7 Hz, 2H), 1.79-1.58 (m, 4H), 1.55-1.32 (m, 2H). LRMS (ESI):(計算值）601.2 (實測值）602.0 (MH)+ 結構 ο ΗΝγΟ S s〇2 (S)-2-(5-乙烷硫醯胺基-1-(2-(甲磺醯基） 乙醯胺基)戊基)-1Η-苯并[d]咪唑-7-羧 醯胺 1_ s jfr- 上。A ! 工Z — « \ 淪s &gt; 〜盏T0 〈声馆朵 1 V « ^ \Γ\ , J. 1 . 起始物質 N η 工z 工 i )^co Ο \一/ 〇 &gt;+4 + tk 〇j〇 1 工〜 4: + v ^ 0 ό 化合物 a Η 實例1 ____J σ\ ON o -226- 134026-2 200916447 製備順序i &lt; D,E D,E 特徵鑒定 (dmso-d6) d(ppm) 1H ： 10.50 (s, 1H), 9.96 (s, 1H), 7.78 (d, J=2.0 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.49 (dd, J=8.8, 2.1 Hz, 1H), 7.37-7.17 (m, 5H), 6.27 (d, J=1.2 Hz, 1H), 5.03 (s, 2H), 4.15 (q, J=6.9 Hz, 1H), 3.45 (q, J=6.9 Hz, 2H), 2.40 (d, J=1.2 Hz, 3H), 2.35 (s, 3H), 1.79-1.28 (m，6H). LRMS (ESI):(計算值）495.2 (實測 值）496.3 (MH)+ |4||«4^VS O . r- ^ ON VD (N ^ 〇 r^H^r^sScsi^^'Y c〆二夂〇〇〆;〆;〆:滅 C M cn CM ^ Hp^ Hr( -V- (dmso-d6) d(ppm) 1H ： 12.42 (s, 1H), 9.89 (t, J=4.9 Hz, 1H), 7.90 (d, J=7.0 Hz, 2H), 7.72 (d, J=7.6 Hz, 1H), 7.64 (s, 1H), 7.43 (t, J=7.4 Hz, 2H), 7.37-7.14 (m, 6H), 5.03 (d, J=3.7 Hz, 2H), 4.28 (q, J=5.3 Hz, 1H), 3.47 (q, J=7.1 Hz, 2H), 2.50-2.44 (m, 2H), 1.78-1.49 (m, 6H), 1.48-1.23 (m, 2H), 0.81 (t, J=7.2 Hz，3H). LRMS (ESI):(計算值）524.2 (實測 值）525.3 (MH)+ 結構 \ 砩鍥 工' 々今 / 械ί ΐΟ \ ‘ _ / δΦ¥ \ / r—( if —TV S ΐ 潜 '~Λ Τ tiH 〇 δ ^ ^ &lt; eti 。4..^ _ X !? u gi \ if / ^ ^ \=cn w 工z —辦 &gt; 樂 \ 1 ^ 〉 rsj i Λ S 粜 X r \\ x 究 起始物質 i V 0 〇=&lt; ^ § υ ^ CM j.i xi;〜 6 C\J X 6 化合物 τ—Η m 132 ! CO CO ί—H 實例 102 s 134026-2 -227 - 200916447 製備順序 D，E u U 特徵鑒定 (dmso-d6) d(ppm) 1H ： 12.42 (s, 1H), 10.07 (t, J=5.1 Hz, 1H), 7.90 (d, J=7.2 Hz, 2H), 7.73 (d, J=7.4 Hz, 1H), 7.64 (s, 1H), 7.43 (t, J-7.4 Hz, 2H), 7.39-7.12 (m, 6H), 5.03 (d, J=3.7 Hz, 2H), 4.28 (q, J=5.1 Hz, 1H), 3.51 (q, J=5.1 Hz, 2H), 2.05-1.99 (m, 1H), 1.78-1.50 (m, 4H), 1.50-1.27 (m, 2H), 1.01-0.97 (m, 2H), 0.80-0.75 (m, 2H). LRMS (ESI)： (計算值）522.2 (實測值）523.3 (MH)+ (dmso-d6) d(ppm) 1H： 12.42 (s, 1H), 7.90 (d, J=7.2 Hz, 2H), 7.73 (d, J=7.4 Hz, 1H), 7.64 (s, 1H), 7.45-7.14 (m, 10H), 5.03 (d, J=3.1 Hz, 2H), 4.27 (q, J=5.3 Hz, 1H), 3.35-3.25 (m, 2H), 2.78 (bs, 3H), 1.76-1.52 (m, 2H), 1.50-1.22 (m，4H). LRMS (ESI):(計算值） 511.2(實測值）512.3 (MH)+ (dmso-d6) d(ppm) 1Η： 12.41 (s, 1H), 7.90 (d, J=7.8 Hz, 2H), 111 (d, J=7.2 Hz, 1H), 7.64 (d, J=0.4 Hz, 1H)，7.43 (t, J=7.8 Hz，2H)， 7.38-7.12 (m, 8H), 5.03 (d, J=2.2 Hz, 2H), 4.28 (q, J=5.1 Hz, 1H), 3.44-3.22 (m, 4H), 1.80-1.60 (m, 2H), 1.60-1.24 (m, 4H), 1.03 ! (t, J=7.2 Hz, 3H)_ LRMS (ESI):(計算值） i 525.2 (實測值）526.3 (MH)+ 結構 丁‘㈤ os? &gt; Ξ _ &lt; .5¾ / s f 5 z工 够i ^ 5¾ v ·峥遛 VO ,J. i , \\ \ 入哪斤 CK又 nLV\ H HN、Cbz s (S)-6-(3-甲基硫脲基)-1-酮基-1-(4-苯基 嘍唑-2-基胺基)己烷-2-基胺基甲酸芊 酯 丫 L H HN'Cbz S (S)-6-(3-乙基硫脲基)-1 -酮基-1 -(4-苯基 嘧唑-2-基胺基)己烧-2-基胺基甲酸芊 酯 起始物質 〇ΛΛΝ又八〜叫 Η - NHCbz ? 2 〇-Λ 人 叫 H NHCbz 2 + /NH2 - C人 叫 LJ - NHCbz 2 + 化合物 m 1—Η 5 \η 2 g Η -228 - 134026-2 200916447 製備順序 U U AA，E 特徵鑒定 ')d(ppm) 1H ： 7.90 (dd, J=8.4, 1.4 ；7.40-7.27 (m, 9H) ； 5.14 (d, J=12.5 ；5.08 (d, J=12.5 Hz, 1H) ； 4.36-4.32 ；3.61-3.57 (m,2H) ； 3.16 (s,6H)； ^(m,2H) ； 1.67-1.62 (m,2H)； l· (m, 2H). LRMS (ESI):(計算值） ;測值）526.3 (MH)+ )d(ppm) 1H : 7.89 (dd，J=8.4, 1.4 :7.40-7.13 (m，9H) ; 5.13 (d，J=12-3 ；5.08 (d, J=12.5 Hz, 1H) ； 4.35-4.33 ；3.54-3.47 (m, 2H) ； 1.91-1.76 (m, 丨3-1.62 (m，2H) ; 1.51-1.46 (m，2H). iSI):(計算值）579.2 (實測值） H)+ )d(ppm) 1H : 7.89 (dd，J=8.4, 1.4 7.40-7.13 (m, 9H) ； 5.14 (d, J=12.5 5.08 (d, J-12.5 Hz, 1H) ； 4.37-4.33 :3.65 (t，J=7.2Hz，2H) ; 1.93-1.69 1.56-1.45 (m，2H). LRMS (ESI): 550.1 (實測值）551.3 (MH)+ (CD30D Hz, 2H) Hz, 1H)； (m, 1H) 1.91-1.7Ί 1.47-1 本 525.2 (f (CD30D Hz, 2H)； Hz, 1H)； (m，3H)； 2H) ； 1.6 ILRMS (I 1580.4 (M (CD30D Hz, 2H)； Hz, 1H)； (m, 1H)； (m, 4H)； (計算值) 結構 ( 土 4 &lt; /° 禁 2 &gt;•&quot;1 0=\ _ 锘 /Ζ：Ε 硇 r\ 、（--1 . j Γ ll xmYl· LlT 硇 c ·5 _ 1 &gt; @3 工' / fl ^ &gt;名 / &quot;g O I一/Z工 « ί^ί 7 Cl· ®-\\ 7 A 蝴 f A , /=0° ^ ^ 工乂 ^ tO &lt; 2 ^ 〇=&lt; 埏驾 Z工 i (ό咖 χ ίΐί Ο έΐί 起始物質 Ο^Λ 人 H NHCbz 2 + 1 1____1 H NHCbz + 2 nh2 k cf3 Η NHCbz 2 + 0 0 f3c 人 c^cf3 化合物 Pi 00 cn H Os cn 實例 g s 134026-2 -229 - 200916447 &lt;r 製備順序 D，E D,E 1 D,E 特徵鑒定 (CD30D) d(ppm) 1H ： 7.90 (dd, J=8.4, 1.4 Hz, 2H) ； 7.41-7.13 (m, 14H) ； 5.14 (d, J=12.5 Hz, 1H) ； 5.08 (d, J=12.3 Hz, 1H) ； 4.35-4.31 (m, 1H) ； 3.91 (s, 2H) ； 3.59 (t, J=6.8 Hz, 2H) ； 1.95-1.68 (m,4H) ； 1.50-1.45 (m, 2H). LRMS (ESI):(計算值）572.2 (實測值） 573.3 (MH)+ (CD30D) d(ppm) 1H ： 7.89 (dd, J=8.6, 1.4 Hz, 2H) ； 7.40-7.13 (m, 9H) ； 5.14 (d, J=12.5 Hz, 1H) ； 5.08 (d, J=12.3 Hz, 1H) ； 4.36-4.33 (m, 1H) ； 4.19 (s, 2H) ； 3.72-3.67 (m, 2H)； 3.35 (s,3H) ； 1.98-1.69 (m,4H) ； 1.53-1.46 (m, 2H). LRMS (ESI):(計算值）526.2 (實測 值）527.3 (MH)+ (CD30D) d(ppm) 1Η ： 7.89 (dd, J=8.4, 1.4 Hz, 2H) ； 7.40-7.12 (m, 9H) ； 5.14 (d, J=12.5 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 4.37-4.34 (m, 1H) ； 3.67 (s, 2H) ； 3.66 (s, 3H) ； 3.62 (t, J=7.2 Hz, 2H) ； 1.90-1.68 (m, 4H) ； 1.56-1.50 (m, 2H). LRMS (ESI):(計算值）554.2 (實測 值）555.4 (MH)+ 結構 Η H、S IJ (S)-l-酮基-6-(2-笨基乙烷硫醯胺基)-1-(4-苯基魂峻-2-基胺基)己烧-2-基胺 基甲酸芊酯 H H^Cbz S (S)-6-(2-甲氧基乙烷硫醯胺基)-1-酮基 -1-(4-笨基p塞σ坐-2-基胺基)己烧-2-基胺 丨基甲酸苄酯 φ5 c以 I 4 \ ^ M ) V.2° 〇=&lt;^ 工號錯 if ^ m Vfl &amp;- X 巴蚪砩 起始物質 H NHCbz 2 ί clro —___ O^C又 叫 H NHCbz ! 2 1 C1Y^ 1 0 人 叫 H NHCbz + 2 丫。〆 0 化合物 ο 寸 Ϊ ο ί-Η —— (N -230 · 134026-2 200916447 1製備順序 D，E |D，E ! D，E 特徵鑒定 (CD30D) d(ppm) 1H ： 7.89 (dd, J=8.4, 1.4 Hz, 2H) ； 7.40-7.12 (m, 11H) ； 6.80 (d, J=8.8 Hz, 2H) ； 5.13 (d, J=12.3 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 4.35-4.31 (m, 1H) ； 3.84 (s, 2H) ； 3.71 (s, 3H) ； 3.58 (t, J=7.0 Hz, 2H)； 2.00-1.65 (m,4H) ； 1.49-1.39 (m, 2H). LRMS (ESI):(計算值）602.2 (實測值） 603.4 (MH)+ (CD30D) d(ppm) 1H ： 7.89 (dd, J=8.6, 1.4 Hz，2H); 7.40-7.23 (m，13H); 5.13 (d，J=12.3 Hz, 1H) ； 5.08 (d, J=12.3 Hz, 1H) ； 4.36-4.32 (m, 1H) ； 3.87 (s, 2H) ； 3.59 (t, J=7.0 Hz, 丨 2H) ; 2.00-1.66 (m，4H) ; 1.51-1.41 (m, 2H). 丨LRMS (ESI):(計算值）606.2 (實測值） 607.3 (MH)+ (CD30D) d(ppm) 1H ： 7.89 (dd, J=8.4, 1.4 Hz, 2H) ； 7.40-7.12 (m, 14H) ； 5.13 (d, J=12.3 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 434-4.30 (m, 1H) ； 3.53 (t, J=6.8 Hz, 2H) ； 3.00 (t, J=7.2 Hz, 2H) ； 2.82 (t, J=8.0 Hz, 2H)； 1.84-1.71 (m, 2H) ； L60-1.56 (m, 2H)； 1.42-1.28 (m, 2H). LRMS (ESI):(計算值） 586.2 (實測值）587.4 (MH)+ 結構 \ A (N 〇 ^ Cl 之 β i-4 V T ^ . ij, H' s UCI (S)-6-(2-(4-氣苯基)乙烷硫醯胺基)-1-酮 基-1-(4-苯基嘧唑-2-基胺基)己烷-2-基 胺基甲酸苄酯 H HNs S Cbz (S)-1 -酮基-6-(3-苯基丙烷硫醯胺基)-1-(4-苯基嘧唑-2-基胺基)己烷-2-基胺 基甲酸苄酯 起始物質 CM ? w \。 ό LJ · NHCbz 2 c,rac, _£J ^ f° 6 化合物j JO S m y—H in -231 - 134026-2 200916447Preparation sequence ZU: &gt;&lt; Characterization (dmso-d6) d (ppm) 1H : 12.84 (s, 1H), 9.41 (s, 1H), 9.21 (d, J = 3.5 Hz, 1H), 9.01 (d , J=7.8 Hz, lH), 7.81 (dd, J=7.6, 1.2 Hz, lH), 7.73-7.64 (m, 3H), 7.34-7.19 (m, 5H), 7.06 (t, J=7.2 Hz, 1H), 5.12 (q, J=6.1 Hz, 1H), 4.23-4.06 (m, 2H), 3.48-3.34 (m, 2H), 3.10 (s, 3H), 2.09-1.74 (m, 2H), 1.63 -1.19 (m, 4H). LRMS (ESI): (calculated) 516.2 (measured value) 517.1 (MH)+ structure H2N 〇HNs^O s , S02 1 (S)-2-(5-(3- Phenylthiourea)-1-(2-(Tsulfonyl)L-guanidino)pentyl)-1Η-benzo[d]imidazole-7-carboxamide The starting material N η /0 CM 〇 c/ \JO f 〇=&lt;〇'§ ^ ? o Compound Example 00 ON -225 - 134026-2 200916447 Preparation Order tux Ν Characterization (dmso-d6) d(ppm) 1H : 12.83 (s, 1H), 9.91 (bs, 1H), 9.20 (d, J=3.1 Hz, 1H), 9.00 (d, J=8.0 Hz, 1H), 7.80 (dd, J=7.4, 1.0 Hz, 1H), 7.73-7.70 (m , 1H), 7.65 (dd, J=7.8, 1.1 Hz, 1H), 7.28 (t, J=7.8 Hz, 1H), 5.12 (q, J=5.7 Hz, 1H), 4.23-4.06 (m, 2H) , 3.45-3.40 (m, 2H), 3.10 (s, 3H), 2.33 (s, 3H), 2.08-1.69 ( m, 2H), 1.62-1.19 (m, 4H). LRMS (ESI): (calculated) 439.1 (measured value) 440.0 (MH) + 1_ _ ... (dmso-d6) d(ppm) 1H : 12.41 (s , 1H), 11.27 '(s, 1H), 10.88 (t, J=5.3 Hz, 1H), 7.88 (d, J=7.2Hz, 4H), 7.74 (d, J=7.6Hz, 4H), 7.62 7.58 (m, 2H), 7.47 (t, J=8.0 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.35-7.12 (m, 6H), 5.01 (d, J=3.5 Hz, 2H ), 4.29 (q, J=5.1 Hz, 1H), 3.60 (q, J=5.7 Hz, 2H), 1.79-1.58 (m, 4H), 1.55-1.32 (m, 2H). LRMS (ESI): ( Calculated value) 601.2 (measured value) 602.0 (MH) + structure ο ΗΝγΟ S s〇2 (S)-2-(5-ethanethioguanidino-1-(2-(methylsulfonyl) acetamide Base) pentyl)-1 Η-benzo[d]imidazole-7-carboxyguanamine 1_s jfr-. A !工Z — « \ 沦s &gt; ~盏T0 〈声馆朵 1 V « ^ \Γ\ , J. 1 . Starting material N η工z工 i )^co Ο \一/ 〇&gt;+ 4 + tk 〇j〇1 〜4: + v ^ 0 ό Compound a 实例 Example 1 ____J σ\ ON o -226- 134026-2 200916447 Preparation sequence i &lt; D, ED, E Characterization (dmso-d6) d(ppm) 1H : 10.50 (s, 1H), 9.96 (s, 1H), 7.78 (d, J=2.0 Hz, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.69 (d, J= 7.8 Hz, 1H), 7.49 (dd, J=8.8, 2.1 Hz, 1H), 7.37-7.17 (m, 5H), 6.27 (d, J=1.2 Hz, 1H), 5.03 (s, 2H), 4.15 ( q, J=6.9 Hz, 1H), 3.45 (q, J=6.9 Hz, 2H), 2.40 (d, J=1.2 Hz, 3H), 2.35 (s, 3H), 1.79-1.28 (m, 6H). LRMS (ESI): (calculated) 495.2 (measured value) 496.3 (MH) + |4|| «4^VS O . r- ^ ON VD (N ^ 〇r^H^r^sScsi^^'Y c 〆二夂〇〇〆;〆;〆: 灭 CM cn CM ^ Hp^ Hr( -V- (dmso-d6) d(ppm) 1H : 12.42 (s, 1H), 9.89 (t, J=4.9 Hz, 1H), 7.90 (d, J=7.0 Hz, 2H), 7.72 (d, J=7.6 Hz, 1H), 7.64 (s, 1H), 7.43 (t, J=7.4 Hz, 2H), 7.37-7.14 ( m, 6H), 5.03 (d, J=3.7 Hz, 2H), 4.28 (q, J=5.3 Hz, 1H), 3.47 (q, J=7.1 Hz, 2H), 2.50-2.4 4 (m, 2H), 1.78-1.49 (m, 6H), 1.48-1.23 (m, 2H), 0.81 (t, J=7.2 Hz, 3H). LRMS (ESI): (calculated) 524.2 (measured value) ) 525.3 (MH) + Structure \ Completion '々今 / ί ΐΟ \ ' _ / δΦ¥ \ / r—( if —TV S 潜 潜 '~Λ Τ tiH 〇δ ^ ^ &lt; eti . 4..^ _ X !? u gi \ if / ^ ^ \=cn w zh -do &gt; music \ 1 ^ 〉 rsj i Λ S 粜X r \\ x starting material i V 0 〇=&lt ; ^ § υ ^ CM ji xi;~ 6 C\JX 6 Compound τ—Η m 132 ! CO CO ί—H Example 102 s 134026-2 -227 - 200916447 Preparation sequence D, E u U Characterization (dmso-d6 ) d(ppm) 1H : 12.42 (s, 1H), 10.07 (t, J=5.1 Hz, 1H), 7.90 (d, J=7.2 Hz, 2H), 7.73 (d, J=7.4 Hz, 1H), 7.64 (s, 1H), 7.43 (t, J-7.4 Hz, 2H), 7.39-7.12 (m, 6H), 5.03 (d, J=3.7 Hz, 2H), 4.28 (q, J=5.1 Hz, 1H ), 3.51 (q, J=5.1 Hz, 2H), 2.05-1.99 (m, 1H), 1.78-1.50 (m, 4H), 1.50-1.27 (m, 2H), 1.01-0.97 (m, 2H), 0.80-0.75 (m, 2H). LRMS (ESI): (calculated) 522.2 (measured value) 523.3 (MH) + (dmso-d6) d (ppm) 1H: 12.42 (s, 1H), 7.90 (d, J=7.2 Hz, 2H), 7.73 (d, J=7.4 Hz, 1H), 7.64 (s, 1H), 7.45-7.14 (m, 10H), 5.03 (d, J=3.1 Hz, 2H), 4.27 ( q, J=5.3 Hz, 1H), 3.35-3.25 (m, 2H), 2.78 (bs, 3H), 1.76-1.52 (m, 2H), 1.50-1.22 (m, 4H). LRMS (ESI): ( Calculated value) 511.2 (measured value) 512.3 (MH) + (dmso-d6) d (ppm) 1Η: 12.41 (s, 1 H), 7.90 (d, J=7.8 Hz, 2H), 111 (d, J=7.2 Hz, 1H), 7.64 (d, J=0.4 Hz, 1H), 7.43 (t, J=7.8 Hz, 2H) , 7.38-7.12 (m, 8H), 5.03 (d, J=2.2 Hz, 2H), 4.28 (q, J=5.1 Hz, 1H), 3.44-3.22 (m, 4H), 1.80-1.60 (m, 2H ), 1.60-1.24 (m, 4H), 1.03 ! (t, J=7.2 Hz, 3H)_ LRMS (ESI): (calculated) i 525.2 (measured value) 526.3 (MH) + structure D (5) os? &gt; Ξ _ &lt; .53⁄4 / sf 5 z work enough i ^ 53⁄4 v · 峥遛 VO , J. i , \\ \ into which CK and nLV \ H HN, Cbz s (S) -6- (3 -methylthioureido)-1-keto-1-(4-phenyloxazol-2-ylamino)hexane-2-ylcarbamic acid oxime ester 丫LH HN'Cbz S (S)- 6-(3-ethylthioureido)-1-keto-1 -(4-phenylpyrazol-2-ylamino)hexan-2-ylaminocarbazate starting material 〇ΛΛΝ八〜叫Η - NHCbz ? 2 〇-Λ Man H NHCbz 2 + /NH2 - C is called LJ - NHCbz 2 + compound m 1 - Η 5 \η 2 g Η -228 - 134026-2 200916447 Preparation sequence UU AA , E characterization ') d (ppm) 1H : 7.90 (dd, J = 8.4, 1.4; 7.40-7.27 (m, 9H); 5.14 (d, J = 12.5; 5.08 (d, J = 12.5 Hz, 1H) ; 4.36-4.32 ; 3.61-3.57 (m, 2H ; 3.16 (s,6H); ^(m,2H) ; 1.67-1.62 (m,2H); l· (m, 2H). LRMS (ESI): (calculated value); measured value) 526.3 (MH) + )d(ppm) 1H : 7.89 (dd, J=8.4, 1.4 :7.40-7.13 (m,9H); 5.13 (d, J=12-3; 5.08 (d, J=12.5 Hz, 1H); 4.35 -4.33 ;3.54-3.47 (m, 2H) ; 1.91-1.76 (m, 丨3-1.62 (m,2H) ; 1.51-1.46 (m,2H). iSI): (calculated value) 579.2 (measured value) H ) + )d(ppm) 1H : 7.89 (dd, J=8.4, 1.4 7.40-7.13 (m, 9H); 5.14 (d, J=12.5 5.08 (d, J-12.5 Hz, 1H); 4.37-4.33: 3.65 (t, J = 7.2 Hz, 2H); 1.93-1.69 1.56-1.45 (m, 2H). LRMS (ESI): 550.1 (measured) 551.3 (MH)+ (CD30D Hz, 2H) Hz, 1H); (m, 1H) 1.91-1.7Ί 1.47-1 This 525.2 (f (CD30D Hz, 2H); Hz, 1H); (m, 3H); 2H) ; 1.6 ILRMS (I 1580.4 (M (CD30D Hz, 2H) ; Hz, 1H); (m, 1H); (m, 4H); (calculated) structure (soil 4 &lt; /° forbidden 2 &gt;•&quot;1 0=\ _ 锘/Ζ:Ε 硇r\ , (--1 . j Γ ll xmYl· LlT 硇c ·5 _ 1 &gt; @3工' / fl ^ &gt;名 / &quot;g OI一/Z工« ί^ί 7 Cl· ®-\\ 7 A Butterfly f A , /=0° ^ ^ Work乂^ tO &lt; 2 ^ 〇= &lt; 埏 Z Z 工 i (ό咖χ ΐ χ Λ Λ Λ Λ H H H H H H H H H H H H H H H H Os cn Example gs 134026-2 -229 - 200916447 &lt;r Preparation order D, ED, E 1 D, E Characterization (CD30D) d (ppm) 1H: 7.90 (dd, J = 8.4, 1.4 Hz, 2H); 7.41-7.13 (m, 14H) ; 5.14 (d, J = 12.5 Hz, 1H); 5.08 (d, J = 12.3 Hz, 1H); 4.35-4.31 (m, 1H); 3.91 (s, 2H) ; 3.59 (t, J=6.8 Hz, 2H) ; 1.95-1.68 (m, 4H) ; 1.50-1.45 (m, 2H). LRMS (ESI): (calculated) 572.2 (measured value) 573.3 (MH)+ (CD30D d(ppm) 1H : 7.89 (dd, J=8.6, 1.4 Hz, 2H); 7.40-7.13 (m, 9H); 5.14 (d, J=12.5 Hz, 1H); 5.08 (d, J=12.3 Hz) , 1H); 4.36-4.33 (m, 1H); 4.19 (s, 2H); 3.72-3.67 (m, 2H); 3.35 (s, 3H); 1.98-1.69 (m, 4H); 1.53-1.46 (m , 2H). LRMS (ESI): (calculated) 526.2 (measured value) 527.3 (MH) + (CD30D) d (ppm) 1Η : 7.89 (dd, J=8.4, 1.4 Hz, 2H) ; 7.40-7.12 ( m, 9H) ; 5.14 (d, J=12.5 Hz, 1H); 5.08 (d, J=12.5 Hz, 1H); 4.37- 4.34 (m, 1H) ; 3.67 (s, 2H) ; 3.66 (s, 3H) ; 3.62 (t, J=7.2 Hz, 2H) ; 1.90-1.68 (m, 4H) ; 1.56-1.50 (m, 2H) LRMS (ESI): (calculated) 554.2 (measured) 555.4 (MH) + structure Η H, S IJ (S)-l-keto-6-(2-phenylethyl thioguanamine)- 1-(4-Phenylshen-2-ylamino) hexyl-2-ylaminocarbazate HH^Cbz S (S)-6-(2-methoxyethanethioguanamine) -1-keto-1-(4-pyl-p-pyrazine-2-ylamino)hexyl-2-ylamine benzyl phthalate φ5 c as I 4 \ ^ M ) V.2° 〇 =&lt;^ Identifier error if ^ m Vfl &amp;- X 蚪砩 蚪砩 starting material H NHCbz 2 ί clro —___ O^C is also called H NHCbz ! 2 1 C1Y^ 1 0 person called H NHCbz + 2 丫. 〆0 compound ο inchΪ ο ί-Η —— (N -230 · 134026-2 200916447 1 Preparation sequence D, E | D, E ! D, E Characterization (CD30D) d (ppm) 1H : 7.89 (dd, J=8.4, 1.4 Hz, 2H); 7.40-7.12 (m, 11H); 6.80 (d, J=8.8 Hz, 2H); 5.13 (d, J=12.3 Hz, 1H); 5.08 (d, J=12.5) Hz, 1H) ; 4.35-4.31 (m, 1H) ; 3.84 (s, 2H) ; 3.71 (s, 3H) ; 3.58 (t, J=7.0 Hz, 2H); 2.00-1.65 (m, 4H); 1.49 -1.39 (m, 2H). LRMS (ESI): (calculated) 602.2 (measured) 603.4 (MH) + (CD30D) d (ppm) 1H: 7.89 (dd, J = 8.6, 1.4 Hz, 2H); 7.40-7.23 (m,13H); 5.13 (d,J=12.3 Hz, 1H); 5.08 (d, J=12.3 Hz, 1H); 4.36-4.32 (m, 1H); 3.87 (s, 2H) ; 3.59 (t, J=7.0 Hz, 丨2H); 2.00-1.66 (m, 4H) ; 1.51-1.41 (m, 2H). 丨LRMS (ESI): (calculated) 606.2 (measured value) 607.3 (MH)+ (CD30D) d(ppm) 1H : 7.89 (dd, J=8.4, 1.4 Hz, 2H); 7.40-7.12 (m, 14H); 5.13 (d, J=12.3 Hz, 1H); 5.08 (d, J= 12.5 Hz, 1H) ; 434-4.30 (m, 1H) ; 3.53 (t, J=6.8 Hz, 2H) ; 3.00 (t, J=7.2 Hz, 2H); 2.82 (t, J=8.0 Hz, 2H) ; 1.8 4-1.71 (m, 2H) ; L60-1.56 (m, 2H); 1.42-1.28 (m, 2H). LRMS (ESI): (calculated) 586.2 (measured value) 587.4 (MH) + structure \ A ( β -4 ^ Cl β i-4 VT ^ . ij, H' s UCI (S)-6-(2-(4-phenylphenyl)ethanethioguanidino)-1-keto-1-( Benzyl 4-phenylpyrazol-2-ylamino)hexane-2-ylcarbamate H HNs S Cbz (S)-1 -keto-6-(3-phenylpropanethioguanamine) Benzyl-1-(4-phenylpyrazol-2-ylamino)hexane-2-ylcarbamate starting material CM ? w \. ό LJ · NHCbz 2 c, rac, _£J ^ f° 6 Compound j JO S m y—H in -231 - 134026-2 200916447

製備順序| Ν 特徵鑒定 (CD30D) d(ppm) 1H ： 7.89 (dd, J=8.4, 1.4 Hz, 2H) ；7.40-7.14 (m, 14H)；5.13 (d, J=12.3 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 4.37-4.33 (m, 1H) ； 3.57 (br, 2H) ； 1.89-1.77 (m, 2H)； 1.67-1.62 (m,2H) ； 1.53-1.46 (m, 2H). LRMS (ESI):(計算值）573.2 (實測值） 574.4 (MH)+ (CD30D) d(ppm) 1H : 7.89 (d, J=8.4 Hz, 2H) ; 7.40-7.12 (m，9H) ; 5.13 (d, J=12.5 Hz， 1H) ; 5.08 (d, J=12.5 Hz，1H) ; 4.36-4.32 (m， 1H) ; 4.00 (s，2H) ; 3.65 (t，J=6.5 Hz, 2H); 11.87-1.68 (m, 4H) ； 1.52-1.37 (m, 11H). 1 LRMS (ESI):(計算值）611.2 (實測值）612.4 (MH)+ (CD30D) d(ppm) 1H : 7.89 (dd，J=8.4, 1.4 Hz, 2H) ； 7.41-7.13 (m, 9H) ； 5.14 (d, J=12.1 Hz, 1H) ； 5Ό9 (d, J=12.1 Hz, 1H) ； 4.37-4.33 (m, 1H) ； 3.78 (s, 2H) ； 3.66 (t, J=7.0 Hz, 2H) ; 1.95-1.64 (m，4H) ; 1.58-1.42 (m，2H). LRMS (ESI):(計算值）511.2 (實測值）512_3 (MH)+ 結構 (S)-1 -酮基-1-(4-苯基噻唑-2-基胺 基)-6-(3-苯基硫脲基)己烷-2-基胺基甲 酸芊酯 &lt; “ 工h㈤ y ^ ^ \ _ 4溫 〇=/ ^ h V ¢- ''1 51 V τ ν r&quot; ^ H H、 S (S)-6-(2-胺基乙烷硫醯胺基)-1-酮基 -1-(4-笨基禮&gt;坐-2~基胺基)己烧-2-基胺 基甲酸芊酯 起始物質 H NHCbz + 2 1 H NHCbz ! 2 + JUB。。 S C J - 工 Z工 &lt;J~&gt;( S 化合物 r-H T—Η ί VO Η 卜 〇〇 r*H -232- 134026-2 200916447 製備順序| ω D，A，E 特徵鑒定 (CD30D) d(ppm) 1H ： 7.89 (dd, J=8.6, 1.4 Hz, 2H) ； 7.40-7.12 (m, 9H) ； 5.14 (d, J=12.5 Hz, 1H) ； 5.08 (d, J=12.5 Hz, 1H) ； 4.81 (s, 2H) ； 4.36-4.33 (m, 1H) ； 3.71-3.66 (m, 2H)； 2.11 (s,3H) ； 1.92-1.67 (m,4H) ； 1.53-1.44 (m, 2H)_ LRMS (ESI) ··(計算值）554.2 (實測 值）555.4 (MH)+ (CD30D) d(ppm) 1H ： 7.90 (dd, J=7.0, 1.4 Hz, 2H) ； 7.40-7.36 (m, 3H) ； 7.32-6.99 (m, 6H) ； 4.27-4.25 (m, 1H) ； 3.91 (s, 2H) ； 3.60 l(t, J=7.0Hz,2H) ； 1.84-1.64 (m,4H) ； 1.46-1.37 (m，11H). LRMS (ESI):(計算值）538.2 (實測值）539.3 (MH)+ 結構 〇=/ 4 ζ CO ^ A 〈 淪1 &lt; 〇^'&quot;5 3¾ ^遛 V fl 〇 1 V ^ 、-、 r-0 ./. Mm. H HN. S Boc (S)-]:-S同基-6-(2-本基乙烧碳酿胺基)· 1-(4.·苯基ρ塞。坐-2-基胺基)己烧-2-基胺 基甲酸第三-丁酯 起始物質 CSJ yi v。 ri 〇 VZ I ό Η〇Λ-^^-ΝΗ2 Boc^，H ατ 1 + 又 \=/ N NH2 化合物 Os τ—Η ί ON 120 - 233 - 134026-2 200916447Preparation sequence | Ν Characterization (CD30D) d (ppm) 1H: 7.89 (dd, J=8.4, 1.4 Hz, 2H); 7.40-7.14 (m, 14H); 5.13 (d, J = 12.3 Hz, 1H); 5.08 (d, J=12.5 Hz, 1H); 4.37-4.33 (m, 1H); 3.57 (br, 2H); 1.89-1.77 (m, 2H); 1.67-1.62 (m, 2H); 1.53-1.46 ( m, 2H). LRMS (ESI): (calculated) 573.2 (measured value) 574.4 (MH) + (CD30D) d (ppm) 1H : 7.89 (d, J = 8.4 Hz, 2H) ; 7.40-7.12 (m , 9H); 5.13 (d, J=12.5 Hz, 1H); 5.08 (d, J=12.5 Hz, 1H); 4.36-4.32 (m, 1H); 4.00 (s, 2H); 3.65 (t, J= 6.5 Hz, 2H); 11.87-1.68 (m, 4H) ; 1.52-1.37 (m, 11H). 1 LRMS (ESI): (calculated) 611.2 (measured value) 612.4 (MH)+ (CD30D) d (ppm) 1H : 7.89 (dd, J=8.4, 1.4 Hz, 2H); 7.41-7.13 (m, 9H); 5.14 (d, J = 12.1 Hz, 1H); 5Ό9 (d, J = 12.1 Hz, 1H); 4.37-4.33 (m, 1H) ; 3.78 (s, 2H) ; 3.66 (t, J=7.0 Hz, 2H) ; 1.95-1.64 (m, 4H) ; 1.58-1.42 (m, 2H). LRMS (ESI) : (calculated) 511.2 (measured value) 512_3 (MH) + structure (S)-1 -keto-1-(4-phenylthiazol-2-ylamino)-6-(3-phenylthiourea Hexyl-2-ylaminocarbazide Ester &lt; "work h (five) y ^ ^ \ _ 4 warm 〇 = / ^ h V ¢ - ''1 51 V τ ν r&quot; ^ HH, S (S)-6-(2-aminoethane thioguanamine Base-1-butanyl-1-(4-stupyl)&gt; sit-2~ylamino) hexyl-2-ylaminocarbazate starting material H NHCbz + 2 1 H NHCbz ! 2 + JUB. . SCJ - Work Z &lt;J~&gt;( S compound rH T-Η ί VO Η 〇〇 r*H -232- 134026-2 200916447 Preparation sequence | ω D,A,E Characterization (CD30D) d( Ppm) 1H: 7.89 (dd, J=8.6, 1.4 Hz, 2H); 7.40-7.12 (m, 9H); 5.14 (d, J=12.5 Hz, 1H); 5.08 (d, J=12.5 Hz, 1H) 4.81 (s, 2H) ; 4.36-4.33 (m, 1H) ; 3.71-3.66 (m, 2H); 2.11 (s, 3H) ; 1.92-1.67 (m, 4H) ; 1.53-1.44 (m, 2H) _ LRMS (ESI) ··(calculated value) 554.2 (measured value) 555.4 (MH)+ (CD30D) d(ppm) 1H : 7.90 (dd, J=7.0, 1.4 Hz, 2H) ; 7.40-7.36 (m, 3H); 7.32-6.99 (m, 6H); 4.27-4.25 (m, 1H); 3.91 (s, 2H); 3.60 l(t, J=7.0Hz, 2H); 1.84-1.64 (m, 4H); 1.46-1.37 (m,11H). LRMS (ESI): (calculated) 538.2 (measured value) 539.3 (MH)+ structure 〇=/ 4 ζ CO ^ A 〈 沦1 &lt;〇^'&quot;5 33⁄4 ^遛V fl 〇1 V ^ , -, r-0 ./. Mm. H HN. S Boc (S)-]:-S synthyl-6-(2-propenyl-carbocarbonic amine)· 1 -(4.·Phenyl ρ. sit-2-ylamino) hexyl-2-ylcarbamic acid tert-butyl ester starting material CSJ yi v. ri 〇VZ I ό Η〇Λ-^^ - ΝΗ2 Boc^,H ατ 1 + again \=/ N NH2 compound Os τ—Η ί ON 120 - 233 - 134026-2 200916447

Μ. 〇 PQ tC &gt;&lt; 〇 ‘a ‘a ‘x 齣 輕 (CD30D) d(ppm) 1H : 8.51 (br, 1H,甲酸 酯）；7.97-7.95 (m, 2H); 7.51-7.46 (m, 3H); 5.12 (dd, J=8.4, 6.3 Hz, 1H) ； 3.58 (t, J=7.0 Hz, 2H) ； 3.49-3.44 (m, 2H) ； 3.01-2.93 (m, 2H) ； 2.79 (s, 3H) ； 2.63-2.58 (m, 1H) ； 2.43 (s, 3H) ； 2.09-1.90 (m, 6H) ； 1.72-1.66 (m, 2H) ; 1.50-1.40 (m, 2H). LRMS (ESI):(計 算值）428.2 (實測值）429.4 (MH)+ (CD30D) d(ppm) 1H ： 7.98-7.95 (m, 2H)； 7.49-7.45 (m, 3H) ； 5.12 (dd, J=8.4, 63 Hz, 1H) ； 3.57 (t, J=7.2 Hz, 2H) ； 2.42 (s, 3H)； 2.06-2.01 (m,4H) ； 1.96-1.86 (m, 1H)； 1.73-1.65 (m, 2H) ； 1.52-1.36 (m, 2H). LRMS (ESI):(計算值）345.2 (實測值） 346.3 (MH)+ \ sl 〉.,l2 、~~/ 入 y '1' f \_ ώ )=co &quot;T xz 4 \ 蚪 / ιό ^ / \ r~ 〉‘1丨Z 谱&lt; A ΪΊ' 圭f CL 0 CO 1 p+v H CL jO 00 Ό $ 沄 r&quot;H -234 - 134026-2 200916447 製備順序 LL, B, Z LL’B, GG 1 特徵鑒定 (CD30D) d(ppm) 1H ： 8.50 (s, 1H) ； 8.06-8.02 (m, 1H) ； 7.98-7.90 (m, 3H) ； 7.55 (dd, J=6.4, 3.1 Hz, 2H) ； 7.39-7.18 (m, 5H) ； 5.15 (d, J=12.3 Hz, 1H) ； 5.08 (d, 1=123 Hz, 1H) ； 4.91-4.88 (m, 1H) ； 3.51-3.31 (m, 2H)； 2.90 (br, 3H) ； 2.06-1.96 (m, 2H) ； 1.70-1.58 (m, 2H) ； 1.58-1.37 (m, 2H). LRMS (ESI)： (計算值）502.2 (實測值）503.4 (MH)+ (CD30D) d(ppm) 1H ： 8.50 (s, 1H) ； 8.07 (d, J二8.2 Hz, 1H); 7.98-7.90 (m，3H) ; 7.55 (dd， J=6.3, 3.3 Hz，2H) ; 7.39-7.19 (m，5H) ; 5.14 (d, J=12.5 Hz, 1H) ； 5.09 (d, J=12.7 Hz, 1H); 4.94-4.91 (m，1H); 3.48-3.47 (m, 1H); 3.13-3.12 (m, 1H) ； 2.05-1.90 (m, 2H) ； 1.65-1.60 (m, 2H) ; 1.53-1.42 (m，2H). LRMS (ESI):(計算值）488.2(實測值）489.4 (MH)+ 結構 一-\ hn'n rmw^a a. w H,cbz I (S)-5-(3-甲基硫脲基)-1-(5-(荅-2-基)-1Η-1，2,4-三唑-3-基)戊基胺基曱酸芊酯 1 CVJ N i 硪 )=OD 叶 \ 'Ί / 4 ^ / _Q —也 &lt; 产_铤 έ5 起始物質 〇 CQ + Μ ίΧ6 8 CQ 工/〇 工 r ο 化合物 Ο Ο 5 (Ν CO m - 235 - 134026-2 200916447 製備順序| LL，B，Z 1 1 LL，B，G 特徵鑒定 (CD30D) d(ppm) 1H ： 9.50 (s, 1H) ； 8.93 (s, 1H) ； 8.09-8.04 (m, 2H) ； 7.85-7.78 (m, 1H)； 7.70-7.68 (m, 1H) ； 7.39-7.17 (m, 5H) ； 5.15 (d, J=12.3 Hz, 1H) ； 5.09 (d, J=12.5 Hz, 1H) ； 4.96-4.92 (m, 1H) ； 3.48-3.35 (m, 2H)； 2.89 (s,3H) ； 2.08-1.98 (m,2H) ； 1.65-1.63 (m, 2H) ； 1.49-1.45 (m, 2H). LRMS (ESI)： (計算值）503.2 (實測值）504.3 (MH)+ (CD30D) d(ppm) 1H ： 7.38-7.28 (m, 7H)； 15.14 (d，J=12.3 Hz, 1H) ; 5.07 (d，J=12.7Hz， 1H); 4.93-4.88 (m，1H);3_91 (s，6H)，3.81 (s， 3H) ; 3.57 (t，J=7.2 Hz，2H) ; 2_42 (s，3H); 2.02-1.93 (m, 2H) ； 1.71-1.66 (m, 2H)； 1.49-1.41 (m，2H). LRMS (ESI):(計算值） 527.2 (實測值)528.3 (MH)+ 結構 \\ Η H F 气 z S (S)-:5-(3-甲基硫脲基)-l-(5-0&gt;奎啉-3-基)-lH-l，2,4-三唑-3-基)戊基胺基甲酸 芊酯 / 〇、 V^\ hn、n —〇 HN'Cbz s (S)-5-乙烷硫醯胺基-1-(5-(3,4,5-三甲氧 基苯基)-1Η-1,2,4-三唑-3-基)戊基胺基 甲酸芊酯 起始物質 Ο CD )CO S 工 /〇 工 rs 〇 m &gt; ? 1 -V 工 τ - &gt;工6 r\jC\ ^ \ \〇 工 / 化合物 S s m •236 · 134026-2 200916447 製備順序| LL，B，G Ill，b，gg 1 特徵鑒定 (CD30D) d(ppm) 1H ： 8.18 (s, 1H) ； 7.97 (d, J=7.6 Hz, 1H) ； 7.60 (d, 1=12 Hz, 1H) ； 7.41-7.26 (m, 6H) ； 5.14 (d, J=12.3 Hz, 1H) ； 5.07 (d, J=12.5 Hz, 1H) ； 4.91-4.86 (m, 1H) ； 3.57 (t, J=7.2 Hz, 2H) ； 2.42 (s, 3H) ； 2.04-1.84 (m, 2H) ； 1.71-1.66 (m,2H) ； 1.51-1.39 (m, 2H). LRMS (ESI):(計算值）515.1 (實測值） 516.2 (MH)+ (CD30D) d(ppm) 1H ： 7.38-7.28 (m, 7H)； 5.13 (d,J= 12.3 Hz, 1H) ； 5.07 (d, J= 12.5 Hz, 1H) ； 4.93-4.83 (m, 1H) ； 3.91 (s, 6H) ； 3.81 (s, 3H) ； 3.48 (br, 1.05H) ； 3.13 (br, 0.95H)； 2.01-1.93 (m,2H) ； 1.62-1.60 (m, 2H)； 1.50-1.39 (m，2H). LRMS (ESI):(計算值） 528.2 (實測值）529.4 (MH)+ 結構 r 一Λ HN、N b/ ‘伽 s (S)-l-(5-(3-溴苯基)-lH-l 二 4-三唑-3-基)-5-乙烷硫醯胺基戊基胺基甲酸芊酯 -v HN^n 〇, H^Cbz s (S)-:5-硫脲基-1-(5-(3,4,5-三甲氧基苯 基)-1Η-1,2,4-三唑-3-基)戊基胺基甲酸 苄酯 起始物質 〇 CQ S 工 οί _ V :ζ工 t3 〇/ 工 〇 CQ +1 \ x〇 工 / 化合物 5 \D Ρ: -237 - 134026-2 200916447Μ. 〇PQ tC &gt;&lt; 〇'a 'a 'x light (CD30D) d(ppm) 1H : 8.51 (br, 1H, formate); 7.97-7.95 (m, 2H); 7.51-7.46 (m, 3H); 5.12 (dd, J=8.4, 6.3 Hz, 1H); 3.58 (t, J=7.0 Hz, 2H); 3.49-3.44 (m, 2H); 3.01-2.93 (m, 2H); 2.79 (s, 3H); 2.63-2.58 (m, 1H); 2.43 (s, 3H); 2.09-1.90 (m, 6H); 1.72-1.66 (m, 2H); 1.50-1.40 (m, 2H). LRMS (ESI): (calculated) 428.2 (measured value) 429.4 (MH) + (CD30D) d (ppm) 1H: 7.98-7.95 (m, 2H); 7.49-7.45 (m, 3H); 5.12 (dd, J=8.4, 63 Hz, 1H); 3.57 (t, J=7.2 Hz, 2H); 2.42 (s, 3H); 2.06-2.01 (m, 4H); 1.96-1.86 (m, 1H); 1.73-1.65 (m, 2H) ; 1.52-1.36 (m, 2H). LRMS (ESI): (calculated) 345.2 (measured value) 346.3 (MH)+ \ sl 〉., l2 , ~~/ into y '1' f \_ ώ )=co &quot;T xz 4 \ 蚪/ ιό ^ / \ r~ 〉'1丨Z spectrum&lt; A ΪΊ' gui f CL 0 CO 1 p+v H CL jO 00 Ό $ 沄r&quot;H -234 - 134026-2 200916447 Preparation order LL, B, Z LL'B, GG 1 Characterization (CD30D) d(ppm) 1H : 8.50 (s, 1H) ; 8.06-8.02 (m, 1H) ; 7.98-7.90 (m, 3H); 7.55 (dd, J=6.4, 3.1 Hz, 2H); 7.39-7.18 (m, 5H); 5.15 (d, J = 12.3 Hz, 1H); 5.08 (d, 1 = 123 Hz, 1H); 4.91-4.88 (m, 1H); 3.51-3.31 (m, 2H); 2.90 (br, 3H); 2.06-1.96 (m, 2H); 1.70-1.58 (m, 2H); 1.58-1.37 ( m, 2H). LRMS (ESI): (calculated) 502.2 (measured value) 503.4 (MH) + (CD30D) d (ppm) 1H : 8.50 (s, 1H) ; 8.07 (d, J 8.2 Hz, 1H 7.98-7.90 (m,3H) ; 7.55 (dd, J=6.3, 3.3 Hz, 2H); 7.39-7.19 (m,5H); 5.14 (d, J=12.5 Hz, 1H); 5.09 (d, J=12.7 Hz, 1H); 4.94-4.91 (m, 1H); 3.48-3.47 (m, 1H); 3.13-3.12 (m, 1H); 2.05-1.90 (m, 2H) ; 1.65-1.60 (m, 2H) ; 1.53-1.42 (m, 2H). LRMS (ESI): (calculated) 488.2 (measured value) 489.4 (MH)+ Structure I-\ hn'n rmw^a a. w H,cbz I (S -5-(3-Methylthioureido)-1-(5-(indol-2-yl)-1Η-1,2,4-triazol-3-yl)pentylamino decanoate 1 CVJ N i 硪)=OD leaf \ 'Ί / 4 ^ / _Q —also &lt; _ 铤έ 5 starting material 〇 CQ + Μ Χ Χ 6 8 CQ work / completion r ο compound Ο Ο 5 (Ν CO m - 235 - 134026-2 200916447 Preparation sequence | LL, B, Z 1 1 LL, B, G Characterization (CD30D) d (ppm) 1H: 9.50 (s, 1H); 8.93 (s, 1H); 8.09-8.04 (m, 2H); 7.85-7.78 (m, 1H); 7.70-7.68 (m, 1H); 7.39-7.17 (m, 5H); 5.15 (d, J = 12.3 Hz, 1H); 5.09 (d, J = 12.5 Hz, 1H); 4.96-4.92 (m , 1H) ; 3.48-3.35 (m, 2H); 2.89 (s, 3H) ; 2.08-1.98 (m, 2H) ; 1.65-1.63 (m, 2H) ; 1.49-1.45 (m, 2H). LRMS (ESI ): (calculated value) 503.2 (measured value) 504.3 (MH) + (CD30D) d (ppm) 1H : 7.38-7.28 (m, 7H); 15.14 (d, J = 12.3 Hz, 1H); 5.07 (d, J = 12.7 Hz, 1H); 4.93-4.88 (m, 1H); 3_91 (s, 6H), 3.81 (s, 3H); 3.57 (t, J = 7.2 Hz, 2H); 2_42 (s, 3H); 2.02-1.93 (m, 2H) ; 1.71-1.66 (m, 2H); 1.49-1.41 (m, 2H). LRMS (ESI): (calculated) 527.2 (measured value) 528.3 (MH) + structure \\ HF gas z S (S)-: 5-(3-methylthioureido)-l-(5-0&gt; quinolin-3-yl)-lH-l,2,4-triazol-3-yl Ethyl amyl amide / hydrazine, V^\ hn, n - 〇HN'Cbz s (S)-5-ethanethioguanamine-1-(5-(3,4,5-trimethoxy) Phenylphenyl)-1Η-1,2,4-triazol-3-yl)pentylaminocarbazate Quality CD ) CO S Work / Completion rs 〇m &gt; ? 1 -V τ - &gt;工6 r\jC\ ^ \ \ Completion / Compound S sm •236 · 134026-2 200916447 Preparation sequence | LL , B, G Ill, b, gg 1 Characterization (CD30D) d (ppm) 1H : 8.18 (s, 1H) ; 7.97 (d, J=7.6 Hz, 1H); 7.60 (d, 1=12 Hz, 1H 7.41-7.26 (m, 6H); 5.14 (d, J = 12.3 Hz, 1H); 5.07 (d, J = 12.5 Hz, 1H); 4.91-4.86 (m, 1H); 3.57 (t, J= 7.2 Hz, 2H) ; 2.42 (s, 3H) ; 2.04-1.84 (m, 2H) ; 1.71-1.66 (m, 2H) ; 1.51-1.39 (m, 2H). LRMS (ESI): (calculated) 515.1 (measured value) 516.2 (MH) + (CD30D) d (ppm) 1H : 7.38-7.28 (m, 7H); 5.13 (d, J = 12.3 Hz, 1H); 5.07 (d, J = 12.5 Hz, 1H) 4.93-4.83 (m, 1H) ; 3.91 (s, 6H) ; 3.81 (s, 3H) ; 3.48 (br, 1.05H) ; 3.13 (br, 0.95H); 2.01-1.93 (m, 2H) ; -1.60 (m, 2H); 1.50-1.39 (m, 2H). LRMS (ESI): (calculated) 528.2 (actual value) 529.4 (MH)+ structure r Λ HN, N b/ ' ga s (S -l-(5-(3-bromophenyl)-lH-l bis 4-triazol-3-yl)-5-ethane thioanthryl pentylaminocarbazate-v HN^n , H^Cbz s (S)-: 5-thioureido-1-(5-(3,4,5-trimethoxyphenyl)-1Η-1,2,4-triazol-3-yl) Benzyl amyl carboxylate starting material 〇CQ S work οί _ V : Completion t3 〇 / Work CQ +1 \ x Completion / Compound 5 \D Ρ: -237 - 134026-2 200916447

製備順序 LL, B, GG LL，B，Z 特徵鑒定 (CD30D) d(ppm) 1H ： 8.18 (s, 1H) ； 7.96 (br, 1H) ； 7.59 (br, 1H) ； 7.41-7.20 (m, 6H) ； 5.13 (d, J=12.5 Hz, 1H) ； 5.07 (d, J=12.9 Hz, 1H) ； 4.93-4.83 (m, 1H) ； 3.48 (br, 1.2H)； 3.13 (br, 0.8H) ；2.02-1.92 (m, 2H) ； 1.62-1.60 (m, 2H) ； 1.48-1.40 (m, 2H). LRMS (ESI)： (計算值）516.1 (實測值）517.3 (MH)+ (CD30D) d(ppm) 1H : 7.38-7.21 (m，7H); 5.13 (d，J=12.3 Hz，1H) ; 5.07 (d，J=12.5 Hz， 1H) ； 4.91-4.85 (m, 1H) ； 3.91 (s, 6H) ； 3.81 (s, 3H) ； 3*43 (br, 2H) ； 2.89 (br, 3H) ； 2.01-1.92 (m,2H) ； 1.63-1.61 (m, 2H) ； L49-1.38 (m，2H)· LRMS (ESI):(計算值）542.2 (實測 值）543.4 (MH)+ 結構 广hn、n B, H^Cbz 8 (S)-l-(5-(3-溴苯基)-lH-l,2,4-三唑-3-基)-5-硫赚基戊基胺基曱酸爷S旨 / C)\—^ hn~n -〇 H^Cbz s (S)-5-(3-甲基硫脲基)-1-(5-(3,4,5-三甲 氧基苯基)-1Η-1,2,4-三唑-3-基)戊基胺 基曱酸苄酯 起始物質 8 CD Jco S 工 工 ϋ ω fx〇\ 工 / 化合物 ( r- ί 00 CO On m H -238 - 134026-2 200916447 製備順序| LL, Β, Ζ LL,B,Z 特徵鑒定 (CD30D) d(ppm) 1H ： 8.18 (s, 1H) ； 7.98-7.96 (d, J=8.0 Hz, 1H) ； 7.60 (d, J=7.6 Hz, 1H) ； 7.41-7.20 (m, 6H) ； 5.13 (d, J=12.5 Hz, 1H) ； 5.07 (d, J=12.5 Hz, 1H) ； 4.88-4.83 (m, 1H) ； 3.43 (br, 2H) ； 2.89 (br, 3H) ； 2.01-1.91 (m, 2H) ； 1.64-1.61 (m, 2H) ； 1.49-1.38 (m, 2H). LRMS (ESI):(計算值）530.1 (實測值) 531.2(MH)+ | (CD30D) d(ppm) 1H ： 8.71 (s, 1H) ； 8.23 (br, 1H) ； 7.38-7.23 (m, 6H) ； 5.13 (d, J=12.3 Hz, 1H) ； 5.07 (d, J=12.3 Hz, 1H) ； 4.88-4.84 (m, 1H) ； 3.43 (br, 2H) ； 2.89 (br, 3H) ； 2.02-1.93 (m, 2H) ； 1.63-1.61 (m, 2H) ； 1.45-1.41 (m, 2H). LRMS (ESI):(計算值）513.2 (實測值） 514.3 (MH)+ 結構 厂一^ HN〜n B, HN.Cbz S (S)-1-(5-(3-溴苯基2,4-三唑-3-基)-5-(3-甲基硫脲基)戊基胺基甲酸 芊酯 hn、N 〇.N H^cbz S (S)- l· -(5-(4-羥基-3-硝基笨基)-1H-1,2,4-三唑-3-基)-5-(3- f基碟脲基)戊基胺基 甲酸苄酯 起始物質 〇 CD O 孓 \ 工 〇 ω 4：r，x d \ +气/=\工 &quot;、工 S i \ ' x 〇&quot; 化合物 00 Ο 2 -239 - 134026-2 200916447 製備順序 LL, Β, Ζ LL，B，G 特徵鑒定 (CD30D) d(ppm) 1H ： 7.42 (d, J=3.9 Hz, 1H) ； 7.37-7.22 (m, 5H) ； 7.14 (d, J=3.9 Hz, 1H); 5.13 (d, J=12.5 Hz，1H); 5.06 (d，J=12.5 Hz, 1H) ； 4.86-4.82 (m, 1H) ； 3.41 (br, 2H)； 2.89 (br, 3H) ； 2.00-1.84 (m, 2H) ； 1.63-1.60 (m, 2H) ； 1.48-1.37 (m, 2H). LRMS (ESI)： (計算值）536.1 (實測值）537.3 (MH)+ (DMSO-d6) d(ppm) 1H ： 7.35-7.23 (m, 7H) ； 5.03-4.98 (m, 2H) ； 4.79 (br, 1H)； 3.43-3.41 (m, 2H) ； 2.34 (s, 3H) ； 1.95-1.70 (m,2H) ； 1.60-1.46 (m,2H) ； 1.42-1.22 (m, 2H)· LRMS (ESI):(計算值）521.1 (實測值） 522.2 (MH)+ 結構 Br HNv S Cbz (S)-1-(5-(5-溴基4 吩-2-基)-1H-1，2,4-三唑-3-基)-5-(3-甲基硫脲基)戊基胺基 甲酸苄酯 HN、Cbz S (S)-1 -(5-(5-溴基嘍吩-2-基)-1H-1，2,4-三唑-3-基)-5-乙烷硫醯胺基戊基胺基 甲酸芊酯 起始物質 〇 1 x - 工 )·η± 工 „ ώ c&gt;=&lt; vn + Y zx o 〇/ V i \ 工 〇 C0 X Φ工产 工 &gt;..ιέ 工 m \ /V i \ X 化合物 g 00 ί -240 · 134026-2 200916447 製備順序 LL, B, Z i 1 1 LL，B，Z 特徵鑒定 (CD30D) d(ppm) 1H ： 7.81 (br, 1H) ； 7.37-7.22 (m, 5H) ； 6.73-6.65 (m, 2H) ； 5.12 (d, J=12.3 Hz, 1H) ； 5.07 (d, J=12.7 Hz, 1H)； 4.88-4.82 (m, 1H) ； 3.40 (br, 2H) ； 2.90 (br, 3H) ； 1.97-1.90 (m, 2H) ； 1.62-1.60 (m, 2H)； 1.44-1.32 (m, 2H). LRMS (ESI) ··(計算值） 486.2 (實測值）487.3 (MH)+ (CD30D) d(ppm) 1H ： 7.78 (br, 2H) ； 7.38-7.21 (m, 5H) ； 6.88 (br, 2H) ； 5.13 (d, J=12.7 Hz, 1H) ； 5.06 (d, J=12.5 Hz, 1H) ； 4.88-4.83 (m, 1H) ； 3.40 (br, 2H) ； 2.90 (br, 3H)； 2.01-1.89 (m,2H) ； 1.62-1.60 (m, 2H)； 1.44-1.38 (m, 2H). LRMS (ESD :(計算值） 468.2 (實測值)469.3 (MH)+ 結構 F HN^U S Cbz (S)-1 -(5-(2-氟基-4-羥苯基)-1H-1，2,4-三唑-3-基)-5-(3-甲基硫脲基)戊基胺基 甲酸芊酯 fΛ HN-M HN. S Cbz (S)-l-(5-(4-羥苯基)-lH-l，2,4-三唑-3-基)-5-(3-曱基硫脲基)戊基胺基曱酸 苄酯 起始物質 〇 CQ ^&quot;1 + ^ κ X &quot;r\JT° X 〇 CQ X )·ηΖ I Χ η=/ + /=\ 工 孓 \ X 化合物 CN 00 (Τ) 00 5 -241 - 134026-2 200916447 製備順序 LL, B, G X, D, Β,Ζ 1 特徵鑒定 (CD30D) d(ppm) 1H ： 8.08 (d, J=6.8 Hz, 0.67H) ； 7.82 (d, J-6.3 Hz, 0.33H) ； 7.61-7.56 (m, 0.33H) ； 7.48 (t, J=7.8 Hz, 0.67H)； 7.37-7.18 (m, 6H) ； 7.10 (t, J=7.4 Hz, 1H)； 5.14-5.01 (m, 2H) ； 4.01 (s, 2H) ； 3.92 (s, 1H) ； 3.61-3.53 (m, 2H) ； 3.42 (s, 3H)； 2.02-1.88 (m, 2H) ； 1.74-1.65 (m, 2H)； 1.54-1.40 (m, 2H). LRMS (ESI):(計算值） 467.2 (實測值）468.2 (MH)+ (CD30D) d(ppm) 1H ： 8.19 (s, 1H) ； 7.92-7.83 (m, 4H) ； 7.51-7.44 (m, 2H) ； 6.68 (s, ,1H) ； 4.80 (t, J=7.6 Hz, 1H) ； 4.14-4.06 (m, 2H) ； 3.50-3.31 (m, 2H) ； 2.90 (br, 3H)； 1.99-1.82 (m,2H) ； 1.67-1.59 (m, 2H)； 1.55-1.33 (m, 2H) ； 1.22 (s, 3H). LRMS (ESI):(計算值)439.2(實測值)440.3 (MH)+ 結構 ^ hn-n H^Cbz S (S)-5-乙烷硫醯胺基-1-(5-(2-甲氧苯 基)-1Η-1,2,4-三唑-3-基)戊基胺基甲酸 芊酯 H 卩丫。 S °Ί (S)-5-(3-甲基硫脲基)-1-(5-(荅-2-基)-1H-吡唑-3-基)戊基胺基甲酸乙酯 起始物質 〇 1 _ Ζ 〇 ? X &quot; j&quot;l + H1 孓 \ 工 W ph .NH 3 Cbz 186 + I 化合物 00 00 實例 -242 - 134026-2 200916447 用以合成本發明化合物之一般程序A至PP係描述於表4 中。各一般程序之特殊實例係於特定實例之所指示步驟中 提供。 表4Preparation order LL, B, GG LL, B, Z Characterization (CD30D) d (ppm) 1H: 8.18 (s, 1H); 7.96 (br, 1H); 7.59 (br, 1H); 7.41-7.20 (m, 6H) ; 5.13 (d, J=12.5 Hz, 1H); 5.07 (d, J=12.9 Hz, 1H); 4.93-4.83 (m, 1H); 3.48 (br, 1.2H); 3.13 (br, 0.8H ;2.02-1.92 (m, 2H) ; 1.62-1.60 (m, 2H) ; 1.48-1.40 (m, 2H). LRMS (ESI): (calculated) 516.1 (measured value) 517.3 (MH)+ (CD30D d(ppm) 1H : 7.38-7.21 (m,7H); 5.13 (d, J = 12.3 Hz, 1H); 5.07 (d, J = 12.5 Hz, 1H); 4.91-4.85 (m, 1H); 3.91 (s, 6H) ; 3.81 (s, 3H) ; 3*43 (br, 2H) ; 2.89 (br, 3H) ; 2.01-1.92 (m, 2H) ; 1.63-1.61 (m, 2H) ; L49-1.38 (m, 2H)· LRMS (ESI): (calculated) 542.2 (measured value) 543.4 (MH) + broad structure hn, n B, H^Cbz 8 (S)-l-(5-(3-bromobenzene) Base)-lH-l,2,4-triazol-3-yl)-5-sulfanyl-pentylamine-based succinic acid s/c)\—^ hn~n -〇H^Cbz s (S -5-(3-Methylthioureido)-1-(5-(3,4,5-trimethoxyphenyl)-1Η-1,2,4-triazol-3-yl)pentyl Amino benzyl phthalate starting material 8 CD Jco S Work ϋ ω fx〇\ Work / Compound ( r- ί 00 CO On m H -238 - 134026-2 200916447 Preparation sequence | LL, Β, Ζ LL, B, Z Characterization (CD30D) d (ppm) 1H : 8.18 (s, 1H) ; 7.98-7.96 (d, J=8.0 Hz, 1H); 7.60 (d, J=7.6 Hz, 1H); 7.41-7.20 (m, 6H); 5.13 (d, J=12.5 Hz, 1H); 5.07 (d, J= 12.5 Hz, 1H); 4.88-4.83 (m, 1H); 3.43 (br, 2H); 2.89 (br, 3H); 2.01-1.91 (m, 2H); 1.64-1.61 (m, 2H); 1.49-1.38 (m, 2H). LRMS (ESI): (calculated) 530.1 (measured) 531.2 (MH) + | (CD30D) d (ppm) 1H : 8.71 (s, 1H) ; 8.23 (br, 1H) ; 7.38 -7.23 (m, 6H); 5.13 (d, J = 12.3 Hz, 1H); 5.07 (d, J = 12.3 Hz, 1H); 4.88-4.84 (m, 1H); 3.43 (br, 2H); 2.89 ( Br, 3H) ; 2.02-1.93 (m, 2H) ; 1.63-1.61 (m, 2H) ; 1.45-1.41 (m, 2H). LRMS (ESI): (calculated) 513.2 (measured value) 514.3 (MH) + Structure Factory I HN~n B, HN.Cbz S (S)-1-(5-(3-Bromophenyl 2,4-triazol-3-yl)-5-(3-methylthiourea Ethyl pentylaminocarbazate hn, N 〇.NH^cbz S (S)- l· -(5-(4-hydroxy-3-nitrophenyl)-1H-1,2,4-tri Zyrid-3-yl)-5-(3-f-based ureido)pentylamino Benzyl methacrylate starting material 〇CD O 孓\ working ω 4:r,xd \ +gas/=\工&quot;,工S i \ ' x 〇&quot; Compound 00 Ο 2 -239 - 134026-2 200916447 Preparation Order LL, Β, Ζ LL, B, G characterization (CD30D) d(ppm) 1H : 7.42 (d, J=3.9 Hz, 1H); 7.37-7.22 (m, 5H) ; 7.14 (d, J=3.9 Hz, 1H); 5.13 (d, J=12.5 Hz, 1H); 5.06 (d, J=12.5 Hz, 1H); 4.86-4.82 (m, 1H); 3.41 (br, 2H); 2.89 (br, 3H) ; 2.00-1.84 (m, 2H) ; 1.63-1.60 (m, 2H) ; 1.48-1.37 (m, 2H). LRMS (ESI): (calc.) 536.1 (measured) 537.3 (MH) + (DMSO -d6) d (ppm) 1H: 7.35-7.23 (m, 7H); 5.03-4.98 (m, 2H); 4.79 (br, 1H); 3.43-3.41 (m, 2H); 2.34 (s, 3H); 1.95-1.70 (m,2H) ; 1.60-1.46 (m,2H) ; 1.42-1.22 (m, 2H)· LRMS (ESI): (calculated) 521.1 (measured value) 522.2 (MH)+ structure Br HNv S Cbz (S)-1-(5-(5-bromo-4-phen-2-yl)-1H-1,2,4-triazol-3-yl)-5-(3-methylthioureido) Benzyl amyl amide HN, Cbz S (S)-1 -(5-(5-bromobens-2-yl)-1H-1,2,4-triazol-3-yl)-5 - Ethyl thioguanamine pentylamine芊 carboxylate starting material 〇 1 x - 工)·η±工 „ ώ c&gt;=&lt; vn + Y zx o 〇/ V i \ 工 C0 X Φ工工工&gt;..ιέ工m \ / V i \ X Compound g 00 ί -240 · 134026-2 200916447 Preparation order LL, B, Z i 1 1 LL, B, Z Characterization (CD30D) d (ppm) 1H : 7.81 (br, 1H) ; 7.37- 7.22 (m, 5H) ; 6.73-6.65 (m, 2H) ; 5.12 (d, J = 12.3 Hz, 1H); 5.07 (d, J = 12.7 Hz, 1H); 4.88-4.82 (m, 1H) ; 3.40 (br, 2H) ; 2.90 (br, 3H) ; 1.97-1.90 (m, 2H) ; 1.62-1.60 (m, 2H); 1.44-1.32 (m, 2H). LRMS (ESI) ··(calculated value) 486.2 (measured value) 487.3 (MH) + (CD30D) d (ppm) 1H : 7.78 (br, 2H) ; 7.38-7.21 (m, 5H) ; 6.88 (br, 2H) ; 5.13 (d, J = 12.7 Hz , 1H); 5.06 (d, J = 12.5 Hz, 1H); 4.88-4.83 (m, 1H); 3.40 (br, 2H); 2.90 (br, 3H); 2.01-1.89 (m, 2H); 1.60 (m, 2H); 1.44-1.38 (m, 2H). LRMS (ESD : (calculated) 468.2 (measured value) 469.3 (MH) + structure F HN^US Cbz (S)-1 -(5-( 2-fluoro-4-hydroxyphenyl)-1H-1,2,4-triazol-3-yl)-5-(3-methylthioureido)pentylaminocarboxylate FΛ HN-M HN. S Cbz (S)-l-(5-(4-hydroxyphenyl)-lH-l,2,4-triazol-3-yl)-5-(3-mercaptothiourea Benzylamino benzyl phthalate starting material 〇CQ ^&quot;1 + ^ κ X &quot;r\JT° X 〇CQ X )·ηΖ I Χ η=/ + /=\工孓\ X Compound CN 00 (Τ) 00 5 -241 - 134026-2 200916447 Preparation order LL, B, GX, D, Β, Ζ 1 Characterization (CD30D) d(ppm) 1H : 8.08 (d, J=6.8 Hz, 0.67H 7.82 (d, J-6.3 Hz, 0.33H); 7.61-7.56 (m, 0.33H); 7.48 (t, J=7.8 Hz, 0.67H); 7.37-7.18 (m, 6H); 7.10 (t , J=7.4 Hz, 1H); 5.14-5.01 (m, 2H) ; 4.01 (s, 2H) ; 3.92 (s, 1H) ; 3.61-3.53 (m, 2H) ; 3.42 (s, 3H); 1.88 (m, 2H) ; 1.74-1.65 (m, 2H); 1.54-1.40 (m, 2H). LRMS (ESI): (calculated) 467.2 (measured value) 468.2 (MH)+ (CD30D) d (ppm) 1H : 8.19 (s, 1H) ; 7.92-7.83 (m, 4H) ; 7.51-7.44 (m, 2H) ; 6.68 (s, ,1H) ; 4.80 (t, J=7.6 Hz, 1H) ; 4.06 (m, 2H); 3.50-3.31 (m, 2H); 2.90 (br, 3H); 1.99-1.82 (m, 2H); 1.67-1.59 (m, 2H); 1.55-1.33 (m, 2H); 1.22 (s, 3H). LRMS (ESI): Value) 439.2 (measured value) 440.3 (MH) + structure ^ hn-n H^Cbz S (S)-5-ethanethioguanidino-1-(5-(2-methoxyphenyl)-1Η- 1,2,4-Triazol-3-yl)pentylaminocarbazate H oxime. S °Ί(S)-5-(3-Methylthioureido)-1-(5-(indol-2-yl)-1H-pyrazol-3-yl)pentylaminocarboxylic acid ethyl ester Substance 〇1 _ Ζ 〇? X &quot;j&quot;l + H1 孓\工W ph .NH 3 Cbz 186 + I Compound 00 00 Example -242 - 134026-2 200916447 General procedure A to PP for the synthesis of the compounds of the invention The system is described in Table 4. Specific examples of each general program are provided in the indicated steps of a particular example. Table 4

程序 圖式 實例 步驟 反應條件 A 1 1 1 R1-NH2 + 又气 R，n1r HO R2 R2 B 1 1 2 TFA, DCM R NHBoc -^R NH2 4N Hci二氧陸圜 C 1 1 3 CSCI2, Et3N d/NH2 _CH2_2!g-^ R _NH2 R T R1 R1 s D 2 2 1 〇 Rh^CI h r』H2 _i-- R^YRl Et3N II E 2 2 2 H Belleau 氏試劑 T ^-^丫 F 3 3 1 0 R〇~N H〇 _Λ_ -- R„、1 Ηυ H1 HOBT, EDC Ν' ^ DMF H G 3 3 2 r-nh2 二硫基醋酸乙a旨· Et3N,THF 1 1 Η 4 11 2 R/NHFmoc ^ 1 5 28 1 Cl ?\ 1.NEt3,THF, — ° H〇入 R ^ Brv^^R 2. CH2N2. Et20 3. HBr J 5 28 2 Br^lR 心、HnH'X R Rl N R EtOH 134026-2 -243- 200916447Program Schematic Example Step Reaction Conditions A 1 1 1 R1-NH2 + Gas R, n1r HO R2 R2 B 1 1 2 TFA, DCM R NHBoc -^R NH2 4N Hci Dioxane C 1 1 3 CSCI2, Et3N d /NH2 _CH2_2!g-^ R _NH2 RT R1 R1 s D 2 2 1 〇Rh^CI hr』H2 _i-- R^YRl Et3N II E 2 2 2 H Belleau's reagent T ^-^丫F 3 3 1 0 R〇~NH〇_Λ_ -- R„,1 Ηυ H1 HOBT, EDC Ν' ^ DMF HG 3 3 2 r-nh2 Dithioacetate A · Et3N, THF 1 1 Η 4 11 2 R/NHFmoc ^ 1 5 28 1 Cl ?\ 1.NEt3,THF, — ° H〇R^ Brv^^R 2. CH2N2. Et20 3. HBr J 5 28 2 Br^lR Heart, HnH'X R Rl NR EtOH 134026- 2 -243- 200916447

程序 圖式 實例 步驟 反應條件 κ 5 28 4 R-NH2 二硫基酷酸；· K2C03, q 二氧陸圜，h2o L 5 29 1 〇 Γ HCI ?\ Ri NHa r βιΆ-^ VVR k2co3, thf/h2o Μ 6 30 2 又 _^2 〇 _ 1 〇 R THF/MeOH HO H N 6 30 3 1 HOBT, EDC R U HO人 R + -- Ri、NAR 1 Et3N, DMAP, DMF H Ο 6 30 4 R 1 R1^1 X M R AcOH,140°C,1h K R P 7 35 1 OH A r^R2 R2vtlR HO R -^ 丫 〇 R EDC, HOBt, 0 DMAP, DMF Q 7 35 2 R i D I1 S NH40AC,甲笨,100°c，2-4h &gt;-N 〇 或 nr u NH40AC.ACOH 160°C, H 微波，5分鐘 R 8 38 1 A BH3 THF &gt; 八 HO 八 R HO R S 8 38 2 Dess-Martin HO R -► 〇/ R ch2ci2 T 8 38 3 又rBr A ^ % Nhk Me〇H ΰ K ^ i 1 u 8 39 1 ^ NH3, MeOH R 乙二醛三聚二水合物 H R 244- 134026-2 200916447 程序 圖式 實例 步驟 反應條件 V 8 39 2 N Br OL NBS, DMF Rr^f !\ K R κ r w 8 39 3 Br^X - Na^SOs, Bu4NSQ4 ^ n r 二氧陸圜，h2o n^r π H X 9 40 2 .N. H?, 10%Pd/C NH。 R Cbz -^ R ^ MeOH Y 10 44 2 R19 人】- L· H 加熱 NH2 h ζ 10 44 3 R1 N=C=S Η H ，NH2 r 丫 r H Et3N，THF ^ ΑΑ 11 45 4 R JRCO)2q_^ R、X nh2 n r Et3N,THF H ΒΒ 11 46 1 b〇r〇°0 g NH2 1 OH -^ R、N 叉O』1 CH?CN, CH2Ci2 u u CC 11 47 1 R1 〇 R n=c=o n nh2 Ft~'T ~—~&quot; r、n人nTRi Et3N, THF Η H DD 12 48 1 I ^eNHz Ri〇-n hoAr P(〇Ph)3 ,吡啶 H ΕΕ 13 49 2 no2 nh2 R MeOH, AcOH R FF 14 121 1 MLJ DCC, DMAP, H R H〇 R1 DCM,r.t. R T 〇 -245- 134026-2 200916447 程序 圖式 實例 步驟 反應條件 GG 14 122 1 又 Ν' W Η Η 严- r^nyn'^Ri DMF, 0 °C r.t. s H R广 NH2 HH 14 123 1 SCS, Et3N, Mel Η ς FT’2 -^ ρΤνΎ3、 DCM,0°C-&gt;r.t. ^ II 15 124 1 '又^_ r、〇h MeOH, 0 °C JJ 16 125 2 H0、 DAST, K2C〇3 厂φ p^Ri DCM，-78〇C—r.t. N^r1 KK 17 126 1 1 眶、h2N、1 H〇 R N2H4 H2〇 h r DCM, 0 °C LL 17 126 2 O .HCI HN、N H2N、人 -- N R Et3N,THF N R H 100°C MM 18 129 1 NH H2N、Λ HC丨 i X N R -- i丫 N R H NaOH, EtOH ^ H 0 至 60°C NN 18 129 2 rthn^A Ri4：X NH H 11〇〇C N R 〇〇 19 147 1 A, ^ ΛΛ Λ in PP 19 147 2 Q 〇 肼 _h2o hn、n ΒΛΛρ AC〇H,90' R八义 134026-2 -246- 200916447 組合物 於第二方面，本發明係提供組合 之化合物，或其N_氧化物、水二3根據本發明 接受之鹽、複合物或前體藥物，或其藥學上可 可接受之載劑、賦形劑或稀釋劑 構物，及藥學上 此項技藝中所習知之方法調配，^化合物可藉任何 徑投藥’包括但不限於非經腸 〜備，以藉任何途 鼻内、名其〜 ^ 舌下、經皮'局部、 轧g内、#脈内或直腸内。 太淼aa vu人t 在某些具體實施例中， 本毛月化合物係以靜脈内方式在 , 商70 &amp;境中投Μ。方：¾ itb 其他具體實施例中，投藥可為 〃 A „ 戈糟由口腔途徑。此辇细 合物可呈液體溶液或懸浮液之形 此專、、且 3 P』 々式，對口服投藥，配方可 片Μ或膠囊形式；而對鼻内配 -¾ Λ' 4.^ 呈女刀末、鼻滴劑或氣 式。本發明之組合物可系統或局部地投予。 。載^之特徵係依投藥途徑而定。於本文中使用之，，藥學上 V . 可接受一詞係意謂無毒性物質，i *八係可與生物系統相容， *如細胞、細胞培養物、組織或生物體，且不會干擾活性 成伤之生物學活性之右抽从 m » 社。因此，根據本發明之組合物， 除了抑制劑以外，可合右接g 』3有稀釋劑、填料、鹽、緩衝劑、安 疋劑]曾溶劑’及此項技藝中所習知之其他物質。藥學上 可接又配方之衣備係描述於例如Remi^⑽氏醫藥科學，第 18 版，A. Gen_ 編著，Mack 出版公司，East〇n，％ 199〇。 於第二方面之-項具體實施例中，此組合物包含化合 物N氧化物、水合物、溶劑合物、藥學上可接受之鹽、 134026-2 •247- 200916447 複合物或前體藥物，如本文中所述之根據本發明化合物， 以至少約30%對掌異構物或非對映異構物過量存在。於本 發明之某些所期望具體實施例中，該化合物、氧化物、 水合物、溶劑合物、藥學上可接受之鹽、複合物或前體藥 物係以至少約50% ’至少約8〇%，或甚至為至少約·對掌 異構物或非對映異構物過量存在。於本發明之某些其他所 期望具體實施例中，該化合物、N_氧化物、水合物、溶劑 .合才勿 '藥學上可接受之鹽、才复合物或前體藥物係以至少約 95% ’或者’至少約98%，或者，至少約對掌異構物或 非對映異構物過量存在。在本發明之其他具體實施例中， »亥化口物、N-氧化物、水合物、溶劑合物、藥學上可接受 之鹽、複合物或前體藥物係以實質上外消旋混合物存在。 於另-項具體實施例中，此組合物進一步包含另—種治療 或抑制劑。 於本文中使用之，，藥學上可接受鹽，，一詞，係意指會保持 ί」上文=確認化合物之所要生物學活性，且顯示最少或無不 期望毒物學作用之鹽。此種鹽之實例包括但不限於與無機 酉文類（例如鹽酸、氫溴酸、硫酸、磷酸 '硝酸等）所形成之 酉文加成鹽’及與有機酸類形成之鹽’該有機酸譬如醋酸、 草酸、酒石酸、琥站酸、顏果酸、抗壞血酸、苯曱酸、鞣 雙羥奈酸、海藻酸、聚麵胺酸、莕磺酸、蓁二磺酸及 來半礼糖醛酸。化合物亦可以熟諳此藝者已知之藥學上可 接又之四級鹽投藥，明確言之，其包括式+ Ζ_之四級銨 鹽’其中R為氫、貌基或竿基，且ζ為抗衡離子，包括氯根、 134026-2 -248- 200916447 溴根、碘根、-〇-烷基、曱笨磺酸根、甲基磺酸根、磺酸根、 磷酸根或羧酸根（譬如苯曱酸根、琥珀酸根、醋酸根、乙醇 酸根、順丁烯二酸根、蘋果酸根、檸檬酸根、酒石酸根、 抗壞灰酸根、苯甲酸根、桂皮酸根、苯乙醇酸根、爷甲酸 根及二苯基醋酸根）。於本文中使用之”鹽”—詞亦音謂涵蓋 複合物’譬如具有鹼金屬或鹼土金屬。 活性化合物係被包含在藥學上可接受之載劑或稀釋劑 中，其量足以傳輸抑制有效量，而不會造成嚴重毒性作用。 對所有上文所提及症狀之活性化合物劑量係在每天約 至300毫克/公斤，或者〇m〇〇毫克/公斤，更一般性地為 每千克接受者體重每天〇·5至約25毫克之範圍内。典型局部 劑量係涵蓋0则％重量/重量之範圍，在適當載劑中。藥學 上可接受衍生物之有效劑量範圍’可以欲被傳輸母體化合 物之重量為基準計算而得。若衍生物本身顯示活性，則有Procedure Schematic Example Step Reaction Conditions κ 5 28 4 R-NH2 Dithiocarbamate; · K2C03, q Dioxane, h2o L 5 29 1 〇Γ HCI ?\ Ri NHa r βιΆ-^ VVR k2co3, thf/ H2o Μ 6 30 2 again _^2 〇_ 1 〇R THF/MeOH HO HN 6 30 3 1 HOBT, EDC RU HO person R + -- Ri, NAR 1 Et3N, DMAP, DMF H Ο 6 30 4 R 1 R1 ^1 XMR AcOH, 140°C, 1h KRP 7 35 1 OH A r^R2 R2vtlR HO R -^ 丫〇R EDC, HOBt, 0 DMAP, DMF Q 7 35 2 R i D I1 S NH40AC, A stupid, 100 °c, 2-4h &gt; -N 〇 or nr u NH40AC.ACOH 160°C, H microwave, 5 minutes R 8 38 1 A BH3 THF &gt; 八 HO 八 R HO RS 8 38 2 Dess-Martin HO R - ► 〇/ R ch2ci2 T 8 38 3 again rBr A ^ % Nhk Me〇H ΰ K ^ i 1 u 8 39 1 ^ NH3, MeOH R Glyoxal trimeric dihydrate HR 244- 134026-2 200916447 Procedure pattern EXAMPLES Steps Reaction Conditions V 8 39 2 N Br OL NBS, DMF Rr^f !\ KR κ rw 8 39 3 Br^X - Na^SOs, Bu4NSQ4 ^ nr Dioxane, h2o n^r π HX 9 40 2 .N. H?, 10% Pd/C NH. R Cbz -^ R ^ MeOH Y 10 44 2 R19 Human]- L· H Heating NH2 h ζ 10 44 3 R1 N=C=S Η H ,NH2 r 丫r H Et3N,THF ^ ΑΑ 11 45 4 R JRCO) 2q_^ R, X nh2 nr Et3N, THF H ΒΒ 11 46 1 b〇r〇°0 g NH2 1 OH -^ R, N Fork O』1 CH?CN, CH2Ci2 uu CC 11 47 1 R1 〇R n=c =on nh2 Ft~'T ~—~&quot; r, n person nTRi Et3N, THF Η H DD 12 48 1 I ^eNHz Ri〇-n hoAr P(〇Ph)3 , pyridine H ΕΕ 13 49 2 no2 nh2 R MeOH, AcOH R FF 14 121 1 MLJ DCC, DMAP, HRH〇R1 DCM, rt RT 〇-245- 134026-2 200916447 Program Schematic Example Step Reaction Conditions GG 14 122 1 Ν' W Η Η 严 - r^nyn '^Ri DMF, 0 °C rt s HR wide NH2 HH 14 123 1 SCS, Et3N, Mel Η FT FT'2 -^ ρΤνΎ3, DCM,0°C-&gt;rt ^ II 15 124 1 'also ^_ r 〇h MeOH, 0 °C JJ 16 125 2 H0, DAST, K2C〇3 Plant φ p^Ri DCM, -78〇C—rt N^r1 KK 17 126 1 1 眶, h2N, 1 H〇R N2H4 H2 〇hr DCM, 0 °C LL 17 126 2 O .HCI HN, N H2N, human -- NR Et3N, THF NRH 100 ° C MM 18 129 1 NH H2N, Λ HC丨i XNR -- i丫NRH NaOH, EtOH ^ H 0 to 60 ° C NN 18 129 2 rthn^A Ri4:X NH H 11〇〇CNR 〇〇19 147 1 A, ^ ΛΛ Λ in PP 19 147 2 Q 〇肼_h2o hn, n ΒΛΛρ AC〇H,90' R VIII 134026 -2 -246- 200916447 Composition In a second aspect, the present invention provides a combined compound, or a N-oxide thereof, a water-based salt, complex or prodrug, or a pharmaceutically acceptable co-available thereof, according to the present invention Accepted carriers, excipients or diluent constructs, and methods known in the art of pharmacy, can be administered by any route, including but not limited to parenteral ~ preparation, to borrow any route Inside, name it ~ ^ sublingual, percutaneous 'local, rolling g, #脉, or rectum. Too aa vu human t In some embodiments, the present lunar compound is administered intravenously in the quotient 70 &amp; Formula: 3⁄4 itb In other specific embodiments, the administration may be 〃 A „ 戈 。 from the oral route. The bismuth complex may be in the form of a liquid solution or suspension, and the 3 P 々 formula, for oral administration The formula may be in the form of tablets or capsules; and the intranasal -3⁄4 Λ' 4.^ is a female knife nose, a nasal drop or a gas type. The composition of the present invention can be administered systemically or locally. The characteristics are determined by the route of administration. As used herein, pharmaceutically V. Acceptable means non-toxic substances, and i*8 is compatible with biological systems, such as cells, cell cultures, tissues. Or the organism, and does not interfere with the biological activity of the active wounded from the m». Therefore, the composition according to the present invention, in addition to the inhibitor, can be combined with the right side, the diluent, the filler, Salts, Buffers, Ampoules] Solvents' and other substances well known in the art. Pharmaceutically acceptable and formulated garments are described, for example, in Remi(10) Medical Science, 18th Edition, A. Gen_ Edited, Mack Publishing Company, East〇n, % 199〇. In the second aspect - item specific In an embodiment, the composition comprises a compound N-oxide, hydrate, solvate, pharmaceutically acceptable salt, 134026-2 • 247-200916447 complex or prodrug, as described herein according to the invention a compound, present in an excess of at least about 30% to the palmo isomer or diastereomer. In certain desirable embodiments of the invention, the compound, oxide, hydrate, solvate, pharmaceutically An acceptable salt, complex or prodrug is present in an excess of at least about 50% 'at least about 8%, or even at least about a palmoisomer or diastereomer. In other preferred embodiments, the compound, N-oxide, hydrate, solvent, pharmaceutically acceptable salt, complex or prodrug is at least about 95% 'or' at least About 98%, or at least about an excess of palmier isomers or diastereomers. In other embodiments of the invention, » Haihuakou, N-oxide, hydrate, solvate a pharmaceutically acceptable salt, complex or prodrug A qualitative racemic mixture is present. In another embodiment, the composition further comprises another therapeutic or inhibitor. As used herein, pharmaceutically acceptable salt, the term means The above will be maintained as a salt which confirms the desired biological activity of the compound and exhibits minimal or no undesirable toxicological effects. Examples of such salts include, but are not limited to, hydrazine addition salts formed with inorganic hydrazines (e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid 'nitric acid, etc.) and salts formed with organic acids, such as organic acids. Acetic acid, oxalic acid, tartaric acid, succinic acid, anaphoric acid, ascorbic acid, benzoic acid, guanidine dihydroxy acid, alginic acid, polyaminic acid, sulfonic acid, sulfonic acid, and uronic acid. The compound can also be administered to a pharmaceutically acceptable quaternary salt known to the artist. Specifically, it includes a quaternary ammonium salt of the formula + Ζ_, wherein R is hydrogen, a top group or a thiol group, and Counterions, including chloride, 134026-2 -248- 200916447 bromide, iodide, -〇-alkyl, sulfonate, methanesulfonate, sulfonate, phosphate or carboxylate (such as benzoate, Succinate, acetate, glycolate, maleate, malate, citrate, tartrate, ascorbic acid, benzoate, cinnamate, phenylglycolate, male formate and diphenylacetate) . As used herein, "salt" - the term is also meant to encompass a composite such as an alkali metal or alkaline earth metal. The active compound is included in a pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver an inhibitory effective amount without causing a serious toxic effect. The active compound dose for all of the above mentioned conditions is about 300 mg/kg per day, or 〇m〇〇 mg/kg, more typically 〇5 to about 25 mg per kg of recipient body weight per day. Within the scope. Typical topical dosages range from 0% by weight/weight in a suitable carrier. The effective dosage range ' of the pharmaceutically acceptable derivative' can be calculated on the basis of the weight of the parent compound to be transferred. If the derivative itself shows activity, then

效劑量可如上述使用衍生物之重量’或藉由熟請此蔽者已 知之其他方式估計。 = 在本發明第二方面之某些具體實施例中，此組合物進一 種_ ’譬如反有意義寡核#酸，其會抑制組織 “化酶基因之表現。核酸層次抑制劑“列如反有音 義养核菩酸）與蛋白質層次抑制劑（意即組 ㈣ ^素活性之抑制劑）之合併㈣，會造成經改良之抑 二於是當與任—種個別使用時所必須之量 制作用所需要抑制劑之量。根據本發明此 乃由之反有意義寡核竑 养核甘駄，係互補至會使組織蛋白去乙醯 134026-2 &gt;249- 200916447 化酶基因編碼之RNA或雙股DNA之區域。 其他抑制劑亦可存在於本發明之組合物 $奋、生4、PA 具中此組合 不會k成無法令人接受之不利作用。 組織蛋白去乙醯化酶活性之抑制 明係提供一種抑制組織蛋白去乙酸化 方法包括使組織蛋白去乙酿化酶，與抑 ，里之根據本發明之化合物’或與抑財效量之根據 二之組合物接觸。組織蛋白去乙醯化酶活性之抑制可 在細胞或多細胞生物體中。若 方本总4 in ± 、、’已中，則根據此方面之 方法係包括使該細胞與抑制有效量之根 物’或與抑制有效量之根據本發明之組合物接觸。若在; 細胞生物體中，則根據本發 物— &quot;此方面之方法係包括對該生 b X 效量之根據本發明之化合物，或抑制有效 Π::據本：明之組合物。生物體較佳為哺乳動物，更佳 . 貝八體實施例中，此方法進一步包括使該 組織蛋白去乙醯化酶或該細胞， 桩顢4 ο夕 與有效®之另一種抑制劑 接觸，或右在多細胞生物體 中，則共同或相繼地投予抑制 有效量之另一種抑制劑。 於另一項具體實施例中，琴古 Μ方去為一種治療對組織蛋白 去乙醯化酶活性抑制劑具回應 “注之疾病之方法，且包括對 有需要之個體投予有效量之根撼 根據本發明之化合物或其組合 物。在某些具體實施例中， 曰 α療方法進一步包括投予有效 里之另一種治療劑’其中★玄盆从， 、 ° 他治療劑為適於治療該疾病 之治療劑。 134026-2 -250- 200916447 / ;本么月化合物會抑制組織蛋白去乙醯化酶活性，故 :係為有用研究工具，供活體外研究組織蛋白去乙醯化 酶，及其在生物學過程中之角色。 組織蛋白去乙醯化酶之酵素活性之度量可使用已 法達成。 作 在-些具體實施例中，組織蛋白去乙醯化酶抑制劑會與 細胞中之所有組織蛋白去乙醯化酶交互作用，且降低其活The effective dose can be estimated as described above using the weight of the derivative or by other means known to those skilled in the art. = In some embodiments of the second aspect of the invention, the composition is in the form of an anti-significant oligonucleic acid which inhibits the expression of the tissue enzyme gene. The combination of the sonic nucleus and the protein level inhibitor (meaning that the inhibitor of the group (IV) activity) (4) will result in an improved remedy, so that it is necessary for the individual use of any kind of individual use. The amount of inhibitor is required. According to the present invention, the anti-significant oligonuclear nucleus is complementary to the region of the RNA or double-stranded DNA which encodes the tissue protein to the acetyl group 134026-2 &gt;249-200916447. Other inhibitors may also be present in the compositions of the present invention. The combination of Fen, Bio 4, and PA has no unacceptable adverse effects. Inhibition of tissue protein deacetylase activity provides a method for inhibiting deproteinization of tissue proteins, including degrading tissue proteins to a brewing enzyme, and inhibiting the compound according to the present invention or The composition of the second is in contact. Inhibition of tissue protein deacetylase activity can be in a cell or multicellular organism. If the method is 4 in ±, "," the method according to this aspect comprises contacting the cell with an inhibitory effective amount of the root or with an inhibitory effective amount of the composition according to the invention. In the case of a cell organism, according to the present invention, the method according to the present invention comprises the compound according to the present invention, or the effective Π:: according to the present invention. Preferably, the organism is a mammal, more preferably. In the embodiment of the babe body, the method further comprises contacting the tissue protein with an acetamylase or the cell, and contacting the other inhibitor with the effective agent. Or right in a multicellular organism, an inhibitory effective amount of another inhibitor is administered in combination or sequentially. In another embodiment, the eclipse is a method of treating a disease in response to a tissue protein deacetylase activity, and includes administering an effective amount to the individual in need thereof.化合物 a compound according to the invention or a composition thereof. In certain embodiments, the 曰α therapy method further comprises administering another therapeutic agent in the active form, wherein the therapeutic agent is suitable for treatment. The therapeutic agent of the disease. 134026-2 -250- 200916447 / ; The compound of this month inhibits the activity of tissue protein deacetylase, so it is a useful research tool for in vitro study of tissue protein deacetylase, And its role in biological processes. The measurement of the enzyme activity of tissue protein deacetylase can be achieved using methods. In some embodiments, tissue protein deacetylase inhibitors are associated with cells. All tissue proteins go to the acetylase interaction and reduce their activity

性。在根據本發明此大&amp;夕_ + I 之—二其他具體實施例中，組織 乙醯化酶抑制劑會與細胞中少於所有之組織蛋白去 :酿化酶交互作用，且降低其活性。在某些具體實施例中， / p制蜊會與一種組織蛋白去乙醯化酶“列如观τ”交 ::其活性’但不會與其他組織蛋白去乙醯化酶(例如 )父互作用或降低其活性。 在本發明之某些具體實施例中，本發明之組織蛋白去乙 醯化酶抑制劑可與此項技藝中已知或其將被發現之另—種 =蛋白去乙醮化酶或舰⑽制劑一起投藥。此種組織蛋 去乙酿化酶或HDAC抑制劑之投藥可相繼地或共同地進 1丁=本發明之某些具體實施例中，組合物係包含本發明 ^織蛋白去乙酿化酶抑制劑及/或反有意義寡核答酸及/ =技Γ已知或其將被發現之另一種組織蛋白去乙釀 孝。在一些具體實施例中’此種組合 份係增效地發生作用，以產生治療作用。 活丨生成 其他組織蛋白去乙醯化酶抑制劑之實例包括但不限於於 鹼醯胺、坎必諾（cambinoi)、捨亭諾、分裂霉素 334026-2 -25]- 200916447 (splitomicin)、苯胺基苯曱醯胺#7及Εχ527。 下述實例係意欲進一步說明本發明之某些具體實施例， 而並非意欲限制本發明之範圍。 檢測實例 檢測實例1 組織蛋白去乙酿化酶酵素活性之抑制 SIRTl-2_3酵素檢測擬案 缓衝劑：50mM HEPES, pH 8.0, 137mM NaCl, 2.7mM KC1，ImM MgCl2 酵素： 組織蛋白去乙醯化酶1 (BioMol目錄#SE-239，人類 重組） 組織蛋白去乙醯化酶2 (自行純化，HisSIRT2) 組織蛋白去乙醯化酶3 (BioMol目錄#SE-270，人類 重組） 受質： CBZ-Lys(Ac)-AMC (自用化合物 MG092496X) NAD+ *· Sigma 目錄 #N-6522 胰蛋白酶： Sigma目錄#T-8003 菸鹼醯胺： Sigma目錄#Ν-3376 儲存溶液： [S] = 30 mM 在 DMSO 中 [I] = 30 mM 在 DMSO 中 [胰蛋白酶]=10毫克/毫升在1 mM HC1中 [菸鹼醯胺]=50mM在DMSO中 [E]=依酵素而定 134026-2 - 252- 200916447 檢測溶液（經稀釋之儲存溶液）： [S] = (U8mM在SIRT緩衝劑中 [E]=依酵素活性與純度而定 [I] = 0.5 mM 在 DMSO 中Sex. In other embodiments according to the present invention, the tissue acetylated enzyme inhibitor interacts with less than all of the tissue proteins in the cell: the brewing enzyme, and reduces its activity. . In some embodiments, the /p system will interact with a tissue protein deacetylase "column like a tau":: its activity 'but not with other tissue proteins deacetylase (for example) parent Interact or reduce its activity. In certain embodiments of the invention, the tissue protein deacetylase inhibitor of the invention may be associated with another species of protein known in the art or which will be discovered by the protein = deacetylase or ship (10) The preparation is administered together. The administration of such a tissue egg dehydrogenase or HDAC inhibitor may be carried out sequentially or in combination. In some specific embodiments of the invention, the composition comprises the present invention. And/or anti-significant oligonucleotides and/or another tissue protein known to be known or to be discovered. In some embodiments, such combinations act synergistically to produce a therapeutic effect. Examples of live tissue-derived other tissue proteins to acetylase inhibitors include, but are not limited to, base guanamine, campinoi, shedino, cleavage 334026-2 -25]- 200916447 (splitomicin), Anilinobenzamide #7 and Εχ527. The following examples are intended to further illustrate certain embodiments of the invention and are not intended to limit the scope of the invention. Test Example Detection Example 1 Inhibition of tissue protein deacetylase activity SIRT1-2_3 enzyme detection buffer: 50 mM HEPES, pH 8.0, 137 mM NaCl, 2.7 mM KC1, 1 mM MgCl2 Enzyme: Tissue protein deacetylation Enzyme 1 (BioMol Catalog #SE-239, Human Recombination) Tissue Protein Deacetylase 2 (Self-purified, HisSIRT2) Tissue Protein Deacetylase 3 (BioMol Catalog #SE-270, Human Recombination) Substrate: CBZ -Lys(Ac)-AMC (self-use compound MG092496X) NAD+ *· Sigma Table of Contents #N-6522 Trypsin: Sigma Catalog #T-8003 Nicotinamide: Sigma Catalog #Ν-3376 Storage Solution: [S] = 30 mM In DMSO [I] = 30 mM in DMSO [trypsin] = 10 mg / ml in 1 mM HC1 [nicotine guanamine] = 50 mM in DMSO [E] = enzyme dependent 134026-2 - 252 - 200916447 Test solution (diluted stock solution): [S] = (U8mM in SIRT buffer [E] = enzyme activity and purity [I] = 0.5 mM in DMSO

淬滅用溶液=在緩衝劑中之胰蛋白酶2毫克/毫升與於驗酉| 胺2mM 檢測擬案： 於黑色平底1/2面積Costar # 3694板中添加： 8微升SIRT緩衝劑 2微升0.5mM抑制劑（或關於對照組為DMS0) (20 /zM最後） 15微升酵素溶液（無酵素之低對照井） @室溫下培養10分鐘 25 微升受質 /NAD+ (90 //M/500 //M 最後） 總體積=50微升 在37°C下培養40-60分鐘（依酵素活性而定）。 藉由添加50微升淬滅用溶液達最後濃度為1毫克/毫升胰蛋 白酶與ImM菸鹼醯胺，使反應淬滅。 將板於黑暗中，在37°C下培養30分鐘。 使用螢光板讀取器（；lEx=360毫微米，；lEm=470毫微米）讀取。 參考資料：S1RT1-2-3螢光計藥物發現套件（BioMol :目錄 #AK-555 ' AK-556 &gt; AK-557) P:\Lead Discovery\SOP-Forms-Templates\SOF\LeadDiscovery SOP's\ HD AC Brief Protocols\ClassIll 在本申請案中舉例之所有化合物均顯示針對一或多種人 134026-2 -253 - 200916447 在本’請案中舉例之所有化合物均顯示針對一或多種人 類、、且織蛋白去乙醯化酶之抑制活性&lt;20 # IC5 〇。 本發明已連同其特殊具體實施例加以描述，但應明 目㈣疋，其係能夠進一步修正，且本申請案係意欲涵蓋一 叙丨生地按照本發明原理之任何本發明變型、用# $ U ^ , 又主用途或調整， 己括出發自本發明揭示内容者，譬如 藝内之P 土々m m 6 +目本發明相關技 已知或為用貫務者，及可應用至 徵者，曰心丁、+. +歧 又&amp;出之必須特 且如下述在隨文所附請求項之範園内者。 134026-2 -254-Quenching solution = Trypsin 2 mg/ml in buffer and test with oxime | Amine 2 mM Test plan: Add in black flat bottom 1/2 area Costar # 3694 plate: 8 μl SIRT buffer 2 μl 0.5 mM inhibitor (or DMS0 for the control group) (20 / zM last) 15 microliters of enzyme solution (low control well without enzyme) @ 10 minutes incubation at room temperature 25 microliters of substrate / NAD + (90 / M /500 //M Last) Total volume = 50 μl cultured at 37 ° C for 40-60 minutes (depending on enzyme activity). The reaction was quenched by the addition of 50 microliters of the quenching solution to a final concentration of 1 mg/ml trypsin and 1 mM nicotinamide. The plate was incubated in the dark for 30 minutes at 37 °C. Read using a fluorescent plate reader (; lEx = 360 nm, ; lEm = 470 nm). Reference: S1RT1-2-3 Fluorometer Drug Discovery Kit (BioMol: Catalog #AK-555 'AK-556 &gt; AK-557) P:\Lead Discovery\SOP-Forms-Templates\SOF\LeadDiscovery SOP's\ HD AC Brief Protocols\ClassIll All compounds exemplified in this application are shown for one or more humans 134026-2 -253 - 200916447 All compounds exemplified in this 'Request' show for one or more human, and woven proteins The inhibitory activity of deacetylase was &lt;20 # IC5 〇. The present invention has been described in connection with the specific embodiments thereof, but it should be understood that it can be further modified, and the present application is intended to cover any variation of the invention in accordance with the principles of the present invention. ^ , the main use or adjustment, including from the disclosure of the present invention, such as the P of the art, the soil of the art, is known or used by the relevant technology, and can be applied to the applicant, 曰Mind, +. + 又 and &amp; must be special and as described below in the accompanying article attached to the scope of the request. 134026-2 -254-

Claims (1)

200916447 十、申請專利範圍： 1. 一種式（I)化合物： Y—L—z——D (I) 受之鹽、 、非對映 或其N-氧化物、水合物、溶劑合物、藥學上可接 前體藥物或複合物，或其外消旋或呈比例混合物 異構物或對掌異構物，其中200916447 X. Patent application scope: 1. A compound of formula (I): Y-L-z——D (I) salt, diastereomer or N-oxide, hydrate, solvate, pharmacy a prodrug or complex, or a racemic or proportional mixture of isomers or palmomerisomers thereof, wherein D係選自包括 Rc a: II X Ra 1 复 Rb II X ,Rh Ra RbD is selected from the group consisting of Rc a: II X Ra 1 complex Rb II X , Rh Ra Rb V、 R3 c II X Rb X Rc V、 Ψ -M、 Rb O XV, R3 c II X Rb X Rc V, Ψ -M, Rb O X X為O或s; Rc ,X is O or s; Rc , 其中 M為氮、氧或硫： W為氮；Wherein M is nitrogen, oxygen or sulfur: W is nitrogen; Μ為氮； 其中當Μ為氡或碲時，Rb係不存在，且 其中當W為氧或硫時，RM系不存在，且 134026-3 200916447 各Ra係獨立選自包括-Η、-Cl-Q烷基、保護基、_Ci_c6烷基 -芳基、芳基、_Cl-C：6烷基-雜芳基、雜芳基、 環烷基、環烷基、-cvc：6烷基-雜環基、雜環基、_c(〇)_〇_ ci -C6 烷基、-CCCO-O-Ci -C6 烷基-雜環基、_c(〇) 〇 Ci _C6 烷基 -烯基、-CCOKKVG 烷基-芳基、_C0_Cf3&amp; ， 其每一個係視情況經取代；且 當M為氮時，Ra係另外選自-C(0)-H ;Μ is nitrogen; wherein when Μ is 氡 or 碲, Rb is absent, and wherein when W is oxygen or sulfur, RM is absent, and 134026-3 200916447 each Ra is independently selected from the group consisting of -Η, -Cl -Q alkyl, protecting group, _Ci_c6 alkyl-aryl, aryl, _Cl-C: 6 alkyl-heteroaryl, heteroaryl, cycloalkyl, cycloalkyl, -cvc:6 alkyl-hetero Cyclo, heterocyclyl, _c(〇)_〇_ ci -C6 alkyl, -CCCO-O-Ci-C6 alkyl-heterocyclyl, _c(〇) 〇Ci _C6 alkyl-alkenyl, -CCOKKVG Alkyl-aryl, _C0_Cf3&amp;, each of which is optionally substituted; and when M is nitrogen, the Ra is additionally selected from -C(0)-H; R%RC ’當存在時，係獨立選自包括_H、_0H、_CN、_α 烷基、-Ο-烧基-芳基、_〇_烧基_雜芳基、-Ci必烧基、_c(〇)_ 烷基、-贿2、-NH-烷基、-C(0)_H、保護基、必必烷基— 方基、芳基、-Ci-C6烷基-雜芳基、_雜芳基、_Ci_c6烷基_ 環烷基、環烷基、烷基-雜環基、雜環基、_C(0)_Q_C3 烷基-芳基、-C(0&gt;C。-C3烷基·雜芳基、_c(0)_c。_c3烷基環 烷基、（(0)-0)-(¾烷基-雜環基、_c(〇)_〇_Ci_C6烷基、 -c(0)-0-Cl -c6烷基-雜環基、_c(〇) 〇 Ci —Q烷基烯基、 _c(0&gt;aci-c6烷基-芳基、-CO-CF3及 ，其每 一個係視情況經取代； 其中當Μ為氮時，R，Rb和彼等所連接之氮原子一起視情 況形成3至9-員雜擇盆 仙朴好 ^ 雜％基、雜方基、雜環基-芳基或雜環基 _雜矛基，其每—個係視情況經取代，且 其中當Ra為-Cl-(：6烧基、·Ci_Q炫基_芳基、必必燒基雜芳 基、-CrQ烷基-雜環基或（]必烷基_環烷基，且y為 1 6、元土夺則Ra與Rc係視情況和碳原子連接，以形 134026-3 200916447 二:至瓜員雜環基、雜環基·芳基、雜 核基-雜環基或雜環基_環燒基 ^雜 代； 母個係視情況經取 Rf係選自包括Η、Cl_c6烷基； Rh係選自包括Η、-OH、_CN、_c c 烷A关其r lC6烷基、-c〇-c6烷基_ac〇_C6 …方基、&lt;vc6烷基_〇_C〇_C6燒基_雜芳基 ==芳基係視情況經取f和彼； 連接之原子—起視情況形成3至9_員雜環基、 基、雜環基-芳基或雜萝其雜 經取代；“雜认雜方基，其每-個係視情況 HA為視情I轉代之雜環基、”基、 環基-雜芳基； Z係選自包括共價鍵、 Ν Γ Γ 美 3 8烷基C°-C3烷基-CA雜烷 0 3、元土 _C〇'C3 烷基-C2-C8烯基-C0-C3 烷基 _、_c _c 、元土 C2。8炔c0-c3燒基…c〇_c6烧基.芳基Ά烧基_、 -C。-C6烷基-芳基(2、雜烷基_、（。烷基-環烷基_c。A 烷基_、_QrC6烷基~環烷基-c^c：6雜烷基_、_C4_C6雜環基 -芳基-c0-c6燒基_、_c4_c6雜環基_芳基必夂雜院基… -Cof6炫基-C4&lt;V雜環基-Co-Q院基-、-C0-C6貌基_C4&lt;V 雜壤基-C〇_C6雜烧基-、-C〇-C6-燒基-雜芳基_C〇_C6烧基… -c〇-cv烧基-雜芳基弋夂雜烷基_、心必雜環基·雜芳基 -c〇-c6烷基-、_C4_C6雜環基_雜芳基_c〇_C6雜烷基_、_c〇_Q 烷基-芳基-(VC：6炔基_、心必烷基_雜芳基A%炔基、 -C0 -C6烧基-環烧基4 A炔基_、_Cq 烧基-雜環基4、 134026-3 200916447 炔基-、-〇)-c6烧基-芳基_C2_C6炔基_c2_C6烯基_、_c〇、C6 烷基-芳基-Q-C6烯基-、_Q_C6烷基-雜芳基_c2_C6烯基_、 -Co -C：6燒基-環烧基-C2 -C；6稀基…Q -C：6燒基·雜環基弋夂 烯基-、_C(rC6炫基-芳基-芳基_Cg_C6烷基…％A垸基_ 芳基-雜芳基-Co-Q烧基_、_c〇_C6烷基-雜芳基_芳基_C『C6_ 烷基-、-C0-C6烷基-雜芳基_雜芳基_c〇_c6_烧基、_c〇C3 烧基-雜芳基-C〇-C3烷基_c2_c8烯基-C0-C3-烷基_、_c〇_C3 烧基-芳基-C0-C3烧基-(：2(8稀基-CG-C3-烧基胃、_Cq_C3烷基 -雜環基-C〇 -C3烧基-C2 -C8浠基-C〇 -C3 -院基-、_cQ _c3垸基_ 環烷基-C〇-C3烷基-C2-C8烯基-C〇-C3-烷基-、_cQ_c3燒基-雜芳基-C〇-C3烧基-c2-c8炔基-C〇-C3-院基-、_c0-c3燒基-芳基-C〇 -C3烧基-C2 -C8块基-C〇 -C3 -烧基-、-C〇 -C3院基-雜環 基-C〇 -C3燒基-C2 -C8炔基_cQ -C3 -烧基-及-C〇 -C3烧基-環燒 基-C0-C3烧基-C2_C8快基-C0-C3_烧基-，其中各烧基、稀 基、炔基、雜烷基、芳基、雜芳基、雜環基及環烷基 部份基團係視情況經取代；且 當W為Ν時，Ζ係進一步選自包括-Ci -C8烷基-C(0)-、-Ci -C8 烷基-S(0)2 -、-芳基-C0 -C8烷基-s(o)2 -、-雜芳基-c0 -c8烷基 -S(0)2 -、_環烷基-C〇 -C8烷基-S(0)2 _、-雜環烷基-c〇 -c8烷基 _s(0)2 …-CVC8 烷基-CH=、-q-Q 烷基-C(CH3)=、-C〇-C6 烷 基-CH=CH-C(0)、-C〇-C4 烷基-C(O)-、-(VC8 烷基-(NH2)C=、 _C〇-C3 院基-Ci -Cg 雜烧基-C0-C3 烧基-C(O)-、-CQ-C3 炫》基 -C2 -C8 烯基-C〇 -C3 烷基-C(O)-、-0) -c3 烷基-c2 -c8 炔基-c〇 -c3 烷基-c(o)-、-c〇 -c6 烷基-芳基-c〇 -c6 烷基-c(o)-、-CG -c6 烷 134026-3 200916447 基-芳基-c2-c6雜烷基-c(o)-、-c〇-c6烷基-環烷基-cG -C6烷 基-c(o)-、-〇)-(：6烷基-環烷基-(：2-0：6雜烷基-c(0)-、-C4-C6 雜壞基-方基-C〇 (6烧基-C(O)-、-C4 -Cg雜¥基_方基-C〇 -C6 雜烷基-c(o)-、-cQ -c6 烷基-c4 -c6 -雜環基-c〇 -C6 烷基-c(0)-、 -c〇 -C6 烷基-c4 -C6 -雜環基-C〇 -c6 雜烷基-c(o)-、-C〇 -C6 -烧基 -雜芳基-C〇 -C6烷基-C(O)-、-C0 -C6 -烷基-雜芳基-Q) -C6雜烷 基-c(o)-、-C4 -C6 雜環基-雜芳基-C0 -C6 烷基-C(O)-、-c4 -c6 雜環基-雜芳基-C0-C6雜烷基-C(O)-、-C0-C6烷基-芳基 -C3 -C6 炔基-C(O)-、-C0 -C6 烷基-雜芳基-C2 -C6 炔基-c(0)-、 -C0-C6烷基-環烷基-CVC：6炔基-C(O)-、-CQ-C6烷基-雜環基 -C3-C6 炔基-C(O)-、-CQ-C6 烷基-芳基-C2-C6 炔基-C2-C6 烯基 -C(O)-、-C0 -C6 烷基-芳基-c2 -C6 烯基-C(O)-、-C〇 -C6 烧基. 雜芳基-CVC6烯基-C(O)-、-C0-C6烷基-環烷基-C2-C6烯基 -C(O)-、-C〇 -C6 烷基-雜環基-C2 -C6 烯基-C(o)-、-C〇 -C6 烷基. ^'基-•基-C〇 -C6燒基-C(O)-、-C〇 -C6院基-芳基-雜芳基R%RC', when present, is independently selected from the group consisting of _H, -_0H, _CN, _α alkyl, - fluorenyl-aryl, 〇 〇 烧 _ heteroaryl, -Ci butyl, _c (〇)_ alkyl, brio 2, -NH-alkyl, -C(0)_H, protecting group, b-alkyl group, aryl group, -Ci-C6 alkyl-heteroaryl, _ Heteroaryl, _Ci_c6 alkyl-cycloalkyl, cycloalkyl, alkyl-heterocyclyl, heterocyclyl, _C(0)_Q_C3 alkyl-aryl, -C(0&gt;C.-C3 alkyl Heteroaryl, _c(0)_c. _c3 alkylcycloalkyl, ((0)-0)-(3⁄4 alkyl-heterocyclyl, _c(〇)_〇_Ci_C6 alkyl, -c(0) -0-Cl-c6 alkyl-heterocyclyl, _c(〇) 〇Ci-Q alkylalkenyl, _c(0&gt;aci-c6 alkyl-aryl, -CO-CF3 and each of them The situation is substituted; wherein when the hydrazine is nitrogen, R, Rb and the nitrogen atom to which they are attached together form 3 to 9-members, and the heteropoly group, the heterocyclic group, the heterocyclic group- Aryl or heterocyclyl-heteropurine, each of which is optionally substituted, and wherein when Ra is -Cl-(:6 alkyl, ·Ci_Q, aryl, aryl, hexyl, heteroaryl , -CrQ alkyl-heterocyclyl or ()-alkyl-cycloalkyl, and y is 1 6. In the case of the meta-grain, Ra and Rc are linked to the carbon atom as appropriate, in the form of 134026-3 200916447. Two: to the melon heterocyclic group, heterocyclic aryl group, heteronuclear group-heterocyclic group or heterocyclic ring. The base is selected from the group consisting of ruthenium and Cl_c6 alkyl groups; the Rh system is selected from the group consisting of ruthenium, -OH, _CN, _c c alkane A and its r lC6 alkyl group. -c〇-c6 alkyl_ac〇_C6 ... square, &lt;vc6 alkyl_〇_C〇_C6 alkyl _heteroaryl == aryl is taken as f and the other; - in the case of formation, 3 to 9_membered heterocyclyl, benzyl, heterocyclyl-aryl or heterocyclic substituted; "hetero-hybrid, each of which depends on the condition HA" And a heterocyclic group, "yl, cyclo-heteroaryl"; Z is selected from the group consisting of a covalent bond, Ν Γ 3 3 3 8 alkyl C ° - C 3 alkyl - CA heteroaloxane 0 3 , Yuan Tu _ C 〇'C3 alkyl-C2-C8 alkenyl-C0-C3 alkyl _, _c _c, tertino C2. 8 alkyne c0-c3 alkyl ... c〇_c6 alkyl. aryl fluorinated _, -C -C6 alkyl-aryl (2, heteroalkyl-, (.alkyl-cycloalkyl-c. A alkyl-, _QrC6 alkyl-cycloalkyl-c^c: 6 heteroalkyl-, _C4_C6 heterocyclic group- -C0-c6 alkyl group _, _c4_c6 heterocyclic group _ aryl group ... -Cof6 leuko-C4 &lt; V heterocyclic group - Co-Q yard --, -C0-C6 appearance base _C4 &lt; V hetero-based-C〇_C6 miscible-, -C〇-C6-alkyl-heteroaryl_C〇_C6 alkyl...-c〇-cv alkyl-heteroaryloxaalkyl _, 心必基基·heteroaryl-c〇-c6 alkyl-, _C4_C6 heterocyclyl-heteroaryl_c〇_C6 heteroalkyl_, _c〇_Q alkyl-aryl-(VC :6 alkynyl-, cardinyl-heteroaryl A% alkynyl, -C0-C6 alkyl-cycloalkyl 4 Aynyl, _Cq alkyl-heterocyclyl 4, 134026-3 200916447 alkynyl -, -〇)-c6 alkyl-aryl_C2_C6 alkynyl_c2_C6 alkenyl, _c〇, C6 alkyl-aryl-Q-C6 alkenyl-, _Q_C6 alkyl-heteroaryl_c2_C6 alkenyl _, -Co -C: 6 alkyl-cycloalkyl-C2 -C; 6 dilute groups...Q -C: 6 alkyl group ·heterocyclyl nonenyl-, _C (rC6 leuko-aryl-aryl _Cg_C6 alkyl...%A fluorenyl_aryl-heteroaryl-Co-Q alkyl group, _c〇_C6 alkyl-heteroaryl-aryl_C『C6_ alkyl-, -C0-C6 Alkyl-heteroaryl-heteroaryl_c〇_c6-alkyl, _c〇C3 alkyl-heteroaryl-C〇-C3 alkyl _c2_c8 alkenyl-C0-C3-alkyl _, _c〇 _C3 alkyl-aryl-C0-C3 alkyl-( 2(8 dilute-CG-C3-alkyl base, _Cq_C3 alkyl-heterocyclyl-C〇-C3 alkyl-C2-C8 fluorenyl-C〇-C3-hospital-, _cQ_c3 fluorenyl _ ring Alkyl-C〇-C3 alkyl-C2-C8 alkenyl-C〇-C3-alkyl-, _cQ_c3 alkyl-heteroaryl-C〇-C3 alkyl-c2-c8 alkynyl-C〇-C3 -院基-,_c0-c3 alkyl-aryl-C〇-C3 alkyl-C2-C8 block-C〇-C3-alkyl-, -C〇-C3,-heterocyclyl-C〇 -C3 alkyl-C2-C8 alkynyl-cQ-C3-alkyl- and -C〇-C3 alkyl-cycloalkyl-C0-C3 alkyl-C2_C8 fast-C0-C3_alkyl-, wherein Each of the alkyl, dilute, alkynyl, heteroalkyl, aryl, heteroaryl, heterocyclyl and cycloalkyl moiety is optionally substituted; and when W is oxime, the lanthanide is further selected from Including -Ci-C8 alkyl-C(0)-, -Ci-C8 alkyl-S(0)2-,-aryl-C0-C8 alkyl-s(o)2-,-heteroaryl- C0 -c8alkyl-S(0)2-, _cycloalkyl-C〇-C8 alkyl-S(0)2 _,-heterocycloalkyl-c〇-c8 alkyl_s(0)2 ...-CVC8 alkyl-CH=, -qQ alkyl-C(CH3)=, -C〇-C6 alkyl-CH=CH-C(0), -C〇-C4 alkyl-C(O)- ,-(VC8 alkyl-(NH2)C=, _C〇-C3 yard-Ci-Cg miscible-C0-C3 alkyl-C(O)-, -CQ-C3 炫)-C2 -C8 alkenyl-C〇-C3 alkyl-C(O)-,-0)-c3 alkyl-c2 -c8 alkynyl-c〇-c3 alkyl-c(o)-, -c〇-c6 Alkyl-aryl-c〇-c6 alkyl-c(o)-, -CG-c6 alkane 134026-3 200916447 yl-aryl-c2-c6 heteroalkyl-c(o)-, -c〇- C6 alkyl-cycloalkyl-cG-C6 alkyl-c(o)-, -〇)-(:6-alkyl-cycloalkyl-(:2-0:6heteroalkyl-c(0)- , -C4-C6 heteroatom-aryl-C〇(6 alkyl-C(O)-, -C4 -Cg hetero-yl-aryl-C〇-C6 heteroalkyl-c(o)-, -cQ -c6 alkyl-c4 -c6 -heterocyclyl-c〇-C6 alkyl-c(0)-, -c〇-C6 alkyl-c4 -C6-heterocyclyl-C〇-c6 heterocycloalkane -C(o)-, -C〇-C6-alkyl-heteroaryl-C〇-C6 alkyl-C(O)-, -C0-C6-alkyl-heteroaryl-Q)-C6 Heteroalkyl-c(o)-, -C4 -C6 heterocyclyl-heteroaryl-C0-C6 alkyl-C(O)-, -c4 -c6 heterocyclyl-heteroaryl-C0-C6 alkyl-C(O)-, -C0-C6 alkyl-aryl-C3 -C6 alkynyl-C(O)-, -C0-C6 alkyl-heteroaryl-C2 -C6 alkynyl-c ( 0)-, -C0-C6 alkyl-cycloalkyl-CVC: 6 alkynyl-C(O)-, -CQ-C6 alkyl-heterocyclyl-C3-C6 alkynyl-C(O)-, -CQ-C6 alkyl-aryl-C2-C6 alkynyl-C2-C6 alkenyl-C(O)-, -C0-C6 alkyl-aryl-c2 -C6 -C(O)-, -C〇-C6 alkyl. Heteroaryl-CVC6 alkenyl-C(O)-, -C0-C6 alkyl-cycloalkyl-C2-C6 alkenyl-C(O )-, -C〇-C6 alkyl-heterocyclyl-C2 -C6 alkenyl-C(o)-, -C〇-C6 alkyl. ^'-yl--yl-C〇-C6 alkyl-C (O)-, -C〇-C6-based-aryl-heteroaryl -C〇-C6院基-C(O)-、-c0-c6烧基-雜芳基-芳基_c〇_c6_燒基 -C(O)-及-C〇 -C6烷基-雜芳基_雜芳基_c〇 _C6 _烷基_c(〇)_ ;或 Z-W係選自包括-C〗-C8烧基-(NH2 )C=N-、-C〗-8烧基-C=N-及 -C! _ 8烧基-C(CH3 )=N- ’當Rc係不存在時； L係選自包括共價鍵、_Cl_C6烷基-、_c〇_c6烷基 -(CRkCR3 h _ 2-C〇-C6 烷基-、_C() _c6 烷基 _(c Ξ _CQ _C6 燒 基-、-Q-Q烧基-芳基_C(rC6燒基…必必院基-雜芳基 -c0-c6烧基-、-CQ-C3烧基-雜環基_Cq_c3烷基…_Cq_C3燒 基-環烷基-c〇-c3烷基_、_Cg_C6烷基芳基_(cr3=cr3)i 134026-3 200916447 C〇-C6烷基-、-C〇-C6 烷基-芳基-(c=c)卜 2-c〇-c6烷基-、 -C〇 -C6 烷基-雜芳基-(CR3 =CR3 h - 2 -C0 -C6 烷基-、-C0 -C6 烷基 -雜芳基-(CEChd-Co-Q 烷基-、-C0-C6 烷基-N(R3)-C(0)-C〇-C3 烷基-、-CQ-C6 烷基-n(r3)-c(s)-cq-c3 烷基-、-C〇-C6 烷 基-N(R3)-C(0)-烯基-CG-C3 烷基-、-CQ-C6 烷基-N(R3)-C(S)-烯 基-C〇 -C3 烷基-、-C〇 -C6 烷基-N(R3 )-C(0)-炔基-C。-C3 烷基-、 -C0-C6 烷基-N(R3)-C(S)-炔基-Cq-C3 烷基-、-Q-C6 烷基 -N(R3 )-(:(0)-(^-C3 烷基-N(R3)-C(0)-、-CQ-C6 烷基-N(R3)-C(S)-CVC3 烷基-N(R3)-C(0)-、-C〇-C6 烷基-N^SKXOKVCs 烷基 -N(R3 )-C(0)-C〇 -C3 烧基-、-C〇 -Cg 娱《基-N(r3 )-C(S)-Ci -C3 烧基 -N(R3)-C(0)-CG-C3 烷基-、-CG-C6 烷基-N^q-CXOKVCs 烷基 -N(R3 )-C(S)-CQ -C3 烷基-、-C〇 -C6 烷基-N(R3 ^(SyC! -C3 烷基 -N(R3 )-C(S)-CQ -C3 烷基-、-CQ -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-、-Q -C6 烷基-C(S)-N(R3 )-CG -C3 烷基-、-C〇 -C6 烷基-C(0)-N(R3 )-C2-C4 烷基-0-C〇-C3 烷基-、-C〇-C6 烷基-C⑸-N(R3)-C2-C4 烷 基-0-〇)-(：3烷基-、-C〇-C6 烷基-C(0)-N(R3)-C2-C4 烷基-N(R3)-C〇 -C3 烷基-、-CG -C6 烷基-C⑸-N(R3 )-C2 -C4 烷基-N(R3 )-C〇 -C3 烷基-、-C〇-C6烷基-C(0)-CG-C3烷基-、-C〇-C6烷基-C(NOH)-C0 -C3 烷基-、-CQ -C6 烷基-C(O)-烯基-CQ -C3 烷基-、-CG -C6 烷 基-C(NOH)-烯基-C〇 -C3 烷基-、-C〇 -C6 烷基-S(0)2 -N(R3 )-C0 -C3 烷基…-仏-仏烷基-风以:^㈦^^-心烷基…-仏-心烷基 -风113)-5(0)2-风113)-〇)-(：3烷基-、-〇)-€6烷基-(：(0)-风113)-S(0)2-CQ-C3 烷基-、-C〇-C6 烷基-N(R3)-C〇-C3 烷基-' -C0-C6 烷基-N(R3 -C3 烷基-烯基-、-CG -C6 烷基-N(R3 )&amp; -C3 烷基 134026-3 -6 - 200916447 -炔基-、-C〇-C6 烷基-N(R7)-C〇-C3烷基-、-C〇-C6 烷基-N(R7)-烷基-烯基-、-C〇-C6烷基-I^I^KVCs烷基-炔基-、 -C0 -C6 烷基-N(R3 )-C2 -C4 烷基-N(R3 )-C(0)-烷基-、-C。-C6 烷基 -N(R3 )-C2 -C4 烷基-N(R3 )-C(S)-烷基-、-CG -C6 烷基-0-C2 -C4 烷 基-N(R3)C(0)-CQ-C3 烷基-、-CG-C6 烷基-S-C2-C4 烷基-N(R3)-C(0)-C〇 -C3 烷基-、-C〇 -C6 烷基-0-C2 -C4 烷基-N(R3 )C(S)-C0 -C3 烷基-、-C〇-C6 烷基-S-C2-C4 烷基-N(R3)C(S)-C〇-C3 烷基-、 -C0 -C6 烷基-N(R3 )-C2 -C3 雜烷基-、-C〇 -C6 烷基-N(R7 )-C2 -C3 雜烷基-、-Q) -C6 烷基-C(0)-N(R3 )-C2 -C3 雜烷基·、-C〇 -C6 烷 基-C(S)-N(R3 )-C2 -C3 雜烷基-、-CG -C6 烷基-C(0)-N(R7 )-C2 -C3 雜烷基-、-C〇-C6 烷基-C(S)-N(R7)-C2-C3 雜烷基-、-C〇-C6 烷 基-N(R3 )-C(O)-C0 -C3 雜烷基-、-C〇 -C6 烷基-N(R3 )-C⑸-C〇 -C3 雜烷基-、-CG -C6 烷基-N(R7 )-C(0)-CVC3 雜烷基-、-C〇 -C6 烷 基-N(R7 )-C(S)-C。-C3 雜烷基-、-C〇 -C6 烷基-S-C〇 -C3 烷基-、 -C〇 -C6 烧基-0-C〇 -C3 烧基-、-C〇 -Cg 烧基-S(0)-C〇 -C3 烧基-、 -c〇-c6 烷基-s(o)2-c〇-c3 烷基-、-c〇-c6 烷基-n(r3)-c(o)-n(r3)-c〇-c3 烷基-、-cG-c6 烷基-n(r3)-c⑸-n(r3)-c〇-c3 烷基 -、-cG -c6 烷基-o-cG -c3 烷基-雜環基-、-cG -c6 烷基-o-c〇 -C3 烷基-環烷基-、-CG-C6烷基-SiCOo^-CVCs烷基-雜環基-、 -C〇-C6 烧基-S(O)0-2_Cq-C3 烧基-環烧基-、-C〇-C6 烧基 -N(R3 )-C〇 -C3 烷基-雜環基-、-C〇 -C6 烷基-N(R3 )-C〇 -C3 烷基-環烷基-、-雜環基-CQ-C6烷基-0-〇)-(：3烷基-、-環烷基 -c0-c6 烷基-o-c〇-c3 烷基-、-雜環基-c〇-c6 烷基-s(o)0_2-C〇 -C3 烧基-、-環烧基-C〇 -Cg 烧基-S(0)〇 - 2 _C〇 -C3 烧基 _、-雜 134026-3 200916447 環基-C〇 -Q烧基-N(R3 )_CG -c3烷基-、-環烷基-CG -c6烷基 -N(R3)-C〇-C3燒基_、_c0-C6 烧基-N(R3)-C(0)-0-C〇-C3烷基-、 -C〇-C6 烧基-N(R3 )-C(S)-〇-C〇-C3 烷基-、-C〇-C6 烷基-O-C(O)-N(R3)-Cq-C3烷基-、_CVC6烷基-o-c⑸-N(R3)-Cq-C3烷基-、 -C〇 -C3 烷基-N(R3 )-C(0)-0-雜環基 _cG _c3 烷基-、_Cg _c3 烷基 -N(R3 )-C(S)-0-雜環基 _c〇 -c3 烷基-、-C〇 -C3 烷基-N(R3 )-C(0)-0-環烧基-CQ-C3烷基-、_cG-C3烷基-N(R3)-C(S)-0-環烷基 -C0 -C3 烷基-、-C〇 -C6 烷基-s(0)2 -雜環基-CG -C3 烷基-、-C〇 -C6 烷基-S(0)2-環烷基-CG-C3烷基-、-CQ-C6 烷基-n(r3)-s(o)2-雜環基-Cq -C3 烧基-、-Cq -c6 烧基-N(R3 )-S(0)2 -環烧基-C〇 -C3 烷基-、-〇)-C3烷基-雜環基-Q-C3烷基-o-c〇-c3烷基-、 -C〇-C3烷基-環烷基-0)-(¾烷基-o-cG-c3烷基-、-CG-C3烷基-雜環基-CQ-C5烷基-N(R3)-CG-C3烷基-、-c〇-c3烷基-環烷基 -Cq-C〗烧基-N(R3)-C〇-C3 烧基-、-Cq-C〗烧基-O-CQ-C3 烧基-雜環基-CQ-C3烷基-、-CG-C3烷基-o-cG-c3烷基-環烷基 -0) -c3烷基-、-Co -C3烷基-雜環基-CQ -C3烷基-S-C〇 -C3烷基-、-C〇 -Cg 烧基-ί衷烧基-C〇 -C3 烧基-S-C〇 -C3 烧基-、-C〇 -C3 烧 基-NO^KVCs烷基-雜環基-c〇-c3烷基-、-c〇-c3烷基 -N(R )-C〇 -C3 炫基-ί哀炫《基 _C〇 -C3 烧基-、-C〇 -C3 烧基-S-C〇 -C3 烧基-雜年基-C〇 -C3烧基-、-C3烧基_S-C〇 -C3烧基-環烧 基-0)-C3 烷基-、-CG-C3 烷基-S(0)2 N(R3 )-CQ-C3 烷基-雜環基 -C〇-C3 烷基―、-CQ-C3 烷基-s(o)2n(r3)-c〇-c3 烷基-環烷基 -C〇-C3 烷基-、_cG-C3 烷基-c(o)-n(r3)-c〇-c3 烷基-雜環基 -C〇-C3 烷基-、-Q-C3 烷基-c(o)-n(r3)-c〇-c3 烷基-環烷基 134026-3 200916447 -c〇-c3 垸基-、_Cq_c3 烧基 _c⑸_N(R3)_C()_C3 烧基，環基 -C〇-C3烷基_、_cD_c3烷基_c⑸-n(R3)_Cq_C3烷基_環烷基 -C0 -C3 貌基-、_c〇 -C3 烧基-C(O)-雜環基-C〇 -C3 烧基-、 烧基-C(〇)-環烧基-Q -C3烧基-、-C〇 -C3烧基-O-C(O)-雜環基 -C〇 -C3 燒基 _、_〇) -C3 烧基-0_C(0)-環烧基-C〇 -C3 燒基 _、 -c0 -C3 烷基-0-C(0)_N(r3 )_Cg _c3 烷基-雜環基 _Cq _c3 烷基 _、 -c0 -C3 烷基 _0_C(0)_N(r3 )_Cq _c3 烷基-環烷基 _Cq _c3 烷基 _、 -c0 -c3 烷基 _ac⑸_n(r3 )_Cg _c3 烷基-雜環基 _C() _c3 烷基 _、 -C〇 -C3烷基-o-c⑸-N(R3 )-Q -C3烷基-環烷基-CG _c3烷基_、 -C〇 -C3 烷基-N(R3 )-C(0)-N(R3 )-C。-C3 烷基-雜環基-Co -c3 燒基 _ 、-Co -C3 烧基-N(R3 )-C(0)-N(R3 )-〇) -C3 烧基-環烧基 _C。_c3 燒 基-、-c〇-c3 烷基-n(r3)-c⑸-n(r3kvc3 烷基-雜環基 _C()_C3 烷基-、-C〇-C3 烷基-N(R3)-C(S)-N(R3KVC3 烷基-環烧基 -c0 -C3 烷基、-c。-C3 烷基-N(R3 )-C(0)-雜環基-c0 -C3 烷基 _、 -Co-Q 院基-N(R3)-C(0)-環院基-Cq-C3 烧基-、-cvc3 規基 -N(R3)-C(S)-雜環基-C〇-C3 烷基-、-C0-C3 烷基-N(R3)-C(S)-環 烧基-C〇 -C3 院基-、-C〇 -C3 烧基-N(R3 )-S(0)2 -N(R3 )-C。-C3 燒基 -雜 ί哀基-C。-C3 烧基-、-C〇-C3 烧基-N(R3 )-S(0)2 -N(R3 )-C。-C3 烧基-ί哀炫基-C〇 -C3院基-' -C〇 -C6烧基-雜環基-C(0)-C。-C6 烧基-、-C〇 -Cg烧基-環烧基-C(0)-C〇 -Cg烧基-' -C〇 -C6燒基 -n(r3)-c(o)-雜環基-C(〇KVC6 烧基-、-Q)-C6 炫基-N(R3)_ C(O)-環烧基-C(0)-C〇 -C6 烧基-、-C〇 -C6 烧基-N(R3 )-C(S)-雜環 基-C(0)-C〇 -C6 烧基-、-C〇 -C6 烧基-N(R3 )-C(S)-環烧基 -C(0)-C〇 -C6 貌基-、-C〇 -C6 炫基-雜環基-S(0)2 -C〇 -C6 燒基 _、 134026-3 200916447 -C〇 -C6烧基-ί哀院基-S(0)2 -C〇 (6烧基-、-C〇 -C6院基-雜環基 -n(r3)-c(o)-c〇-c6 烷基-、-c〇-c6 烷基-環烷基-n(r3)-c(o)-c0-c6 烷基-、-CQ-C6 烷基-雜環基-0-C(0)-CG-C6 烷基-、 _C〇 -C6烧基-環烧基-0-C(0)-CQ -C6炫基-、-C〇 -C6烧基-雜環 基-N(R3)-C⑸-C〇-C6 烷基-、-Co-Q 烷基-環烷基-N(R3)-C(S)-c〇 -C6 烷基-、-C〇 -C6 烷基-雜環基-〇-C(S)-C〇 -c6 烷基-、-c〇 -c6 烷基-環烷基-0-C(S)-C〇 -C6 烷基-、-C〇 -C3 烷基-CH=N-O-C0 -C3 烷基-、-C。-C3 烷基-C=N(0H)C(0)-N(R3 )-C2 -C4 -烷基-S-S-烷基-、-C〇 -C6 烷基-雜烷基-C〇 -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-、 -C〇-C6烷基-雜烷基-C〇-C6烷基-C⑸-N(R3)-C〇-C3烷基-、 -Q-Q烷基-芳基-雜芳基-C〇-C6烧基-、-C0-C6烧基-雜芳基 -芳基-C0-C6烷基-、-C〇-C6烷基-雜芳基-雜芳基_c0-C6烷基-、 -c0 -C6 烷基-芳基-芳基-CQ -C6 烷基-、-Ci -C3 烷基-N(R3 )-C(0)-Q-c?烷基-、4-(¾烷基-n(r3)-c⑸-q-c?烷基-、-cG-c3烷 基-烯基-C(0)-C〇-C6 烧基-、-C〇-C6 ^s-n(r3)-c(o)-n(r3)- CXCO-q -C3 烷基-、-C〇 -C3 烷基-s-芳基-c0 -C6 烷基-N(R3 )C(0)-Ci-Q 烷基-、-c0-c3 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烷基-NO^-QSKVCs 烷基-、-CG-C3 烷基-O-C(O)-N(R3)-芳基-C〇 -C6 烧基-N(R3 )-(:(0)4 -C3 烧基-、-C0 -C3 烷基 -O-C⑸-N(R3)-芳基-C〇-C6 烷基-NO^KXOKVCs 烷基-、 -C0-C3 烷基-0-C(0)-N(R3)-芳基-C0-C6 烷基-NO^KXSHVCs 烷基-、-C〇-C3 烷基-0-C(S)-N(R3)-芳基-C〇-C6 烷基-N(R3)-QSVQ -C3 烷基-、-C〇-C3 烷基-0-C(0)-N(R3)-雜芳基 _C〇_c6 烧基-N(R3 )-C(0)-Ci -C3 烧基-、-C〇 -C3 烧基-0-C(S)-N(R3 )-雜芳 基-C〇-C6 烧基-N(R3 )-(:(0)-(^-03 烧基-、-C〇-C3 烷基 -0-C(0)-N(R3)-雜芳基-C0-C6 烷基-N(R3 烷基-、 -C〇-C3 烷基-〇-C(S)-N(R3)-雜芳基-C0-C6 烷基-N(R3)-C⑸-CVQ 烷基-、-CG-C3 烷基-0-C(0)-N(R3)-雜環基-C()_C6 烷基 -N(R3 )-(:(0)-(^-C3烷基-、-C〇-C3 烷基-0-C(S)-N(R3)-雜環基 -C〇-C6 烷基-N^q-CXCO-CVCs 烷基-、-CQ-C3 烷基 _〇·(：(〇)_ N(R3)-雜環基-C〇_C6烷基_N(r3)_C⑸_Cl_C3烷基-、-c。^院 基-〇-C(S)-N(R3)-雜環基-C。-C6 烷基-N(R3 -C3 烷基 _、 -C〇-C3 烷基-〇-C(0)-N(R3)-環烷基-CVC6 烷基-N(R3)_ (〇)_ 134026-3 -13- 200916447 C! -C3烷基-、-CG -C3烷基-O-C⑶-N(R3)-環烷基-CQ -C6烷基 -N(R3 )-(:(0)-(^-C3烷基-、-C〇-C3 烷基-0-C(0)-N(R3)-環烷基 -C0-C6 烷基-NCI^KXSKVQ 烷基-、-C〇-C3 烷基-O-C(S)-N(R3)-環烷基-C〇-C6 烷基-NKI^KXSKVCs 烷基-、-C〇-C3 烷 基-S(0)2-N(R3)-芳基-C〇-C6 烷基-NCRq-CCOKVQ 烷基-、 -C〇 -C3 烷基-S(0)2 -N(R3)-芳基-C〇 -C6 烷基-N(R3 VCXSyQ -C3 烷 基-、-C〇 -C3 烷基-S(0)2 -N(R3)-雜芳基-C0 -C6 烷基-N(R3 )-C(0)-q -C3 烷基-、-C〇-C3 烷基-s(o)2-n(r3)-雜芳基-C〇-C6 烷基 -NCI^KXSKVCs烷基-、-C〇-C3 烷基-S(0)2-N(R3)-雜環基 -C0 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C〇 -C3 烷基-S(0)2 -N(R3 )-雜環基-Q)-C6烷基-N(R3)-C⑸-q-Cs烷基-、-C〇-C3烷基 -S(0)2-N(R3)-環烷基-CQ-C6 烷基^Rq-CXOKVCs 烷基-、 -C〇 -C3 烷基-S(0)2 -N(R3)-環烷基-C〇 -C6 烷基-N(R3 KXSKi -c3 烷基-、-C0-C3 烷基-n(r3)-s(o)2-n(r3)-芳基-C〇-C6 烷基 -N(R3 )-(:(0)-(^ -C3 烷基-、-C0 -C3 烷基-N(R3 )-S(0)2 -N(R3 )-芳基 -C〇 -C6 烧基-N(R3 -C3 烧基-、-C〇 -C3 烧基-N(R3 )-S(0)2 ~ N(R3)-雜芳基-C0 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C0 -C3 烷 基-N(R3 )-S(0)2 -N(R3)-雜芳基-C〇 -C6 烷基-N(R3 -C3 燒 基-、-〇)-(：3烷基-&gt;^3)-5(0)2召见3)-雜環基-〇)-(：6烷基 -N(R3 )-C(0)-Ci -C3 烧基-、-C〇 -C3 烧基-N(R3 )-S(0)2 -N(R3 )-雜環 基-C〇-C6 烧基-N^ )-C⑸-Ci -C3 院基-、-C〇-C3 烧基-N(R3)_ S(0)2-N(R3)-環烷基-C〇-C6 烷基烷基-、 (^-(^烷基召妒:^⑼:召妒丨-環烷基心心烷基-叫汉3)、 CXS)-^ -C3院基-、-C〇 -C3烧基-雜環基-〇-芳基-C〇-C6烧基 134026-3 -14· 200916447 -N(R3 )((0)-(^ -C3 烧基-、-C〇 -C3 烧基-雜環基 芳基-C0 -C6 烧基-N(R3 -C；3烧基-、-C0 -Q3烧基-雜環基_〇_芳基 -C0 -C6烧基-N(R3 yCOC! -C3烧基-、-C〇 -C3燒基-雜環基各 芳基-C〇 -Q烧基-N(R3 -C：3烷基-、-C〇 _c3烷基_雜環 基-〇-雜芳基-C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基 _、_C〇 _C3 烷 基-雜環基-S-雜芳基-Co-Q烷基-N(R3 )-(:(0)-(^ -C3烷基_、 -C0-C3 烧基-雜環基-〇-雜芳基 _c〇-C6 烧基-N(R3 -C3 烧基-、-C0-C3烧基-雜環基-S-雜芳基-C0-C6院基_n(R3)_ cxsyc! -C3烷基_、-Q -c：3烷基-雜環基-〇-雜環基_Cq _C6烷基 -N^KXCO-C^-C3烧基-、-CG-C3烷基-雜環基各雜環基 -C〇 -C6 烧基-N(R3 )-(：(0)-(：! -C3 烧基·、-Co -C3 烧基-雜環基 _〇_ 雜環基-CQ -C6燒基-N(R3 -C3烧基-、-c3烷基_雜 環基-s-雜環基-Cq-C6院基 _N(R3&gt;QS)_Ci_C3院基-、_c〇_C3 院基-雜環基-0-環烷基-CQ -Q烷基-N(R3 ycxco-q -C3烷基_ 、-Q) -c3 烷基-雜環基 _s_環烷基 _Cq _C6 烷基 _n(r3 )_c(〇)_Ci &amp; 烷基-、-CG-C3烷基-雜環基-〇-環烷基_C()_C6烷基_N(R3)_ CXSK^ -C：3烷基、-CG -C：3烷基-雜環基-S-環烷基-CG -c6烷基 -N(R3)'C⑸-Cl -c3 烧基-、-C〇-C3 烧基-C(0)-雜環基 _〇_ 芳基 _C〇 C6 烧基-N(R3 -C3 烧基-、-C〇 -C3 院基-C(S)-雜環 基-o-芳基-C〇-C6 烧基-NO^KXOK^-Cs 烧基-、-C0-C3 烷基 -C(0)-雜環基 _s-芳基-c0-c6 烧基-N(R3 )-0(0)-(^ -C3 從基-、 -C〇-C3 燒基-C(〇)-雜環基 _〇_ 芳基 _C〇_C6 烷基 _n(r3)_c(s)_ C! -C3院基-、-C〇 _Cs烷基_c⑸_雜環基各芳基_c〇 %烷基 _n(r3)-c(〇)-ci-c3烷基-、-C〇-C3烷基-C(S)-雜環基-〇-芳基 134026-3 -15- 200916447 -C〇 -c6 烷基 _N(R3 )_C⑸_Cl _c3 烷基-、-Q _C3 烷基 _C(〇)·雜環 基-S-芳基-c0 -C6 烷基-N(R3 ycoq -C3 烷基-、-c0 -C3 烷基 -C(S)-雜環基_s_芳基_c〇_C6烷基烷基—、 -c〇-C3 烷基-C(O)-雜環基-〇-雜芳基-C0-C6 烷基-N(R3)-C(〇)-q %燒基_、_C〇 -c：3烷基_哪)_雜環基_〇_雜芳基_c〇 %烷基 -N(R3 )_C(0)_Ci _c3 烷基 _、_c〇 _c3 烷基 _c(〇)雜環基 _s 雜芳基 -C〇-C6 燒基_N(R3)_C(〇)_Ci_C3烧基-、_Q_C3 烧基 _c(〇)_ 雜環 基-O-雜芳基-C0 -C6烧基-N(R3 )-C⑶-q -C3烷基-、-C〇 _c3烷 基-C(s)-雜環基-s-雜芳基_C〇 -c6烷基-N(R3 )_c(〇)_Ci _c3烧基_ 、-C0 -c3烷基-c⑸-雜環基_α雜芳基_c〇 _c6烷基_n(r3 )_c(s)_ q -c：3烷基·、-c〇 烷基_c(0)_雜環基_s雜芳基_c〇 q烷基 -n(r3 )_c⑸-Ci —A烷基_、_c〇 烷基-c(s)_雜環基_s_雜芳基 -Co -c6 烷基 _N(R3 &gt;c⑶_Ci _C3 烷基 _、_c。_C3 烷基 _c(〇)_雜環 基-O-雜環基-C〇 -Q 烷基-N(R3 )-C(0)_Cl _(：3 烷基 _、_Cq _c3 烷 基-C(S)-雜環基_〇·雜環基_c〇 _c6烷基_n(r3 )_c(〇)_Ci 烷基_ 、-c〇 -c3烷基-C(0)-雜環基_s_雜環基_c〇 _c6烷基-n(r3 )_c⑼— q -C3烷基-、_cG 烷基_c(〇)_雜環基_〇·雜環基_c『c6烷基 _N(R3 WSKVC^ n从基C(s)•雜環基雜環基 -Q-c：6 烧基-N(R3K：(0)_Ci_C3 炫基…Cg_C3 烧基-c(s)_ 雜環 基-0-雜環基-C〇-C6焼基嫌3)_c⑸_Ci必燒基_、必必烷 基-c(0)·雜環基_s_雜環基_Q (6烧基娜3 )‘c⑸_c成基_ 、-Co -c3烧基-C(S)_雜環基_s_雜環基_c。A烧基-聊)（⑸· Q -c3烷基-、-C〇 {成基_c(0)_雜環基_α環烧基_c〇夂烧基 N(R ) QCO-q -C3垸基…C{rc3貌基_c⑻雜環基·〇環烧基 134026-3 -16- 200916447 —C0-C6 燒基-N^yCCOKVq烧基-、-cQ-c3 烧基-C(O)-雜環 基-S-環烷基-CG -Q 烷基-N(R3 )-0(0)-(^ -C3 烷基 _、-〇) -C3 烷 基-C(O)-雜環基_〇_環烷基_cQ _c6烷基_N(R3 )_c(s)_Ci _c3烷基_ 、-C。-C3烧基-c⑸-雜環基_s_環烷基_c。_c6烷基_N(R3 )_c(0)_ ci C3規基_、_〇) -C：3烧基-C(S)-雜環基-〇-環烧基_cQ -C6院基 _N(R3 -C3 烷基-、-C〇-C3 烷基-C(O)-雜環基-S-環烷基 -c0-C6烧基_N(R3)_C⑸_Ci_C3烷基-、_c〇_c3烷基_c⑸雜環 基-S-環烷基-CQ -Q烷基-N(R3 -C3烷基-、-C(rc3烷基 -N(R3)-C(〇)_雜環基 _〇_ 芳基 _c〇_C6 烷基 _n(r3)_c(〇)_Ci_C3 烷 基-、-C0-C3烷基-N(R3)-C(S)-雜環基-〇-芳基_C〇_C6烷基 _N(R3)-c(〇)-ci-C3烷基-、-C〇-C3烷基-N(R3)-C(0)-雜環基-s-芳基-Co -C6 烧基-N(R3 )((0)4 -C3 烧基-、-C〇 _c3 烧基·N(Rs)_ c(0)-雜環基-0-芳基 _c〇_c6 烷基 _n(r3)_qs)_Ci_C3 烷基 _、 -c0-C3 烷基-n(r3)-c⑸-雜環基 _s_芳基 _c〇_c6 烷基 _N(R3)_ CCCO-q -C3烷基-、-C〇_c3烷基-N(R3)_c⑸_雜環基_〇芳基 -C〇-C6 烷基烷基-、-CG-C3 烷基-n(r3)-c(o)-雜環基-S-芳基-c0 -c6烷基-N(R3 )-C⑸-C! -C3烷基-、-Q _c3 烧基-N(R3 )-C(S)-雜環基-S-芳基-c0 -C6 烷基-N(R3 )-C⑸-Ci -C3 烷基-、-C〇-C3烷基-N(R3 )-C(0)-雜環基-〇-雜芳基_c〇_C6烷 基-N(R )-(3(0)-(^ -C3 炫基-、-C〇-C3 院基-N(R3)-C(S)-雜環基 雜芳基-C〇 院基-N(R3 )-(:(0)-(^ -C3 烧基-、-c0 -c3 燒基 -N(R3)-C(0)-雜環基-s-雜芳基-C〇-C6 炫基-N^KXOKVC^ 烧基-、-c0-C3規基-n(r3 )-c(o)-雜環基-o-雜芳基_c〇_C6院 基-N(R )-C⑸-C；3 烧基-、-C〇 -C3 燒基-N(R3 )-C(S)-雜環基 134026-3 -17· 200916447 雜芳基-C0 -C6 烧基-N(R3 ΗΧΟ)-。-C3 烧基-、_c0 -C3 烷基 -n(r3)-c(s)-雜環基 _〇雜芳基 _c〇_c6 烷基 _N(R3)_C⑸_Ci_C3 烷基-、-CVC3烷基-N(R3 )-C(0)胃雜環基_s_雜芳基_c〇 烷基 -NCRi-CXSK^ -c3 烧基-、-Cq-C3 烧基-N(R3)-C(S)-雜環基-S_ 雜芳基-c0-c6烷基-N^KXSKVC^烷基-、-C〇_C3烷基 -N^KXO)-雜環基 _〇_雜環基·q_C6 烷基 _n(r3)_c(〇)_Ci C3 烧基-、-CQ -C3烧基-N(R3 )-C(S)-雜環基_〇_雜環基_Cq _c6烧基 -N(R3 -C3 烧基-、-C〇 -C3 院基-N(R3 )-C(0)-雜環基 _s_ 雜環基-Q-q烷基_n(R3)_c(0)_Ci_C3烷基-、_C『C3烷基 -N(R3)-C(0)-雜環基_〇·雜環基_c〇_C6烷基_摩3)七⑸&amp; 烧基-、-CQ -C3烧基-N(R3 )-C(S)-雜環基_S-雜環基_cG -C6烧基 -N(R3烷基-、-C〇-C3 烷基-N(R3)-C(S)-雜環基 _〇_ 雜環基-(VC6 烷基-N(R3)-C(S)-Cl-C3 烷基-、_Cq_C3 烷基 -n(r3)-c(o)_雜環基各雜環基 _c〇_C6 烷基 _N(R3)_C⑻ 烧基-、-C〇 -C：3烧基-N(R3 )-C(S)-雜環基雜環基_c6烧基 -N^q-CXSK^-C^ 烷基-、-C〇-C3 烷基-N(R3)-C(〇)-雜環基 _〇_ 環烷基-CQ-C6 烷基-N(R3 )-(：(0)-(：!-C3 烷基 _、_C(rC3 烷基 -n(r3)-c(s)-雜環基-〇-環烷基 _C(rC6 烷基 _n(r3k：(〇)_Ci_C3 烷基-、-CG -C：3烷基-N(R3 )-C(0)-雜環基各環烷基_Cq 烷基 -N(R3 )-C(0)-C】-C3 烷基-、-C〇 -C3 烷基-N(R3 )_C(0)_雜環基 _〇_ 環烧基-cvc：6烷基-n(r3)-c⑸-cvc：3烷基-、-C(rc3烧基 -n(r3)-c(s)-雜環基-s_環烧基 _C()_C6 烷基 _n(R3)_c(〇)_Ci_C3 烷基-、-Q) -C：3烷基-N(R3 )-C(S)-雜環基_〇_環烷基_c〇 _c6烷基 -N^KXSKVC^ 烷基-、-C〇-C3 烷基-N(R3)_c(〇)_雜環基 _s_ 134026-3 -18- 200916447 環烷基-CG-C6烷基-Nd^-QSKVCs烷基-、-C〇-C3烷基 -N(R3 )-C(S)-雜環基 _s-環烷基-CQ -C6 烷基-N(R3 -C3 烷 基-、-C〇-C3 烷基 _s(0)2-雜環基-O-芳基-C0-C6 烷基-N(R3)-¢:(0)-(^ -C3 烷基-、_C〇 _C3 烷基 _s(〇)2 _雜環基 _s_ 芳基 _c〇 _C6 烷基-N(R3 )-(:(0)-(^ -C3 炫基-、-C〇 -C3 烧基-S(0)2 -雜環基-〇-芳基-C〇 -C6 烷基-N(R3 )-C⑸-C3 烷基-、-C〇 -C3 烷基-S(0)2 -雜環基-S-芳基 _C(rc6 烷基 _N(R3 )_c⑸_Cl _c3 烷基-、_c〇 _c3 烷基-S(O)2-雜環基_〇_雜芳基_c0-C6烧基-N^KXCO-Ci-Cs 烧基-、-c0-c3烷基-s(0)2-雜環基-s-雜芳基-c0-c6烷基 -n(r3 )-C(〇)-Ci -C3 烷基-、-c0 -c3 烷基-s(o)2 -雜環基-〇-雜芳 基-C〇-C6 烷基-NCRq-QSKVCs烷基-、-C〇-C3 烷基-S(0)2-雜 環基-S-雜芳基-c0-c6 烧基-N^KXSKi -C3 烧基-、-C〇-C3 烷基-s(0)2-雜環基-0-雜環基 _Cq-C6 烷基-N(R3 )-(：(0)-(：! -C3 炫基-、-CVC3烷基-s(0)2-雜環基-S-雜環基-c〇-c6烷基 -N(R3)-C(〇HVC3 烷基-、-C〇-C3 烷基-s(o)2-雜環基-〇-雜環 基-c〇-c6 烷基-n(r3)-c⑸-CVC3 烷基-、-C0-C3 烷基-S(0)2-雜 環基-S-雜環基-CVC6 烷基-N(R3 hCXShCi -C3 烷基-、-C〇-C3 烷基-s(0)2-雜環基-0_環烷基 _cQ-C6 烷基-N(R3 )-(:(0)-(^ -C3 院基-、-C〇-C3烷基-s(0)2-雜環基-s-環烷基-Co-Q烷基 •N(R3 &gt;C(0)-C1 -C3 烷基-、-C〇 -C3 烷基-S(0)2 -雜環基-Ο-環烷 基-CQ-C6 烷基-Nd^KXSKVCs 烷基-、-CQ-C3 烷基-S(0)2-雜 環基-S-環烷基 _CG -c6 烧基-N(R3 VCXSVCi -C3 烧基-、-C〇 -C3 烧基-雜環基-N(R3)-芳基-c0 -C6烷基-N(R3 )-(:(0)-(^ -C3烷基 -、-c〇-c3 烷基-雜環基 _n(r3)-芳基-c〇-c6 烷基-N(R3)-C(s)- 134026-3 -19- 200916447 q-c：3烷基—、-cvc：3烷基-雜環基_N(R3)_雜芳基_c〇_C6烷基 -N(R3 )-(:(0)-(^ -C3 烷基-、-C0-C3 烷基-雜環基 _N(R3)_雜芳基 -Ο)%烧基-N^KXS)^ A烧基-、-Cq_C3烧基_雜環基 -N(R3)-雜環基-C(rC6 烷基-n(r3 )_c(〇)_Ci 七3 烷基 _、_Cq _C3 烷 基-雜環基-N(R3)-雜環基-Q -C6烷基-N(R3 )-c⑸-C3烷基-、-C〇 -C3 烷基-雜環基 _n(R3 )-環烷基 _cG _c6 烷基-N(R3 )-C(0)_ C! -C3烷基-、-A烷基-雜環基_N(R3)_環烷基％ &amp;烷基 -N(R3 XO-Ci -C3 烷基-、-C0-C3 烷基-C(〇)-雜環基 _n(R3 )-芳 基-C〇 -C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-Cq -C3 烷基-C(S)-雜 環基-N(R3)-芳基 _C〇 _c6 烷基 _n(r3 )_c(〇)_Ci _C3 烷基 _、_c〇 % 烧基-c(o)-雜環基_N(R3)_芳基_c〇_C6烷基_n(r3) c⑸_Ci &amp; 烧基-、-Q-C：3烷基-C(S)-雜環基-N(R3)-芳基_C〇_C6烷基 N(R ycO-Ci -C3 烧基-、-CG-C3 烧基-C(0)-雜環基-N(R3)-雜 芳基-C〇 -C6 烧基-N(R3 -C3 烧基-、-C0 -C3 烧基-C(S)- 雜環基-N(R3)-雜芳基 _C〇 _c6 烷基 _N(R3 )_c(〇)_Ci _C3 烷基—、 -c〇-c3 烷基-c(o)-雜環基 _n(R3)_雜芳基 _c〇_C6 烧基 _n(r3)_ QSK：! -C3烷基-' _c〇_c3烷基_c⑸_雜環基_n(r3)_雜芳基 -C〇-C6 烷基·NKR'CO-Ci-Cs 烷基-、-C〇-C3 烷基-c(〇)-雜環 基-N(R3)-雜環基 _C()_C6烷基 _N(R3)_c(〇)_Ci _C3 烷基 _、_c〇&amp; 垸基-c(s)-雜環基_N(R3)_雜環基_Cq_C6烷基 NW )-(:(0)-(^-(¾烷基-、-Q-Cs 烷基-C(〇)-雜環基-N(R3)-雜 環基-C〇-C6 烷基-NO^KXSKVCs 烷基·、-CG-C3 烷基-C(S)-雜環基-N(R3)-雜環基_C。_c6烷基_N(R3 )_C⑸_Ci _C3烷基-、 -C0-C3烷基-C(〇)-雜環基-n^3)-環烷基_C()_C6烷基 134026-3 -20· 200916447 -N(R3 )-(:(0)-(^ -C3 烧基-、-C〇 -C3 烧基-C(S)-雜環基 _n(R3 )-環 烷基-CG-C6 烧基-N(R3 )-0：(〇)-(：】-C3 烧基-、_C()_C3 烧基 _c(〇)_ 雜環基-N(R3)-環烷基-CG -C6烷基-N(R3 )-(^): -C3烷基-、 -C0-C3 烷基-C(S)-雜環基-N(R3)-環烷基-CQ-C6 烧基-N(R3)-QSKVC3烷基-、-C〇-C3烷基-N(R3)-C(0)，環基_N(R3)4 基-Q-C6 烷基-NO^-QCO-Ci -C3 烷基-、-C(rc3 烷基 _n(R3)_ C(S)-雜環基-N(R3)-芳基-CG -C6 烷基-N(R3 ΗΧΟ): -C3 烷基-、-C〇-C3 烷基-N(R3)-C(0)-雜環基-N(R3)-芳基 _C〇_C6 烷基 -N^ycXSHVC^ 烷基-、-C〇-C3 烧基-N(R3)-C(S)-雜環基 -N(R3)-芳基-C〇 -C6 烷基-N(R3 )-(:(8)-(^ -C3 烷基-、_C〇 _c3 烷基 -N(R3)-C(0)-雜環基-N(R3)-雜芳基-C〇-C6 烷基-N(R3)-C(0)- Q -C3烷基-、-C0-C3烷基-N(R3 )-C⑸-雜環基_N(r3 )_雜芳基 -C〇-Q 烧基-N(R3 KX〇)-C],C3 烧基-、-C0-C3 烧基-N(R3 )-C(0)-雜環基-N(R3)-雜芳基-C〇 -C6烷基-N(R3 VCOC】-C3烷基-、 -C0-C3 烷基-N(R3)-C(S)-雜環基-N(R3)-雜芳基-C0-C6 烷基 -N(R -C3 烧基-、-C〇 -C3 烧基-N(R3 )-C(0)-雜環基 -N(R3)-雜環基-Q _c6 烷基 _N(R3 )_c(〇)_Ci &amp; 烷基-、烷 基-N(R3)-C(S)-雜環基-N(R3)-雜環基-〇)-(：6烷基-N(R3)-C(0)-Ci -C3 烷基-、-CG -c3 烷基-N(R3 )-C(0)-雜環基-N(R3)-雜環基 'C〇-C6 烷基-NO^KXSKVq 烷基-、-C〇-C3 烷基-N(R3)-C(S)-雜環基-N(R3)-雜環基_Cg _c6烷基_N(R3 )_c⑸_Ci _C3烷基-、 -C0-C3 烧基-N(R3)-C(〇)-雜環基-N(R3)-環烷基-CG-C6 烷基 -N^KXOK^-Cs 烷基-、-Q-Cg 烷基-N(R3)-C(S)-雜環基 -N(R3)-環烷基_C6 烷基 _N(R3 )_c(〇)_Ci _C3 烷基-、_Cq _C3 烷 134026-3 -21 - 200916447 基-N(R3)-C(0)-雜環基-N(R3)_環烷基 _q_C6 烷基 _n(r3)_c(s)_ q -C3 烧基-、-CG-C3 烷基-N(R3 )-C(S)-雜環基-N(R3)-環烷基 -C0·。6 炫基-N^KXSK^-q 烷基-、-C〇-C3 烷基-S(0)2-雜環 基-N(R3)-芳基-C。-C6 烷基-N(R3 )-(:(0)-(^ -C3 烷基-、-C。-C3 烷 基-S(0)2_雜環基 _n(R3)-芳基 _c〇-C6 烷基-N(R3 KXSA -C3 烷 基-、-C0-C3烧基-s(o)2-雜環基_N(R3)_雜芳基_c〇_C6烷基 -N(R3 )-(:(0)4 -C3 烷基-、-CG -C3 烷基-S(0)2 -雜環基-N(R3 )-雜芳基-c0-c6烷基-n(r3)-c⑸-CVC3烷基-、-c0-c3烷基 -S(0)2-雜環基-N(R3)-雜環基-C0-C6 烷基-N(R3 )-C(0)-Ci -C3 烷 基-、-C〇-C3烷基-S(0)2-雜環基-N(R3)-雜環基-C〇-C6烷基 -风113)-(：(8)-(：1-(：3烷基-、-〇);烷基-5(0)2-雜環基-&gt;^3)-環烷基-CQ-C6烧基-N^KXOKVCs烧基-' -CG-C3烷基 -S(0)2 -雜環基-N(R3)-環烷基-C〇 -C6 烷基-N(R3 WS)-。】-C3 烷 基-、-C〇-C6 烷基-N(R3)-C(0)-C〇-C6 烷基-雜環烷基-C(O)-C〇 -C3烷基-、-CG -C6烷基-N(R3 )-C⑸-CQ -C6烷基-雜環烷基 -c(o)-cvc3烧基-、-C〇-C6炫基-N(R3)-C(〇KVC6烧基-雜環 烷基-C(S)-C〇 -C3 烷基-、-C。-C6 烷基-N(R3 )-C(S)-C。-C6 烷基-雜環烷基-C(S)-C〇-C3 烷基-、-C〇-C6 烷基-n(r3)-c(o)-c〇-c6 烷基-雜環烷基-C(0)-N(R3 )-〇) -C3 烷基-、-CQ -C6 烷基-N(R3 )-(:⑸-^-仏烷基-雜環烷基-c(o)-n(r3)-c〇-c3烷基-、-cvc6 烷基-n(r3)-c(o)-c〇-c6 烷基-雜環烷基-C⑸-N(R3)-CG-C3 烷 基-、-c〇-c6 烷基-N(R3)-C(S)-C〇-C6 烷基-雜環烷基-C(s)-N(R3 )-C〇 -c3 烷基-、-C〇 -C6 烷基-C(0)-C。-C6 烷基-雜環烷基 -〇：0)-风113)-(^-(：3烷基-、-(：。-(：6烷基-〇：5)-(：。-(：6烷基-雜環 134026-3 -22- 200916447 烷基-C(0)-N(R3)-Cg-C3 烷基-、-CQ-C6 烷基-C(0)-CG-C6 烷基-雜環烷基-C(S)-N(R3)-C〇-C3 烷基-、-CG-C6 烷基-c(s)-c〇-c6 烷基-雜環烷基-C(S)-N(R3)-CG-C3烷基-、-c〇-c6烷基 -o-c〇-c3 烷基-C(0)-N(R3)-C〇-C3 烷基-及-c〇-c6 烷基 -0-C(S)-N(R3)-C〇-C3烷基-，其中前文所提及L之各烷基、 烯基、炔基、雜烷基、環烷基、雜環烷基、雜環基、 芳基及雜芳基部份基團係視情況經取代；其中 各Y係獨立選自包括Η、烷基、雜烷基、環烷基、雜環基、 環烷基烷基、雜環基烷基、芳基、芳烷基、雜芳基、 雜芳烷基、芳基-雜芳基、芳基-雜芳烷基、雜芳基-烷基 芳基、芳基-芳基、芳基-芳烧基、芳基-烧基芳基、芳基 -c0-c3烷基-o-c0-c3 烷基-芳基、芳基-c0-c3 烷基-s(o)〇_2-c0-c3烷基-芳基、-C〇-C3烷基-S(O)0_2-C0-C3烷基-芳基、芳 基-C0-C3烷基-N(R3)-C〇-C3烷基-芳基、芳基-c〇-c3烷基 -C(O)-N(R3)-C0-C3 烷基-芳基、芳基-C0-C3 烷基-C⑸-N(R3)-C〇 -C3 烷基-芳基、芳基-C0 -C3 烷基-N(R3 )-C(O)-C0 -C3 烷基-芳基、芳基-C〇-C3烷基-N(R3 )-C(S)-C0-C3烷基-芳基、雜芳 基-雜芳基、雜芳基-芳基、雜芳基-芳烧基、芳基-烧基 雜芳基、雜芳基-芳基-芳基、芳基-芳基-芳基、芳基-雜 芳基-芳基、芳基-雜芳基-雜芳基、雜芳基-雜芳基-雜芳 基、雜芳基-雜芳基-芳基、芳基-芳基-雜芳基、雜芳基-芳基-芳烷基、芳基-芳基-烷基雜芳基、雜芳基-芳基-烷 基芳基、芳基-芳基-烷基芳基、芳基-芳基-芳烷基、芳 基-芳基-雜芳烷基、雜芳基-芳基-雜芳基、雜芳基-芳基- 134026-3 23· 200916447 雜芳烷基、雜芳基-芳基_烷基雜芳基、雜芳基_雜芳烷 基、雜芳基-烧基雜芳基、雜環基_雜芳基、環烷基_芳基、 環烷基-雜芳基、雜芳基-雜環基、雜芳基_環烷基、芳基 -¾烷基、雜環基-芳基、芳基_雜環基、雜環基_烷基-芳 基、雜環基-烷基雜芳基、環烷基_烷基芳基、環烷基_ 烷基雜芳基、芳基_烷基-雜環基、芳基_烷基環烷基、雜 芳基-烷基環烷基、雜芳基-烷基雜環基、芳烷基_芳基、 芳基-芳烷基、芳基-雜芳烷基、雜芳基_芳烷基、雜芳基 -雜芳烷基、雜芳基-C0-C：3烷基-O-C0-C3烷基-芳基、雜芳 基-C0-C3烷基-O-C0-C3烷基-雜芳基、芳基_c0-c3烷基 -〇-〇) -C3烷基-雜芳基、雜芳基_c〇 _c3烷基_N(R3 )_c〇 _c3烷基 -芳基、芳基-C0-C3烷基-N(R3KVC3烷基-雜芳基、雜芳基 -C〇-C：3烷基-N(R3)-C〇-C3烷基-雜芳基、雜芳基-c0-c3烷基 -C(O)-N(R3)-C0-C3 烷基-芳基、芳基-C0-C3 烷基-C(0)-N(R3)-co -c3烷基-雜芳基、雜芳基-C〇 -C3烷基-C(0)-N(R3 )-C〇 -C3烷 基-雜芳基、芳基-C〇 -C3烷基-C⑸-N(R3 )-C〇 -C3烷基-芳基、 芳基-C〇-C3烷基-C(S)-N(R3)-C〇-C3烷基-雜芳基、雜芳基 -C〇 -C3烷基-C(S)-N(R3 )-C0 -C3烷基-芳基、雜芳基-C〇 -C3烷基 -C(S)-N(R3 )-C〇 -C3 烷基-雜芳基、雜芳基-C〇 -C3 烷基-N(R3 )-C(O)-C0 -C3 烷基-芳基、雜芳基-C0 -C3 烷基-N(R3 )-C(O)-C0 -C3 烷基-雜芳基、芳基-C〇 -C3烷基-N(R3 )-C(O)-C0 -C3烷基-雜芳 基、芳基-c〇-c3烷基-N(R3)-C(S)-C0-C3烷基-芳基、芳基 -C〇-C3烷基-N(R3)-C⑸-c〇-c3烷基-雜芳基、雜芳基-c〇-c3 烷基-N(R3)-C(S)-C〇-C3烷基-芳基、雜芳基-c〇-c3烷基 134026-3 -24- 200916447 -N(R3 )-C(S)-C〇 -C3 烷基-雜芳基、R3 -雜環基 _Q _c3 烷基、R3 _ 環烷基-C0-C3 烷基、（R3)(R3a)N-C2-C4 烷基-〇-芳基-、 (R3 )(R3 a )N-C2 -C4 烷基-S(0)〇 - 2 -芳基-、（r3 欣3 a )n_C2 _C4 烷基 -〇-雜芳基-、（R3)(R3a)N-C2-C4 烷基-S(O)0_2_雜芳基-、C〇_c3 炫基-芳基-c0-C3烷基、C0-C3烷基-雜芳基_C(rC3烷基、芳 基-c! -C3烷基-雜芳基、芳基-C! -c3烷基-芳基、雜芳基 -c〗-Cs烷基-芳基、雜芳基-Ci -C3烷基-雜芳基、R3 _雜環基 -Q)-C3 烧基-N(R3 )-C(0)-N(R3)-雜芳基-、R3 _雜環基 _c〇_c3 烷 基-N(R3)-C(0)-N(R3)-芳基-、R3_ 環烷基 _c〇_C3 烷基 -^^-(:⑼-风的-雜芳基…圮-環烷基-仏^烷基-风只3)-C(0)-N(R3)-芳基-、R3 -雜環基-Q -C3 烷基-N(R3 )-C(S)-N(R3 )-雜芳基-、R3 -雜環基-C〇 -C3 烷基-N(R3 )-C(S)-N(R3)-芳基-、 R3 -環烷基-C〇 -C3 烧基-N(R3 )-C(S)-N(R3)-雜芳基-、R3 -環烷 基-C0-C3 炫基-N(R3)-C(s)-N(R3)-芳基-、雜芳基 _C(〇)-C0-C6 烷基-雜芳基-、雜芳基-C(0)-C〇-C6烷基-芳基-、芳基 -C(O)-C0 -C6烧基-芳基-、芳基-C(〇)-C0 -C6烧基-雜芳基-、 雜方基 _C(〇)-N(R3)-C〇-C6 烧基-芳基-、雜芳基 _c(〇)-N(R3)_ C0-C6烷基-雜芳基-、雜芳基_s(〇)2-C0-C6烷基-雜芳基-、 雜芳基-S(O)2-C0-C6院基-芳基-、芳基-S(〇)0_2_c0-C6烧基-方基、方基_C〇 -C3烧基-S(0)〇 _ 2 -C〇 -Cg烧基-雜芳基、 R3-O-C(O)-N(R3)-C0-C3烷基-雜芳基-、R3-〇-C(〇)-N(R3)-C0-C3 烷基-芳基-、R3-0-C(s)-N(R3)-C〇-C3烷基-雜芳基-、 R3-0-C(S)-N(R3)-C〇-C3 烧基-芳基-、R3-C(0)-雜環基 _c〇-C3 烷基-雜芳基-、R3-C(0)-雜環基-Q-Cs烷基-芳基-、r3-C(0)- 134026-3 -25- 200916447 環烷基-C0-C3烷基-雜芳基-、r3-c(o)-環烷基-c0-c3烷基_ 芳基-、R3 -雜環基-C〇 -C3 烷基-N(R3 )-C(0)-N(R3 )-C0 -c3 烷基-雜芳基-、R3 -雜環基-C〇 -C3烷基-N(R3 )-S(0)2 -C〇 -C3烷基_雜 芳基-' R3 -雜環基-C〇 -C3烷基-N(R3 )-S(0)2 -C0 -C3烷基-芳基· 、R3 -環烷基-C0 -C3 烷基-N(R3 )-S(0)2 -C〇 -C3 烷基-雜芳基 _、 R3-環烷基-C0-C3 烷基-N(R3)-S(O)2-C0-C3 烷基-芳基-、r3_ 雜環基-C0 -C3烷基-N(R3 )-C(O)-C0 -C3烷基-雜芳基-、R3 _雜 環基-Cq -C3烷基-N(R3 )-C(0)-CQ -C3烷基-芳基-、R3 -環淀基 -c〇-c3烷基-N(R3)-C(O)-C0-C3烷基-雜芳基-、R3_環炫基 -0) -C3 烧基-N(R3 )-(：(0)-〇) -C3 烧基-芳基-、R3 _雜環基 _c。_c3 烧基-N(R3 )-C⑸-C〇 -C3烧基-雜芳基-、R3 —雜環基_c〇 _c3院 基-N(R3)-C(S)-C0-C3烷基-芳基-、R3-環烷基_c〇_c3烷基 -N(R3)-C(S)-C0-C3烷基-雜芳基-、R3-環烷基_c〇_c3烷基 -N(R3 )-C(S)-C0 -C3 烧基-芳基-、R3 -C(0)-C〇 -C3 炫基-雜芳基 _ 、R3-C(O)-C0-C3烷基-芳基_、雜環基-c(0)-、芳族多環、 非芳族多環、混合之芳基與非芳基多環、多雜芳基、 非芳族多雜環及混合之芳基與非芳基多雜環，其每一 個係視情況被一或多個選自R3、R4或R7之基團取代； 或 各Y係獨立選自包括 a -芳基-C0 -C3院基-N(Rj )((0)-(^ -C7炫基-，其中d -C7烷基 係視情況被部份基團取代，該部份基團選自包括 -N(R3 )-0:(0)-(^ -C5 烧基-(C2 -C4 稀基）〇. i -c3 烧基-Ο-A2 b、 -N^KXC^N^KVC5 烷基 _(C2_C4 烯基）〇 i_Ci_C3 烷基 134026-3 -26· 200916447 -O-A2 b、-N(R3 )-C(0)-0-CVC5 烷基-(C2 -C4 烯基)〇 _ i -Ci -c3 烷基 -O-A2 b、炫基-(C2-C4 稀基）q 4-C^-Cg 烧基 -O-A2 b、-N(R3 )-S(0)2 -N(R3 -C5 烷基-(C2 -C4 烯基）〇 —丨 _Cl _C3 炫基-O-A2 b 及-N(R3 )-S(0)2 -C! -C5 烧基-(C2 -C4 烯基）〇 _ 丨 4 -C3 烷基-O-A2 b， A2 a -次雜芳基-C0 -C3 烷基-N(R3 )-(2(0)-(^ -C7 烷基-，其中 Cl _c7 烧基係視情況被部份基團取代，該部份基團選自包括 -N(R3 )-(:(0)-(^ -C5 烷基-(C2 -C4 烯基）G _ 丨-C3 烷基-〇-A2 b、 -N^KXCO-NO^KVQ 烷基-(C2-C4 烯基 烷基 -0-A2 b、-N(R3 )-(：(0)-0-(：! -C5 烧基-(c2 -C4 烯基)〇 _ i -c3 院基 -0-A2 b、-N(R3 )4 -C5 烷基-(C2 -C4 烯基)0 〗-Cl _c3 烷基 _〇_A2 b 、-N(R3 )-S(0)2 -N(R3 )-Q -C5 烧基-(C2 -C4 稀基）〇 - i _Cl _c3 烷基 -0-A2 b 及-N(R3 )-S(0)2 -Cl -C5 烷基-(C2 烯基）G _ i -C3 烷基 -0-A2b，及 BkBi-NCR3 )-(:(0)-(^-C：7烷基_，其中q-q烷基係視情況被 -NR3-B3取代，其中B3之胺係與B2之酸連接，以形成肽 鍵；且其中 八23與A2b —起為共價鍵，且係連接以形成環；及 B1、B2及B3各獨立為天然或合成胺基酸，及當任何Bl、B2 及B3係連結在一起時，其係經由肽鍵連結在一起； 各R·5與1^係獨立選自包括_H、_〇H、_c(〇)H、雜環基、Ci_C6 燒基、C2-C6 烯基、c2-C6炔基、_c2-C4烷基-〇Ra、_c(〇)_〇_ C2-C4烷基-NRaRa、雜烷基、c〇_c6烷基雜芳基、c(〇)cF3、 -C(0)-NH2 ' -C(0)-NH-C! -C6 ^ , -NH2 ' C3 -C6 if ^ ^ &gt; -C{ -C6 134026-3 -11 - 200916447 烧基芳基、雜芳基-芳基、芳基及烷基雜芳基，其中各 烧基、烯基、炔基、雜烷基、環烷基、雜環基、芳基 及雜芳基部份基團係視情況經取代； 各 R4 係獨立選自包括 _H、_C(NRa)_N(Ra)2、Ci_C6 烷基、C2_C6 烯基、C2 -C6 炔基、-c6 烷基-Ra、-C〇 -C6 烷基-〇-Ra、-c0 -C6 烷基-S(O)0_2-Ra、_C〇_C6 烷基 _c(〇)_〇Ra、_C〇_c6 烷基 _c(〇)_ N(R3)(R3a)、_C()_C6 烷基 _c⑸_N(R3)(R3a)、_CH=CH_c(〇)_〇Ra、 -CH=CH-C(0)-N(R3)(R3a)、_CH=CH-C(S)-N(R3)(R3a)、-N(R3)-C(0)-CF3、-N(R3)-C2-C6 烷基-N(R3)(R3a)、烷基 -N(R3)(R3a)、_N(R3)_c(〇)_CrC6 烷基 _r3、_n(r3)_c(s)_Ci_C6 烧基-R3、-N(R3)-S(0)2-C丨-C6 烷基-R3、_s(0)2-N(R3)R3a、 •〇-C2-C6 烷基-N(R3)(R3a)、_S(〇)〇 2_C2_C6烷基 _N(R3)(R3a)、 -S-R3、-S(〇)0_2-C2-C6 烧基-R3、a%環烧基、環烷 基-Ra、雜環基、-(να雜環基_Ra、_0_Cg_C4烷基_環烷基、 -S(〇V2-C0-C4烷基-環烷基、_0_C2_C4烷基_雜環基（當烷基 係經由雜環基中之N連結時）、_〇_C〇_C4烷基-雜環基（當 烷基係經由雜環基中之C連結時）、_s(〇)〇厂^必烷基― 雜環基（當烷基係經由雜環基中之c連結時）、_s(〇)〇 i_ Q-C：4烷基-雜環基（當烷基係經由雜環基中之n連結 時）、AOVQ-Q烧基-雜環基、烧基_雜環基 -c(o)-〇ra(當⑥基係經由雜環基中之c連結時）、_〇(乂 院基-料基-C(〇)-〇Ra(a基係經由雜環基中之n連結 日寺）、-〇-環烧基-C(〇)-〇Ra、芳基_c(〇) 0Ra、⑽芳基 C(o) OR、_s(〇)0 _】-c0 -C4貌基.雜環基_c(〇) 〇Ra (當烷基係 134026-3 •28- 200916447 經由雜環基中之c連結時）、-S(0)〇-i-c2-c4烷基-雜環基 _C(0)-〇Ra (當烷基係經由雜環基中之N連結時）、 -S(〇)2-C〇-C4 烷基-雜環基-C(0)-0Ra、-S(〇)0-2-環烷基 -C(0)-0Ra、_S(〇)〇 2_ 芳基 _C(〇)_〇Ra、_S(〇)0-2-雜芳基 •C(0)-〇Ra、_〇_C〇_C4 烷基 _芳基、_s(〇)〇-2_Cc)_C4 烷基-芳基、 -〇-C〇-C4院基-雜芳基、-S(〇)〇_2_C〇_C4烧基-雜方基、 -〇-C(〇)-N(R3)-C0-C4 烷基-芳基、-0-C(S)-N(R3)-〇&gt;-C4 烷基-芳 基、-〇-C(O)-N(R3)-C0-C4 烷基-雜芳基、-0-C ⑸-NKRVCo-C； 院基-雜芳基、-〇-C(O)-N(R3)-C0-C4 烷基-環烷基、-〇-cxs)_ N(R3)-CQ-C4 烷基-環烷基、-〇_C(〇)-N(R3)-C〇-C4 烷基-雜環 基、-〇-C(S)-N(R3 )-CG -c4 烷基-雜環基、-〇-CQ -C4 烷基-雜環 基-芳基（當烷基係經由雜環基中之c連結時）、_〇_C2_c4 燒基-雜環基-芳基（當烷基係經由雜環基中之N連結 時）、-O-C0 -C：4烧基-雜環基_雜芳基（當烧基係經由雜環基 中之C連結時）、_〇_C2_C4烷基_雜環基_雜芳基（當烷基係 經由雜環基中之N連結時）、_ac〇_C4烷基_雜環基_環烷 基（當烷基係經由雜環基中之C連結時）、_0_C2_C4烷基_ 雜環基-環烷基（當烷基係經由雜環基中之N連結時）、 '0-CVC4烷基-雜環基_雜環基（當烷基係經由雜環基中之 C連結時）、叹2(4烧基·雜環基_雜環基（當燒基係經由 雜環基中之N連結時)、_S(〇)。_ i _c。Α烧基，環基-芳基 (當烧基係經由雜環基中之c連結時）、_s(Hc丄 基-雜m基（當絲係經由雜環基中之 ^ 、s(0)2 -cQ -c4烷基♦環基_芳基、 、 v )o-i-CG-C4烷基_雜環基 134〇26- •29- 200916447 -雜芳基（當烧基係經由雜環基中之c連結時）、 c2-c4烧基-雜環基_雜芳基（當烧基係經由雜環基中= 連結時）、/S(〇)2-Co-C4烧基_雜環基·雜芳基、π 烧基雜％、基-¾烧基（當烧基係經由雜環基中之c連結 時）、Α〇κ2(4烧基_雜環基_環烧基（當院基係經由雜 環基中之Ν連結時）、鱗—㈣院基·雜環基·環燒基、 -S⑼◦.「CVQ烧基-雜環基_雜環基（當烧基係經由雜環基 中之C連、”。時）、-S(〇)〇1_C2_C4院基_雜環基_雜環基（當烧 基係經由雜環基中之N連結時）、-s(〇)2 -c。-c4烷基-雜環 基-雜環基、-n(r3k：2_C4烷基·雜環基、·N(R3)_C2_C4烷基_ 環烷基、-N(R3 )-C2 -C：4烷基-雜芳基、_N(R3 )_c2 _c4烷基-芳 基、-n(r3)-c(o)-n(r3)_C()_C4 烷基 _雜環基 _R3、_N(R3)_c⑸_ N(R3 )-Cq -C4 烧基-雜環基 _r3、_N(R3 &gt;c(〇)_n(r3 )_c。_c4 烷基 _ ί哀烧基-R3、-N(R3)-C(S)-N(R3)-C〇-C4 烷基-環烷基 _R3、 -N(R3 )-C(0)-N(R3 )-C0 -C4 烧基-芳基 _r3、_N(R3 )_c⑸_n(r3 )_-C〇-C6院基-C(O)-, -c0-c6alkyl-heteroaryl-aryl_c〇_c6_alkyl-C(O)- and -C〇-C6 alkyl-heteroaryl_heteroaryl_c〇_C6 _ alkane Base _c(〇)_ ; Or Z-W is selected from the group consisting of -C〗-C8 alkyl-(NH2)C=N-, -C〗-8 burning base-C=N- and -C!  _ 8 alkyl-C(CH3)=N- ' when the Rc system is absent;   The L system is selected from the group consisting of a covalent bond, _Cl_C6 alkyl-, _c〇_c6 alkyl-(CRkCR3 h _ 2-C〇-C6 alkyl-, _C() _c6 alkyl _(c Ξ _CQ _C6 alkyl-, -Q-Q-alkyl-aryl-C (rC6 alkyl group ... must be based on -heteroaryl-c0-c6 alkyl group -, -CQ-C3 alkyl-heterocyclyl-Cq_c3 alkyl..._Cq_C3 alkyl-cycloalkyl-c〇-c3 alkyl _, _Cg_C6alkylaryl_(cr3=cr3)i 134026-3 200916447 C〇-C6 alkyl-, -C〇-C6 alkyl-aryl-(c=c)b 2-c〇-c6 alkyl-,  -C〇 -C6 alkyl-heteroaryl-(CR3 =CR3 h - 2 -C0 -C6 alkyl-, -C0 -C6 alkyl-heteroaryl-(CEChd-Co-Q alkyl-, -C0-C6 alkyl-N(R3)-C(0)-C〇-C3 alkyl-, -CQ-C6 alkyl-n(r3)-c(s)-cq-c3 alkyl-, -C〇-C6 alkyl-N(R3)-C(0)-alkenyl-CG-C3 alkyl-, -CQ-C6 alkyl-N(R3)-C(S)-alkenyl-C〇-C3 alkyl-, -C〇 -C6 alkyl-N(R3)-C(0)-alkynyl-C. -C3 alkyl-,  -C0-C6 alkyl-N(R3)-C(S)-alkynyl-Cq-C3 alkyl-, -Q-C6 alkyl-N(R3)-(: (0)-(^-C3 alkyl-N(R3)-C(0)-, -CQ-C6 alkyl-N(R3)-C(S)-CVC3 alkyl-N(R3)-C(0)-, -C〇-C6 alkyl-N^SKXOKVCs alkyl-N(R3)-C(0)-C〇-C3 alkyl-, -C〇 -Cg Entertainment "Base-N(r3)-C(S)-Ci-C3 alkyl-N(R3)-C(0)-CG-C3 alkyl-, -CG-C6 alkyl-N^q-CXOKVCs alkyl-N(R3)-C(S)-CQ-C3 alkyl-, -C〇 -C6 alkyl-N (R3 ^(SyC!  -C3 alkyl-N(R3)-C(S)-CQ-C3 alkyl-, -CQ -C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, -Q-C6 alkyl-C(S)-N(R3)-CG-C3 alkyl-, -C〇 -C6 alkyl-C(0)-N(R3)-C2-C4 alkyl-0-C〇-C3 alkyl-, -C〇-C6 alkyl-C(5)-N(R3)-C2-C4 alkyl-0-〇)-(: 3 alkyl-, -C〇-C6 alkyl-C(0)-N(R3)-C2-C4 alkyl-N(R3)-C〇-C3 alkyl-, -CG -C6 alkyl-C(5)-N(R3)-C2 -C4 alkyl-N(R3)-C〇-C3 alkyl-, -C〇-C6 alkyl-C(0)-CG-C3 alkyl-, -C〇-C6 alkyl-C(NOH)-C0-C3 alkyl-, -CQ-C6 alkyl-C(O)-alkenyl-CQ-C3 alkyl-, -CG -C6 alkyl-C(NOH)-alkenyl-C〇-C3 alkyl-, -C〇 -C6 alkyl-S(0)2 -N(R3)-C0-C3 alkyl...-仏-仏alkyl-wind to: ^(七)^^-Heartyl...-仏-Heartyl-wind 113)-5(0)2-wind 113)-〇)-(: 3 alkyl-, -〇)-€6 alkyl-(: (0)-wind 113)-S(0)2-CQ-C3 alkyl-, -C〇-C6 alkyl-N(R3)-C〇-C3 alkyl-'-C0-C6 alkyl-N (R3-C3 alkyl-alkenyl-, -CG -C6 alkyl-N(R3)&amp;  -C3 alkyl 134026-3 -6 - 200916447 - alkynyl-, -C〇-C6 alkyl-N(R7)-C〇-C3 alkyl-, -C〇-C6 alkyl-N(R7)-alkyl-alkenyl-, -C〇-C6 alkyl-I^I^KVCs alkyl-alkynyl-,  -C0 -C6 alkyl-N(R3)-C2 -C4 alkyl-N(R3)-C(0)-alkyl-, -C. -C6 alkyl-N(R3)-C2 -C4 alkyl-N(R3)-C(S)-alkyl-, -CG -C6 alkyl-0-C2 -C4 alkyl-N(R3)C(0)-CQ-C3 alkyl-, -CG-C6 alkyl-S-C2-C4 alkyl-N(R3)-C(0)-C〇-C3 alkyl-, -C〇 -C6 alkyl-0-C2 -C4 alkyl-N(R3)C(S)-C0-C3 alkyl-, -C〇-C6 alkyl-S-C2-C4 alkyl-N(R3)C(S)-C〇-C3 alkyl-,  -C0 -C6 alkyl-N(R3)-C2 -C3 heteroalkyl-, -C〇 -C6 alkyl-N(R7)-C2 -C3 heteroalkyl-, -Q) -C6 alkyl-C(0)-N(R3)-C2 -C3 heteroalkyl·, -C〇 -C6 alkyl-C(S)-N(R3)-C2 -C3 heteroalkyl-, -CG -C6 alkyl-C(0)-N(R7)-C2 -C3 heteroalkyl-, -C〇-C6 alkyl-C(S)-N(R7)-C2-C3 heteroalkyl-, -C〇-C6 alkyl-N(R3)-C(O)-C0-C3 heteroalkyl-, -C〇 -C6 alkyl-N(R3)-C(5)-C〇-C3 heteroalkyl-, -CG -C6 alkyl-N(R7)-C(0)-CVC3 heteroalkyl-, -C〇 -C6 alkyl-N(R7)-C(S)-C. -C3 heteroalkyl-, -C〇 -C6 alkyl-S-C〇-C3 alkyl-,  -C〇 -C6 burnt base-0-C〇 -C3 burn base -, -C〇 -Cg alkyl-S(0)-C〇 -C3 alkyl-,  -c〇-c6 alkyl-s(o)2-c〇-c3 alkyl-, -c〇-c6 alkyl-n(r3)-c(o)-n(r3)-c〇-c3 alkyl-, -cG-c6 alkyl-n(r3)-c(5)-n(r3)-c〇-c3 alkyl-, -cG -c6 alkyl-o-cG -c3 alkyl-heterocyclyl-, -cG -c6 alkyl-o-c〇 -C3 alkyl-cycloalkyl-, -CG-C6 alkyl-SiCOo^-CVCs alkyl-heterocyclyl-,  -C〇-C6 alkyl-S(O)0-2_Cq-C3 alkyl-cycloalkyl-, -C〇-C6 alkyl-N(R3)-C〇-C3 alkyl-heterocyclyl-, -C〇 -C6 alkyl-N(R3)-C〇-C3 alkyl-cycloalkyl-, -heterocyclyl-CQ-C6 alkyl-0-oxime)-(: 3 alkyl-, -cycloalkyl-c0-c6 alkyl-o-c〇-c3 alkyl-, -heterocyclyl-c〇-c6 alkyl-s(o)0_2-C〇-C3 alkyl-, -cycloalkyl-C〇-Cg alkyl-S(0)〇 - 2 _C〇 -C3 alkyl _, -hetero 134026-3 200916447 cyclyl-C〇-Q alkyl-N(R3)_CG-c3 alkyl-, -cycloalkyl-CG-c6 alkyl-N(R3)-C〇-C3 alkyl group _, _c0-C6 alkyl-N(R3)-C(0)-0-C〇-C3 alkyl-,  -C〇-C6 alkyl-N(R3)-C(S)-〇-C〇-C3 alkyl-, -C〇-C6 alkyl-O-C(O)-N(R3)-Cq-C3 alkyl-, _CVC6 alkyl-o-c(5)-N(R3)-Cq-C3 alkyl-,  -C〇 -C3 alkyl-N(R3)-C(0)-0-heterocyclyl _cG _c3 alkyl-, _Cg _c3 alkyl-N(R3)-C(S)-0-heterocyclyl _c〇 -c3 alkyl-, -C〇 -C3 alkyl-N(R3)-C(0)-0-cycloalkyl-CQ-C3 alkyl-, _cG-C3 alkyl-N(R3)-C(S)-0-cycloalkyl-C0-C3 alkyl-, -C〇 -C6 alkyl-s(0)2-heterocyclyl-CG-C3 alkyl-, -C〇 -C6 alkyl-S(0)2-cycloalkyl-CG-C3 alkyl-, -CQ-C6 alkyl-n(r3)-s(o)2-heterocyclyl-Cq-C3 alkyl-, -Cq -c6 alkyl-N(R3)-S(0)2-cycloalkyl-C〇-C3 alkyl-, -〇)-C3 alkyl-heterocyclyl-Q-C3 alkyl-o-c〇-c3 alkyl-,  -C〇-C3 alkyl-cycloalkyl-0)-(3⁄4 alkyl-o-cG-c3 alkyl-, -CG-C3 alkyl-heterocyclyl-CQ-C5 alkyl-N(R3)-CG-C3 alkyl-, -c〇-c3 alkyl-cycloalkyl-Cq-C]alkyl-N(R3)-C〇-C3 alkyl-, -Cq-C]alkyl-O-CQ-C3 alkyl-heterocyclyl-CQ-C3 alkyl-, -CG-C3 alkyl-o-cG-c3 alkyl-cycloalkyl-0)-c3 alkyl-, -Co-C3 alkyl-heterocyclyl-CQ-C3 alkyl-S-C〇-C3 alkyl-, -C〇 -Cg 烧基-ί心烧基-C〇 -C3 烧基-S-C〇 -C3 烧基-, -C〇 -C3 alkyl-NO^KVCs alkyl-heterocyclyl-c〇-c3 alkyl-, -c〇-c3 alkyl-N(R)-C〇 -C3 炫基-ί哀炫 "基_C〇 -C3 烧基-, -C〇 -C3 alkyl group-S-C〇 -C3 alkyl group-hetero-based group-C〇-C3 alkyl group-, -C3 alkyl group _S-C〇 -C3 alkyl group-cycloalkyl group-0)-C3 alkyl group, -CG-C3 alkyl-S(0)2 N(R3)-CQ-C3 alkyl-heterocyclyl-C〇-C3 alkyl-, -CQ-C3 alkyl-s(o)2n(r3)-c〇-c3 alkyl-cycloalkyl-C〇-C3 alkyl-, _cG-C3 alkyl-c(o)-n(r3)-c〇-c3 alkyl-heterocyclyl-C〇-C3 alkyl-, -Q-C3 alkyl-c(o)-n(r3)-c〇-c3 alkyl-cycloalkyl 134026-3 200916447 -c〇-c3 thiol-, _Cq_c3 burning base _c(5)_N(R3)_C()_C3 burning base, Cyclo-C〇-C3 alkyl _, _cD_c3alkyl_c(5)-n(R3)_Cq_C3alkyl-cycloalkyl-C0-C3 Topography-, _c〇 -C3 alkyl-C(O)-heterocyclyl-C〇-C3 alkyl-,   Pyridyl-C(〇)-cycloalkyl-Q-C3 alkyl-, -C〇 -C3 alkyl-O-C(O)-heterocyclyl-C〇-C3 alkyl _, _〇) -C3 burnt base-0_C(0)-cycloalkyl-C〇-C3 burnt base _,  -c0 -C3 alkyl-0-C(0)_N(r3)_Cg _c3 alkyl-heterocyclyl _Cq _c3 alkyl _,  -c0 -C3 alkyl _0_C(0)_N(r3 )_Cq _c3 alkyl-cycloalkyl _Cq _c3 alkyl _,  -c0 -c3 alkyl _ac(5)_n(r3)_Cg _c3 alkyl-heterocyclyl _C() _c3 alkyl _,  -C〇-C3 alkyl-o-c(5)-N(R3)-Q-C3 alkyl-cycloalkyl-CG-c3 alkyl-,  -C〇 -C3 alkyl-N(R3)-C(0)-N(R3)-C. -C3 alkyl-heterocyclyl-Co-c3 alkyl group _, -Co -C3 alkyl-N(R3)-C(0)-N(R3)-〇) -C3 alkyl-ring group _C. _c3 burning base -, -c〇-c3 alkyl-n(r3)-c(5)-n(r3kvc3 alkyl-heterocyclyl _C()_C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-N (R3KVC3 alkyl-cycloalkyl-c0-C3 alkyl, -c. -C3 alkyl-N(R3)-C(0)-heterocyclyl-c0-C3 alkyl _,  -Co-Q 院基-N(R3)-C(0)-ring courtyard-Cq-C3 alkyl-, -cvc3 group -N(R3)-C(S)-heterocyclyl-C〇-C3 alkyl-, -C0-C3 alkyl-N(R3)-C(S)-cycloalkyl-C〇-C3 -C〇 -C3 alkyl-N(R3)-S(0)2 -N(R3)-C. -C3 烧基-杂 哀 基 基-C. -C3 burning base -, -C〇-C3 alkyl-N(R3)-S(0)2 -N(R3)-C. -C3 alkyl group - 哀 炫 - - C 〇 - C3 院 - ' -C〇 -C6 alkyl-heterocyclyl-C(0)-C. -C6 burning base -, -C〇-Cg alkyl-cycloalkyl-C(0)-C〇-Cg alkyl-'-C〇-C6 alkyl-n(r3)-c(o)-heterocyclyl-C(〇 KVC6 burning base -, -Q)-C6 炫-N(R3)_ C(O)-cycloalkyl-C(0)-C〇-C6 alkyl-, -C〇 -C6 alkyl-N(R3)-C(S)-heterocyclic-C(0)-C〇-C6 alkyl-, -C〇 -C6 alkyl-N(R3)-C(S)-cycloalkyl-C(0)-C〇-C6 -C〇 -C6 leuko-heterocyclyl-S(0)2 -C〇 -C6 alkyl group _,   134026-3 200916447 -C〇 -C6烧基-ί哀院基-S(0)2 -C〇 (6-base -, -C〇 -C6-homo-heterocyclyl-n(r3)-c(o)-c〇-c6 alkyl-, -c〇-c6 alkyl-cycloalkyl-n(r3)-c(o)-c0-c6 alkyl-, -CQ-C6 alkyl-heterocyclyl-0-C(0)-CG-C6 alkyl-,  _C〇 -C6 alkyl-cycloalkyl--0-C(0)-CQ-C6 炫-, -C〇-C6 alkyl-heterocyclic group-N(R3)-C(5)-C〇-C6 alkyl-, -Co-Q alkyl-cycloalkyl-N(R3)-C(S)-c〇-C6 alkyl-, -C〇 -C6 alkyl-heterocyclyl-indole-C(S)-C〇-c6 alkyl-, -c〇 -c6 alkyl-cycloalkyl-0-C(S)-C〇-C6 alkyl-, -C〇 -C3 alkyl-CH=N-O-C0-C3 alkyl-, -C. -C3 alkyl-C=N(0H)C(0)-N(R3)-C2 -C4-alkyl-S-S-alkyl-, -C〇 -C6 alkyl-heteroalkyl-C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-,  -C〇-C6 alkyl-heteroalkyl-C〇-C6 alkyl-C(5)-N(R3)-C〇-C3 alkyl-,  -Q-Q alkyl-aryl-heteroaryl-C〇-C6 alkyl-, -C0-C6 alkyl-heteroaryl-aryl-C0-C6 alkyl-, -C〇-C6 alkyl-heteroaryl-heteroaryl_c0-C6 alkyl-,  -c0 -C6 alkyl-aryl-aryl-CQ-C6 alkyl-, -Ci -C3 alkyl-N(R3)-C(0)-Q-c? alkyl-, 4-(3⁄4 alkyl-n(r3)-c(5)-q-c? alkyl-, -cG-c3 alkyl-alkenyl-C(0)-C〇-C6 alkyl-, -C〇-C6 ^s-n(r3)-c(o)-n(r3)- CXCO-q -C3 alkyl-, -C〇 -C3 alkyl-s-aryl-c0 -C6 alkyl-N(R3)C(0)-Ci-Q alkyl-, -c0-c3 alkyl-o-aryl _C〇_C6 alkyl _n(R3)c(s)_ q -C3 alkyl-, -Cq -C3 alkyl-S-aryl-C〇-c6 alkyl-N (R3 plant (5)-heart-C3 alkyl-, -C〇 -C3 alkyl-O-heteroaryl-c0 -c6 alkyl-N(R3)((0)4 -C3 alkyl-, -C0 -C3 alkyl-S-heteroaryl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C〇 -C3 alkyl-0-heteroaryl _c〇 -c6 alkyl-N (R3 VCXSVCj -C3 院基-, -C0 -C3 alkyl-S-heteroaryl-c0-C6 alkyl-N(R3)-C(5)-C--C3 炫-, -C〇-C3 alkyl-O-heterocyclyl-c〇-C6 alkyl-N^KXOHVq 134026-3 •10- 200916447 alkyl-, -CQ -C3 alkyl-S-heterocyclyl _c. _c6 alkyl group _N(R3)_c(〇)_Ci _c3 alkyl-, -CG -C3 alkyl-O-heterocyclic group _Cg _c6 alkyl group _N(R3)_c(5)_Ci _c3 alkyl-, -C. -C3 alkyl-S-heterocyclyl _cQ _c6 alkyl _N(R3 )_QS)_Ci _c3 alkyl-, -C. -C3 alkyl-O-cycloalkyl-C. _c6 burning base collar R3)_C(0)_C "C3 alkyl-, -C. -C3 炫-S-cycloalkyl _cQ -c6 alkyl-N(R3)-(: (0);  -C3 alkyl-, -c. -C3 alkyl-O-ring alkyl _c. -C6 alkyl-N (R3 hCXSKi -C3 alkyl-, -CG-C3 alkyl-S-cycloalkyl _Q-C6 alkyl alkyl-, -C0 -C3 alkyl-N(R3)-aryl _c〇 -C6 alkyl-N(R3)-(: (0)4 -C3 alkyl-, -C〇 -C3 alkyl-N(R3)-aryl _c0 -C6 alkyl-N(R3)-C(5)-C3 alkyl-, -C〇-C3 alkyl-N(R3)-heteroaryl-C〇-C6 alkyl-N(R3)-C(0)-Q-C3 alkyl-, -C〇 -C3 alkyl-N(R3)-heteroaryl-C0-C6 alkyl-N(R3)-alkyl-, -C〇-C3 alkyl-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)-0(0)-(^-C3 院基-, -C〇 -C3 alkyl-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3 yCOCi -C3 alkyl-, -C〇 -C3 alkyl-N(R3)-cycloalkyl-C〇-C6 alkyl-N^KXOKVCs alkyl·, -C〇-C3 alkyl-N(R3)-cycloalkyl-C〇-C6 alkyl-N (R3-C3 alkyl-, -C〇 -C3 alkyl-N(R3)-C(0)-〇-aryl-C〇-C6 alkyl-N^KXCO-q-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-0-aryl-C〇-C6 alkyl-N(R3)-(11(0)-(11]-Cg alkyl-,  -C0 -C3 alkyl-N(R3)-C(0)-S-aryl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C〇 -C3 alkyl-N(R3)-C(0)-0-aryl-C〇-C6 alkyl-N(R3)-COCi-C]alkyl-, -C0-C3 院-N(R3)-C(S)-0-aryl-C0-C6 alkyl-NCI^KXSKVq alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-S-aryl-C〇-C6 alkyl-N^i-CXSKVCs alkyl·, -CG-C3 alkyl-N(R3)-C(0)-0-heteroaryl-c0-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C〇 -C3 alkyl 134026-3 200916447 -N(R3)-C(S)-0-heteroaryl _c〇 _C6 alkyl-N(R3)_c(〇)_Ci % alkyl _,  -Co-Q alkyl-N(R3)-C(0)-S-heteroaryl-C〇-C6 alkyl-N(R3)-C(0)_ C!  -C3 alkyl-, _C〇 _C3 alkyl _N(R3 )_c(〇)_aheteroaryl _c〇 C6 alkyl-n(r3)-c(5)-Cl-C3 alkyl-, -C〇-C3 alkyl-N(R3)_c(5)_〇_heteroaryl-C〇-C6 alkyl-NO^CXSK^-Cs alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-oxime-heterocyclyl-CVQ alkyl-NO^KXOHVCs from base-, _C〇_C3 alkyl-N(R3)-C(S)-0-heterocyclyl _c6 alkyl _N(R3)_c(〇)_Ci _c3 alkyl _,   -C0 -C3 alkyl-N(R3)-C(0)-fluorene-heterocyclyl-C〇-c6 alkyl-N(R3)-C(S)-Cii-c3 alkyl-, -cG -c3 alkyl group _N(R3 yQsya heterocyclic group _c〇 _c6 alkyl group -N^KXSK^ -C3 炫基-, -C〇-C3 alkyl-N(R3)-C(0)-0-cycloalkyl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 炫基-, -C. -c3 alkyl-N(R3)-C(S)-0-cycloalkyl-CQ-c6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C{) -c3 alkyl-N(R3)-C(0)-0-cycloalkyl-CG-C6 alkyl-N(R3-C3 alkyl-,   -C0 -C: 3 alkyl-N(R3)-C(S)-0-cycloalkyl-C. -C6 alkyl-N(R3)-C(S)-Q-C3 alkyl-, -C0 -C3 alkyl-C(0)-N(R3)-aryl-C〇-c6 alkyl _N(R3)_ QCO-q -C3 alkyl-, -C〇 -C3 alkyl-C(S)-N(R3)-aryl-C〇 _c6 alkyl-N(R3-C3 alkyl-, -C〇 -C3 alkyl-C(0)-N(R3)-aryl-C〇-C6 alkyl-N^KXSKVQ alkyl-, -C〇-C3 alkyl-C(5)-N(R3)-aryl _0)-(! ! 6烧基-]^(113)-(^(8)-(1; 1-(113 yard base -, -(^-(1! 3 Xuanji - (1! (0)-1^(foot 3)-heteroaryl-C0-C6 alkylalkyl-, -C〇-C3 alkyl-C(S)-N(R3)-heteroaryl-C〇-C6 alkyl-N^XXOK^-Q alkyl-,  -C〇-C3 burning base-(1! (0)-Wind 113)-Hole ^•基-C〇-C6 Institute-N(R3)C(S)-Ci_C3 Alkyl-, -C〇 -C3 alkyl-C(5)-N(R3)-heteroaryl-C〇-C6 alkyl-N(R3)C(S)-hospital-, -C0-C3 alkyl-C(0)-N(R3)-heterocyclyl-C〇-C6 alkyl 134026-3 -12- 200916447 -NKRSKXOKVCg alkyl-, -C〇-C3 alkyl-C(S)-N(R3)-heterocyclyl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C. -C3 alkyl-C(0)-N(R3)-heterocyclyl-CG-C6 alkylalkyl-, -CG-C3 alkyl-C(S)-N(R3)-heterocyclyl-C〇-C6 alkyl-N^y-CXSK^-C^ alkyl-,  -C〇 -C3 alkyl-C(0)-N(R3)-cycloalkyl·〇) -C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -CG-C3 alkyl-C(S)-N(R3)-cycloalkyl-C〇-C6 alkyl-N(R3)-CXOKVq alkyl-, -Q-Q alkyl-C(0)-N(R3)-cycloalkyl-〇)-(: 6 alkyl-NXRq-CXSK^-C3 alkyl-, -C〇-C3 alkyl-C(5)-N(R3)-cycloalkyl-C〇-C6 alkyl-NO^-QSKVCs alkyl-, -CG-C3 alkyl-O-C(O)-N(R3)-aryl-C〇-C6 alkyl-N(R3)-(: (0)4 -C3 burning base -, -C0 -C3 alkyl-O-C(5)-N(R3)-aryl-C〇-C6 alkyl-NO^KXOKVCs alkyl-,  -C0-C3 alkyl-0-C(0)-N(R3)-aryl-C0-C6 alkyl-NO^KXSHVCs alkyl-, -C〇-C3 alkyl-0-C(S)-N(R3)-aryl-C〇-C6 alkyl-N(R3)-QSVQ-C3 alkyl-, -C〇-C3 alkyl-0-C(0)-N(R3)-heteroaryl _C〇_c6 alkyl-N(R3)-C(0)-Ci-C3 alkyl-, -C〇 -C3 alkyl--0-C(S)-N(R3)-heteroaryl-C〇-C6 alkyl-N(R3)-(: (0)-(^-03 burning base -, -C〇-C3 alkyl -0-C(0)-N(R3)-heteroaryl-C0-C6 alkyl-N (R3 alkyl-,   -C〇-C3 alkyl-〇-C(S)-N(R3)-heteroaryl-C0-C6 alkyl-N(R3)-C(5)-CVQ alkyl-, -CG-C3 alkyl-0-C(0)-N(R3)-heterocyclyl-C()_C6 alkyl-N(R3)-(: (0)-(^-C3 alkyl-, -C〇-C3 alkyl-0-C(S)-N(R3)-heterocyclyl-C〇-C6 alkyl-N^q-CXCO-CVCs alkyl-, -CQ-C3 alkyl _〇·(: (〇)_N(R3)-heterocyclyl-C〇_C6 alkyl_N(r3)_C(5)_Cl_C3 alkyl-, -c. ^院基-〇-C(S)-N(R3)-Heterocyclyl-C. -C6 alkyl-N (R3 - C3 alkyl _,   -C〇-C3 alkyl-〇-C(0)-N(R3)-cycloalkyl-CVC6 alkyl-N(R3)_(〇)_ 134026-3 -13- 200916447 C!  -C3 alkyl-, -CG-C3 alkyl-O-C(3)-N(R3)-cycloalkyl-CQ-C6 alkyl-N(R3)-(: (0)-(^-C3 alkyl-, -C〇-C3 alkyl-0-C(0)-N(R3)-cycloalkyl-C0-C6 alkyl-NCI^KXSKVQ alkyl-, -C〇-C3 alkyl-O-C(S)-N(R3)-cycloalkyl-C〇-C6 alkyl-NKI^KXSKVCs alkyl-, -C〇-C3 alkyl-S(0)2-N(R3)-aryl-C〇-C6 alkyl-NCRq-CCOKVQ alkyl-,  -C〇 -C3 alkyl-S(0)2 -N(R3)-aryl-C〇-C6 alkyl-N (R3 VCXSyQ -C3 alkyl-, -C〇 -C3 alkyl-S(0)2-N(R3)-heteroaryl-C0-C6 alkyl-N(R3)-C(0)-q-C3 alkyl-, -C〇-C3 alkyl-s(o)2-n(r3)-heteroaryl-C〇-C6 alkyl-NCI^KXSKVCs alkyl-, -C〇-C3 alkyl-S(0)2-N(R3)-heterocyclyl-C0-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C〇 -C3 alkyl-S(0)2-N(R3)-heterocyclyl-Q)-C6alkyl-N(R3)-C(5)-q-Csalkyl-, -C〇-C3 alkyl-S(0)2-N(R3)-cycloalkyl-CQ-C6 alkyl^Rq-CXOKVCs alkyl-,  -C〇 -C3 alkyl-S(0)2-N(R3)-cycloalkyl-C〇-C6 alkyl-N (R3 KXSKi-c3 alkyl-, -C0-C3 alkyl-n(r3)-s(o)2-n(r3)-aryl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C0 -C3 alkyl-N(R3)-S(0)2 -N(R3)-aryl-C〇-C6 alkyl-N(R3-C3 alkyl-, -C〇 -C3 alkyl-N(R3)-S(0)2 ~ N(R3)-heteroaryl-C0-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C0 -C3 alkyl-N(R3)-S(0)2 -N(R3)-heteroaryl-C〇-C6 alkyl-N(R3-C3 alkyl-, -〇)-(: 3 alkyl-&gt; ^3)-5(0)2 summoned 3)-heterocyclyl-〇)-(: 6 alkyl-N(R3)-C(0)-Ci-C3 alkyl-, -C〇 -C3 alkyl-N(R3)-S(0)2-N(R3)-heterocyclic-C〇-C6 alkyl-N^)-C(5)-Ci-C3 -C〇-C3 alkyl-N(R3)_S(0)2-N(R3)-cycloalkyl-C〇-C6 alkylalkyl-,  (^-(^alkyl call: ^(9): Called-cycloalkyl heart-alkyl-called Han 3),  CXS)-^ -C3 yard base -, -C〇-C3 alkyl-heterocyclyl-fluorene-aryl-C〇-C6 alkyl 134026-3 -14· 200916447 -N(R3 )((0)-(^ -C3 alkyl-, -C〇 -C3 alkyl-heterocyclyl aryl-C0-C6 alkyl-N (R3-C; 3 burning base -, -C0 -Q3 alkyl-heterocyclyl-〇-aryl-C0-C6 alkyl-N (R3 yCOC!  -C3 burning base -, -C〇 -C3 alkyl-heterocyclyl each aryl-C〇-Q alkyl-N (R3 -C: 3 alkyl-, -C〇 _c3 alkyl_heterocyclyl-indole-heteroaryl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl _, _C〇 _C3 alkyl-heterocyclyl-S-heteroaryl-Co-Qalkyl-N(R3)-(: (0)-(^-C3 alkyl_,  -C0-C3 alkyl-heterocyclyl-fluorene-heteroaryl _c〇-C6 alkyl-N (R3-C3 alkyl-, -C0-C3 alkyl-heterocyclyl-S-heteroaryl-C0-C6 yard base_n(R3)_ cxsyc!  -C3 alkyl _, -Q -c: 3-alkyl-heterocyclyl-fluorene-heterocyclyl_Cq _C6 alkyl-N^KXCO-C^-C3 alkyl-, -CG-C3 alkyl-heterocyclyl heterocyclyl-C〇-C6 alkyl-N(R3)-(: (0)-(: !  -C3 烧基·, -Co -C3 alkyl-heterocyclic group _〇_heterocyclyl-CQ-C6 alkyl-N (R3-C3 alkyl-, -c3 alkyl-heterocyclyl-s-heterocyclyl-Cq-C6 yard base _N(R3&gt; QS)_Ci_C3 yard base -, _c〇_C3 院-Heterocyclyl-0-cycloalkyl-CQ-Q-alkyl-N (R3 ycxco-q-C3 alkyl _, -Q) -c3 alkyl-heterocyclyl _s_cycloalkyl _Cq _C6 alkyl _n(r3 )_c(〇)_Ci &  alkyl-, -CG-C3 alkyl-heterocyclyl-fluorenyl-cycloalkyl-C()-C6 alkyl_N(R3)_ CXSK^ -C: 3 alkyl, -CG -C: 3-alkyl-heterocyclyl-S-cycloalkyl-CG-c6 alkyl-N(R3)'C(5)-Cl-c3 alkyl-, -C〇-C3 alkyl-C(0)-heterocyclyl _〇_aryl _C〇 C6 alkyl-N (R3 -C3 alkyl-, -C〇 -C3 Institute-C(S)-Heterocyclyl-O-aryl-C〇-C6 alkyl-NO^KXOK^-Cs alkyl-, -C0-C3 alkyl-C(0)-heterocyclic group _s-aryl-c0-c6 alkyl-N(R3)-0(0)-(^-C3 from base-,  -C〇-C3 alkyl-C(〇)-heterocyclic group _〇_ aryl _C〇_C6 alkyl _n(r3)_c(s)_ C!  -C3 yard base -, -C〇 _Csalkyl-c(5)_heterocyclylylaryl_c〇 %alkyl _n(r3)-c(〇)-ci-c3 alkyl-, -C〇-C3 alkyl-C(S)-heterocyclyl-fluorene-aryl 134026-3 -15- 200916447 -C〇 -c6 alkyl _N(R3 )_C(5)_Cl _c3 alkyl-, -Q _C3 alkyl _C(〇)·heterocyclic-S-aryl-c0 -C6 alkyl-N (R3 ycoq -C3 alkyl-, -c0 -C3 alkyl-C(S)-heterocyclyl_s_aryl_c〇_C6 alkylalkyl-,   -c〇-C3 alkyl-C(O)-heterocyclyl-fluorene-heteroaryl-C0-C6 alkyl-N(R3)-C(〇)-q %alkyl group_, _C〇 -c: 3 alkyl_which)_heterocyclyl_〇_heteroaryl_c〇 %alkyl-N(R3)_C(0)_Ci _c3 alkyl _, _c〇 _c3 alkyl _c(〇)heterocyclyl _s heteroaryl-C〇-C6 alkyl _N(R3)_C(〇)_Ci_C3 alkyl-, _Q_C3 alkyl group _c(〇)_heterocyclic group -O-heteroaryl-C0-C6 alkyl-N(R3)-C(3)-q-C3 alkyl-, -C〇 _c3 alkyl-C(s)-heterocyclyl-s-heteroaryl_C〇-c6alkyl-N(R3)_c(〇)_Ci _c3 alkyl _ , -C0 -c3alkyl-c(5)-heterocyclyl-αheteroaryl_c〇 _c6alkyl_n(r3 )_c(s)_ q -c: 3 alkyl·, -c〇 alkyl_c(0)_heterocyclyl_sheteroaryl_c〇 qalkyl-n(r3)_c(5)-Ci-Aalkyl-, _c〇 alkyl-c(s)_heterocyclyl_s_heteroaryl-Co-c6 alkyl _N(R3 &gt; c(3)_Ci _C3 alkyl _, _c. _C3 alkyl _c(〇)_heterocyclic-O-heterocyclic-C〇-Q alkyl-N(R3)-C(0)_Cl _(: 3 alkyl _, _Cq _c3 alkyl-C(S)-heterocyclyl-oxime.heterocyclyl_c〇 _c6alkyl_n(r3)_c(〇)_Ci alkyl_, -c〇 -c3alkyl-C(0)-heterocyclyl_s_heterocyclyl-c〇 _c6alkyl-n(r3)_c(9)-q-C3alkyl-, _cG alkyl_c(〇)_heterocyclyl_〇·heterocyclyl_c『c6 alkyl _N(R3 WSKVC^ n from base C(s)•heterocyclylheterocyclyl-Q-c: 6 burning base - N (R3K: (0)_Ci_C3 炫基...Cg_C3 alkyl group-c(s)_heterocyclic group-0-heterocyclic group-C〇-C6 fluorene group 3)_c(5)_Ci must be burned _, Bitane-c(0).heterocyclyl_s_heterocyclyl_Q (6-carina) 3 'c(5)_c becomes _, -Co-c3 alkyl-C(S)_heterocyclyl_s_heterocyclyl-c. A base - chat) ((5) · Q-c3 alkyl-, -C〇{基基_c(0)_heterocyclyl_αcycloalkyl _c〇夂alkyl N(R ) QCO-q -C3 fluorenyl...C{rc3morphyl_c(8)heterocyclyl·〇 Cycloalkyl 134026-3 -16- 200916447 —C0-C6 alkyl-N^yCCOKVq alkyl-, -cQ-c3 alkyl-C(O)-heterocyclic-S-cycloalkyl-CG-Q alkyl-N(R3)-0(0)-(^-C3 alkyl _, -〇3 -C3 alkyl-C(O)-heterocyclyl-〇-cycloalkyl-cQ _c6 alkyl_N(R3)_c(s)_Ci _c3 alkyl_, -C. -C3 alkyl-c(5)-heterocyclyl_s_cycloalkyl-c. _c6 alkyl_N(R3)_c(0)_ ci C3 base _, _〇) -C: 3-alkyl-C(S)-heterocyclic-indole-ring group _cQ-C6-based _N(R3-C3 alkyl-, -C〇-C3 alkyl-C(O)-heterocyclyl-S-cycloalkyl-c0-C6 alkyl-N(R3)_C(5)_Ci_C3 alkyl-, _c〇_c3 alkyl_c(5)heterocyclyl-S-cycloalkyl-CQ-Q-alkyl-N (R3-C3 alkyl-, -C(rc3alkyl-N(R3)-C(〇)_heterocyclyl _〇_ aryl _c〇_C6 alkyl _n(r3)_c(〇)_Ci_C3 alkyl-, -C0-C3 alkyl-N(R3)-C(S)-heterocyclyl-fluorenyl-aryl-C〇_C6 alkyl _N(R3)-c(〇)-ci-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-heterocyclyl-s-aryl-Co-C6 alkyl-N(R3)((0)4-C3 alkyl-, -C〇 _c3 alkyl group N(Rs)_ c(0)-heterocyclic group-0-aryl _c〇_c6 alkyl _n(r3)_qs)_Ci_C3 alkyl _,  -c0-C3 alkyl-n(r3)-c(5)-heterocyclyl _s_aryl _c〇_c6 alkyl _N(R3)_ CCCO-q -C3 alkyl-, -C〇_c3alkyl-N(R3)_c(5)_heterocyclyl-nonylaryl-C〇-C6 alkylalkyl-, -CG-C3 alkyl-n(r3)-c(o)-heterocyclyl-S-aryl-c0-c6alkyl-N(R3)-C(5)-C!  -C3 alkyl-, -Q _c3 alkyl-N(R3)-C(S)-heterocyclyl-S-aryl-c0-C6 alkyl-N(R3)-C(5)-Ci-C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-heterocyclyl-indole-heteroaryl_c〇_C6 alkyl-N(R)-(3(0)-(^ -C3 Hyun--, -C〇-C3 Institute-N(R3)-C(S)-Heterocyclyl Heteroaryl-C〇 Institute-N(R3)-(: (0)-(^ -C3 burning base -, -c0 -c3 alkyl group -N(R3)-C(0)-heterocyclyl-s-heteroaryl-C〇-C6 炫基-N^KXOKVC^ 烧基-, -c0-C3 group -n(r3)-c(o)-heterocyclyl-o-heteroaryl_c〇_C6 院-N(R)-C(5)-C; 3 burning base -, -C〇 -C3 alkyl-N(R3)-C(S)-heterocyclic group 134026-3 -17· 200916447 Heteroaryl-C0-C6 alkyl-N(R3 ΗΧΟ)-. -C3 burning base -, _c0 -C3 alkyl -n(r3)-c(s)-heterocyclyl _oxaheteroaryl _c〇_c6 alkyl _N(R3)_C(5)_Ci_C3 alkyl-, -CVC3 alkyl-N(R3)-C(0) gastric heterocyclic _s_heteroaryl_c〇 alkyl-NCRi-CXSK^-c3 alkyl-, -Cq-C3 alkyl-N(R3)-C(S)-heterocyclyl-S_heteroaryl-c0-c6alkyl-N^KXSKVC^alkyl-, -C〇_C3 alkyl-N^KXO)-heterocyclic group _〇_heterocyclyl group q_C6 alkyl _n(r3)_c(〇)_Ci C3 alkyl group-, -CQ-C3 alkyl-N(R3)-C(S)-heterocyclyl-indole_heterocyclyl_Cq_c6 alkyl-N(R3-C3 alkyl-, -C〇 -C3 院-N(R3)-C(0)-heterocyclyl _s_heterocyclyl-Q-qalkyl_n(R3)_c(0)_Ci_C3 alkyl-, _C『C3 alkyl-N(R3)-C(0)-heterocyclyl-〇·heterocyclyl_c〇_C6 alkyl_Mo 3)7(5)&amp;  Burning base -, -CQ -C3 alkyl-N(R3)-C(S)-heterocyclyl_S-heterocyclyl_cG-C6 alkyl-N (R3 alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-heterocyclyl _〇_heterocyclyl-(VC6 alkyl-N(R3)-C(S)-Cl-C3 alkyl-, _Cq_C3 alkyl-n(r3)-c(o)_heterocyclyl heterocyclyl _c〇_C6 alkyl _N(R3)_C(8) alkyl-, -C〇 -C: 3-alkyl-N(R3)-C(S)-heterocyclylheterocyclyl-c6 alkyl-N^q-CXSK^-C^ alkyl-, -C〇-C3 alkyl-N(R3)-C(〇)-heterocyclyl _〇_cycloalkyl-CQ-C6 alkyl-N(R3)-(: (0)-(: ! -C3 alkyl _, _C(rC3 alkyl-n(r3)-c(s)-heterocyclyl-indole-cycloalkyl _C(rC6 alkyl _n(r3k: (〇)_Ci_C3 alkyl-, -CG -C: 3-alkyl-N(R3)-C(0)-heterocyclylcycloalkyl-Cq alkyl-N(R3)-C(0)-C]-C3 alkyl-, -C〇 -C3 alkyl-N(R3)_C(0)_heterocyclyl _〇_cycloalkyl-cvc: 6 alkyl-n(r3)-c(5)-cvc: 3 alkyl-, -C(rc3 alkyl-n(r3)-c(s)-heterocyclyl-s_cycloalkyl _C()_C6 alkyl _n(R3)_c(〇)_Ci_C3 alkyl-, -Q) -C: 3-alkyl-N(R3)-C(S)-heterocyclyl-indole-cycloalkyl-c〇 _c6 alkyl-N^KXSKVC^ alkyl-, -C〇-C3 alkyl-N(R3)_c(〇)_heterocyclyl _s_ 134026-3 -18- 200916447 cycloalkyl-CG-C6 alkyl-Nd^-QSKVCs alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-heterocyclic group _s-cycloalkyl-CQ-C6 alkyl-N (R3-C3 alkyl-, -C〇-C3 alkyl _s(0)2-heterocyclyl-O-aryl-C0-C6 alkyl-N(R3)-¢: (0)-(^ -C3 alkyl-, _C〇 _C3 alkyl _s(〇)2 _heterocyclyl _s_ aryl _c〇 _C6 alkyl-N(R3)-(: (0)-(^ -C3 炫基-, -C〇 -C3 alkyl-S(0)2-heterocyclyl-oxime-aryl-C〇-C6 alkyl-N(R3)-C(5)-C3 alkyl-, -C〇 -C3 alkyl-S(0)2-heterocyclyl-S-aryl _C(rc6 alkyl_N(R3)_c(5)_Cl _c3 alkyl-, _c〇 _c3 alkyl-S(O)2-heterocyclyl-indole_heteroaryl_c0-C6 alkyl-N^KXCO-Ci-Cs alkyl-, -c0-c3alkyl-s(0)2-heterocyclyl-s-heteroaryl-c0-c6alkyl-n(r3)-C(〇)-Ci-C3 alkyl-, -c0 -c3 alkyl-s(o)2-heterocyclyl-indole-heteroaryl-C〇-C6 alkyl-NCRq-QSKVCs alkyl-, -C〇-C3 alkyl-S(0)2-heterocyclo-S-heteroaryl-c0-c6 alkyl-N^KXSKi-C3 alkyl-, -C〇-C3 alkyl-s(0)2-heterocyclyl-0-heterocyclyl _Cq-C6 alkyl-N(R3)-(: (0)-(: !  -C3 炫基-, -CVC3 alkyl-s(0)2-heterocyclyl-S-heterocyclyl-c〇-c6 alkyl-N(R3)-C(〇HVC3 alkyl-, -C〇-C3 alkyl-s(o)2-heterocyclyl-fluorene-heterocyclic group-c〇-c6 alkyl-n(r3)-c(5)-CVC3 alkyl-, -C0-C3 alkyl-S(0)2-heterocyclo-S-heterocyclyl-CVC6 alkyl-N (R3 hCXShCi -C3 alkyl-, -C〇-C3 alkyl-s(0)2-heterocyclyl-0-cycloalkyl _cQ-C6 alkyl-N(R3)-(: (0)-(^ -C3 yard base -, -C〇-C3 alkyl-s(0)2-heterocyclyl-s-cycloalkyl-Co-Q alkyl •N(R3 &gt; C(0)-C1 -C3 alkyl-, -C〇 -C3 alkyl-S(0)2-heterocyclyl-fluorenyl-cycloalkyl-CQ-C6 alkyl-Nd^KXSKVCs alkyl-, -CQ-C3 alkyl-S(0)2-heterocyclo-S-cycloalkyl _CG-c6 alkyl-N (R3 VCXSVCi -C3 alkyl-, -C〇 -C3 alkyl-heterocyclyl-N(R3)-aryl-c0-C6 alkyl-N(R3)-(: (0)-(^-C3 alkyl-, -c〇-c3 alkyl-heterocyclyl _n(r3)-aryl-c〇-c6 alkyl-N(R3)-C(s)- 134026-3 -19- 200916447 q-c: 3 alkyl-, -cvc: 3-alkyl-heterocyclyl-N(R3)_heteroaryl_c〇_C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C0-C3 alkyl-heterocyclic group _N(R3)_heteroaryl-fluorene)% alkyl-N^KXS)^ A-alkyl-, -Cq_C3 alkyl _heterocyclyl-N(R3)-heterocyclyl-C(rC6 alkyl-n(r3)_c(〇)_Ci 七3 alkyl _, _Cq _C3 alkyl-heterocyclyl-N(R3)-heterocyclyl-Q-C6 alkyl-N(R3)-c(5)-C3 alkyl-, -C〇 -C3 alkyl-heterocyclyl _n(R3)-cycloalkyl _cG _c6 alkyl-N(R3)-C(0)_ C!  -C3 alkyl-, -Aalkyl-heterocyclyl_N(R3)_cycloalkyl% &amp; Alkyl-N (R3 XO-Ci-C3 alkyl-, -C0-C3 alkyl-C(oxime)-heterocyclic group _n(R3)-aryl-C〇-C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -Cq -C3 alkyl-C(S)-heterocyclo-N(R3)-aryl _C〇 _c6 alkyl _n(r3 )_c(〇)_Ci _C3 alkyl _, _c〇 % alkyl-c(o)-heterocyclyl_N(R3)_aryl_c〇_C6 alkyl_n(r3) c(5)_Ci &amp;   Burning base -, -Q-C: 3-alkyl-C(S)-heterocyclyl-N(R3)-aryl_C〇_C6 alkyl N(R ycO-Ci -C3 alkyl-, -CG-C3 alkyl-C(0)-heterocyclyl-N(R3)-heteroaryl-C〇-C6 alkyl-N (R3-C3 alkyl-, -C0 -C3 alkyl-C(S)-heterocyclyl-N(R3)-heteroaryl _C〇 _c6 alkyl _N(R3)_c(〇)_Ci _C3 alkyl-,  -c〇-c3 alkyl-c(o)-heterocyclic group _n(R3)_heteroaryl _c〇_C6 alkyl group _n(r3)_ QSK: !  -C3 alkyl-' _c〇_c3 alkyl_c(5)_heterocyclyl_n(r3)_heteroaryl-C〇-C6 alkyl·NKR'CO-Ci-Cs alkyl-, -C〇-C3 alkyl-c(〇)-heterocyclic group-N(R3)-heterocyclic group _C()_C6 alkyl _N(R3)_c(〇)_Ci _C3 alkyl _, _c〇&amp;  Mercapto-c(s)-heterocyclyl_N(R3)_heterocyclyl_Cq_C6 alkyl NW )-(: (0)-(^-(3⁄4 alkyl-, -Q-Cs alkyl-C(〇)-heterocyclyl-N(R3)-heterocyclyl-C〇-C6 alkyl-NO^KXSKVCs alkyl·, -CG-C3 Alkyl-C(S)-heterocyclyl-N(R3)-heterocyclyl-C. _c6 alkyl_N(R3)_C(5)_Ci _C3 alkyl-,  -C0-C3 alkyl-C(oxime)-heterocyclyl-n^3)-cycloalkyl-C()-C6 alkyl 134026-3 -20· 200916447 -N(R3 )-(: (0)-(^ -C3 burning base -, -C〇 -C3 alkyl-C(S)-heterocyclyl _n(R3)-cycloalkyl-CG-C6 alkyl-N(R3)-0: (〇)-(: 】-C3 burning base -, _C()_C3 alkyl group _c(〇)_heterocyclyl-N(R3)-cycloalkyl-CG-C6 alkyl-N(R3)-(^):  -C3 alkyl-,  -C0-C3 alkyl-C(S)-heterocyclyl-N(R3)-cycloalkyl-CQ-C6 alkyl-N(R3)-QSKVC3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0), Cyclo-N(R3)4-based-Q-C6 alkyl-NO^-QCO-Ci-C3 alkyl-, -C(rc3 alkyl _n(R3)_C(S)-heterocyclyl-N(R3)-aryl-CG-C6 alkyl-N(R3 ΗΧΟ):  -C3 alkyl-, -C〇-C3 alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-aryl _C〇_C6 alkyl-N^ycXSHVC^ alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-aryl-C〇-C6 alkyl-N(R3)-(: (8)-(^-C3 alkyl-, _C〇_c3 alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-heteroaryl-C〇-C6 alkyl-N(R3)-C(0)-Q-C3 alkyl-, -C0-C3 alkyl-N(R3)-C(5)-heterocyclyl_N(r3)_heteroaryl-C〇-Q alkyl-N(R3 KX〇)-C], C3 burning base -, -C0-C3 alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-heteroaryl-C〇-C6 alkyl-N(R3 VCOC)-C3 alkyl-,  -C0-C3 alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-heteroaryl-C0-C6 alkyl-N(R-C3 alkyl-, -C〇 -C3 alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-heterocyclyl-Q _c6 alkyl _N(R3 )_c(〇)_Ci &amp;  alkyl-, Alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-heterocyclyl-indole-(: 6-alkyl-N(R3)-C(0)-Ci-C3 alkyl-, -CG -c3 alkyl-N(R3)-C(0)-heterocyclyl-N(R3)-heterocyclyl 'C〇-C6 alkyl-NO^KXSKVq alkyl-, -C〇-C3 alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-heterocyclyl_Cg_c6alkyl_N(R3)_c(5)_Ci _C3 alkyl-,  -C0-C3 alkyl-N(R3)-C(〇)-heterocyclyl-N(R3)-cycloalkyl-CG-C6 alkyl-N^KXOK^-Cs alkyl-, -Q-Cg alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-cycloalkyl-C6 alkyl _N(R3)_c(〇)_Ci _C3 alkyl-, _Cq _C3 alkane 134026-3 -21 - 200916447 yl-N(R3)-C(0)-heterocyclyl-N(R3)_cycloalkyl_q_C6 alkyl_n(r3)_c(s)_ q - C3 burning base -, -CG-C3 alkyl-N(R3)-C(S)-heterocyclyl-N(R3)-cycloalkyl-C0. 6 炫基-N^KXSK^-q alkyl-, -C〇-C3 Alkyl-S(0)2-heterocyclyl-N(R3)-aryl-C. -C6 alkyl-N(R3)-(: (0)-(^ -C3 alkyl-, -C. -C3 alkyl-S(0)2_heterocyclyl _n(R3)-aryl _c〇-C6 alkyl-N (R3 KXSA -C3 alkyl-, -C0-C3 alkyl-s(o)2-heterocyclyl_N(R3)_heteroaryl_c〇_C6 alkyl-N(R3)-(: (0)4 -C3 alkyl-, -CG-C3 alkyl-S(0)2-heterocyclyl-N(R3)-heteroaryl-c0-c6alkyl-n(r3)-c(5)-CVC3 alkyl-, -c0-c3 alkyl-S(0)2-heterocyclyl-N(R3)-heterocyclyl-C0-C6 alkyl-N(R3)-C(0)-Ci-C3 alkyl-, -C〇-C3 alkyl-S(0)2-heterocyclyl-N(R3)-heterocyclyl-C〇-C6 alkyl-wind 113)-(: (8)-(: 1-(: 3 alkyl-, -〇); Alkyl-5(0)2-heterocyclic-&gt; ^3)-Cycloalkyl-CQ-C6 alkyl-N^KXOKVCs alkyl-'-CG-C3 alkyl-S(0)2-heterocyclyl-N(R3)-cycloalkyl-C〇- C6 alkyl-N(R3 WS)-. 】-C3 alkyl-, -C〇-C6 alkyl-N(R3)-C(0)-C〇-C6 alkyl-heterocycloalkyl-C(O)-C〇-C3 alkyl-, -CG-C6 alkyl-N(R3)-C(5)-CQ-C6 alkyl-heterocycloalkyl-c(o)-cvc3 alkyl-, -C〇-C6 leuko-N(R3)-C(〇KVC6 alkyl-heterocycloalkyl-C(S)-C〇-C3 alkyl-, -C. -C6 alkyl-N(R3)-C(S)-C. -C6 alkyl-heterocycloalkyl-C(S)-C〇-C3 alkyl-, -C〇-C6 alkyl-n(r3)-c(o)-c〇-c6 alkyl-heterocycloalkyl-C(0)-N(R3)-〇)-C3 alkyl-, -CQ -C6 alkyl-N(R3 )-(: (5)-^-nonyl-heterocycloalkyl-c(o)-n(r3)-c〇-c3 alkyl-, -cvc6 alkyl-n(r3)-c(o)-c〇-c6 alkyl-heterocycloalkyl-C(5)-N(R3)-CG-C3 alkyl-, -c〇-c6 alkyl-N(R3)-C(S)-C〇-C6 alkyl-heterocycloalkyl-C(s)-N(R3)-C〇-c3 alkyl-, -C〇 -C6 alkyl-C(0)-C. -C6 alkyl-heterocycloalkyl-fluorene: 0)-Win 113)-(^-(: 3 alkyl-, -(: . -(: 6 alkyl-〇: 5)-(: . -(: 6-alkyl-heterocyclic ring 134026-3 -22- 200916447 alkyl-C(0)-N(R3)-Cg-C3 alkyl-, -CQ-C6 alkyl-C(0)-CG-C6 alkyl-heterocycloalkyl-C(S)-N(R3)-C〇-C3 alkyl-, -CG-C6 alkyl-c(s)-c〇-c6 alkyl-heterocycloalkyl-C(S)-N(R3)-CG-C3 alkyl-, -c〇-c6alkyl-oc〇-c3 alkyl-C(0)-N(R3)-C〇-C3 alkyl- and -c〇-c6 alkyl-0-C(S)-N( R3)-C〇-C3 alkyl-, Wherein each of the alkyl groups of L mentioned above,  Alkenyl, Alkynyl, Heteroalkyl, Cycloalkyl, Heterocycloalkyl, Heterocyclic group,  The aryl and heteroaryl moiety are optionally substituted; Wherein each Y line is independently selected from the group consisting of alkyl, Heteroalkyl, Cycloalkyl, Heterocyclic group,  Cycloalkylalkyl, Heterocyclylalkyl, Aryl, Aralkyl group, Heteroaryl,  Heteroaralkyl, Aryl-heteroaryl, Aryl-heteroarylalkyl, Heteroaryl-alkyl aryl, Aryl-aryl, Aryl-aryl base, Aryl-alkyl aryl, Aryl-c0-c3 alkyl-o-c0-c3 alkyl-aryl, Aryl-c0-c3 alkyl-s(o)〇_2-c0-c3 alkyl-aryl, -C〇-C3 alkyl-S(O)0_2-C0-C3 alkyl-aryl, aryl-C0-C3 alkyl-N(R3)-C〇-C3 alkyl-aryl, Aryl-c〇-c3 alkyl-C(O)-N(R3)-C0-C3 alkyl-aryl, aryl-C0-C3 alkyl-C(5)-N(R3)-C〇-C3 alkyl-aryl, aryl-C0-C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-aryl, aryl-C〇-C3 alkyl-N(R3)-C(S)-C0-C3 alkyl-aryl, Heteroaryl-heteroaryl, Heteroaryl-aryl, Heteroaryl-arylalkyl, Aryl-alkylated heteroaryl, Heteroaryl-aryl-aryl, Aryl-aryl-aryl, Aryl-heteroaryl-aryl, Aryl-heteroaryl-heteroaryl, Heteroaryl-heteroaryl-heteroaryl, Heteroaryl-heteroaryl-aryl, Aryl-aryl-heteroaryl, Heteroaryl-aryl-aralkyl, Aryl-aryl-alkylheteroaryl, Heteroaryl-aryl-alkylaryl, Aryl-aryl-alkylaryl, Aryl-aryl-aralkyl, Aryl-aryl-heteroarylalkyl, Heteroaryl-aryl-heteroaryl, Heteroaryl-aryl- 134026-3 23· 200916447 Heteroarylalkyl, Heteroaryl-aryl-alkylheteroaryl, Heteroaryl-heteroarylalkyl, Heteroaryl-alkylidene, Heterocyclyl-heteroaryl, Cycloalkyl-aryl,  Cycloalkyl-heteroaryl, Heteroaryl-heterocyclyl, Heteroaryl-cycloalkyl, Aryl-3⁄4 alkyl, Heterocyclyl-aryl, Aryl-heterocyclyl, Heterocyclyl-alkyl-aryl, Heterocyclyl-alkylheteroaryl, Cycloalkyl-alkylaryl, Cycloalkyl-alkylheteroaryl, Aryl-alkyl-heterocyclyl, Aryl-alkylcycloalkyl, Heteroaryl-alkylcycloalkyl, Heteroaryl-alkylheterocyclyl, Aralkyl-aryl,  Aryl-aralkyl, Aryl-heteroarylalkyl, Heteroaryl-aralkyl, Heteroaryl-heteroarylalkyl, Heteroaryl-C0-C: 3-alkyl-O-C0-C3 alkyl-aryl, Heteroaryl-C0-C3 alkyl-O-C0-C3 alkyl-heteroaryl, Aryl-c0-c3 alkyl-〇-〇)-C3 alkyl-heteroaryl, Heteroaryl_c〇 _c3 alkyl_N(R3)_c〇 _c3 alkyl-aryl, aryl-C0-C3 alkyl-N (R3KVC3 alkyl-heteroaryl, Heteroaryl-C〇-C: 3-alkyl-N(R3)-C〇-C3 alkyl-heteroaryl, Heteroaryl-c0-c3 alkyl-C(O)-N(R3)-C0-C3 alkyl-aryl, aryl-C0-C3 alkyl-C(0)-N(R3)-co-c3 alkyl-heteroaryl, Heteroaryl-C〇-C3 alkyl-C(0)-N(R3)-C〇-C3 alkyl-heteroaryl, aryl-C〇-C3 alkyl-C(5)-N(R3)-C〇-C3 alkyl-aryl,  aryl-C〇-C3 alkyl-C(S)-N(R3)-C〇-C3 alkyl-heteroaryl, Heteroaryl-C〇-C3 alkyl-C(S)-N(R3)-C0-C3 alkyl-aryl, Heteroaryl-C〇-C3 alkyl-C(S)-N(R3)-C〇-C3 alkyl-heteroaryl, Heteroaryl-C〇-C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-aryl, Heteroaryl-C0-C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-heteroaryl, Aryl-C〇-C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-heteroaryl, Aryl-c〇-c3 alkyl-N(R3)-C(S)-C0-C3 alkyl-aryl, Aryl-C〇-C3 alkyl-N(R3)-C(5)-c〇-c3 alkyl-heteroaryl, Heteroaryl-c〇-c3 alkyl-N(R3)-C(S)-C〇-C3 alkyl-aryl, Heteroaryl-c〇-c3 alkyl 134026-3 -24- 200916447 -N(R3)-C(S)-C〇-C3 alkyl-heteroaryl, R3 -heterocyclyl _Q _c3 alkyl, R3 _ cycloalkyl-C0-C3 alkyl, (R3)(R3a)N-C2-C4 alkyl-〇-aryl-,  (R3)(R3 a )N-C2 -C4 alkyl-S(0)〇 - 2 -aryl-, (r3 欣3 a )n_C2 _C4 alkyl-〇-heteroaryl-, (R3)(R3a)N-C2-C4 alkyl-S(O)0_2_heteroaryl-, C〇_c3 leuko-aryl-c0-C3 alkyl, C0-C3 alkyl-heteroaryl_C (rC3 alkyl, Aryl-c!  -C3 alkyl-heteroaryl, aryl-C!  -c3 alkyl-aryl, Heteroaryl-c--Cs alkyl-aryl, Heteroaryl-Ci-C3 alkyl-heteroaryl, R3 _heterocyclyl-Q)-C3 alkyl-N(R3)-C(0)-N(R3)-heteroaryl-, R3 _heterocyclic group _c〇_c3 alkyl-N(R3)-C(0)-N(R3)-aryl-, R3_cycloalkyl _c〇_C3 alkyl -^^-(: (9)-Wind-heteroaryl...圮-cycloalkyl-仏^alkyl-wind only 3)-C(0)-N(R3)-aryl-, R3 -heterocyclyl-Q-C3 alkyl-N(R3)-C(S)-N(R3)-heteroaryl-, R3 -heterocyclyl-C〇-C3 alkyl-N(R3)-C(S)-N(R3)-aryl-,  R3 -cycloalkyl-C〇-C3 alkyl-N(R3)-C(S)-N(R3)-heteroaryl-, R3 -cycloalkyl-C0-C3 leuko-N(R3)-C(s)-N(R3)-aryl-, Heteroaryl _C(〇)-C0-C6 alkyl-heteroaryl-, Heteroaryl-C(0)-C〇-C6 alkyl-aryl-, Aryl-C(O)-C0-C6 alkyl-aryl-, aryl-C(〇)-C0-C6 alkyl-heteroaryl-,  Heterocyclic group _C(〇)-N(R3)-C〇-C6 alkyl-aryl-, Heteroaryl _c(〇)-N(R3)_ C0-C6 alkyl-heteroaryl-, Heteroaryl_s(〇)2-C0-C6 alkyl-heteroaryl-,  Heteroaryl-S(O)2-C0-C6-homo-aryl-, aryl-S(〇)0_2_c0-C6 alkyl-square group, Square _C〇 -C3 alkyl-S(0)〇 _ 2 -C〇 -Cg alkyl-heteroaryl,   R3-O-C(O)-N(R3)-C0-C3 alkyl-heteroaryl-, R3-〇-C(〇)-N(R3)-C0-C3 alkyl-aryl-, R3-0-C(s)-N(R3)-C〇-C3 alkyl-heteroaryl-,  R3-0-C(S)-N(R3)-C〇-C3 alkyl-aryl-, R3-C(0)-heterocyclic group _c〇-C3 alkyl-heteroaryl-, R3-C(0)-heterocyclyl-Q-Csalkyl-aryl-, r3-C(0)- 134026-3 -25- 200916447 cycloalkyl-C0-C3 alkyl-heteroaryl-, R3-c(o)-cycloalkyl-c0-c3 alkyl_aryl-, R3 -heterocyclyl-C〇-C3 alkyl-N(R3)-C(0)-N(R3)-C0-c3 alkyl-heteroaryl-, R3 -heterocyclyl-C〇-C3 alkyl-N(R3)-S(0)2 -C〇-C3 alkyl-heteroaryl-' R3 -heterocyclyl-C〇-C3 alkyl-N (R3)-S(0)2 -C0 -C3 alkyl-aryl·, R3 -cycloalkyl-C0-C3 alkyl-N(R3)-S(0)2-C〇-C3 alkyl-heteroaryl _,  R3-cycloalkyl-C0-C3 alkyl-N(R3)-S(O)2-C0-C3 alkyl-aryl-, R3_heterocyclyl-C0-C3 alkyl-N(R3)-C(O)-C0-C3 alkyl-heteroaryl-, R3 _heterocyclyl-Cq-C3 alkyl-N(R3)-C(0)-CQ-C3 alkyl-aryl-, R3 -cycloalkyl-c〇-c3 alkyl-N(R3)-C(O)-C0-C3 alkyl-heteroaryl-, R3_cyclosyl-0) -C3 alkyl-N(R3)-(: (0)-〇) -C3 alkyl-aryl-, R3 _heterocyclyl _c. _c3 alkyl-N(R3)-C(5)-C〇-C3 alkyl-heteroaryl-, R3—heterocyclic group —c〇 _c3 院-N(R3)-C(S)-C0-C3 alkyl-aryl-, R3-cycloalkyl-c〇_c3 alkyl-N(R3)-C(S)-C0-C3 alkyl-heteroaryl-, R3-cycloalkyl-c〇_c3 alkyl-N(R3)-C(S)-C0-C3 alkyl-aryl-, R3 -C(0)-C〇 -C3 炫基-heteroaryl _ , R3-C(O)-C0-C3 alkyl-aryl _, Heterocyclyl-c(0)-, Aromatic polycyclic,  Non-aromatic polycyclic, Mixed aryl and non-aryl polycyclic, Polyheteroaryl,  Non-aromatic polyheterocyclic rings and mixed aryl and non-aryl polyheterocyclic rings, Each of them is selected from one or more selected from R3, Substituting a group of R4 or R7;   Or each Y line is independently selected from the group consisting of a-aryl-C0-C3, and N(Rj)((0)-(^-C7)-, Wherein d-C7 alkyl is optionally substituted by a moiety; The moiety is selected from the group consisting of -N(R3)-0: (0)-(^ -C5 alkyl group - (C2 - C4 dilute base) 〇.  i -c3 alkyl-oxime-A2 b, -N^KXC^N^KVC5 alkyl_(C2_C4 alkenyl)〇i_Ci_C3 alkyl 134026-3 -26· 200916447 -O-A2 b,-N(R3 )- C(0)-0-CVC5 alkyl-(C2-C4 alkenyl)〇_i-Ci-c3 alkyl-O-A2 b, leuko-(C2-C4 dilute)q 4-C^-Cg alkyl-O-A2 b, -N(R3)-S(0)2-N(R3-C5 alkyl-(C2-C4 alkenyl)〇-丨_Cl _C3 炫-O-A2 b and - N(R3)-S(0)2 -C! -C5 alkyl-(C2 -C4 alkenyl)〇_ 丨4 -C3 alkyl-O-A2 b, A2 a-heteroaryl-C0 -C3 Alkyl-N(R3)-(2(0)-(^-C7 alkyl-, wherein the Cl_c7 alkyl group is optionally substituted by a moiety selected from the group consisting of -N(R3) -(:(0)-(^-C5 alkyl-(C2-C4 alkenyl)G _ 丨-C3 alkyl-〇-A2 b, -N^KXCO-NO^KVQ alkyl-(C2-C4 olefin Base alkyl-0-A2 b, -N(R3)-(:(0)-0-(:! -C5 alkyl-(c2 -C4 alkenyl)〇_i-c3 yard base-0-A2 b , -N(R3 )4 -C5 alkyl-(C2 -C4 alkenyl)0 〗 -Cl _c3 alkyl_〇_A2 b , -N(R3 )-S(0)2 -N(R3 )-Q -C5 alkyl-(C2 -C4 dilute) 〇-i _Cl _c3 alkyl-0-A2 b and -N(R3)-S(0)2 -Cl-C5 alkyl-(C2 alkenyl)G _ i -C3 alkyl-0-A2b, and BkBi -NCR3)-(:(0)-(^-C:7 alkyl_, wherein the qq alkyl group is optionally substituted by -NR3-B3, wherein the amine of B3 is linked to the acid of B2 to form a peptide bond; And wherein 八23 and A2b are covalent bonds and are joined to form a ring; and B1, B2 and B3 are each independently a natural or synthetic amino acid, and when any of Bl, B2 and B3 are linked together, They are linked together via peptide bonds; each R·5 and 1^ are independently selected from the group consisting of _H, 〇H, _c(〇)H, heterocyclic, Ci_C6 alkyl, C2-C6 alkenyl, c2- C6 alkynyl, _c2-C4 alkyl-〇Ra, _c(〇)_〇_C2-C4 alkyl-NRaRa, heteroalkyl, c〇_c6 alkylheteroaryl, c(〇)cF3, -C (0)-NH2 ' -C(0)-NH-C! -C6 ^ , -NH2 ' C3 -C6 if ^ ^ &gt; -C{ -C6 134026-3 -11 - 200916447 aryl aryl, heteroaryl a aryl-aryl group, an aryl group and an alkylheteroaryl group, wherein each alkyl group, alkenyl group, alkynyl group, heteroalkyl group, cycloalkyl group, heterocyclic group, aryl group and heteroaryl group are optionally used Substituted; each R4 is independently selected from the group consisting of _H, _C(NRa)_N(Ra)2, Ci_C6 alkyl, C2_C6 alkenyl, C2-C6 alkynyl, -c6 alkyl-Ra, -C〇-C6 alkane Base-〇-Ra, -c0 -C6 -S(O)0_2-Ra, _C〇_C6 alkyl_c(〇)_〇Ra, _C〇_c6 alkyl_c(〇)_ N(R3)(R3a), _C()_C6 alkane Base_c(5)_N(R3)(R3a), _CH=CH_c(〇)_〇Ra, -CH=CH-C(0)-N(R3)(R3a), _CH=CH-C(S)-N(R3 )(R3a), -N(R3)-C(0)-CF3, -N(R3)-C2-C6 alkyl-N(R3)(R3a), alkyl-N(R3)(R3a), _N (R3)_c(〇)_CrC6 alkyl_r3, _n(r3)_c(s)_Ci_C6 alkyl-R3, -N(R3)-S(0)2-C丨-C6 alkyl-R3, _s( 0) 2-N(R3)R3a, •〇-C2-C6 alkyl-N(R3)(R3a), _S(〇)〇2_C2_C6 alkyl_N(R3)(R3a), -S-R3,- S(〇)0_2-C2-C6 alkyl-R3, a% cycloalkyl, cycloalkyl-Ra, heterocyclic, -(ναheterocyclyl_Ra, _0_Cg_C4 alkyl-cycloalkyl, -S( 〇V2-C0-C4 alkyl-cycloalkyl, _0_C2_C4 alkyl-heterocyclyl (when the alkyl group is bonded via N in the heterocyclic group), _〇_C〇_C4 alkyl-heterocyclic group ( When the alkyl group is bonded via C in the heterocyclic group, _s(〇)〇^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ I_ QC: 4 alkyl-heterocyclic group (when the alkyl group is bonded via n in the heterocyclic group), AOVQ-Q alkyl group-heterocyclic group, alkyl group-heterocyclic group-c (o) )-〇ra (when the 6-base is linked via c in the heterocyclic group), _〇 (乂院基-基-C(〇)-〇Ra (a-based via the n-linking day in the heterocyclic group) Temple), -〇-cycloalkyl-C(〇)-〇Ra, aryl_c(〇) 0Ra, (10) aryl C(o) OR, _s(〇)0 _]-c0 -C4 appearance base. Heterocyclic group _c(〇) 〇Ra (when alkyl group 134026-3 •28- 200916447 is linked via c in a heterocyclic group), -S(0)〇-i-c2-c4 alkyl-heterocyclic ring -C(0)-〇Ra (when the alkyl group is bonded via N in the heterocyclic group), -S(〇)2-C〇-C4 alkyl-heterocyclyl-C(0)-0Ra, -S(〇)0-2-cycloalkyl-C(0)-0Ra, _S(〇)〇2_ aryl_C(〇)_〇Ra, _S(〇)0-2-heteroaryl•C (0)-〇Ra, _〇_C〇_C4 alkyl-aryl, _s(〇)〇-2_Cc)_C4 alkyl-aryl, -〇-C〇-C4,hetero-heteroaryl,- S(〇)〇_2_C〇_C4 alkyl-heterocyclyl, -〇-C(〇)-N(R3)-C0-C4 alkyl-aryl,-0-C(S)-N(R3 )-〇&gt;-C4 alkyl-aryl, -〇-C(O)-N(R3)-C0-C4 alkyl-heteroaryl,-0-C(5)-NKRVCo-C; Aryl, -〇-C(O)-N(R3)-C0-C4 alkyl-cycloalkyl, -〇-cxs)_N(R3)-CQ-C4 alkyl-cycloalkyl, -〇_ C(〇)-N(R3)-C〇-C4 alkyl-heterocyclyl, -〇-C(S)-N(R3)-CG-c4 alkyl-heterocyclyl, -〇-CQ-C4 Alkyl-heterocyclyl-aryl (when the alkyl group is linked via c in the heterocyclic group), _〇_C2_c4 alkyl-heterocyclyl-aryl (when the alkyl group is via the N in the heterocyclic group) When linking), -O-C0 -C: 4 alkyl-heterocyclyl-heteroaryl (when the alkyl group is linked via C in the heterocyclic group), _〇_C2_C4 alkyl_heterocyclyl-heteroaryl (when When the alkyl group is bonded via N in the heterocyclic group, _ac〇_C4 alkyl_heterocyclyl-cycloalkyl (when the alkyl group is bonded via C in the heterocyclic group), _0_C2_C4 alkyl_heterocyclic ring a base-cycloalkyl group (when the alkyl group is bonded via N in the heterocyclic group), '0-CVC4 alkyl-heterocyclyl-heterocyclic group (when the alkyl group is linked via C in the heterocyclic group) , sigh 2 (4 alkyl group, heterocyclic group - heterocyclic group (when the alkyl group is bonded via N in the heterocyclic group), _S (〇). _ i _c. fluorenyl group, cyclo-aryl group ( When the alkyl group is linked via c in the heterocyclic group, _s(Hc 丄-hetero m group (when the silk is via the heterocyclic group, s(0) 2 -cQ -c4 alkyl ♦ ring group) _aryl, v) oi-CG-C4 alkyl_heterocyclyl 134〇26- •29- 200916447 -heteroaryl (when the alkyl group is linked via c in the heterocyclic group), c2-c4 -heterocyclyl-heteroaryl (when the alkyl group is linked via a heterocyclic group =), /S(〇)2-Co-C4 alkyl group_heterocyclyl-heteroaryl, π aryl , base -3⁄4 burning (when the alkyl group is linked via c in the heterocyclic group), Α〇κ2 (4 alkyl group-heterocyclic group-cycloalkyl group (when the system is linked via a heterocyclic group), scales (4) Institute base · Heterocyclyl · Cycloalkyl, -S (9) ◦. "CVQ alkyl-heterocyclyl-heterocyclyl (when the alkyl group is linked via C in a heterocyclic group, "), -S(〇)〇1_C2_C4, a ketone group, a heterocyclic group, a heterocyclic group (when When the alkyl group is linked via N in the heterocyclic group, -s(〇)2-c. -c4 alkyl-heterocyclyl-heterocyclyl, -n(r3k: 2_C4 alkyl. heterocyclyl, ·N(R3)_C2_C4 alkyl-cycloalkyl, -N(R3)-C2 -C:4 Alkyl-heteroaryl, _N(R3)_c2_c4alkyl-aryl, -n(r3)-c(o)-n(r3)_C()_C4 alkyl-heterocyclyl_R3, _N(R3 )_c(5)_ N(R3)-Cq-C4 alkyl-heterocyclic group _r3, _N(R3 &gt;c(〇)_n(r3)_c._c4 alkyl_ ί 哀 烧 -R3, -N(R3) -C(S)-N(R3)-C〇-C4 alkyl-cycloalkyl-R3, -N(R3)-C(0)-N(R3)-C0-C4 alkyl-aryl_r3 , _N(R3 )_c(5)_n(r3 )_ C0-C4烷基-芳基-R3、q烷基雜芳基 -R3、-N(R3)-C(S)-N(R3)_C〇_C4 烷基 _雜芳基 _r3、_c〇_Q 烷基 -0-C(0)-Ra、-C〇-C4 烷基-N(R3)-C(〇)-〇-Ra、_〇)-(：4 烷基 -N(R3)-C⑸-0-Ra、-C0-C4 烧基-雜環基 _c(0)-0-Ra、-C〇-C4 烷 基-環烷基-C(0)-0-Ra、-C〇 -C4 烷基-雜芳基 _c(0)-0-Ra、-C〇 -C4 烷基-芳基-C(0)-0-Ra、_N(R3)-C2-C4烷基-雜環基、 -N(R3)-C2-C4烷基-環烷基、-N(R3)-C2-C4烷基-雜芳基、 -N(R3)_C2-C4烷基-芳基、F、Cl、Br、I、-CF3、-S03H、 -CN、芳基、雜芳基、環烧基及雜環基，其中前文所提 134026-3 -30- 200916447 及R4之各烷基、烯基、炔基 '環烷基 '雜環基、芳基及 雜芳基部份基團係視情況經取代； 各R7與R、獨立選自包括_H、Ci_Q烷基…c2_c6烯基、 c2-c6块基、Cl_c^烧基、Ra_〇_C2_Q烷基…Ra_s(〇)M_ CVQ烷基_、、保護基、C】_C6烷基 -〇((〇)-、芳基_c〇_c4烷基傾〇)_、雜芳基_c。夂烷基 -0-c(0)-、芊基 _ac(0)·' 雜環基 _Ci _c6 烷基 _、環烷基 , 烷基-、雜芳基必-c6烧基-、芳基_Cl-c6^基…其中各 4 烧基、稀基、炔基、雜炫基、芳基、雜芳基、環炫基、 下基及雜環基部份基團係獨立視情況經取代；其條件 是 R7為-ORa，當連接至喇哚基部份基團之^^原子時；且 其中在HRh)基團中，R3與_和彼等所連接之氮原子 一起視情況形成雜環基。 2. 如請求項1之化合物，其中^^^^^，^，以及尺“之各烷 , 基、烯基、炔基、雜烷基、環烷基、雜環基、芳基及雜芳 基部份基團係獨立視情況被一或多個獨立選自r4之基團 取代。 3. 如請求項1之化合物，其中丫丄，2，^妒，俨，尺3及尺33之各烷 基、烯基、炔基、雜烷基、環烷基、雜環基、芳基及雜芳 基知基團係獨立視情況被一或多個基團取代，取代基獨 立選自酮基、-OH、-CN、Cl_C6烷基、Ci_c^氧基、_N〇2、 N(R )2、-N(R7)(R7a)、鹵基、_SH、_s_Ci_C6烷基、___C「C6 烷基、-S-CCCO-Ci-C：6烷基及單-至全-自kCi_C6烷基。 134026-3 &gt;31 - 200916447 4. 如靖求項丨之化合物，其中r4之&amp; 烷基部份基團係視情 況被取代基取代，取代基選自包括-OH、-N02及CG-C6烷基 -C(0)-N(R3)(R3a)。 5. 如請求項1之化合物，其中z之各烷基、烯基、炔基、雜 烧基、芳基、雜芳基環烷基及雜環基部份基圑係獨立視情 況被一或多個取代基取代，取代基獨立選自包括酮基、 -OH、-CN、Q-Q烷基、q-Q烷氧基、-N02、-N(R3)(R3a)、 鹵基、-SH及單-至全，化Ci_C6烷基。 6. 如請求項1之化合物，其中l係選自包括 -C〇 -C6 烷基-N(R3 )-C〇 -C3 烷基-’其中當-C0 -C6 烷基為-C6 烧基時，其係視情況被取代基取代，取代基選自包括_Ci_c3 烧基-ORa、-C「C3 烷基-N(R3)(R3a)、-Q-C3 烷基-C(0)ORa 及 C0 -C3 院基-C(0)-N(R3 )(R3 a); -C0 -C6 烷基-N(R3 )-C(O)-C0 -C3 烷基-，其中當-C〇 -C6 烷基為 Ci-C6烷基時’其係視情況被取代基取代，取代基選自包括 -(VQ 烷基-〇Ra、-q-Cs 烷基-NR3R3a、-CGC3 烷基-C(0)0Ra 及 C〇 -C3 烷基-C(0)-N(R3 )(R3 a); -C0-C6 烧基-N(R3)-C(O)-C0-C3 烧基-，其中-C〇-C3 烧基為 Q -C3烧基’其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、-c(o)-N(R3)-Cg-C3 烷基-Y、-C⑸-N(R3)-C〇-C3 烷基-Y、-n(r3)-c(o)-C〇 -C3 烷基-c4 -C6 環烷基-、-N(R3 )-C(S)-C〇 -C3 烷基-C4 -C6 環烷基 -、-N(R3)-C〇-C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-C4-C6 雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基 134026-3 -32- 200916447 -ORa、-N(R3)-C〇-C3 烷基-C〇-C3 雜烷基-Υ、-N(R3)-C(O)-O-C0-C3 烷基-Y、-n(r3)-c⑸-o-cQ-c3 烷基-y、-n(r3)-s(o)2-c〇-c3 烷基 -Y、-n(r3)-c(o)-n(r3)-c〇-c3 烷基-Y ' -n(r3)-c(s)-n(r3)-c0-c3 烷基-υ、-n(r3)-c(o)-c〇-c3 烷基-c〇-c3雜環基、-n(r3)-c(s)-C〇 -C3 烷基-CG -C3 雜環基、-N(R3 )-C(0)-CG -C3 烷基-C〇 -C3 雜環基 -Y、-n(r3)-c(s)-c〇-c3 烷基-C〇-C3 雜環基-Y 及-n(r3)-s(o)2-n(r3)-c〇-c3 烷基-Y ; -c0-c6 烷基-N(R3)-C(S)-C〇-C3 烷基-，其中-c〇-c3 烷基為 q -c3烷基，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、-c(o)-n(r3)-c〇-c3 烷基-Y、-C(S)-N(R3)-C〇-C3 烷基-Y、-n(r3)-c(o)-c0 -C3 烷基-C4 -C6 環烷基-、-N(R3 )-C(S)-CQ -C3 烷基-C4 -C6 環烷基-、-N(R3)-C〇-C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-C4-C6 雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基 -ORa、-N(R3 )-C〇 -C3 烷基-C〇 -C3 雜烷基-Y、-N(R3 )-C(O)-O-C0 -C3 烷基-Y、-n(r3)-c⑸-o-cQ-c3 烷基-Y、-n(r3)-s(o)2-c〇-c3 烷基 -Y、-N(R3)-C(O)-N(R3)-C0-C3 烷基-Y、-n(r3)-c(s)-n(r3)-c〇-c3 烷基-y、-n(r3)-c(o)-c〇-c3烷基-c〇-c3雜環基、-n(r3)-c(s)-c0 -C3 烷基-CG -C3 雜環基、-N(R3 )-C(0)-CQ -C3 烷基-CG -C3 雜環基 -Y、-N(R3)-C(S)-C〇-C3 烷基-C〇-C3 雜環基-Y 及-n(r3)-s(o)2-Ν(Κ3)-〇)-(：3 烷基-Y ; -c〇 -c6烷基-c(o)-c〇 -c3烷基-，其中當-c0 -c6烷基為q -c3 烷基時，其係視情況被取代基取代，取代基選自包括-N(R3 )-C(〇)-c〇 -C3 烷基-Y、-N(R3 )-C(S)-C〇 -C3 烷基-Y、-C(0)-N(R3 )(R3 a)、 134026-3 -33- 200916447 -C(S)-N(R3)(R3a)、-C(0)-N(R3)-C〇-C3 烷基-Υ、-C(S)-N(R3)-C0-C3 烷基-Y、-N(R3)-C(0)-Cq-C3 烷基-C4-C6 環烷基-、-N(R3)-C(s)-C〇 -C3 烷基-C4 -C6 環烷基…-N(R3 )-C〇 -C3 烷基-Y、-N(R3 )(R3 a)、 -N(R3 )-C〇 -C3 烷基-C4 -C6 雜環基、-N(R3 )-C2 -C3 烷基-N(R3 )(R3 a)、 -N(R3 )-C2 -C3 烷基-ORa -、-N(R3 )-C〇 -C3 雜烷基-Y、-N(R3 )-C(0)-〇-C0 -C3 烷基-Y、-N(R3 )-C(S)-O-C0 -C3 烷基-Y、-N(R3 )-S(0)2 -C0 -C3 烷基-Y、-N(R3)-C(O)-N(R3)-C0-C3 烷基-Y、-NO^KXSVN^i-Co-Cg 烧基 -Y 、 -N(R3)-C(0)-C〇-C3 烧基 -C〇-C3 雜環 基、 -N(R3)-C(S)-C〇 -C3 烧基-C〇 -C3 雜環基、-N(R3 )-C(0)-C〇 -c3 烧基-C〇 -C3 雜 環基-Y、-N(R3)-C⑸-C〇-C3 烷基-C〇-C3 雜環基-Y 及-N(R3)-s(o)2-n(r3)-c〇-c3 烷基-Y ; -C0 -C6 烧基-(^)-〇)-(：3烧基-，其中當-〇)-(^6烧基為（：1-(：3 烷基時’其係視情況被取代基取代，取代基選自包括-N(R3 )-C(0)-C〇 -C3 烷基-Y、-N(R3 )-C(S)-C〇 -C3 烷基-Y、-C(0)-N(R3 )(R3 a) 、-C(S)-N(R3)(R3a)、-C(O)-N(R3)-C0-C3 烷基-Y、-C(S)-N(R3)-C〇-C3 烷基-y、-n(r3)-c(o)-c〇-c3 烷基-C4-C6 環烷基-、-n(r3)-c⑸-C0 -C3 烷基-C4 -C6 環烷基-、-N(R3 )-C〇 -C3 烷基-Y ' -N(R3 )(R3 a)、 -N(R3)-CG-C3 烷基-C4-C6雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a) 、-N(R3 )-C2 -C3 烷基-〇Ra -、-N(R3 )-C0 -C3 雜烷基-Y、-N(R3 )-C(0)-〇-C0 -C3 烷基-Y、-N(R3 )-C(S)-O-C0 -C3 烷基-Y、-N(R3 )-S(0)2 -C0 -C3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3：)^ 基-Y、-N(R3)-C⑸-N(R3)-0：0-(：3烧基-丫、-风113)-〇：〇)-〇)-(：3烧基-〇)-(：3雜環基、-风113)- c(s)-c〇-c3烷基-c〇-c3雜環基、-n(r3)-c(o)-c〇-c3烷基-c〇-c3雜 環基-Y、-N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環基-Y 及-N(R3 )-S(0)2 - 134026-3 -34- 200916447 N(R3)-C()-C3 烷基-Υ ; -C〇 -Q烧基-，其中當-C0 -C6院基為Q -C6烧基時，其係視 情況被取代基取代’取代基選自包括-N(R3 )-C(0)-CG -c3烷基 -Y、-N(R3)-C(0)-C〇-C3烧基-雜環基及_N(R3)-C(0)-C。-C3烷基-環烷基； -C0 -C6 烧基-C(0)-N(R3 )-C0 -C3 烷基-，其中當 _c0 -C3 烷基為 Q -C：3烷基時，其係視情況被取代基取代，取代基選自包括 -C(0)-N(R3)-C〇-C3 烷基-Y、-C(O)-雜環基、_c(0)-N(R3)(R3a)、 芳基-芳基、芳基-雜芳基、-雜芳基-芳基、雜芳基-雜芳基、 雜芳基、雜環基-雜芳基及雜環基； -c〇-c6烷基-雜烷基-c〇-c6烷基-c(o)-n(r3)-c〇-c3烷基-，其 中當-C0 -C3烷基為q -c3烷基時，其係視情況被取代基取代， 取代基選自包括-C(0)-N(R3)-C〇-C3烷基-Y、-C(o)-雜環基、 -C(0)-N(R3)(R3a)、芳基-芳基、芳基-雜芳基、_雜芳基_芳基、 雜芳基-雜芳基、雜芳基、雜環基-雜芳基及雜環基； -C〇 -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當-C〇 -c6 烷基為 G -C6烧基時’其係視情況被取代基取代，取代基選自包括 -N(R7)(R7a)、-N(R3)(Rh)、_N(R3)-C(O)-C0-C3 烷基-Y、-N(r3)_ C(0)-0-C〇-C3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及-N(R3)-S(0)2-C〇-C3 烷基-Y ; -C〇-C6烷基-雜芳基-C0-C3烷基-，其中當-C0-C3烷基為 q -c3烷基時，其係視情況被取代基取代，取代基選自包括 -C〇-C3 烧基-N(R3)-C(〇)-C〇-C3 烧基-N(R3)(R3a)、-N(R3)-C(0)-c0-c3 烷基-y、-n(r3)-c(o)-o-cg-c3 烷基-y、-n(r3)-c(o)-n(r3)- 134026-3 -35- 200916447 C〇 -C3 烧基-Y 及-N(R3 )-S(0)2 -C。-C3 烧基-Υ ; -C0-C6烧基-芳基-C0-C3烧基-，其中當_c〇-C3烧基為Ci-C〗 烷基時’其係視情況被取代基取代，取代基選自包括_n(r3 )-C(0)-C。-C3 烧基-Y、-N(R3 )-C(0)-C。-C3 烧基-Y、-N(R3 )-C(0)-〇-C〇 -C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-C〇 -C3 烷基-Y 及-N(R3 )-S(0)2 _ C0-C3 烷基-Y ; -C〇-C6烷基-芳基-雜芳基-C0-C3烷基-，其中當-C〇-C3烷基 為q -C3烷基時’其係視情況被取代基取代，取代基選自包 括-N(R3)-C(0)-C()-C3 烧基-Y、-N(R3)-C(0)-C〇-C3 烧基-Y、 -n(r3)-c(o)-〇-cq-c3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及 -N(R3)-S(0)2-Q)-C3 烷基-Y; -c0-c6烷基-雜芳基-雜芳基-c0-c3烷基-，其中當-C〇-C3烷 基為q -c3烷基時，其係視情況被取代基取代，取代基選自 包括-N(R3)-C(O)-C0-C3 烷基-Y、-N(R3)-C(O)-C0-C3 烷基-Y、 -N(R3)-C(0)-0-C〇-C3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及 -N(R3)-S(0)2-C〇-C3 烷基-Y ; -c0-c6烷基-雜芳基-C〇-C3烷基-，其中當-c0-c3烷基為 Q-C3烷基時，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-c(o)-o-c〇-c3 烷基-Y、-n(r3)-c(o)-n(r3)-c〇-c3 烷基-Y 及 -N(R3 )-S(0)2 -C〇 -C3 烷基-Y ; -C〇 -C6 烷基-〇-C(0)-N(R3 )-C〇 -C3 烷基-，其中當-C0 -c3 烷基為 Cl -C3烧基時，其係視情況被基團取代’取代基選自 -C(0)-0Ra、-C(S)-ORa、-C(0)-N(R3 烷基、-CXSVNCRi-CrQ 134026-3 ·36· 200916447 烷基、-C(0)-N(R3)(R3a)-、-C(S)-N(R3)(R3a)-、-C(O)-N(R3)-C0-C3 烷基-芳基、-c(s)-n(r3)-cvc3 烷基-芳基、-c(o)-n(r3kvc3 燒 基-雜芳基、-C ⑸-N(R3)-C〇-C3 烷基-雜芳基、-C(0)-N(R3)-Cq&lt;：3 烷基-環烷基、-C(S)-N(R3 )-CG -C3烷基-環烷基、-C(O)-雜環基、 -C(S)-雜環基、-C(0)-N(R3)-C〇-C3 烷基-Y、-C(S)-N(R3)-C0-C3 燒 基-Y 、-C(0)-N(R3)-雜環基、-C(s)-N(R3)-雜環基、 -c(o)-n(r3)-c〇-c3 烷基-雜環烷基及-C(s)-N(R3)-CQ-C3 烷基 _雜 環烷基； -c0 -C6 烷基-0-C(S)-N(R3 )-C〇 -C3 烷基-，其中當-C0 -C3 烷基為 Q -C；3烧基時，其係視情況被基團取代，取代基選自 -C(0)-ORa、-C(S)-ORa、-C3烷基、-C3 烷基、-C(0)-N(R3)(R3a)-、-C(S)-N(R3)(R3a)-、-C(0)-N(R3)-C〇-C3 烷基-芳基、-(^)-Ν(Ι13Κν(：3 烷基-芳基、-C(0)-N(R3)-Cg-C3 境 基-雜芳基、-C(S)-N(R3)-C〇-C3 烷基-雜芳基、-C(0)-N(R3KVC3 烷基-環烷基、-C(S)-N(R3)-Cg-C3烷基-環烷基、-c(o)-雜環基、 -C(S)-雜環基、-C(0)-N(R3)-C〇-C3 烷基-Y、-C ⑸-N(R3)-C〇-C3^ 基-Y、-C(0)-N(R3)-雜環基、-C⑸-N(R3)-雜環基、 -C(0)-N(R3)-CG-C3 烷基-雜環烷基及-C(S)-N(R3)-CG-C3 烷基-雜 環烷基；且 _Ci _匚3炫1基-N(R3 )-C(0)-Ci -C7烧基-’其中Ci -C3烧基係視情 況被-C(0)N(R3 )-(：! -C3烷基-A1 a取代，且Q -C7烷基係視情況被 取代基取代，取代基選自包括-N(R3 )-(:(0)-0-(^ -C3烷基-A1 b、 -N(R3 烧基-A1 b、-N(R3 )4(0)2-(^-C3 烷基-A1 b、 -N(R3 -C3 烷基-A1 b、-N(R3)-C(0)-N(R3 -C3 烷基 134026-3 -37- 200916447 烷基-Alb，其中 A1 3與A1 b係獨立選自包括烷基、烯基及保護基；或 八13與Alb-起經由-C2-C6次烷基-、-C2-C6次烯基_、_C2_C6 次炔基-或-C〇-C3烷基-雜芳基-C0-C3烷基-連結基形成視情 況經取代之環。 7. 如請求項1之化合物，其中l係選自包括 -Q -C6烧基-N(R3 )-C0 -C；3烧基-，其中q -C6烧基係視情況被 取代基取代，取代基選自包括-q-C4烷基-〇Ra、-(^-&lt;：6烷基 -N(R3 )(R3 a)-、-c0 -C4 烷基-C(0)0Ra 及-C〇 -C3 烷基-C(0)-N(R3 )(R3 a ^ -C〇 -C：6烷基-N(R3 )-C(O)-C0 -C3烷基-’其中q -C6烷基係視情 況被取代基取代，取代基選自包括烷基-0(Ra)-、-CQ-C6 烷基-C(0)0(Ra)-及-C6 烷基-N(R3 )(R3 a)-;及 _C〇 -C6烷基-C(0)-N(R3 )-C〇 -C3烷基-，其中Q -C6烷基係視情 況被取代基取代，取代基選自包括-CG-C6烷基-0(Ra)-、-C0-C6 烷基-C(0)0(Ra)-、-CG-C3 烷基-C(0)-N(R3)(R3a)及-CQ-C6 烷基 -N(R3)(R3a)-。 8. 如請求項1之化合物，其中L係選自包括 -C〇 -C6烷基-N(R3 )-(:(0)-(^ -C7烷基-，其中q -C7烷基係視情 況被取代基取代，取代基選自包括-N(R7)(R7a)、-N(R3)C(0)-C〇-C3 烷基-雜環基、_n(r3)-c(o)-c〇-c6 烷基芳基-Ra、 -N(R3 )-(:(0)-(^ -C6 烷基-Ra 及-N(R3 )-C(O)-O-C0 -C3 烷基-Y，其中 雜環基係視情況經取代； -C〇 -C6烷基-C(0)-N(R3 -C7烷基-，其中q -C6烷基係視情 況被-N(R7)(R7a)取代； 134026-3 •38- 200916447 -C0 -C6烷基-C(0)-N(R3 -C7烷基-，其中c! -C7烷基係視情 況被取代基取代，取代基選自包括芳基_芳基、芳基_雜芳 基、雜芳基-雜芳基、雜芳基-芳基及雜芳基；及 -c! -C3烷基-N(R3 KXCO-C! -c7烷基-，其中q -C3烷基係視情 況被-C(0)N(R3 )-(：! -(¾烷基-A1 a取代，且q -C7烷基係視情況 被取代基取代，取代基選自包括_N(R3 )_c(〇)〇_Ci _C3烷基_Ai b 、-^3)-(:(0)-(^-C3 院基-A1 b、-N(R3 )-8(0)2-(^-(:3 烷基-A1 b、 -N(R3 )-C(0)-N(R3 -C3 烷基 _Ai b 及 _N(R3 )_s(〇)2 _n(r3 ) Ci 4 烷 基-A1 b，其中 Aj a與A! b係獨立選自包括烷基、烯基及保護基；或 Ala與Alb —起經由-(：2-(：6次烷基、-C2-C6次烯基、-C2-C6 次快基、-C0-C3烧基-雜芳基-Q-C3烷基-連結基或-Q-C3烷基 -¾基-CQ -C：3烧基-連結基形成視情況經取代之環。 9. 如請求項1之化合物’其中l係選自包括 -C〇 -C7烷基-N(R3 )-C(0)-雜環基-c0 -C6烷基-，其中q -C7烷 基係視情況被-C〇 -C3烷基-C(〇)〇Ra或-Ci -C3烧基-〇Ra取代；與 -C〇 -C：7烷基-O-C(O)-雜環基-C0 -c6烷基-，其中q -C7烷基係 視情況被-C〇 -C3烧基-C(0)0Ra或-C〇 -C3烧基-〇Ra取代。 10. 如請求項1之化合物’其中L係選自包括共價鍵、-(chj 4_ 、-(CH2)0.4-(CR3 =CR3)-(CH2)0.4-、-(CH2)〇.4-(CeC)-(CH2)0-4-、 -(CH2)〇.3N(R3)C(0)- ' -(CH2)0.3-C(O)N(R3)- &gt; -(CH2)〇.3N(R3)C(0)-(CRa=CRa)- ^ -(CH2)0.3.N(R3HCH2)2.4N(R3)C(O)- ^ -(CH2)〇.3-0-(CH2)2.4-N(R3)C(0)- ^ -(CH2)〇.3C(〇HCH2)0.3- ^ -(CH2)〇.3- (CRa=CRa)-C(O)-(CH2)0.3- ^ -(CH2)0.3C(〇HCRa=CRaHCH2)0.3- ' 134026-3 -39- 200916447 _C0 -C6 烧基-N(R3 )-C(0)-雜環基-C〇 -C3 烧基-、-C〇 -C6 院基-S(0)2 -雜環基-C〇-C3 烧基-、-(CH2)〇_3-S(0)2-N(R3)-(CH2)〇_3-、 -(CH2 )〇. 3 N(R3 )-S(0)2 -(CH2 )〇. 3 -、-(CH2)〇.3N(R3HCH2)0.3-、 -(^2)0.3^^)-(^2)^3-(0^=0^)- ' -(CH2)0-3C=N-O-(CH2)0.3-' -(CH2)〇.3N(R7)-(CH2)0.3- &gt; -(CH2)〇.3S-(CH2)〇.3- ' -(CH2)〇,3〇-(ch2)〇_3-、_(ch2)。.3s(o)-(ch2)0.3-、-(CH2)0.3S(O)2-(CH2)0.3-、 -(CH2)0.3CH=CH-(CH2)2-3-、-(CH2)0-3N(R3)-C(0)-N(R3)-(CH2)0-3 、-(CH2 )〇. 3 N(R3 )-C(0)-0-(CH2 )〇. 3 、 -(CH2)〇.30-C(0)-N(R3)- (CH2 )0.3- 、 -(CH2 )0 _ 3 N(R3 )-C(0)-N(R3 )-S(0)2 -(CH2 )〇 — 3 -及 -(CH2 )〇. 3 N(R3 )-C(0)-N(R3 )-C(0)-(CH2 )〇. 3 - 〇 11. 如請求項1之化合物，其中、B2及B3係獨立選自包括 D-Gly、L-Gly、D-Pro、L-Pro、D-Tyr、L-Tyr、D-Tyr(ORa)、 L-Tyr(ORa)、D-Phe、L-Phe、D-PheR4、L-PheR4、D-Aib、L-Aib、 D-Ala、L-Ala、D-ProRg、L-P1OR3、D-Ile、L-Ile、. D-Leu、L-Leu、 D-PheR3、L-PheR3、D-Pip 及 L-Pip。 12. 如請求項1之化合物，其中R/與R7 a之各烷基、烯基、炔基、 雜烷基、苄基及雜環基部份基團係獨立視情況被一或多個 取代基取代，取代基選自包括酮基、-OH、-CN、Ci -C6烷 基、CVC6烷氧基、-N02、-N(R3)(R3a)、鹵基、-SH及單-至 全-鹵化CVQ烷基。 13. 如請求項i之化合物，其中各γ係獨立選自包括芳族多 環、非芳族多環、混合之芳基與非芳基多環、多雜芳基、 非芳族多雜環、混合之芳基及非芳基多雜環，其每一個係 視情況經取代。 134026-3 •40- 200916447 Μ.如請求項i之化合物， 装朴* 各γ係獨立1P έ 6 k w 基-方基、雜芳基、芳基-雜芳基、4 、自匕括方基、芳 雜環基及雜環基-雜芳基，、雜芳基芳基、環燒基、 、母―，係視a情況經取代。 其中D為 C/ Rb lw、 15·如請求項1之化合物 16·如請求項1之化合物 17.如請求項1之化合物 18·如請求項1之化合物，其中D為 wx ,ϊ(r Rb RC x 或 I ^ Ra -卜w\_义_ 其中D為 I r .f—w\ ,Rh 其中D為 $ i r —%肩 n S (T II X Rb ,Rh X 'N、/CH3 19.如請求項1之化合物 20·如請求項1之化合物 21.如請求項1之化合物 II S 其中D為 其中X為〇。 其中X為S。 22.如請求化合物，其中俨、 ^ 及尺係獨立選自包括-Η、 23如嗜二、η钱基、芳基、雜芳基及芳基院基_。 -二1=合物’…與妒和彼等所連接之氮原子 起屯成3至9_貝雜環基、雜芳基或雜環基_芳基， 雜=基、雜芳基及雜環基_芳基係視情況經取代。” 24.如响求項】之化合物，其中㈣❿係獨立選自包括丑、 —1 C6 院基 ' c3 -C6 環烷基、_q〇)cf3、_c(〇)h、_c c 燒基-C(〇)ORa、雜環基、_Q _Q規基_〇Ra、&amp; _q次貌基，· :基、c2-Q__c厂w基芳基、芳基、_c〇_Q貌基雜芳6 土及A -C3烷基-C(〇)N(Ra)-雜芳基。 134026-3 41 · 200916447 25 j π未項丨之化合物，其 ^ A w 一 係镯立選自包括-C1&lt;： 烷基方基、第三-丁基芊基及芳基。 6 26.如請求項i之化合物，其 ^ ，、K係獨立選自包括乙醇、 四虱-2Η-哌喃、苯基及苄基。 27‘如請求項k化合物，其中R3#R3a係獨立為〔「以基。 28.如請，項！之化合物，其中^N(R3)(R3a)基團中，r3與於a ί彼等所連接之氮原子—起視情況形成環，選自包括嗎福 林基、、氫t井基、六氫峨咬基、四氫峨洛基及一氮四 基。 29.如清求項！之化合物，其中R4係選自包括η、、 -s(〇)2鄭3)(R3a)、-so#、_0_C2_C4烷基雜環基、_ac= 烷基-芳基、-O-Co-C：4烷基-雜芳基、_〇_C(〇)N(R3)_C〇_C4烷基 芳基、-〇-C(〇)N(R3 )-C〇 -C：4烷基-雜芳基、_0_c〇 π*烷基_雜環基 -芳基、-〇-C0 -C：4烷基-雜環基-雜芳基、_N(R3 )_C2 &amp;烷基，雜環 \ 基、-(CH2)0_4〇Ra、-(CH2)0_4N(R3)(R3a)、-F、-Cl、-Br、-CF3、 -CN、-CH2OH、-OH、-〇CH3、-N02、Ph、芳基、雜芳基、 -N(R3)C(〇)CH2R3、-N(R3)S02CH2Ra、-〇(CH2)2_4N(R3)(R3a)、 -SRa 、 -S(〇)CH2R3 、 -S02CH2Ra 、 -(CH2)0.4C(O)ORa 、 -CH=CHC(〇)〇Ra、-CH=CHC(0)N(R3)(R3a)、-N(R3)C(0)CF3 及 -N(R3)(CH2)2N(R3)(R3a)。 3〇.如請求項1之化合物，其中Rh為-CH3 ° 31. 如請求項1之化合物，其中Rh為_Cf3。 32. 如請求項1之化合物，其中l係選自包括 134026-3 -42- 200916447C0-C4 alkyl-aryl-R3, qalkylheteroaryl-R3, -N(R3)-C(S)-N(R3)_C〇_C4 alkyl-heteroaryl_r3, _c〇 _Q alkyl-0-C(0)-Ra, -C〇-C4 alkyl-N(R3)-C(〇)-〇-Ra, _〇)-(:4 alkyl-N(R3) -C(5)-0-Ra, -C0-C4 alkyl-heterocyclyl-c(0)-0-Ra, -C〇-C4 alkyl-cycloalkyl-C(0)-0-Ra, -C 〇-C4 alkyl-heteroaryl_c(0)-0-Ra, -C〇-C4 alkyl-aryl-C(0)-0-Ra, _N(R3)-C2-C4 alkyl- Heterocyclyl, -N(R3)-C2-C4 alkyl-cycloalkyl, -N(R3)-C2-C4 alkyl-heteroaryl, -N(R3)_C2-C4 alkyl-aryl, F, Cl, Br, I, -CF3, -S03H, -CN, aryl, heteroaryl, cycloalkyl and heterocyclic groups, wherein each of the alkyl groups of 134026-3 -30-200916447 and R4 mentioned above, Alkenyl, alkynyl 'cycloalkyl' heterocyclyl, aryl and heteroaryl moiety are optionally substituted; each R7 and R, independently selected from the group consisting of _H, Ci_Q alkyl...c2_c6 alkenyl, C2-c6 block group, Cl_c^alkyl group, Ra_〇_C2_Q alkyl group...Ra_s(〇)M_CVQ alkyl group,, protecting group, C]_C6 alkyl-〇((〇)-, aryl group_c 〇_c4 alkyl deuterated) _, heteroaryl _c. decyl-0-c(0)-, fluorenyl _ac(0)·' heterocyclic group _Ci _c6 alkyl-, cycloalkyl, alkyl-, heteroaryl-c6 alkyl-, aryl-Cl-c6^ group, wherein each 4 alkyl, dilute, alkynyl, heterodyne, aromatic The radical, heteroaryl, cyclodextrin, lower group and heterocyclyl moiety are independently substituted as appropriate; the condition is that R7 is -ORa when attached to the ^^ atom of the Lahyl moiety And wherein in the HRh) group, R3, together with _ and the nitrogen atom to which they are attached, form a heterocyclic group as appropriate. 2. The compound of claim 1, wherein ^^^^^,^, and each of the "alkanes, alkenyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl" The radical moiety is independently substituted by one or more groups independently selected from r4. 3. The compound of claim 1, wherein each of 丫丄, 2, ^妒, 俨, 尺3 and 尺 33 Alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl groups are independently substituted by one or more groups, the substituents being independently selected from keto groups , -OH, -CN, Cl_C6 alkyl, Ci_c^oxy, _N〇2, N(R)2, -N(R7)(R7a), halo, _SH, _s_Ci_C6 alkyl, ___C "C6 alkyl, -S-CCCO-Ci-C: 6-alkyl and mono- to all-from kCi_C6 alkyl. 134026-3 &gt;31 - 200916447 4. Compounds such as 靖 求 ,, where r4 & alkyl moiety The group is optionally substituted by a substituent selected from the group consisting of -OH, -N02 and CG-C6 alkyl-C(0)-N(R3)(R3a). 5. The compound of claim 1, wherein Each alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroarylcycloalkyl and heterocyclic moiety of z Independently substituted by one or more substituents, the substituents are independently selected from the group consisting of keto, -OH, -CN, QQ alkyl, qQ alkoxy, -N02, -N(R3)(R3a), halogen a compound of the formula 1, wherein l is selected from the group consisting of -C〇-C6 alkyl-N(R3)-C〇-C3 alkyl- Wherein, when the -C0-C6 alkyl group is a -C6 alkyl group, it is optionally substituted with a substituent selected from the group consisting of _Ci_c3 alkyl-ORa, -C "C3 alkyl-N(R3) (R3a). , -Q-C3 alkyl-C(0)ORa and C0-C3, -C(0)-N(R3)(R3 a); -C0 -C6 alkyl-N(R3)-C(O -C0 -C3 alkyl-, wherein when -C〇-C6 alkyl is a Ci-C6 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -(VQ alkyl-〇Ra, - q-Cs alkyl-NR3R3a, -CGC3 alkyl-C(0)0Ra and C〇-C3 alkyl-C(0)-N(R3)(R3 a); -C0-C6 alkyl-N (R3 -C(O)-C0-C3 alkyl-, wherein -C〇-C3 is a Q-C3 alkyl group, which is optionally substituted with a substituent selected from the group consisting of -N(R3)-C (0)-C〇-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -c(o)-N(R3)-Cg-C3 alkyl- Y, -C(5)-N(R3)-C〇-C 3 alkyl-Y, -n(r3)-c(o)-C〇-C3 alkyl-c4 -C6 cycloalkyl-, -N(R3)-C(S)-C〇-C3 alkyl- C4 -C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C〇-C3 alkyl-C4-C6 heterocycle , -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl 134026-3 -32- 200916447 -ORa, -N(R3)-C 〇-C3 alkyl-C〇-C3 heteroalkyl-fluorene, -N(R3)-C(O)-O-C0-C3 alkyl-Y, -n(r3)-c(5)-o-cQ-c3 Alkyl-y, -n(r3)-s(o)2-c〇-c3 alkyl-Y, -n(r3)-c(o)-n(r3)-c〇-c3 alkyl-Y '-n(r3)-c(s)-n(r3)-c0-c3 alkyl-υ, -n(r3)-c(o)-c〇-c3 alkyl-c〇-c3 heterocyclic group , -n(r3)-c(s)-C〇-C3 alkyl-CG-C3 heterocyclic group, -N(R3)-C(0)-CG-C3 alkyl-C〇-C3 heterocyclic group -Y, -n(r3)-c(s)-c〇-c3 alkyl-C〇-C3 heterocyclyl-Y and -n(r3)-s(o)2-n(r3)-c〇 -c3 alkyl-Y; -c0-c6 alkyl-N(R3)-C(S)-C〇-C3 alkyl-, wherein -c〇-c3 alkyl is q-c3 alkyl, The case is substituted by a substituent selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y , -c(o)-n(r3)-c〇-c3 alkyl-Y, -C(S)-N(R3)-C〇-C3 alkyl-Y, -n(r3)-c(o )- C0 -C3 alkyl-C4 -C6 cycloalkyl-, -N(R3)-C(S)-CQ-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkane -Y, -N(R3)(R3a), -N(R3)-C〇-C3 alkyl-C4-C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)( R3a), -N(R3)-C2-C3 alkyl-ORa, -N(R3)-C〇-C3 alkyl-C〇-C3 heteroalkyl-Y, -N(R3)-C(O) -O-C0 -C3 alkyl-Y, -n(r3)-c(5)-o-cQ-c3 alkyl-Y, -n(r3)-s(o)2-c〇-c3 alkyl-Y, -N(R3)-C(O)-N(R3)-C0-C3 alkyl-Y, -n(r3)-c(s)-n(r3)-c〇-c3 alkyl-y,- n(r3)-c(o)-c〇-c3 alkyl-c〇-c3 heterocyclic group, -n(r3)-c(s)-c0-C3 alkyl-CG-C3 heterocyclic group, - N(R3)-C(0)-CQ-C3 alkyl-CG-C3 heterocyclyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-C〇-C3 heterocyclic group -Y and -n(r3)-s(o)2-Ν(Κ3)-〇)-(:3 alkyl-Y; -c〇-c6 alkyl-c(o)-c〇-c3 alkyl - wherein, when the -c0-c6 alkyl group is a q-c3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(〇)-c〇-C3 alkyl- Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -C(0)-N(R3)(R3 a), 134026-3 -33- 200916447 -C(S)- N(R3)(R3a), -C(0)-N(R3)-C〇-C3 alkyl-oxime, -C(S)-N(R3)-C0-C3 alkane -Y, -N(R3)-C(0)-Cq-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C(s)-C〇-C3 alkyl-C4-C6 ring Alkyl...-N(R3)-C〇-C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C〇-C3 alkyl-C4-C6 heterocyclic, -N (R3)-C2 -C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl-ORa-, -N(R3)-C〇-C3 heteroalkyl-Y, -N(R3)-C(0)-〇-C0 -C3 alkyl-Y, -N(R3)-C(S)-O-C0-C3 alkyl-Y, -N(R3)-S( 0)2 -C0 -C3 alkyl-Y, -N(R3)-C(O)-N(R3)-C0-C3 alkyl-Y, -NO^KXSVN^i-Co-Cg alkyl-Y -N(R3)-C(0)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-C(S)-C〇-C3 alkyl-C〇-C3 Cyclol, -N(R3)-C(0)-C〇-c3 alkyl-C〇-C3 heterocyclyl-Y, -N(R3)-C(5)-C〇-C3 alkyl-C〇-C3 Heterocyclyl-Y and -N(R3)-s(o)2-n(r3)-c〇-c3 alkyl-Y; -C0 -C6 alkyl-(^)-〇)-(:3 A base-, wherein when -()-(6) is a group of (:1-(:3 alkyl), the substituent is optionally substituted by a substituent selected from the group consisting of -N(R3)-C(0) -C〇-C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -C(0)-N(R3)(R3 a) , -C(S) -N(R3)(R3a), -C(O)-N(R3)-C0-C3 alkyl-Y, -C(S)-N(R3)-C〇-C3 Base-y, -n(r3)-c(o)-c〇-c3 alkyl-C4-C6 cycloalkyl-, -n(r3)-c(5)-C0-C3 alkyl-C4-C6 cycloalkyl -, -N(R3)-C〇-C3 alkyl-Y '-N(R3)(R3 a), -N(R3)-CG-C3 alkyl-C4-C6 heterocyclic group, -N(R3 )-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl-〇Ra-, -N(R3)-C0-C3 heteroalkyl-Y, -N( R3)-C(0)-〇-C0-C3 alkyl-Y, -N(R3)-C(S)-O-C0-C3 alkyl-Y, -N(R3)-S(0)2 -C0 -C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C〇-C3:)^yl-Y, -N(R3)-C(5)-N(R3)-0 :0-(:3 alkyl-oxime, -wind 113)-〇:〇)-〇)-(:3 alkyl-oxime)-(:3 heterocyclic group, -wind 113)-c(s)- C〇-c3 alkyl-c〇-c3 heterocyclic group, -n(r3)-c(o)-c〇-c3 alkyl-c〇-c3 heterocyclic group-Y, -N(R3)-C (S)-C〇-C3 Alkyl-C〇-C3 Heterocyclyl-Y and -N(R3)-S(0)2 - 134026-3 -34- 200916447 N(R3)-C()-C3 Alkyl-oxime; -C〇-Q alkyl-, wherein when the -C0-C6 building group is a Q-C6 alkyl group, it is optionally substituted with a substituent. The substituent is selected from the group consisting of -N(R3)- C(0)-CG-c3alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-heterocyclyl and _N(R3)-C(0)-C. -C3 alkyl-cycloalkyl; -C0-C6 alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when _c0-C3 alkyl is Q-C:3 alkyl , which is optionally substituted by a substituent selected from the group consisting of -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(O)-heterocyclyl, _c(0)- N(R3)(R3a), aryl-aryl, aryl-heteroaryl, -heteroaryl-aryl,heteroaryl-heteroaryl,heteroaryl,heterocyclyl-heteroaryl and hetero a ring group; -c〇-c6 alkyl-heteroalkyl-c〇-c6 alkyl-c(o)-n(r3)-c〇-c3 alkyl-, wherein when -C0-C3 alkyl is q When the -c3 alkyl group is optionally substituted with a substituent, the substituent is selected from the group consisting of -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(o)-heterocyclic group, -C(0)-N(R3)(R3a), aryl-aryl, aryl-heteroaryl, _heteroaryl-aryl, heteroaryl-heteroaryl, heteroaryl, heterocyclic -heteroaryl and heterocyclic; -C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein -C〇-c6 alkyl is G-C6 alkyl When it is optionally substituted with a substituent selected from the group consisting of -N(R7)(R7a), -N(R3)(Rh), _N(R3)-C(O)-C0-C3 alkyl- Y, -N(r3)_ C(0)-0-C〇-C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C〇-C3 Alkyl-Y and -N(R3)-S(0)2-C〇-C3 alkyl-Y; -C〇-C6 alkyl-heteroaryl-C0-C3 alkyl-, wherein -C0- When the C3 alkyl group is a q-c3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -C〇-C3 alkyl-N(R3)-C(〇)-C〇-C3 alkyl group- N(R3)(R3a), -N(R3)-C(0)-c0-c3 alkyl-y, -n(r3)-c(o)-o-cg-c3 alkyl-y, -n (r3)-c(o)-n(r3)-134026-3 -35- 200916447 C〇-C3 alkyl-Y and -N(R3)-S(0)2-C. -C3 alkyl-oxime; -C0-C6 alkyl-aryl-C0-C3 alkyl-, wherein when _c〇-C3 alkyl is Ci-C alkyl, it is optionally replaced by a substituent The substituent is selected from the group consisting of _n(r3)-C(0)-C. -C3 alkyl group -Y, -N(R3)-C(0)-C. -C3 alkyl-Y,-N(R3)-C(0)-〇-C〇-C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C〇-C3 alkane -Y and -N(R3)-S(0)2 _ C0-C3 alkyl-Y; -C〇-C6 alkyl-aryl-heteroaryl-C0-C3 alkyl-, wherein -C When the 〇-C3 alkyl group is a q-C3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)-C()-C3 alkyl-Y, -N. (R3)-C(0)-C〇-C3 alkyl-Y, -n(r3)-c(o)-〇-cq-c3 alkyl-Y, -N(R3)-C(0)- N(R3)-C〇-C3 alkyl-Y and -N(R3)-S(0)2-Q)-C3 alkyl-Y; -c0-c6alkyl-heteroaryl-heteroaryl- C0-c3 alkyl-, wherein when -C〇-C3 alkyl is q-c3 alkyl, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(O)-C0 -C3 alkyl-Y, -N(R3)-C(O)-C0-C3 alkyl-Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y,-N (R3)-C(0)-N(R3)-C〇-C3 alkyl-Y and -N(R3)-S(0)2-C〇-C3 alkyl-Y; -c0-c6 alkyl -heteroaryl-C〇-C3 alkyl-, wherein when -c0-c3 alkyl is Q-C3 alkyl, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C (0)-C〇-C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-Y, -N(R3)-c(o)-oc〇-c3 alkyl -Y, -n(r3)-c(o)- n(r3)-c〇-c3 alkyl-Y and -N(R3)-S(0)2 -C〇-C3 alkyl-Y; -C〇-C6 alkyl-〇-C(0)- N(R3)-C〇-C3 alkyl-, wherein when the -C0-c3 alkyl group is a Cl-C3 alkyl group, it is optionally substituted by a group. The substituent is selected from -C(0)-0Ra, -C(S)-ORa, -C(0)-N(R3 alkyl, -CXSVNCRi-CrQ 134026-3 ·36· 200916447 alkyl, -C(0)-N(R3)(R3a)-,- C(S)-N(R3)(R3a)-, -C(O)-N(R3)-C0-C3 alkyl-aryl, -c(s)-n(r3)-cvc3 alkyl-aryl , -c(o)-n(r3kvc3 alkyl-heteroaryl, -C(5)-N(R3)-C〇-C3 alkyl-heteroaryl, -C(0)-N(R3)-Cq&lt ;:3 alkyl-cycloalkyl, -C(S)-N(R3)-CG-C3 alkyl-cycloalkyl, -C(O)-heterocyclyl, -C(S)-heterocyclyl , -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(S)-N(R3)-C0-C3 alkyl-Y, -C(0)-N(R3) -heterocyclyl, -C(s)-N(R3)-heterocyclyl, -c(o)-n(r3)-c〇-c3 alkyl-heterocycloalkyl and -C(s)-N (R3)-CQ-C3 alkyl-heterocycloalkyl; -c0-C6 alkyl-0-C(S)-N(R3)-C〇-C3 alkyl-, wherein -C0-C3 alkyl When it is a Q-C; 3 alkyl group, it is optionally substituted by a group selected from -C(0)-ORa, -C(S)-ORa, -C3 alkyl, -C3 alkyl, - C(0 )-N(R3)(R3a)-, -C(S)-N(R3)(R3a)-, -C(0)-N(R3)-C〇-C3 alkyl-aryl, -(^ )-Ν(Ι13Κν(:3 alkyl-aryl, -C(0)-N(R3)-Cg-C3-based-heteroaryl, -C(S)-N(R3)-C〇-C3 Alkyl-heteroaryl, -C(0)-N (R3KVC3 alkyl-cycloalkyl, -C(S)-N(R3)-Cg-C3 alkyl-cycloalkyl, -c(o)- Heterocyclyl, -C(S)-heterocyclyl, -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(5)-N(R3)-C〇-C3^- Y, -C(0)-N(R3)-heterocyclyl, -C(5)-N(R3)-heterocyclyl, -C(0)-N(R3)-CG-C3 alkyl-heterocycloalkyl And -C(S)-N(R3)-CG-C3 alkyl-heterocycloalkyl; and _Ci _匚3 11 yl-N(R3)-C(0)-Ci-C7 alkyl-' Wherein the Ci-C3 alkyl group is optionally substituted by -C(0)N(R3)-(:!-C3 alkyl-A1a, and the Q-C7 alkyl group is optionally substituted with a substituent selected from the group consisting of Including -N(R3)-(:(0)-0-(^-C3 alkyl-A1 b, -N(R3 alkyl-A1 b, -N(R3)4(0)2-(^-C3 Alkyl-A1 b, -N(R3 -C3 alkyl-A1 b, -N(R3)-C(0)-N(R3-C3 alkyl 134026-3 -37- 200916447 alkyl-Alb, wherein A1 3 and A1 b are independently selected from the group consisting of alkyl, alkenyl and protecting groups; or octa 13 and Alb- via -C2-C6 alkyl-, -C2-C6-alkenyl-, _C2 The _C6-alkynyl- or -C〇-C3 alkyl-heteroaryl-C0-C3 alkyl-linker forms a ring which is optionally substituted. 7. The compound of claim 1, wherein l is selected from the group consisting of -Q-C6 alkyl-N(R3)-C0-C; 3-alkyl-, wherein the q-C6 alkyl group is optionally substituted with a substituent, The substituent is selected from the group consisting of -q-C4 alkyl-〇Ra, -(^-&lt;:6-alkyl-N(R3)(R3 a)-, -c0-C4 alkyl-C(0)0Ra and - C〇-C3 alkyl-C(0)-N(R3)(R3 a ^ -C〇-C: 6 alkyl-N(R3)-C(O)-C0-C3 alkyl-' where q - The C6 alkyl group is optionally substituted with a substituent selected from the group consisting of alkyl-0(Ra)-, -CQ-C6 alkyl-C(0)0(Ra)-, and -C6 alkyl-N (R3). (R3 a)-; and _C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein the Q-C6 alkyl group is optionally substituted with a substituent, a substituent Selected from the group consisting of -CG-C6 alkyl-0(Ra)-, -C0-C6 alkyl-C(0)0(Ra)-, -CG-C3 alkyl-C(0)-N(R3)( And R.sup.5. 0)-(^-C7 alkyl-, wherein the q-C7 alkyl group is optionally substituted by a substituent selected from the group consisting of -N(R7)(R7a), -N(R3)C(0)-C 〇-C3 alkyl-heterocyclic group, _n(r3)-c(o)-c〇-c6 alkylaryl-Ra, -N(R3)-(:(0)-(^-C6 alkyl- Ra And -N(R3)-C(O)-O-C0-C3 alkyl-Y, wherein the heterocyclic group is optionally substituted; -C〇-C6 alkyl-C(0)-N(R3-C7 Alkyl-, wherein q-C6 alkyl is optionally substituted by -N(R7)(R7a); 134026-3 •38- 200916447 -C0 -C6 alkyl-C(0)-N(R3 -C7 alkyl - wherein c! -C7 alkyl is optionally substituted with a substituent selected from the group consisting of aryl-aryl, aryl-heteroaryl, heteroaryl-heteroaryl, heteroaryl-aryl and Heteroaryl; and -c! -C3 alkyl-N (R3 KXCO-C! -c7 alkyl-, wherein q-C3 alkyl is optionally taken as -C(0)N(R3)-(:! (3⁄4 alkyl-A1 a substituted, and the q-C7 alkyl group is optionally substituted by a substituent selected from the group consisting of _N(R3)_c(〇)〇_Ci_C3 alkyl_Ai b , -^3 )-(:(0)-(^-C3 院-A1 b, -N(R3 )-8(0)2-(^-(:3 alkyl-A1 b, -N(R3)-C( 0)-N(R3 -C3 alkyl_Ai b and _N(R3 )_s(〇) 2 _n(r3 ) Ci 4 alkyl-A1 b, wherein Aj a and A! b are independently selected from the group consisting of alkyl groups , alkenyl and protecting group; or Ala and Alb together via -(:2-(:6-alkyl, -C2-C6-alkenyl, -C2-C6-fraction, -C0-C3 alkyl-hetero aryl-Q-C3 alkyl-linker or -Q-C3 alkyl-3⁄4 -CQ -C: 3 burn-yl - linking group formed of an optionally substituted ring. 9. The compound of claim 1 wherein l is selected from the group consisting of -C〇-C7 alkyl-N(R3)-C(0)-heterocyclyl-c0-C6 alkyl-, wherein q-C7 alkyl Depending on the case, it is substituted by -C〇-C3 alkyl-C(〇)〇Ra or -Ci-C3 alkyl-〇Ra; and -C〇-C:7-alkyl(OC)-heterocyclyl- C0-c6 alkyl-, wherein the q-C7 alkyl group is optionally substituted by -C〇-C3 alkyl-C(0)0Ra or -C〇-C3 alkyl-〇Ra. 10. The compound of claim 1 wherein L is selected from the group consisting of a covalent bond, -(chj 4_ , -(CH2)0.4-(CR3 =CR3)-(CH2)0.4-, -(CH2)〇.4- (CeC)-(CH2)0-4-, -(CH2)〇.3N(R3)C(0)- '-(CH2)0.3-C(O)N(R3)- &gt; -(CH2)〇 .3N(R3)C(0)-(CRa=CRa)- ^ -(CH2)0.3.N(R3HCH2)2.4N(R3)C(O)- ^ -(CH2)〇.3-0-(CH2 ))-(CR3)〇(3)-^-(CH2)〇.3C(〇HCH2)0.3-^ - ^ -(CH2)0.3C(〇HCRa=CRaHCH2)0.3- ' 134026-3 -39- 200916447 _C0 -C6 alkyl-N(R3)-C(0)-heterocyclyl-C〇-C3 alkyl -, -C〇-C6 Institute-S(0)2-Heterocyclyl-C〇-C3 alkyl-,-(CH2)〇_3-S(0)2-N(R3)-(CH2) 〇_3-, -(CH2)〇. 3 N(R3 )-S(0)2 -(CH2 )〇. 3 -, -(CH2)〇.3N(R3HCH2)0.3-, -(^2)0.3 ^^)-(^2)^3-(0^=0^)- ' -(CH2)0-3C=NO-(CH2)0.3-' -(CH2)〇.3N(R7)-(CH2) 0.3- &gt; -(CH2)〇.3S-(CH2)〇.3- '-(CH2)〇, 3〇-(ch2)〇_3-, _(ch2). .3s(o)-(ch2)0.3-, -(CH2)0.3S(O)2-(CH2)0.3-, -(CH2)0.3CH=CH-(CH2)2-3-, -(CH2) 0-3N(R3)-C(0)-N(R3)-(CH2)0-3, -(CH2)〇. 3 N(R3)-C(0)-0-(CH2)〇. 3 , -(CH2)〇.30-C(0)-N(R3)-(CH2)0.3- , -(CH2 )0 _ 3 N(R3 )-C(0)-N(R3 )-S(0) 2 -(CH2 )〇— 3 - and -(CH2 )〇. 3 N(R3 )-C(0)-N(R3 )-C(0)-(CH2 )〇. 3 - 〇11. a compound of 1, wherein the B2 and B3 lines are independently selected from the group consisting of D-Gly, L-Gly, D-Pro, L-Pro, D-Tyr, L-Tyr, D-Tyr (ORa), L-Tyr (ORa) ), D-Phe, L-Phe, D-PheR4, L-PheR4, D-Aib, L-Aib, D-Ala, L-Ala, D-ProRg, L-P1OR3, D-Ile, L-Ile, D-Leu, L-Leu, D-PheR3, L-PheR3, D-Pip and L-Pip. 12. The compound of claim 1, wherein each of the alkyl, alkenyl, alkynyl, heteroalkyl, benzyl and heterocyclyl groups of R/ and R7a is independently substituted by one or more Substituent, the substituent is selected from the group consisting of keto, -OH, -CN, Ci-C6 alkyl, CVC6 alkoxy, -N02, -N(R3)(R3a), halo, -SH and mono-to-all - Halogenated CVQ alkyl. 13. The compound of claim i, wherein each gamma is independently selected from the group consisting of aromatic polycyclic, non-aromatic polycyclic, mixed aryl and non-aryl polycyclic, polyheteroaryl, non-aromatic polyheterocyclic Mixed aryl groups and non-aryl polyheterocycles, each of which is optionally substituted. 134026-3 •40- 200916447 Μ.If the compound of claim i, 装装* each γ is independent 1P έ 6 kw aryl-aryl, heteroaryl, aryl-heteroaryl, 4, self-branched , an aromatic heterocyclic group and a heterocyclic group-heteroaryl group, a heteroarylaryl group, a cycloalkyl group, a parent group, are substituted in the case of a. Wherein D is C/Rb lw, 15 is a compound of claim 1 and the compound of claim 1 is as claimed in claim 1. The compound of claim 1 is the compound of claim 1, wherein D is wx, ϊ(r Rb RC x or I ^ Ra - Bu w\_ meaning _ where D is I r .f — w\ , Rh where D is $ ir —% shoulder n S (T II X Rb , Rh X 'N, /CH3 19. A compound of claim 1 wherein the compound of claim 1 is as claimed in claim 1 wherein compound D is the compound of claim 1 wherein D is wherein X is oxime. wherein X is S. 22. as claimed, wherein 俨, ^ and 尺Independently selected from the group consisting of -Η, 23, such as bismuth, η, aryl, heteroaryl, and aryl. _. -2 == '', and 妒 and the nitrogen atom to which they are attached 3 to 9-benztyl, heteroaryl or heterocyclyl-aryl, hetero-, heteroaryl and heterocyclyl-aryl are optionally substituted." 24. (4) The lanthanide is independently selected from the group consisting of ugly, -1 C6-based 'c3 -C6 cycloalkyl, _q〇) cf3, _c(〇)h, _c c alkyl-C(〇)ORa, heterocyclic, _Q _Q regulation base _〇Ra, &amp; _q sub-formation base, ·: base, c2-Q__c factory w-based aryl, Fang , _c〇_Q pheno-hetero 6 soil and A-C3 alkyl-C(〇)N(Ra)-heteroaryl. 134026-3 41 · 200916447 25 j π unresolved compound, its ^ A w A series of bracelets are selected from the group consisting of -C1&lt;:alkylaryl, tert-butylfluorenyl and aryl. 6 26. The compound of claim i, wherein the ^, K are independently selected from the group consisting of ethanol, tetraterpene- 2Η-pyran, phenyl and benzyl. 27' The compound of claim k, wherein R3#R3a is independently ["based. 28. For example, the compound of the item, wherein ^N(R3)(R3a) In the group, r3 and the nitrogen atom to which a ί is attached are formed into a ring, which is selected from the group consisting of phenoline, hydrogen t, hexammine, tetrahydrofuranyl and A compound of the formula IV, wherein R4 is selected from the group consisting of η, -s(〇)2 Zheng 3)(R3a), -so#, _0_C2_C4 alkylheterocyclyl, _ac=alkane Base-aryl, -O-Co-C: 4 alkyl-heteroaryl, _〇_C(〇)N(R3)_C〇_C4 alkylaryl, -〇-C(〇)N(R3 )-C〇-C: 4 alkyl-heteroaryl, _0_c〇π*alkyl-heterocyclyl-aryl, -〇-C0-C: 4 alkyl-heterocyclyl-heteroaryl, _N ( R3)_C2 &amp; Base, heterocycle \ group, -(CH2)0_4〇Ra, -(CH2)0_4N(R3)(R3a), -F, -Cl, -Br, -CF3, -CN, -CH2OH, -OH, -〇 CH3, -N02, Ph, aryl, heteroaryl, -N(R3)C(〇)CH2R3, -N(R3)S02CH2Ra, -〇(CH2)2_4N(R3)(R3a), -SRa, -S (〇)CH2R3, -S02CH2Ra, -(CH2)0.4C(O)ORa, -CH=CHC(〇)〇Ra, -CH=CHC(0)N(R3)(R3a), -N(R3)C (0) CF3 and -N(R3)(CH2)2N(R3)(R3a). 3. The compound of claim 1, wherein Rh is -CH3 ° 31. The compound of claim 1, wherein Rh is _Cf3. 32. The compound of claim 1 wherein l is selected from the group consisting of 134026-3 -42- 200916447 200916447200916447 200916447200916447 134026-3 -45- 200916447134026-3 -45- 200916447 r3 〜s、s\ N〇H R3R3 ~s, s\ N〇H R3 -46- 134026-3 200916447-46- 134026-3 200916447 134026-3 -47- 200916447134026-3 -47- 200916447 其中 八1&amp;與八11}係獨立選自包括烷基、烯基及保護基 '，且 各A係獨立選自N、CH或C (當A係連接至Y或Z時），其 中可以有0、1、2或3個氮。 33.如請求項1之化合物，其中Z係選自包括Wherein the eight 1&amp; and eight 11} are independently selected from the group consisting of alkyl, alkenyl and protecting groups, and each A is independently selected from N, CH or C (when the A is linked to Y or Z), which may be 0, 1, 2 or 3 nitrogens. 33. The compound of claim 1, wherein the Z is selected from the group consisting of A； R3A; R3 Ό. AΌ. A '/a I .k (CH2£ V &gt; ,(〇Η2)σ3 αό&gt;Α^ (CH2)〇-3 R3 h m . δ &quot;V,.%A、f(CH2“ ,Α-λ'/a I .k (CH2£ V &gt; ,(〇Η2)σ3 αό&gt;Α^ (CH2)〇-3 R3 h m . δ &quot;V,.%A,f(CH2" ,Α-λ (CH2)〇-3 °'3 A- A^/A(CH2)〇-3 °'3 A- A^/A ϋ〇3 A ,A (CH2)^ ,x、(ch2&lt;—4Ϋ〇3 A , A (CH2)^ , x, (ch2&lt;-4 134026-3 -48· 200916447 \,134026-3 -48· 200916447 \, 其中各A係獨立為氮、-CH=或-C(R4)=，其中可以有0、1、 2或3個氮。 34.如請求項1之化合物，其中各Υ係獨立選自包括 134026-3 -49- 200916447Each of the A lines is independently nitrogen, -CH= or -C(R4)=, wherein there may be 0, 1, 2 or 3 nitrogens. 34. The compound of claim 1, wherein each of the steroids is independently selected from the group consisting of 134026-3 -49-200916447 134026-3 -50- 200916447134026-3 -50- 200916447 134026-3 -51 - 200916447134026-3 -51 - 200916447 134026-3 -52 200916447134026-3 -52 200916447 134026-3 -53- 200916447134026-3 -53- 200916447 134026-3 -54- 200916447134026-3 -54- 200916447 134026-3 •55- 200916447134026-3 •55- 200916447 134026-3 -56- 200916447134026-3 -56- 200916447 // 各A係獨立為氮 2或3個氮； -C(H)=或_C(R4)= ’其中可以有〇、1、 &amp; B各獨立為天然或合成胺基酸； Mi_M2係選自包括共價鍵、=N(R3)CH2—、—CH2n(r3)_、 -S(O)0_2-CH2-、_CH2S(O)0_2- ' -〇_ch2-、-CH2-0-、-C(0)N(Ra)-、 -N(R3)C(0)-、-S02N(R3)-、-N(R3)S02-、-CH(Ra)CH2-、-CH2CH(Ra)-、-N=C(Ra)-、-C(Ra)=N-、-CH2-CH2-、-CH=CH-、-CH(Ra)-CH(Ra)-、 134026-3 -57- 200916447 -C(Ra)=C(Ra)-、-CH2-、-C(Ra)(Ra)-、-S-、_N(R3)-及不存在 ^ΛΑΛ/ I s/vJdv m3係選自包括’ 又及人； r3 (9)0.2 m4係選自包括’ k0〆’ \s〆' ’及共價鍵； r3 其中當％ -M2為共價鍵時，m4為^ 及 (9)0-2 W : \°v^ ^v°y VVVN^ I Dj -D2係選自包括 WWVEach A is independently 2 or 3 nitrogens; -C(H)= or _C(R4)= 'wherein 可以, 1, &amp; B are each independently a natural or synthetic amino acid; Mi_M2 is selected from Including covalent bond, =N(R3)CH2—, —CH2n(r3)_, -S(O)0_2-CH2-, _CH2S(O)0_2- '-〇_ch2-, -CH2-0-,- C(0)N(Ra)-, -N(R3)C(0)-, -S02N(R3)-, -N(R3)S02-, -CH(Ra)CH2-, -CH2CH(Ra)- , -N=C(Ra)-, -C(Ra)=N-, -CH2-CH2-, -CH=CH-, -CH(Ra)-CH(Ra)-, 134026-3 -57- 200916447 -C(Ra)=C(Ra)-, -CH2-, -C(Ra)(Ra)-, -S-, _N(R3)- and the absence of ^ΛΑΛ/ I s/vJdv m3 are selected from the group consisting of ' and human; r3 (9) 0.2 m4 is selected from the group consisting of 'k0〆' \s〆' and covalent bonds; r3 where % -M2 is a covalent bond, m4 is ^ and (9) 0- 2 W : \°v^ ^v°y VVVN^ I Dj -D2 is selected from WWV 其中*表示對Q之連接 c,' D3係選自包括共價鍵、 其中\&gt;、與係視 R3 0)〇-2 W 1 ，V5，’，及丨'〜、 情況經取代； d4係選自包括士 ’奸及你 其中乂，1、係視情況經取代’ Ει~Ε2係選自包括 134026-3 -58- 200916447Where * indicates a connection to Q, 'D3 is selected from the group consisting of a covalent bond, where \&gt;, and the system R3 0) 〇-2 W 1 , V5, ', and 丨 '~, the case is replaced; d4 The line is selected from the group consisting of the traitor and the cockroaches of yours. 1. The system is replaced by the case 'ι~Ε2 is selected from the group consisting of 134026-3 -58- 200916447 e3係選自包括-C(0)_、_c⑸_、_CH2_、_c(OH)2_A C=NR3_; 且 R6係選自包括-Η、-CrQ烷基、-(VQ烯基、-c2_c6炔基、 -q-C：6雜烷基、雜環*_c〇_C6烷基_、芳基_c〇_C6烷基_、雜 芳基-C〇 -c6 烷基-、c3 _c6 環烷基 _c〇 A 烷基 _、n(R3 )(r3 a )_Ci 烷基-、N(R3)(R3a)_C(0)_Ci_C4*_AN(R3)(R3a)_c(s)_c「c^ V 基-，其中各烷基、烯基、炔基 '雜烷基、環烷基、芳基、 雜芳基或雜環基部份基團係視情況經取代。 35.如請求項34之化合物，其中r6之各烷基、烯基、炔基、雜 烷基、環烷基、芳基、雜芳基及雜環基部份基團係獨立視 情況被一或多個獨立選自R4之基團取代。 36.如請求項34之化合物，其中R6係選自包括 CO (CH2)〇.3 、(ch2)CThe e3 is selected from the group consisting of -C(0)_, _c(5)_, _CH2_, _c(OH)2_A C=NR3_; and R6 is selected from the group consisting of -Η, -CrQ alkyl, -(VQ alkenyl, -c2_c6 alkynyl, -qC: 6 heteroalkyl, heterocyclic ring *_c〇_C6 alkyl_, aryl_c〇_C6 alkyl_, heteroaryl-C〇-c6 alkyl-, c3 _c6 cycloalkyl_c〇 A alkyl group, n(R3)(r3 a )_Ci alkyl-, N(R3)(R3a)_C(0)_Ci_C4*_AN(R3)(R3a)_c(s)_c"c^ V base-, Wherein each alkyl, alkenyl, alkynyl 'heteroalkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl moiety is optionally substituted. 35. The compound of claim 34, wherein r6 Each of the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl moieties is independently substituted by one or more groups independently selected from R4, as appropriate. 36. The compound of claim 34, wherein R6 is selected from the group consisting of CO(CH2)〇.3, (ch2)C (ch2)〇》(ch2)〇 fl hi ' (CH2)〇&gt;3Fl hi ' (CH2)〇&gt;3 R3^ 又, R3、 r(CH‘ ^ d R3R3^ again, R3, r(CH' ^ d R3 σ (CH2)5&quot; 及 A (CH‘3 37·如明求項1之化合物，其中R7係選自包括-H、視情況經取 代之 Cl~c6烧基、-(CH2)2_4ORa、-OMe、-CH2)2-4N(R3)(R3a)、 _C(0)0第三-丁基、-c(〇)〇-苄基、-(ch2)2-嗎福啉基及 _(ch2)2- 六氫P比呼基。 134026-3 -59· 200916447 38. 如請求項1之化合物，其中 Rc Ra ^—&lt;c&gt;Rb D為 S ; W與M為氮； 以與以為#; Rb為-〇-烷基-芳基或-〇-烷基-雜芳基，其中該烷基、芳基 及雜芳基部份基團係視情況經取代； Z為-(VC8烷基-; L 為共價鍵、-C〇 _c6 烷基-N(R3 )c(〇)_C(} &amp; 烷基-、_c〇 % 烷 基-N(R3 )C(S)-C〇 -C3 烷基-、-C〇 -C6 烷基-C(0)N(R3 )-C〇 -C3 烷基-或-C〇 -C6 烷基-C(S)N(R3 )-CG -C3 烷基-;且 Y係選自包括烧基、芳基、雜芳基、芳基-芳基、雜芳 基-芳基-、芳基-雜芳基-及多環，其中各烷基、芳基、雜 芳基及多環係視情況經取代。 39. 如請求項1之化合物，其中 R° I i-W V , ^ D為 x ; W為氮； Re 為-Η ; Rh 為-C〇 -Cg 烧基-〇-C〇 -Cg 烧基-芳基或-C〇 -Cg 烧基-0-C〇 -Cg 燒基-雜^基，其中規基、·方基及雜方基部i分基團係視情 況經取代； Z 為-Ci -C8 炫&gt; 基-; L為共價鍵、-Q -C6烷基-N(R3 )C(O)-C0 -C3烷基或-Q -C6烷 134026-3 -60· 200916447 基-α：ο)Ν(ιι3κνί：3烷基；且 γ係選自包括烷基、芳基、雜芳基、芳基-芳基、雜芳 基-芳基-、芳基-雜芳基-及多環，其中各烷基、芳基、雜 芳基及多環係視情況經取代。 40. —種式（II)化合物： n1 (II) 或其N-氧化物、水合物、溶劑合物、藥學上可接受之鹽、 前體藥物或複合物，或其外消旋與呈比例混合物、非對映 ，. x 異構物或對掌異構物，其中R係選自包括：σ (CH2)5&quot; and A (CH'3 37. The compound of claim 1, wherein R7 is selected from the group consisting of -H, optionally substituted Cl~c6 alkyl, -(CH2)2_4ORa, -OMe , -CH2)2-4N(R3)(R3a), _C(0)0 tert-butyl, -c(〇)〇-benzyl, -(ch2)2-norfosolinyl and _(ch2) 2-Hexahydrogen P is more than a base. 134026-3 -59· 200916447 38. The compound of claim 1, wherein Rc Ra ^—&lt;c&gt; Rb D is S; W and M are nitrogen; and the meaning is #; Rb is -〇-alkyl-aryl Or a fluorenyl-alkyl-heteroaryl group, wherein the alkyl, aryl and heteroaryl moiety are optionally substituted; Z is -(VC8 alkyl-; L is a covalent bond, -C 〇_c6 alkyl-N(R3)c(〇)_C(} & alkyl-, _c〇% alkyl-N(R3)C(S)-C〇-C3 alkyl-, -C〇- C6 alkyl-C(0)N(R3)-C〇-C3 alkyl- or -C〇-C6 alkyl-C(S)N(R3)-CG-C3 alkyl-; and Y is selected from Including alkyl, aryl, heteroaryl, aryl-aryl, heteroaryl-aryl-, aryl-heteroaryl- and polycyclic, wherein each alkyl, aryl, heteroaryl and polycyclic 39. The compound of claim 1, wherein R° I iW V , ^ D is x; W is nitrogen; Re is -Η; Rh is -C〇-Cg alkyl-〇-C〇 -Cg alkyl-aryl or -C〇-Cg alkyl-O-C〇-Cg alkyl-hetero, wherein the base group, the square group and the hetero-group base i group are optionally substituted; Z is -Ci -C8 dazzle &gt; base -; L is a covalent bond, -Q -C6 alkyl-N(R3 )C (O)-C0-C3 alkyl or -Q-C6 alkane 134026-3 -60· 200916447 ke-α: ο) Ν (ιι3κνί: 3 alkyl; and γ is selected from the group consisting of alkyl, aryl, heteroaryl Alkyl, aryl-aryl, heteroaryl-aryl-, aryl-heteroaryl- and polycyclic, wherein each alkyl, aryl, heteroaryl and polycyclic ring is optionally substituted. a compound of formula (II): n1 (II) or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, prodrug or complex thereof, or a racemic to proportional mixture thereof, An enantiomer, an x-isomer or a palmomer, wherein the R is selected from the group consisting of: 134026-3 -61 - 200916447134026-3 -61 - 200916447 D係選自包括D is selected from 其中Ri為選用之取代基，且nl為0-4。 41.如請求項1之化合物，其中Wherein Ri is an optional substituent and nl is 0-4. 41. The compound of claim 1, wherein W為氮或氧； Μ為氮； Ra、Rb 及 Rc 為-Η ; Ζ 為-C8 烷基-或-Ci -c8 烷基-C(O)-; 134026-3 •62- 200916447 L 為-CVC6烷基-N(R3)C(O)-C0-C3烷基；且 Y為烷基、芳基、雜芳基、雜芳基_芳基或芳基_雜芳基， 其中院基、芳基及雜芳基係視情況經取代。 42. 如請求項41之化合物，其中γ之烷基、芳基及雜芳基係視 情況被取代基取代，取代基選自包括烷氧基、烷基、芳基、 -0-烷基-雜芳基及_〇_烷基_芳基。 43. 如請求項1之化合物，豆中 -i—W、/Rh /1 ο 1 D 為 S ; W為氮或氧； Rc 為-Η ; Rh為Η或-Ci-Q烷基，其中該烷基係視情況經取代； Z 為-C! -C8 烷基-或-C8 烷基-c(0)-; L 為-C〇 -C6 烷基-N(R3 )C(O)-C0 -C3 烷基；且 Y為烷基、芳基、雜芳基、雜芳基-芳基或芳基_雜芳基， 其中烧基、芳基及雜芳基係視情況經取代。 、44.如請求項43之化合物，其中υ之烷基、芳基及雜芳基係視 情況被取代基取代，取代基選自包括烷氧基、烷基、芳基、 -0-烷基-雜芳基及·〇_烷基-芳基。 45.如請求項1之化合物，其中 1-W Μ D為 χ ; W與Μ為氮； Ra、Rb 及 Rc 為-Η; 134026-3 200916447 R3為-Η或CVQ烷基； Ζ為視情況經取代之-C8烷基-; L係選自包括 -C〇 -C6 烧基-C(0)-N(R3 )-C。-C3 烧基-、-C。-C6 烧基-N(R3 )-C(0)-N(R3 )-C〇 -C3 烧基-或-C〇 -C6 烧基-0-C〇 -C3 烧基-C(0)-N(R3 )-C0 -C3 烧基_ ’其中當C〇 -C3烧基為C】-C3烧基時，此Q -C3烧基係視 情況被-C(O)-N(R3)-C0-C3烧基-Y、芳基、雜芳基、-雜芳基_ 芳基、-芳基-雜芳基、-芳基-芳基雜芳基-雜芳基、_N(R3 )(R3 a) 或-N(R3)-Y取代，其中各雜芳基或芳基部份基團係視情況 經取代； -C〇-C6烷基-雜烷基-CG-C6烷基-C(0)-N(R3 )-C〇-C3烷基…其 中當c0-c：3烷基為烷基時，此烷基係視情況被雜 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 -Q-Q烷基-N(R3)C(O)-C0-C3烷基-，其中當c〇-C3烷基為 C1-C3烷基時’此Q-C3烷基係視情況被_N(R3)(R3a)、 -N(R3)-Y、-N(R3)-C(0)-0-C〇-C3 烷基-Y、-NH2、-nh-s(o)2-y、 -NH-C(O)-NH-C0-C3 烷基-Y、-NH-雜芳基-芳基或-N(R3)C(0)- C0 -C3烷基-γ取代；且 各Υ係獨立選自包括Η、烷基、環烷基、芳基、雜環基、 雜芳基-芳基、芳基-雜芳基、雜環基_〇-、芳基_n(r3) c(〇)_ 雜芳基、雜芳基_n(r3)-c(o)-雜芳基、芳基-N(R3)-C(0)-芳基、 雜環基-c〇-c6烧基_N(R3)-C(0)-雜芳基及 B2_Bl_N(R3)-C(0)-Cl-C7烷基_，其中烷基、環烷基、芳基、 雜芳基及雜環基部份基團係視情況經取代，且Ci _c7烷基係 134026-3 -64- 200916447 視情況被-NR3_B3取代，及B3之胺係與B2之酸連接，以形成 肽鍵，且其中當γ為B2_Bl摩3)_c(〇)_Ci_C7烷基_時，則讀 L為共價鍵；其中 ，其係藉由肽鍵連 、L-ile 及 D-Phe-4-CF3。 當任何B1、B2及B3係連接在一起時 接’且B1、B2及B3係獨立選自包括D-pro 46.如請求項1之化合物，豆中 ^ T ' l—W\ /Rh D為 贫； i , W為氮； Rm; R為Η或-C! -C6烧基，其中該烧基係視情況經取代； R3為-H或(VC6烷基； Z為視情況經取代之-C8烷基-; L係選自包括 -c〇-c6 烧基-C(0)-N(R3)-C〇-C3 烷基-、_c0-C6 烷基-N(R3)-C(0)- N(R3 )-Q -C3 烷基-或-C0 -C6 烷基-0-C〇 -C3 烷基 _c(〇)_n(r3 )_c〇 £ V 烧基_，其中當C〇_C3烷基為ci -C3烷基時，此q -C3烷基係視 情況被-C(0)-N(R3 )-C〇-C3烧基-Y、芳基、雜芳基、_雜芳基_ 芳基、-芳基-雜芳基、-芳基-芳基、雜芳基-雜芳基、 -N(R3)(R3a)或-N(R3)-Y取代，其中各雜芳基或芳基部份基團 係視情況經取代； -C〇 -C6 炫基-雜烧基-C0 -C6 烧基-C(0)-N(R3 )-C〇 -C3 烧基-，其 中當Co-Q烷基為Q -C3烷基時’此C! -C3烷基係視情況被雜 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 134026-3 -65- 200916447 -Co-Q烷基-N(R3)C(O)-C0-C3烷基-’其中當c〇_c3烷基為 C^-C^烧基時，此Ci-Cs烧基係視情況被_N(R3)(R3a&gt;、 -N(R3)-Y、-N(R3)-C(O)-O-C0-C3 烷基-Y、-NH2、-NH-S(〇)2-Y、 -NH-C(0)-NH-C〇-C3 烷基-Y 、-NH-雜芳基 _ 芳基戋 -n(r3)c(o)-c〇-c3烷基-Y取代；且 各Υ係獨立選自包括Η、烷基、環燒基、芳基、雜環基、 雜芳基-芳基、芳基-雜芳基、雜環基_0_、芳基_N(R3)_C(0)_ 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(R3)_c(〇)_芳基、 雜環基-C0-C6 烷基-n(r3)-C(0)_ 雜芳基及 B2 _b1_n(r3)_c(〇)_ cvcwm烧基、環烧基、芳基、雜芳基及雜環基 部份基團係視情況經取代，且基係視情況被 -NR3-B3取代’及以之胺係與B2之酸連接，以形成肽鍵，且 /、田¥為8 -B WKXOKVC^基-時，則2與[為共價 鍵； ' 其中 ^任何B1、B2及B3係連接在-起時 接且B1、B2及B3係獨立選自包括D-Pr〇· 47.如請求項1之化合物，其中 ’其係藉由肽鍵連 L-ile 及 D-Phe-4-CF3。 Ra Rb .Μ X W與Μ為氮； Ra、於及Rc為、Η; R3為-H或Cl_C6燒基； z為視情況經取代之_Ci_Cs院基 134026-3 -66 - 200916447 L係選自包括 -c0 -C6 烷基-C(0)-N(R3 )-C。-C3 烷基-、-c。-C6 烷基-N(R3 )-C(0)-N(R3 )-C〇 -C3 烧基-或-C〇 -C6 炫基-〇-C〇 -C3 烧基-C(0)-N(R3 )-C〇 -C3 烷基-’其中當C0-C3烷基為Ci-q烷基時，此烷基係視 情況被-C(0)-N(R3 )-C〇-C3烷基-Y、-雜芳基-芳基、雜芳基、 雜芳基-雜芳基、-N(R3)(R3a)或-N(R3)-Y取代，其中各雜芳基 或芳基部份基團係視情況經取代； -C0-C6 烷基-雜烷基-C〇-C6 烷基-C(0)-N(R3)-C〇-C3 烷基-，其 中當C〇 -C3炫基為Q -C3烧基時，此C〗-C3烧基係視情況被雜 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 -C〇-C6烷基-N(R3)C(0)-C〇-C3烷基-，其中當c0-C3烷基為 Q -C：3烷基時，此c! -C3烧基係視情況被_n(R3)-C(O)-O-C0-C3 烷基-Y、-NH2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-Y、-NH-雜芳基-芳基 ' -N(R3 )C(O)-C0 -C3 烷基-Y、_N(R3 )(R3 a)或-N(R3 )-Y 取代；且 各Y係獨立選自包括H、烷基、環烷基、芳基、雜芳基、 雜芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_n(r3)_c(〇)_ 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(r3)_c(〇)_芳基、 雜環基-C0-C6 烷基-N(R3)-C(〇)-雜芳基及 ^-ΒίΝ^ΚΧΟ)-Q -C7烷基-，其中環烷基、芳基、雜芳基、雜環基及烷基 部份基團係視情況被一、二或三個取代基取代，取代基選 自包括i基、烷氧基、視情況經取代之q _C6烷基、烷氧羰 基-、-OH、-CN、-CXCO-OH、視情況經取代之芳基、視情 況經取代之-烷基芳基、視情況經取代之雜芳基、視情況 134026-3 -67- 200916447 經取代之-O-Cn -c6烷基-芳基、視情況經取代之-cxco-o-Ci -c6 炫基、-NH2、視情況經取代之-芳基_雜環基及視情況經取 代之稠合雜環’且q -C7烷基係視情況被-NR3 -B3取代，及 B3之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 B2 -B1 -N(R3 -C7烷基-時，則Z與L為共價鍵；其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接’且B1、B2及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 48.如請求項1之化合物，其中 Rc ’、 —W\ /Rh D為 S ; W為氮； Rc 為-Η ; Rh為Η或-C! -C：6烷基，其中該烷基係視情況經取代； R3 為-HSCi-Q 烷基； Z為視情況經取代之-C8烷基-; L係選自包括 -C〇-C6 烷基-C(0)-N(R3)-Cq-C3烷基-、-Cg-C6 烷基-n(r3)-c(o)-N(R3 )-C〇 -C3 烷基-或-C〇 -C6 烷基-0-C〇 -C3 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當C〇 -C：3烷基為q -C3烷基時，此q -C3烷基係視 情況被-C(0)-N(R3 )-C〇-C3烷基-Y、-雜芳基-芳基、雜芳基、 雜芳基-雜芳基、-N(R3)(R3a)或_N(R3)_Y取代，其中各雜芳基 或芳基部份基團係視情況經取代； -c0 -C6 烷基-雜烷基-C0 -Q 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其 中當C〇 -C3烧基為q -C3烧基時，此q -C3炫基係視情況被雜 134026-3 •68- 200916447 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 -Co-Q烧基-N(R3)C(0)-C〇-C3烧基-，其中當c〇_C3烷基為 Ci -C3烧基日守’此C! -C3烧基係視情況被_n(r3 )_c(〇)_〇_c〇—C3 烷基-Y、-NH2、-NH-S(0)2-Y、-NH-C(〇)-NH-CVC3 烷基-Y、-NH- 雜芳基-芳基、-N(R3 )C(O)-C0 -C3 烷基 _Y、_N(R3 )(R3 a)或 _N(R3 )_γ 取代；且 各Y係獨立選自包括H、烷基、環烷基、芳基、雜芳基、 雜芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_n(r3)_c(〇)_ 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(r3)_c(〇)芳基、 雜環基-C0-C6 烧基-n(r3)-c(o)-雜芳基及 B2_Bl_N(R3)_c(〇)_ CrC7烧基-’ |中環炫基、芳基、雜芳基、雜環基及烧基 部份基團係視情況被一 自包括鹵基、烧氧基、 '二或三個取代基取代，取代基選 視情況經取代之q -c6烷基、烷氧羰 V 基-、-OH、-CN、-C(0)_0H、視情況經取代之芳基、視情 況經取代之-烷基芳基、視情況經取代之雜芳基、視情況 經取代之-O-Ci -C：6烧基-芳基、視情況經取代之（⑼_〇(1 烧基、_NH2、視情況經取代之_芳基_雜環基及視情況經取 代之稠合雜環’且Ci_C7烷基係視情況被-NR3-B3取代，及 B3之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 B2-Bl-N(R3)-C(〇)-Ci必院基-時，則WL為共價鍵； 其中 當任何Bi、B2及B3係連接在—起時 接’且B1、B2及B3係獨立選自 49.如請求項1之化合物，其中 其係藉由肽鍵連 包括 D-Pro、L-ile 及 D-Phe-4-CF3。 134026-3 -69- 200916447 D為 χ ; W與M為氮； Ra、Rb 及 Rc 為-Η ; R3為-H或Ci-C6烷基； z為視情況經取代之-Ci -Cg烧基-， L為 -C〇-C6烷基-N(R3)C(0)-C〇-C3烷基-，其中當C〇-C3烷基為 ci -C3烷基時，此q -C3烷基係視情況被-N(R3 )-C(0)-0-C〇 -C3 烷基-Y、-NH2、-NH-S(0)2-Y、-NH-C(0)-NH-CG-C3 烷基-Y、-NH-雜芳基-芳基、-N(R3 )C(O)-C0 -C3 烷基-Y、-N(R3 )(R3 a)或-N(R3 )-Y 取代；且 各Y係獨立選自包括H、烷基、環烷基、芳基、雜芳基、 雜芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_N(R3 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基-N(R3)-C(0)-芳基、 雜 ％ 基-C0-C：6 烷基-N(R3)-C(〇)-雜芳基及 BZ-Bi-NCRi-CCO)-C1-C7烷基_，其中環烷基、芳基、雜芳基、雜環基及烷基 係視情況經取代，且〇1&lt;7烷基係視情況被_NR3_B3取代’ 及B之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 Β -Β -N(R3)_C(0)_Ci_C7烷基_時，則/與匕為共價鍵；其中 4何B B及係連接在一起時，其係藉由肢鍵連 接且B、B2及B3係獨立選自包括D pr〇、L ile及D phe 4 CF3。 50.如請求項1之化合物，其中 134026-3 -70- 200916447W is nitrogen or oxygen; hydrazine is nitrogen; Ra, Rb and Rc are -Η; Ζ is -C8 alkyl- or -Ci-c8 alkyl-C(O)-; 134026-3 •62- 200916447 L is - CVC6 alkyl-N(R3)C(O)-C0-C3 alkyl; and Y is alkyl, aryl, heteroaryl, heteroaryl-aryl or aryl-heteroaryl, wherein The aryl and heteroaryl groups are optionally substituted. 42. The compound of claim 41, wherein the alkyl, aryl and heteroaryl groups of gamma are optionally substituted with a substituent selected from the group consisting of alkoxy, alkyl, aryl, -0-alkyl- Heteroaryl and 〇-alkyl-aryl. 43. The compound of claim 1, wherein -i-W, /Rh /1 ο 1 D is S; W is nitrogen or oxygen; Rc is -Η; Rh is Η or -Ci-Q alkyl, wherein The alkyl group is optionally substituted; Z is -C! -C8 alkyl- or -C8 alkyl-c(0)-; L is -C〇-C6 alkyl-N(R3)C(O)-C0 -C3 alkyl; and Y is alkyl, aryl, heteroaryl, heteroaryl-aryl or aryl-heteroaryl, wherein the alkyl, aryl and heteroaryl are optionally substituted. 44. The compound of claim 43, wherein the alkyl, aryl and heteroaryl groups of the oxime are optionally substituted with a substituent selected from the group consisting of alkoxy, alkyl, aryl, -0-alkyl - Heteroaryl and 〇-alkyl-aryl. 45. The compound of claim 1, wherein 1-W Μ D is χ; W and Μ are nitrogen; Ra, Rb and Rc are -Η; 134026-3 200916447 R3 is -Η or CVQ alkyl; Substituted -C8 alkyl-; L is selected from the group consisting of -C〇-C6 alkyl-C(0)-N(R3)-C. -C3 burnt base -, -C. -C6 alkyl-N(R3)-C(0)-N(R3)-C〇-C3 alkyl- or -C〇-C6 alkyl--0-C〇-C3 alkyl-C(0)- N(R3)-C0-C3 alkyl group _ 'When C〇-C3 alkyl group is C】-C3 alkyl group, this Q-C3 alkyl group is optionally treated as -C(O)-N(R3)- C0-C3 alkyl-Y, aryl, heteroaryl, -heteroaryl_aryl, -aryl-heteroaryl, -aryl-arylheteroaryl-heteroaryl, _N(R3)( R3 a) or -N(R3)-Y substituted wherein each heteroaryl or aryl moiety is optionally substituted; -C〇-C6 alkyl-heteroalkyl-CG-C6 alkyl-C (0)-N(R3)-C〇-C3 alkyl...wherein when c0-c:3 alkyl is alkyl, the alkyl group is optionally heteroaryl, -N(R3)(R3a) or -N(R3)-Y substituted; and -QQ alkyl-N(R3)C(O)-C0-C3 alkyl-, wherein when c〇-C3 alkyl is C1-C3 alkyl, 'this Q- The C3 alkyl group is optionally taken as _N(R3)(R3a), -N(R3)-Y, -N(R3)-C(0)-0-C〇-C3 alkyl-Y, -NH2, - Nh-s(o)2-y, -NH-C(O)-NH-C0-C3 alkyl-Y, -NH-heteroaryl-aryl or -N(R3)C(0)-C0 - C3 alkyl-γ substituted; and each oxime is independently selected from the group consisting of fluorene, alkyl, cycloalkyl, aryl, heterocyclic, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl -, aryl _n(r3) c(〇)_heteroaryl, heteroaryl_n(r3)-c(o)-heteroaryl, aryl-N(R3)-C(0)-aryl , heterocyclyl-c〇-c6 alkyl-N(R3)-C(0)-heteroaryl and B2_Bl_N(R3)-C(0)-Cl-C7 alkyl-, wherein alkyl, naphthenic The aryl group, the aryl group, the heteroaryl group and the heterocyclic group are optionally substituted, and the Ci_c7 alkyl group 134026-3 -64- 200916447 is optionally substituted by -NR3_B3, and the amine of B3 and B2 Acid-bonded to form a peptide bond, and wherein when γ is B2_BlMo 3)_c(〇)_Ci_C7 alkyl_, then read L is a covalent bond; wherein, by peptide bonding, L-ile and D -Phe-4-CF3. When any B1, B2 and B3 are linked together, and B1, B2 and B3 are independently selected from the group consisting of D-pro. 46. The compound of claim 1, in the bean ^ T ' l - W \ /Rh D is Poor; i, W is nitrogen; Rm; R is hydrazine or -C! -C6 alkyl, wherein the alkyl group is optionally substituted; R3 is -H or (VC6 alkyl; Z is optionally substituted - C8 alkyl-; L is selected from the group consisting of -c〇-c6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, _c0-C6 alkyl-N(R3)-C(0 )-N(R3)-Q-C3 alkyl- or -C0-C6 alkyl-0-C〇-C3 alkyl_c(〇)_n(r3)_c〇£ V alkyl group _, wherein when C〇 When the _C3 alkyl group is a ci-C3 alkyl group, the q-C3 alkyl group is optionally taken as -C(0)-N(R3)-C〇-C3 alkyl-Y, aryl, heteroaryl, _ Heteroaryl-aryl, -aryl-heteroaryl, -aryl-aryl, heteroaryl-heteroaryl, -N(R3)(R3a) or -N(R3)-Y substituted, each of which A heteroaryl or aryl moiety is optionally substituted; -C〇-C6 炫-hetero-C0-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl - wherein when the Co-Q alkyl group is a Q-C3 alkyl group, the C!-C3 alkyl group is optionally substituted with a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; And 134026-3 -65- 200916447 -Co-Qalkyl-N(R3)C(O)-C0-C3 alkyl-' wherein when c〇_c3 alkyl is C^-C^alkyl, this Ci-Cs is burned The base system is optionally _N(R3)(R3a&gt;, -N(R3)-Y, -N(R3)-C(O)-O-C0-C3 alkyl-Y, -NH2, -NH-S (〇) 2-Y, -NH-C(0)-NH-C〇-C3 alkyl-Y, -NH-heteroaryl_arylindole-n(r3)c(o)-c〇-c3 alkyl-Y substituted; and each lanthanide is independently selected from the group consisting of an anthracene, an alkyl group, a cycloalkyl group, an aryl group, a heterocyclic group, a heteroaryl-aryl group, an aryl-heteroaryl group, a heterocyclic group_0_, Aryl-N(R3)_C(0)_heteroaryl,heteroaryl-N(R3)-C(0)-heteroaryl, aryl_n(R3)_c(〇)_aryl, hetero Cyclo-C0-C6 alkyl-n(r3)-C(0)_heteroaryl and B2 _b1_n(r3)_c(〇)_ cvcwm alkyl, cycloalkyl, aryl, heteroaryl and heterocyclic The base moiety is optionally substituted, and the base is optionally substituted by -NR3-B3' and the amine is linked to the acid of B2 to form a peptide bond, and /, Tian ¥ is 8 -B WKXOKVC^ Base-time, then 2 is [is a covalent bond; 'where ^ any B1, B2, and B3 are connected at the time - and B1, B2, and B3 are independently selected from the group consisting of D-Pr〇. 47. a compound of 1 A peptide bonded L-ile and D-Phe-4-CF3. Ra Rb .Μ XW and Μ are nitrogen; Ra, and Rc are, Η; R3 is -H or Cl_C6 alkyl; z is optionally substituted _Ci_Cs 134026-3 -66 - 200916447 L is selected from Including -c0 -C6 alkyl-C(0)-N(R3)-C. -C3 alkyl-, -c. -C6 alkyl-N(R3)-C(0)-N(R3)-C〇-C3 alkyl- or -C〇-C6 炫-〇-C〇-C3 alkyl-C(0)- N(R3)-C〇-C3 alkyl-' wherein when the C0-C3 alkyl group is a Ci-q alkyl group, the alkyl group is optionally taken as -C(0)-N(R3)-C〇-C3 Alkyl-Y,-heteroaryl-aryl, heteroaryl, heteroaryl-heteroaryl, -N(R3)(R3a) or -N(R3)-Y substituted, wherein each heteroaryl or aryl The radical moiety is optionally substituted; -C0-C6 alkyl-heteroalkyl-C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when C When the 〇-C3 炫 is a Q-C3 alkyl group, the C-C3 alkyl group is optionally substituted with a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; and -C〇 -C6 alkyl-N(R3)C(0)-C〇-C3 alkyl-, wherein when c0-C3 alkyl is Q-C:3 alkyl, this c!-C3 alkyl group is optionally _n(R3)-C(O)-O-C0-C3 alkyl-Y, -NH2, -NH-S(0)2-Y, -NH-C(0)-NH-C〇-C3 alkane -Y,-NH-heteroaryl-aryl'-N(R3)C(O)-C0-C3 alkyl-Y, _N(R3)(R3a) or -N(R3)-Y substituted; And each Y is independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇, aryl-n ( R3)_c(〇)_ Miscellaneous , heteroaryl-N(R3)-C(0)-heteroaryl, aryl_n(r3)_c(〇)_aryl, heterocyclyl-C0-C6 alkyl-N(R3)- C(〇)-heteroaryl and ^-ΒίΝ^ΚΧΟ)-Q-C7 alkyl-, wherein cycloalkyl, aryl, heteroaryl, heterocyclic and alkyl moiety are optionally Substituted with two or three substituents selected from the group consisting of i-, alkoxy, optionally substituted q-C6 alkyl, alkoxycarbonyl-, -OH, -CN, -CXCO-OH, optionally Substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl, optionally 134026-3 -67- 200916447 substituted -O-Cn-c6 alkyl-aryl, Substituted -cxco-o-Ci-c6 leukoyl, -NH2, optionally substituted-aryl-heterocyclyl and optionally substituted fused heterocycles and q-C7 alkyl as appropriate Substituted by -NR3 -B3, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein when γ is B2 -B1 -N (R3 -C7 alkyl-, then Z and L are covalent bonds Wherein, when any of B1, B2 and B3 are linked together, they are linked by a peptide bond' and B1, B2 and B3 are independently selected from the group consisting of D-Pro, L-ile and D- Phe-4-CF3. 48. The compound of claim 1, wherein Rc ', -W\ /Rh D is S; W is nitrogen; Rc is -Η; Rh is deuterium or -C!-C:6 alkyl, wherein the alkyl group Substituted as appropriate; R3 is -HSCi-Q alkyl; Z is optionally substituted -C8 alkyl-; L is selected from -C〇-C6 alkyl-C(0)-N(R3)- Cq-C3 alkyl-, -Cg-C6 alkyl-n(r3)-c(o)-N(R3)-C〇-C3 alkyl- or -C〇-C6 alkyl-0-C〇- C3 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when C〇-C:3 alkyl is q-C3 alkyl, this q-C3 alkyl group is optionally -C(0)-N(R3)-C〇-C3 alkyl-Y,-heteroaryl-aryl, heteroaryl, heteroaryl-heteroaryl, -N(R3)(R3a) or _ N(R3)_Y substituted wherein each heteroaryl or aryl moiety is optionally substituted; -c0 -C6 alkyl-heteroalkyl-C0 -Q alkyl-C(0)-N(R3 )-C〇-C3 alkyl-, wherein when the C〇-C3 alkyl group is a q-C3 alkyl group, the q-C3 danthene group is optionally 134026-3 •68- 200916447 aryl, -N ( R3) (R3a) or -N(R3)-Y substituted; and -Co-Q alkyl-N(R3)C(0)-C〇-C3 alkyl-, wherein when c〇_C3 alkyl is Ci -C3 burning base day guard 'this C! -C3 burning base system as the case By _n(r3)_c(〇)_〇_c〇—C3 alkyl-Y, -NH2, -NH-S(0)2-Y, -NH-C(〇)-NH-CVC3 alkyl- Y, -NH-heteroaryl-aryl, -N(R3)C(O)-C0-C3 alkyl-Y, _N(R3)(R3a) or _N(R3)_γ are substituted; and each Y Independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇, aryl_n(r3)_c (〇)_heteroaryl, heteroaryl-N(R3)-C(0)-heteroaryl, aryl_n(r3)_c(indenyl)aryl, heterocyclyl-C0-C6 alkyl- n(r3)-c(o)-heteroaryl and B2_Bl_N(R3)_c(〇)_CrC7 alkyl-'|cyclohexyl, aryl, heteroaryl, heterocyclic and alkyl group Depending on the case, it is substituted by a halogen group, an alkoxy group, a 'two or three substituents, and the substituent is optionally substituted with a q-c6 alkyl group, an alkoxycarbonyl group V-, -OH, -CN, -C(0)_0H, optionally substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl, optionally substituted -O-Ci-C:6 alkyl - aryl, optionally substituted ((9) _ 〇 (1 alkyl, _NH2, optionally substituted aryl) heterocyclyl and, as appropriate The fused heterocyclic ring' and the Ci_C7 alkyl group are optionally substituted by -NR3-B3, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein γ is B2-Bl-N(R3)- C(〇)-Ci必院基-, then WL is a covalent bond; wherein when any Bi, B2 and B3 are connected at the same time, and B1, B2 and B3 are independently selected from 49. A compound of 1, wherein the peptide is linked to include D-Pro, L-ile and D-Phe-4-CF3. 134026-3 -69- 200916447 D is χ; W and M are nitrogen; Ra, Rb and Rc are -Η; R3 is -H or Ci-C6 alkyl; z is optionally substituted -Ci-Cg alkyl -, L is -C〇-C6 alkyl-N(R3)C(0)-C〇-C3 alkyl-, wherein when the C〇-C3 alkyl group is a ci-C3 alkyl group, the q-C3 alkane The base system is optionally -N(R3)-C(0)-0-C〇-C3 alkyl-Y, -NH2, -NH-S(0)2-Y, -NH-C(0)-NH -CG-C3 alkyl-Y, -NH-heteroaryl-aryl, -N(R3)C(O)-C0-C3 alkyl-Y, -N(R3)(R3 a) or -N( R3)-Y substituted; and each Y is independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇_ , aryl_N(R3 heteroaryl, heteroaryl-N(R3)-C(0)-heteroaryl, aryl-N(R3)-C(0)-aryl, hetero-l-C0 -C: 6 alkyl-N(R3)-C(〇)-heteroaryl and BZ-Bi-NCRi-CCO)-C1-C7 alkyl-, wherein cycloalkyl, aryl, heteroaryl, hetero The cyclic group and the alkyl group are optionally substituted, and the 〇1 &lt;7 alkyl group is optionally substituted by _NR3_B3 and the amine of B is linked to the acid of B2 to form a peptide bond, and wherein γ is Β-Β -N(R3)_C(0)_Ci_C7alkyl_, then / with 匕Bond; wherein B B 4 where lines and are connected together by lines which connect the limb bond and B, B2 and B3 is independently selected from the group comprising D pr〇 lines, L ile and D phe 4 CF3. 50. The compound of claim 1 wherein: 134026-3 -70- 200916447 D 為 j&lt; ; w為氮； Re 為-Η ; Rh為H或-Ci-q烷基，其中該烷基係視情況經取代； R3為41或(^-(：6烷基； z為視情況經取代之-C8烷基-; L為 -c〇-c6烷基-N(R3)C(O)-C0-C3烷基-，其中當c0-c3烷基為 Cl -c3院基時，此Ci _c3烷基係視情況被_n(r3 )_c(〇)_〇_c〇 (3 烧基-Y、-NH2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-Y、-NH-雜芳基-芳基、-N(R3 )C(O)-C0 -C3 烷基-Y、-N(R3 )(R3 a)或-N(R3)-Y 取代；且 各Y係獨立選自包括Η、烷基、環烷基、芳基、雜芳基、 雜芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_n(r3)_c(〇)_ 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(R3)-C(0)-芳基、 雜環基-c0-c6 烷基-N(R3)-C(0)-雜芳基及 y-Bi-N^KXO)-q-c：7烷基_，其中環烷基、芳基、雜芳基、雜環基及烷基 係視情況經取代，且Cl_C7烷基係視情況被_NR3_B3取代， 及B3之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 BlBi-NO^-CCOKVC#基-時，則Ζ與L為共價鍵； 其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接且B、B2及B3係獨立選自包括D_pro、L-ile及D-Phe-4-CF3。 134026-3 -71 - 200916447 51.如請求項1之化合物，其中 .τ τ 卜 W\c，、Rb D為 义 ; W與Μ為氮； Ra、Rb 及 Rc 為-Η ; R3為^或心-心烷基； Z為視情況經取代之-C! -C8烷基-; L為 -C〇-C6烷基-N(R3)C(0)-C〇-C3烷基-，其中當c〇-c3烷基為 Cl -c3烷基時，此Cl -C3烷基係視情況被-N(R3 )-C(〇)-0-C〇-C3 烷基-Y、-NH2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-Y、-NH-雜芳基-芳基、-N(R3)C(0)-C〇-C3 烷基-Y、-N(R3)(R3a)或-N(R3)-Y 取代；且 各Y係獨立選自包括H、烧基、環烧基、芳基、雜芳基、 雜芳基-芳基、芳基-雜芳基、雜環基_〇_、芳基_N(R3 )_c(〇)_ 雜芳基、雜芳基-N(R3)-C(0)-雜芳基、芳基_n(R3)-C(0)-芳基、 雜環基-C0-C：6 燒基-N(R3)-C(0)-雜芳基及 b2-B q -C：7烷基-，其中環烷基、芳基、雜芳基、雜環基及烷基 係視情況被一、二或三個取代基取代，取代基選自包括鹵 基、烧氧基、視情況經取代之q -c6烧基、炫氧幾基_、_〇H、 -CN、-C(0)_0H、視情況經取代之芳基、視情況經取代之_ 烷基芳基、視情況經取代之雜芳基、視情況經取代之 -ο-e! -c6烷基-芳基、視情況經取代之_c(〇) 〇 Ci %烷基、 -ΝΗΖ、視情況經取代之-芳基-雜環基及視情況經取代之稠 134026-3 -72- 200916447 合雜環， ” ’且Cl-C7烷基係視情況被-NR3-B3取代，及B3之胺係 ’、B之酸連接’以形成肽鍵，且其中當Y為^-B1 -N(R3)-C(0)-Cl-C7烷基-時，則Z與L·為共價鍵；其中 田任何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接且β1、B2及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 52·如明求項1之化合物，豆中 &lt;~~W、/Rh D為 2 ; w為氮； Re 為-H ; 為Η或-C6烷基，其中該烷基係視情況經取代 R為屯或^-仏烷基； Z為視情況經取代之-C8烷基-; L為 c —燒基_N(R3)C(〇K〇_C3烷基-，其中當c〇_c3烷基為 Ul Cg境基時’此Cl _C3烷基係視情況被O 烧基-Υ χτττ -NH2、-NH-S(0)2-Y、-NH-C(0)-NH-C〇-C3 烷基-Υ、-ΝΗ- 雜芳其 ^ 您 '芳基、-N(R3)C(O)-C0-C3烷基-Y、-N(R3)(R3a)或-N(R3)-Y 取代；且 各Y係獨立選自包括Η、烷基、環烷基、芳基、雜芳基、 雜芳基、芳基、芳基-雜芳基、雜環基-〇_、芳基-N(R3 )-C(0)-’、石卷、雜芳基-N(R3)-C(0)-雜芳基、芳基-N(R3)-C(0)-芳基、 ’、 i -Co-Q 烷基-N(R3)-C(0)-雜芳基及 W-BlNd^KXO)-CpC：7境基-，其中環烷基、芳基、雜芳基、雜環基及烷基 134026-3 •73· 200916447 印仇丨月二散一 '二或三個取代基取代，取代基選自包括i 基、烷氧基、視情況經取代之Ci_C6烷基、烷氧羰基_、_〇H、 -CN ' -C(0)-0H、視情況經取代之芳基、視情況經取代之_ 烷基芳基、視情況經取代之雜芳基、視情況經取代之 -0-c! 炫基-芳基、視情況經取代之_c⑼_〇_Ci (6烷基、 -NH2、視情況經取代之_芳基-雜環基及視情 況經取代之稠 合雜％，且Ci-C：7烷基係視情況被旧以七3取代，及B3之胺係 B之@夂連接，以形成肽鍵，且其中當γ為Β2_βΐ _n(r3 )_c(〇)_ Q -C：7烷基-時，則z與l為共價鍵； 其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接，且B1、B2及B3係獨立選自包括D_Pr〇、L_ile及D phe 4 CF3。 53.如請求項1之化合物，其中D is j&lt;; w is nitrogen; Re is -Η; Rh is H or -Ci-q alkyl, wherein the alkyl group is optionally substituted; R3 is 41 or (^-(:6 alkyl; z is Substituted -C8 alkyl-; L is -c〇-c6 alkyl-N(R3)C(O)-C0-C3 alkyl-, wherein c0-c3 alkyl is Cl-c3 When this Ci _c3 alkyl group is optionally treated by _n(r3 )_c(〇)_〇_c〇(3 alkyl-Y, -NH2, -NH-S(0)2-Y, -NH-C (0)-NH-C〇-C3 alkyl-Y, -NH-heteroaryl-aryl, -N(R3)C(O)-C0-C3 alkyl-Y, -N(R3)(R3 a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of anthracene, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, Heterocyclyl-〇_, aryl_n(r3)_c(〇)_heteroaryl,heteroaryl-N(R3)-C(0)-heteroaryl, aryl_n(R3)-C (0)-aryl, heterocyclyl-c0-c6 alkyl-N(R3)-C(0)-heteroaryl and y-Bi-N^KXO)-qc:7 alkyl-, wherein cycloalkane The aryl group, the aryl group, the heteroaryl group, the heterocyclic group and the alkyl group are optionally substituted, and the Cl_C7 alkyl group is optionally substituted by _NR3_B3, and the amine of B3 is bonded to the acid of B2 to form a peptide bond, and Where γ is BlBi-NO^-CCOKVC# base, then Ζ L is a covalent bond; wherein when any of B1, B2 and B3 are linked together, they are linked by a peptide bond and B, B2 and B3 are independently selected from the group consisting of D_pro, L-ile and D-Phe-4- 51. 134026-3 -71 - 200916447 51. The compound of claim 1, wherein .τ τ Bu W\c, Rb D is a meaning; W and Μ are nitrogen; Ra, Rb and Rc are -Η; R3 is ^ or heart-heart alkyl; Z is optionally substituted -C! -C8 alkyl-; L is -C〇-C6 alkyl-N(R3)C(0)-C〇-C3 alkyl- Wherein when the c〇-c3 alkyl group is a Cl-c3 alkyl group, the Cl-C3 alkyl group is optionally taken as -N(R3)-C(〇)-0-C〇-C3 alkyl-Y,- NH2, -NH-S(0)2-Y, -NH-C(0)-NH-C〇-C3 alkyl-Y, -NH-heteroaryl-aryl, -N(R3)C(0 -C〇-C3 alkyl-Y, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, hetero Aryl, heteroaryl-aryl, aryl-heteroaryl, heterocyclyl-〇, aryl_N(R3)_c(〇)_heteroaryl,heteroaryl-N(R3)-C (0)-heteroaryl, aryl_n(R3)-C(0)-aryl, heterocyclyl-C0-C: 6 alkyl-N(R3)-C(0)-heteroaryl and b2-B q -C: 7 alkyl-, wherein cycloalkyl, aryl The heteroaryl group, the heterocyclic group and the alkyl group are optionally substituted by one, two or three substituents selected from the group consisting of a halogen group, an alkoxy group, optionally substituted q-c6 alkyl group, and an aerobic group. Base _, _ 〇 H, -CN, -C(0)_0H, optionally substituted aryl, optionally substituted _alkylaryl, optionally substituted heteroaryl, optionally substituted -ο-e! -c6alkyl-aryl, optionally substituted _c(〇) 〇Ci %alkyl, -ΝΗΖ, optionally substituted-aryl-heterocyclyl and optionally substituted Thick 134026-3 -72- 200916447 Heterocyclic, "' and Cl-C7 alkyl is optionally substituted by -NR3-B3, and the amine of B3', the acid linkage of B to form a peptide bond, and wherein When Y is ^-B1 -N(R3)-C(0)-Cl-C7 alkyl-, then Z and L· are covalent bonds; wherein any B1, B2 and B3 systems are linked together, Linked by peptide bonds and β1, B2 and B3 are independently selected from the group consisting of D-Pro, L-ile and D-Phe-4-CF3. 52. The compound of claim 1, wherein &lt;~~W, /Rh D is 2; w is nitrogen; Re is -H; is Η or -C6 alkyl, wherein the alkyl group is optionally substituted R is hydrazine or ^-decylalkyl; Z is optionally substituted -C8 alkyl-; L is c-alkyl-N(R3)C(〇K〇_C3 alkyl-, wherein when c〇_ When the c3 alkyl group is an Ul Cg-based group, the Cl_C3 alkyl group is optionally O-alkyl-Υ χτττ -NH2, -NH-S(0)2-Y, -NH-C(0)-NH-C. 〇-C3 alkyl-Υ, -ΝΗ-heteroaryl ^ you' aryl, -N(R3)C(O)-C0-C3 alkyl-Y, -N(R3)(R3a) or -N( R3)-Y substituted; and each Y is independently selected from the group consisting of anthracene, alkyl, cycloalkyl, aryl, heteroaryl, heteroaryl, aryl, aryl-heteroaryl, heterocyclyl-indole , aryl-N(R3)-C(0)-', silliman, heteroaryl-N(R3)-C(0)-heteroaryl, aryl-N(R3)-C(0)- Aryl, ', i-Co-Q alkyl-N(R3)-C(0)-heteroaryl and W-BlNd^KXO)-CpC:7-based, wherein cycloalkyl, aryl, hetero Aryl, heterocyclic and alkyl 134026-3 • 73· 200916447 印仇丨二二一一二 or three substituents substituted, substituents selected from the group consisting of i groups, alkoxy groups, as appropriate Substituting Ci_C6 alkyl, alkoxycarbonyl _, _〇H, -CN '-C(0)-0H, optionally substituted aryl, optionally substituted _alkylaryl, optionally substituted Heteroaryl, optionally substituted -O-c! leuko-aryl, optionally substituted _c(9)_〇_Ci (6-alkyl, -NH2, optionally substituted aryl-heterocyclic a fused or heterogeneously substituted hydroxy group, and the Ci-C:7 alkyl group is optionally substituted with -7, and the amine group B of B3 is bonded to form a peptide bond, and wherein γ is When Β2_βΐ _n(r3 )_c(〇)_ Q -C:7 alkyl-, then z and l are covalent bonds; wherein when any of B1, B2 and B3 are linked together, they are by peptide bonds And the B1, B2, and B3 are independently selected from the group consisting of D_Pr〇, L_ile, and D phe 4 CF3. 53. The compound of claim 1, wherein C Ru D為 S ； W與Μ為氮； Ra、Rb 及 1^為-Η ; R3 為-Η ; R4為Η或F ; z為視情況經取代之-Ci -C8烷基-; L係選自包括 -C〇 -C6烷基-C(0)-N(R3 )-C0 -C3烷基-，其中當C〇 -C3烷基為 Ci -c：3烷基時，此Cl _c：3烷基係視情況被_C(0)_N(R3 )_Cq _C3烧基 -Y、-雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； 134026-3 -74- 200916447 -C〇 -C6 烧基-雜烷基 -C6 烷基 _c(〇)-N(R3 )-C。-C3 烷基-，其 中當C0-(：3烷基為q -C3烷基時，此Cl _C3烷基係視情況被雜 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 -C0-C6烧基-N(R3)c(0)-C〇-C3烷基_，其中當c〇_c3烷基為 Q -C3烧基時，此Ci _c3烷基係視情況被_N(R3 )c(〇)_Cg A烷基 _Y、-N(R3)(R3a)或-N(R3)-Y取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳 基、芳基-雜芳基及BiBLNiR3)—CCOKVG；烷基_，其中芳基 與雜芳基係視情況經取代，且Ci_C7烷基係視情況被 -NR -B取代，及B3之胺係與^之酸連接，以形成肽鍵，且 其中當Y為B2-Bi_N(R3)_c(〇HVC7烷基_時，則z與[為共價 鍵；其中 當任何Β1、β2及B3係連接在一起時’其係藉由肽鍵連 接，且 B、B 及 B3 係獨立選自包括 D-Pro、L-ile 及 D-Phe-4-CF3。 54.如請求項1之化合物，其中C Ru D is S; W and Μ are nitrogen; Ra, Rb and 1^ are -Η; R3 is -Η; R4 is Η or F; z is optionally substituted -Ci-C8 alkyl-; Selected from the group consisting of -C〇-C6 alkyl-C(0)-N(R3)-C0-C3 alkyl-, wherein when C〇-C3 alkyl is Ci-c:3 alkyl, this Cl_c: The 3 alkyl group is optionally taken as _C(0)_N(R3)_Cq_C3 alkyl-Y,-heteroaryl-aryl, heteroaryl, -N(R3)(R3a) or -N(R3)- Y substituted; 134026-3 -74- 200916447 -C〇-C6 alkyl-heteroalkyl-C6 alkyl_c(〇)-N(R3)-C. -C3 alkyl-, wherein when C0-(:3 alkyl is q-C3 alkyl, this Cl_C3 alkyl group is optionally heteroaryl, -N(R3)(R3a) or -N(R3) -Y substituted; and -C0-C6 alkyl-N(R3)c(0)-C〇-C3 alkyl-, wherein when c〇_c3 alkyl is Q-C3 alkyl, this Ci_c3 alkyl Depending on the case, it is substituted by _N(R3)c(〇)_Cg Aalkyl_Y, -N(R3)(R3a) or -N(R3)-Y; and each Y is independently selected from the group consisting of alkyl and aromatic. a base, a heteroaryl group, a heteroaryl-aryl group, an aryl-heteroaryl group and a BiBLNiR3)-CCOKVG; an alkyl group, wherein the aryl group and the heteroaryl group are optionally substituted, and the Ci_C7 alkyl group is optionally -NR-B substitution, and the amine of B3 is linked to the acid of the group to form a peptide bond, and wherein when Y is B2-Bi_N(R3)_c (〇HVC7 alkyl_, then z and [is a covalent bond) Wherein, when any of the Β1, β2 and B3 lines are joined together, they are linked by a peptide bond, and B, B and B3 are independently selected from the group consisting of D-Pro, L-ile and D-Phe-4-CF3. 54. The compound of claim 1, wherein D為 t W為氮； Rc 為-H ; 其中該燒基係視情況經取代； Rh為H或-C1-C6烷基 R3 為-H ; R4為Η或F ; Ζ為視情況經取代之-q -C8烷基-; 134026-3 -75- 200916447 L係選自包括 -c〇-c6烷基-C(O)-N(R3)-C0-C3烷基-，其中當c0-c3烷基為 q -C3烷基時，此Ci -C3烷基係視情況被-C(0)-N(R3 )-CG -c3烷基 -Y、·雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； -C〇-C6 烷基-雜烷基-C〇-C6 烷基-C(0)-N(R3)-C〇-C3烷基-，其 中當C〇 -C：3烧基為q -C3炫基時，此q -C3院基係視情況被雜 芳基、-N(R3)(R3a)或·Ν(κ3)_γ取代；及 -C0-C6烧基-N(R3)C(O)-C0-C3烧基_ ,其中當C0-C3烧基為 Q -C：3烧基時’此Ci 4烷基係視情況被_N(R3 )c(〇)_c。_c3烷基 -γ、_N(R3)(R3a)或-N(R3)-Y取代；且 各γ係獨立選自包括烷基、芳基、雜芳基雜芳基_芳基、 芳基-雜芳基及ΒίΒΚβΚΧΟΚ：〆7烷基-，其中芳基與雜 芳基係視情況經取代，且Ci_C7烷基係視情況被 代，及B3之胺係與B2之酸連接，以形成肽鍵，且其中當Y 為B N(R -C7烧基-時，則Z與L·為共價鍵； 其中 何B、B及B3係連接在一起時，其係藉由肽鍵連 接，且 B、β2 及 B3係獨立選自包括 D-Pro、L-ile 及 D-Phe-4-CF3。 55.如請求項1之化合物，其中D is t W is nitrogen; Rc is -H; wherein the alkyl group is optionally substituted; Rh is H or -C1-C6 alkyl R3 is -H; R4 is hydrazine or F; hydrazine is optionally substituted -q -C8 alkyl-; 134026-3 -75- 200916447 L is selected from the group consisting of -c〇-c6 alkyl-C(O)-N(R3)-C0-C3 alkyl-, wherein c0-c3 When the alkyl group is a q-C3 alkyl group, the Ci-C3 alkyl group is optionally taken as -C(0)-N(R3)-CG-c3alkyl-Y, .heteroaryl-aryl,heteroaryl , -N(R3)(R3a) or -N(R3)-Y substituted; -C〇-C6 alkyl-heteroalkyl-C〇-C6 alkyl-C(0)-N(R3)-C〇 -C3 alkyl-, wherein when the C〇-C:3 alkyl group is a q-C3 succinyl group, the q-C3 phenyl group is optionally heteroaryl, -N(R3)(R3a) or Ν( Κ3)_γ substitution; and -C0-C6 alkyl-N(R3)C(O)-C0-C3 alkyl group, wherein when the C0-C3 alkyl group is a Q-C:3 alkyl group, this Ci 4 alkane The base system is _N(R3)c(〇)_c as appropriate. _c3 alkyl-γ, _N(R3)(R3a) or -N(R3)-Y substituted; and each γ is independently selected from the group consisting of alkyl, aryl, heteroarylheteroaryl-aryl, aryl- Heteroaryl and ΒίΒΚβΚΧΟΚ: 〆7 alkyl-, wherein the aryl and heteroaryl groups are optionally substituted, and the Ci_C7 alkyl group is optionally substituted, and the amine of B3 is linked to the acid of B2 to form a peptide bond. And wherein when Y is BN (R-C7 alkyl group-, then Z and L· are covalent bonds; wherein when B, B and B3 are linked together, they are linked by peptide bonds, and B, The β2 and B3 are independently selected from the group consisting of D-Pro, L-ile and D-Phe-4-CF3. 55. The compound of claim 1, wherein W與Μ為氮； Ra、妒及Rc為_Η; 134026-3 -76- 200916447 R3 為-Η ; R4為Η或F ; z為視情況經取代之-Ci -C8烷基-; L係選自包括 -c0-c6烷基-C(O)-N(R3)-C0-C3烷基-，其中當c〇-c3烷基為 Ci -C3烷基時，此Ci -C3烷基係視情況被-C(0)-N(R3 )-CG -C3烷基 -Y、-雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； -C0-C6 烷基-雜烷基-C〇-C6 烷基-CCCO-NCRM-Co-C^ 烷基-，其 中富C〇 -〇3烧基為C! -C3烧基日tj· ’此C! -C3烧基係視情況被雜 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 -C〇-C6烷基-N(R3)C(0)-C〇-C3烷基_，其中當c0-C3烷基為 C! -C3烷基時，此Q -C3烷基係視情況被-N(R3 )C(0)-CQ -C3烷基 -Y、-N(R3)(R3a)或-N(R3)-Y取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基_芳 基、芳基-雜芳基及烷基·，其中芳基 與雜芳基係視情況被一、二或三個取代基取代，取代基選 自包括鹵基、烷氧基、視情況經取代之Ci_c6烷基、烷氧羰 基_、-OH、_CN、_C(0)-0H、視情況經取代之芳基、視情 況經取代之-烷基芳基、視情況經取代之雜芳基、視情況 經取代之-O-C】-C6烧基-芳基、視情況經取代之_c(〇)_〇 Ci _匸6 烷基、-NH2、視情況經取代之-芳基·雜環基及視情況經取 代之稠合雜環，且Q-C：7烷基係視情況被-Nr3_b3取代，及 B3之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 Β2 -Β1 -N(R3 -C7 烷基-時，則 ζ 與 L 為共價鍵； 134026-3 -77- 200916447 其中 田 &lt;壬何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接且B、B2及B3係獨立選自包括D 、L ib及。 56.如請求項1之化合物，i中 I r .卜W、〆 D為 贫； w為氮； Rc 為-H ; R為Η或-C! -C：6烷基，其中該烷基係視情況經取代； R3 為-Η ; R4為Η或F ; ζ為視情況經取代之-Ci -C8烷基-; L係選自包括 _C〇 -C6 基-C(0)-N(R3 )-C〇 -C3 院基-，其中當 C〇 -C3 烧基為 q -C3烷基時，此q -C3烷基係視情況被-C(0)-N(R3 )-C〇-C3烷基 -Y、-雜芳基-芳基、雜芳基、-N(R3)(R3a)或-N(R3)-Y取代； -C〇-C6 烷基-雜烷基-C〇-C6 烷基-C(0)-N(R3)-C〇-C3 烷基-，其 中當C〇 -C3炫基為C] -C3烧基時’此C! -C3烧基係視情況被雜 芳基、-N(R3)(R3a)或-N(R3)-Y取代；及 -C0-C6烷基-N(R3)C(0)-C〇-C3烷基-，其中當c〇-c3烷基為 c! -C3烷基時，此Q -C3烷基係視情況被-N(R3 )C(0)-C〇 -c3烷基 -Y、-N(R3)(R3a)或-N(R3)-Y取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳 基、芳基-雜芳基及BlBLNO^K^CO-Ci-Cy烷基-，其中芳基 134026-3 -78- 200916447 與雜方基係視情況被一、二或三個取代基取代，取代基選 自包括豳基、烷氧基、視情況經取代之Cl —C：6烷基、烷氧幾 基-、-OH、-CN、_C(0)-〇H、視情況經取代之芳基、視情 況經取代之-烷基芳基、視情況經取代之雜芳基、視情況 經取代之-o-q -c6烷基-芳基、視情況經取代之_c(0)_0_Ci _C6 烧基、-NH2、視情況經取代之_芳基_雜環基及視情況經取 代之稠合雜環，且Cl_C7烷基係視情況被_犯^七3取代，及 B3之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 Β2 -Β1 -N(R3 -C7烷基-時，則ζ與L為共價鍵；其中 當任何Bi '妒及B3係連接在一起時，其係藉由肽鍵連 接，且B1、B2及B3係獨立選自包括D_Pr〇、L_ile及D phe 4_CF3。 57.如請求項1之化合物，其中 D為 2 ； W與Μ為氮； Ra、為-Η ; R3 為-Η ; R4為Η或F ; z為視情況經取代之_Ci _c8烷基_ ; L為 -C0-C6烷基-N(R3)C(〇)_C〇_C3烷基_，其中當c〇_c3烷基為 Cl C3烷基時，此Cl -(：3烷基係視情況被-N(R3 )C(0)-Q) -C3烷基 -Y、-N(R3 )(R3 a)或 _N(R3)_γ 取代；且 各Υ係獨立選自包括烧基、芳基、雜芳基、雜芳基-芳 134026-3 -79· 200916447 基、方基-雜芳基及B2_Bi-N(R3&gt;c(〇)_Ci_C7烷基_，其中芳基 與雜=基係視情況經取代，且Ci_c7烧基係視情況被 NR -B3取代，及B3之胺係與B2之酸連接，以形成肽鍵，且 其中當Y為bib1—N(R3)-C(0)_Ci_C7烷基_時，則2與^為共價 鍵；其中 田住何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接，且 B B及B3係獨立選自包括D-Pro、L-ile及D-Phe-4-CF3。 58.如請求項1之化合物，其中 卜 W、/ D為 X ; w為氮； Re 為-H ; Rh為Η或-Cl _C6烷基，其中該烷基係視情況經取代； R3 為-H ; 八·為Η或F ; Ζ為視情況經取代之-C〗-C8烷基-; L為 -C〇-C6烷基_n(R3)C(O)-C0-C3烷基-，其中當c0-c3烷基為 ci -C3燒基時，此Q _c3烷基係視情況被-N(R3 )C(0)-C〇 -C3烷基 _γ、或-n(r3)-y取代；且 各丫係獨立選自包括烷基、芳基、雜芳基、雜芳基-芳 基、芳基-雜芳基及BkB1 -N^XCCO-Ci -C7烷基-，其中芳基 與雜芳基係視情況經取代，且Ci -C7烷基係視情況被 134026-3 -80- 200916447 -NR3-B3取代，及B3之胺係與B2之酸連接，以形成肽鍵，且 其中當Y為B2 -B1 -N(R3 )-01(0)-(^ -Ο；烧基-時，則z與l為共價 鍵； 其中 當任何B1、B2及护係連接在一起時，其係藉由肽鍵連 接，且 B1、B2 及 B3 係獨立選自包括 D-Pro、L-ile 及 D-Phe-4-CF3。 59.如請求項1之化合物，其中 Γ . τ τ “丫 M、Rb D為 Ϊ ; w與Μ為氮； Ra、Rb 及 Rc 為-Η ; R3 為-Η ; R4為Η或F ; Ζ為視情況經取代之-C8烷基-; L為 -C〇-C6烷基-N(R3)C(0)-C〇-C3烷基_，其中當c〇_c3烷基為 ci -C3烧基時，此q -C：3烧基係視情況被_n(R3 )C(〇)-C〇 -C3娱:基 各γ係獨立選自包括烷基、芳基、雜芳基雜芳基-芳基、 芳基-雜芳基及B2 -B1 -N(R3 )-C(0)-Cl _c7烷基_，其中芳基與雜 芳基係視情況被一、二或三個取代基取代，取代基選自包 括鹵基、烷氧基、視情況經取代之Ci 烷基、烷氧羰基_、 -OH、-CN、-C(0)-OH、視情況經取代之芳基、視情況經取 134026-3 -81 - 200916447 代之-烷基芳基、視情況經取代之雜芳基、視情況經取代 之-o-c! a烷基-芳基、視情況經取代之_q0)_0_Ci %烷基、 NH2、視情況經取代之_芳基_雜環基及視情況經取代之稠 &amp;雜，且q -C·；燒基係視情況被-NR3 -B3取代，及B3之胺係 '、B之酸連接，以形成肽鍵，且其中當γ為b2# _n(R3)-C(0)~ ci -A燒基-時，則z與L為共價鍵；其中 當任何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接，且 /' \ 1 B、B2 及 B3 係獨立選自包括 D-Pro、L-ile 及 D-Phe-4-CF3。 6〇·如請求項1之化合物，其中 卜 W、 D為I ； W為氮； Re 為-Η ; R為Η或-C：6烧基，其中該烧基係視情況經取代； R3 為-H ; V. R4為Η或F ; Ζ為視情況經取代之-C! -C8炫基-; L為 -C〇-C6烷基_N(R3)C(〇)_C〇_C3烷基-，其中當c〇 C3烷基為 &gt;元基時，此c] -C3烷基係視情況被-N(R3 )c(o)-cQ -c3烷基 1、-叫113)(1^)或叫113)_¥取代；且 各Y係獨立選自包括烷基、芳基、雜芳基、雜芳基_芳 基、芳基-雜芳基及BLbLNO^-C⑼-Ci-Cy烷基-，其中芳基 134026-3 -82- 200916447 與雜芳基係視情況被一、二或三個取代基取代，取代基選 自包括齒基、烷氧基、視情況經取代之Ci_C6烷基、烷氧羰 基-、-OH、-CN、-C(〇K)H、視情況經取代之芳基、視情 況經取代之-烷基芳基、視情況經取代之雜芳基、視情況 經取代之_0_Cl _(：6烷基-芳基、視情況經取代之-CCCO-O-C! -c6 烷基、-NH2、視情況經取代之-芳基_雜環基及視情況經取 代之稠合雜環，且Cl_C7烷基係視情況被_NR3_B3取代，及 B3之胺係與B2之酸連接，以形成肽鍵，且其中當γ為 Β -Β 烷基-時，則2與1為共價鍵； 其中 备任何B1、B2及B3係連接在一起時，其係藉由肽鍵連 接，且 Β、β2 及 B3 係獨立選自包括 D-Pr〇、L-ile 及 D-Phe-4-CF3。 61. 如吻求項1之化合物，其中選自包括視情況經取代之芳基、 視情況經取代之-烷基芳基、視情況經取代之雜芳基、視 it況、’工取代之_〇_Ci A烷基_芳基、視情況經取代之 -C(〇)-〇'Cl_C6絲、視情況經取代之·芳基雜環基及視情況 經取代之稠合雜環之取代基係本身進一步視情況在烧基、 芳基雜芳基或雜環基部份基團上被取代基取代，取代基 選自包括叹心垸基-烧氧基、_CF3、_〇_芳基、炫氧基、 -NH-C(〇)-Cl_C6烷基、齒素、Ci_Q烷基、_〇_(齒基取代之烷 基）及-0-烷基_N(烷基）2。 62. 如請求項1之化合物，其中 各Y係獨立選自包括烷基、芳基、芳基-芳基、雜芳基、 134026-3 -83- 200916447 雜環基及雜環基-雜 芳基-雜芳基、雜芳基-芳基、環烷基、 芳基’其每一個係視情況經取代； L係選自包括 -Q-C6烧基姆3k：g_C3烧基·，其中當％&amp;烧基為（A 烷基時，其係視情況被取代基取代，取代基選自包括 烧基-ORa、基娜3)(R3a)、_Cq_C3 燒基 _c(〇)〇Ra 及3 C〇 -C3 炫基-C(0)-N(R3 )(R3 a ); -c0-c6^基-戰3)-C(〇KVC3烧基-，其中當_c〇_c6烷基為 Ci -C0院基時，其係視情況被取代基取代，取代基選自包括 -CVC3 烷基-ORa、-Ci-q 烷基-NR3R3a、_CgC3 烷基 _c(〇)〇Ra&amp; C〇-C3 烷基-C(0)-N(R3)(R3a); -C0-C6 烷基-N(R3)-C(O)-C0-C3 烷基-，其中 _c〇_c3 烷基為 Q -Cs炫基’其係視情況被取代基取代，取代基選自包括W and hydrazine are nitrogen; Ra, 妒 and Rc are _Η; 134026-3 -76- 200916447 R3 is -Η; R4 is Η or F; z is optionally substituted -Ci-C8 alkyl-; Selected from the group consisting of -c0-c6 alkyl-C(O)-N(R3)-C0-C3 alkyl-, wherein when the c〇-c3 alkyl group is a Ci-C3 alkyl group, the Ci-C3 alkyl group Depending on the case -C(0)-N(R3)-CG-C3 alkyl-Y,-heteroaryl-aryl, heteroaryl, -N(R3)(R3a) or -N(R3)-Y Substituted; -C0-C6 alkyl-heteroalkyl-C〇-C6 alkyl-CCCO-NCRM-Co-C^ alkyl-, wherein the C〇-〇3 alkyl group is C!-C3 alkyl base tj · 'This C! -C3 alkyl group is optionally substituted with a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; and -C〇-C6 alkyl-N(R3)C( 0) -C〇-C3 alkyl_, wherein when the c0-C3 alkyl group is C!-C3 alkyl, the Q-C3 alkyl group is optionally taken as -N(R3)C(0)-CQ-C3 Alkyla-Y, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl a heteroaryl group and an alkyl group, wherein the aryl group and the heteroaryl group are optionally substituted by one, two or three substituents selected from the group consisting of a halogen group, an alkoxy group, and optionally a Ci_c6 alkyl group. ,alkyl Carbonyl _, -OH, _CN, _C(0)-0H, optionally substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl, optionally substituted -OC 】-C6 alkyl-aryl, optionally substituted _c(〇)_〇Ci _匸6 alkyl, -NH2, optionally substituted-aryl-heterocyclic group, and optionally substituted Heterocyclic, and QC:7 alkyl is optionally substituted by -Nr3_b3, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein γ is Β2- -1 -N (R3 -C7 alkyl) - When, then ζ is a covalent bond with L; 134026-3 -77- 200916447 where the field B1, B2 and B3 are linked together by peptide bonds and B, B2 and B3 Independently selected from the group consisting of D, L ib and 56. The compound of claim 1, i r. i, W, 〆D is lean; w is nitrogen; Rc is -H; R is Η or -C! -C : 6 alkyl, wherein the alkyl group is optionally substituted; R 3 is -Η; R 4 is Η or F; ζ is optionally substituted -Ci -C8 alkyl -; L is selected from the group consisting of _C〇- C6 yl-C(0)-N(R3)-C〇-C3 院-, wherein when C〇-C3 is q-C3 alkyl This q-C3 alkyl group is optionally taken as -C(0)-N(R3)-C〇-C3 alkyl-Y,-heteroaryl-aryl, heteroaryl, -N(R3) (R3a) Or -N(R3)-Y substituted; -C〇-C6 alkyl-heteroalkyl-C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein When the C〇-C3 炫 is C]-C3, the C!-C3 alkyl group is optionally substituted with a heteroaryl group, -N(R3)(R3a) or -N(R3)-Y; C0-C6 alkyl-N(R3)C(0)-C〇-C3 alkyl-, wherein when c〇-c3 alkyl is c!-C3 alkyl, this Q-C3 alkyl group is optionally -N(R3)C(0)-C〇-c3alkyl-Y, -N(R3)(R3a) or -N(R3)-Y substituted; and each Y is independently selected from the group consisting of alkyl, aryl , heteroaryl, heteroaryl-aryl, aryl-heteroaryl and BlBLNO^K^CO-Ci-Cy alkyl-, wherein aryl 134026-3 -78- 200916447 and the heterocyclic group are optionally Substituted by one, two or three substituents selected from the group consisting of fluorenyl, alkoxy, optionally substituted C1-C:6 alkyl, alkoxy--, -OH, -CN, _C(0 -〇H, optionally substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl, optionally substituted -oq-c6alkyl-aryl , optionally substituted _c(0)_0_Ci _C6 alkyl, -NH2, optionally substituted aryl/heterocyclyl, and optionally substituted fused heterocycle, and Cl_C7 alkyl is optionally _ ^ ^ 7 3 substitution, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein when γ is Β2 -Β1 -N (R3 -C7 alkyl-, then ζ and L are covalent bonds Wherein, when any Bi '妒 and B3 lines are linked together, they are linked by a peptide bond, and B1, B2 and B3 are independently selected from the group consisting of D_Pr〇, L_ile and D phe 4_CF3. 57. The compound of claim 1, wherein D is 2; W and hydrazine are nitrogen; Ra is -Η; R3 is -Η; R4 is Η or F; z is optionally substituted _Ci_c8 alkyl _ L is -C0-C6 alkyl-N(R3)C(〇)_C〇_C3 alkyl_, wherein when c〇_c3 alkyl is Cl C3 alkyl, this Cl -(:3 alkyl Optionally substituted with -N(R3)C(0)-Q)-C3alkyl-Y, -N(R3)(R3a) or _N(R3)_γ; and each lanthanide is independently selected from the group consisting of alkyl , aryl, heteroaryl, heteroaryl-aryl 134026-3 -79· 200916447 base, aryl-heteroaryl and B2_Bi-N (R3&gt;c(〇)_Ci_C7 alkyl_, wherein aryl and hetero= The base system is optionally substituted, and the Ci_c7 alkyl group is optionally substituted by NR-B3, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein Y is bib1-N(R3)-C ( 0) _Ci_C7 alkyl _, then 2 and ^ are covalent bonds; wherein when the live B1, B2 and B3 lines are linked together, they are linked by peptide bonds, and BB and B3 are independently selected from the group consisting of D -Pro, L-ile and D-Phe-4-CF3. 58. The compound of claim 1, wherein W, / D is X; w is nitrogen; Re is -H; Rh is deuterium or -Cl _C6 alkane Base, where The base system is substituted as appropriate; R3 is -H; VIII is hydrazine or F; hydrazine is optionally substituted -C--C8 alkyl-; L is -C〇-C6 alkyl_n(R3)C (O)-C0-C3 alkyl-, wherein when the c0-c3 alkyl group is a ci-C3 alkyl group, the Q_c3 alkyl group is optionally taken as -N(R3)C(0)-C〇-C3 alkane Substituting _γ, or -n(r3)-y; and each lanthanide is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, and BkB1-N^ XCCO-Ci-C7 alkyl-, wherein the aryl and heteroaryl groups are optionally substituted, and the Ci-C7 alkyl group is optionally substituted by 134026-3 -80-200916447 -NR3-B3, and the amine of B3 Attached to the acid of B2 to form a peptide bond, and wherein when Y is B2 -B1 -N(R3)-01(0)-(^-Ο; alkyl group-, then z and l are covalent bonds; When any of B1, B2 and the protector are joined together, they are linked by a peptide bond, and B1, B2 and B3 are independently selected from the group consisting of D-Pro, L-ile and D-Phe-4-CF3. The compound of claim 1, wherein Γ. τ τ "丫M, Rb D is Ϊ; w and Μ are nitrogen; Ra, Rb and Rc are -Η; R3 is -Η; R4 is Η or F; The situation has been replaced - C8 L- is -C〇-C6 alkyl-N(R3)C(0)-C〇-C3 alkyl-, wherein when c〇_c3 alkyl is ci-C3 alkyl, this q-C : 3 is based on the condition of _n(R3)C(〇)-C〇-C3 entertainment: the γ series are independently selected from the group consisting of alkyl, aryl, heteroarylheteroaryl-aryl, aryl a heteroaryl group and a B2 -B1 -N(R3)-C(0)-Cl _c7 alkyl group, wherein the aryl group and the heteroaryl group are optionally substituted by one, two or three substituents selected from the group consisting of Including halogen, alkoxy, optionally substituted Ci alkyl, alkoxycarbonyl, -OH, -CN, -C(0)-OH, optionally substituted aryl, optionally taken 134026- 3 -81 - 200916447 Instead of alkylaryl, optionally substituted heteroaryl, optionally substituted -oc! aalkyl-aryl, optionally substituted _q0)_0_Ci % alkyl, NH2, optionally substituted _aryl-heterocyclic group and optionally substituted thick &amp; and q -C ·; the alkyl group is optionally substituted by -NR3 -B3, and the amine of B3', The acid of B is linked to form a peptide bond, and wherein when γ is b2#_n(R3)-C(0)~ci-A alkyl group, then z and L are covalent bonds; wherein when any B1, B2 And B3 series When connected together, which system is connected by a peptide bond, and / '\ 1 B, B2 and B3 is independently selected from the group comprising lines D-Pro, L-ile and D-Phe-4-CF3. 6. The compound of claim 1, wherein W and D are I; W is nitrogen; Re is -Η; R is hydrazine or -C: 6 alkyl, wherein the alkyl group is optionally substituted; R3 is -H ; V. R4 is Η or F ; Ζ is optionally substituted -C! -C8 炫 -; L is -C〇-C6 alkyl _N(R3)C(〇)_C〇_C3 Base-, wherein when c〇C3 alkyl is &gt; elementary group, this c]-C3 alkyl group is optionally taken as -N(R3)c(o)-cQ-c3 alkyl 1, - 113 () 1^) or 113)_¥substitution; and each Y is independently selected from the group consisting of alkyl, aryl, heteroaryl, heteroaryl-aryl, aryl-heteroaryl, and BLbLNO^-C(9)-Ci- Cyalkyl-, wherein aryl 134026-3 -82- 200916447 and heteroaryl are optionally substituted by one, two or three substituents selected from the group consisting of a dentate group, an alkoxy group, optionally substituted Ci_C6 alkyl, alkoxycarbonyl-, -OH, -CN, -C(〇K)H, optionally substituted aryl, optionally substituted -alkylaryl, optionally substituted heteroaryl ___ _ (6 alkyl-aryl, optionally substituted - CCCO-OC! -c6 alkyl, -NH2, optionally substituted - aryl - heterocyclic ring) And a fused heterocyclic ring substituted as appropriate, and the Cl_C7 alkyl group is optionally substituted by _NR3_B3, and the amine of B3 is linked to the acid of B2 to form a peptide bond, and wherein γ is Β-Β alkyl - when, 2 and 1 are covalent bonds; wherein any of the B1, B2 and B3 lines are linked together by a peptide bond, and the Β, β2 and B3 are independently selected from the group consisting of D-Pr〇, L-ile and D-Phe-4-CF3. 61. A compound of the formula 1 which is selected from the group consisting of an optionally substituted aryl group, optionally substituted an alkylaryl group, optionally substituted Heteroaryl, depending on the conditions, 'work-substituted _〇_Ci A alkyl-aryl, optionally substituted-C(〇)-〇'Cl_C6 silk, optionally substituted aryl heterocyclic group And the substituent of the fused heterocyclic ring which is optionally substituted, optionally further substituted with a substituent on the alkyl group, the arylheteroaryl group or the heterocyclic group moiety, and the substituent is selected from the group consisting of sin - alkoxy, _CF3, _〇_aryl, methoxy, -NH-C(〇)-Cl_C6 alkyl, dentate, Ci_Q alkyl, _〇_ (dentyl-substituted alkyl) and -0 -alkyl-N(alkyl) 2. 62. The compound of claim 1, wherein each Y is independently selected from the group consisting of alkyl, aryl, aryl-aryl, heteroaryl, 134026-3-83-200916447 heterocyclyl, and heterocyclyl-heteroaryl- Each of a heteroaryl group, a heteroaryl-aryl group, a cycloalkyl group, and an aryl group is optionally substituted; the L series is selected from the group consisting of -Q-C6-combustyl 3k:g_C3 alkyl group, wherein when %&amp When the alkyl group is (A alkyl group, it is optionally substituted by a substituent selected from the group consisting of an alkyl group -ORa, a genus 3) (R3a), a _Cq_C3 alkyl group _c(〇) 〇Ra, and a 3 C group. 〇-C3 炫-C(0)-N(R3)(R3 a ); -c0-c6^base-war 3)-C(〇KVC3 alkyl-, wherein when _c〇_c6 alkyl is Ci In the case of -C0, it is optionally substituted by a substituent selected from -CVC3 alkyl-ORa, -Ci-q alkyl-NR3R3a, _CgC3 alkyl-c(〇)〇Ra&amp;C〇- C3 alkyl-C(0)-N(R3)(R3a); -C0-C6 alkyl-N(R3)-C(O)-C0-C3 alkyl-, wherein _c〇_c3 alkyl is Q-Cs 炫基' is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)-CG-C3 烷基-Y、_N(R3)-C(s)-CQ-C3 烷基-Y、 -C(0)-N(R3)-C〇-C3 烧基-Y、-C(S)-N(R3)-C〇-C3 烧基-Y、 -N(R3 )-C(0)-CQ -C3 烷基-C4 -C6 環烷基-、-N(R3 )-C(S)-CG -C3 烷基 -C4 -C6 環烷基-、-N(R3 )-C。-C3 烷基-Y、-N(R3 )(R3 a)、-N(R3 )-C。-C3 烷基-C4 -C6 雜環基、-N(R3 )-C2 -C3 烷基-N(R3 )(R3 a)、-N(R3 )-C2 -C3 烧基-ORa、-N(R3 )-C〇 -C3 炫基-C〇 -C3 雜烧基-Y、-N(R3 )-C(0)-0· C0-C3 烷基-Y、NKRq-CXSKKVCg 烷基-Y、-N(R3)-S(0)2-C〇-C3 烷基-Y、-N(R3)-C(O)-N(R3)-C0-C3 烧基-Y、-N(R3)-C⑸-N(R3)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-C〇-C3 雜環基、-N(R3)-C(S)-C〇 -C3 烧基-C〇 -C3 雜環基、-N(R3 )-C(0)-C〇 -C3 烧基-C〇 -c3 雜 環基-Y、-N(R3 )-C⑸-C。-C3 烧基-C。-C3 雜環基-Y 及 _N(R3 )-S(〇)2 - 134026-3 -84- 200916447 N(R3)-C〇-C3 烷基-Υ ; -c〇-c6 烷基-n(r3)-c(s)-c〇-c3 烷基-，其中-C〇-C3 烷基為 Q -c3烷基，其係視情況被取代基取代，取代基選自包括 -n(r3)-c(o)-c〇-c3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、-C(O)-N(R3)-Cg-C3 烷基-Y、-C(S)-N(R3)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇 -C3烷基-c4 -C6環烷基-、-N(R3 )-C⑸-CQ -C3烷基-C4 -C6環烷基 -、-N(R3)-C〇-C3 烷基-Y、-N(R3)(R3a)、-N(R3)-C〇-C3 烷基-C4-C6 雜環基、-N(R3)-C2-C3 烷基-N(R3)(R3a)、-N(R3)-C2-C3 烷基 ( -ORa、-n(r3)-c〇-c3 烷基-C〇-C3 雜烷基-Y、-n(r3)-c(o)-o-c〇-c3 烷基-y、-n(r3)-c⑸-〇-cG-c3 烷基-y、-n(r3)-s(o)2-cg-c3 烷基 •Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y、-n(r3)-c(s)-n(r3)-c〇-c3 烷基-y、-n(r3)-c(o)-c〇-c3烷基-c〇-c3雜環基、-n(r3)-c(s)-C〇 -C3 烷基-C〇 -C3 雜環基、-N(R3 )-(：(0)-(：〇 -C3 烷基-C〇 -C3 雜環基 -Y、-N(R3)-C(S)-C〇-C3 烷基-CVC3 雜環基-Y 及-n(r3)-s(o)2-n(r3)-c〇-c3 烷基-Y ; -c0-c6烷基-c(o)-c〇-c3烷基-，其中當-C0-C6烷基為q -c3 f ^ 烷基時，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y 、-N(R3)-C(S)-C〇-C3 烷基-Y 、 -C(0)-N(R3)(R3a)、-C(S)-N(R3)(R3a)、-C(O)-N(R3)-C0-C3 烷基-Y、 -C⑸-N(R3 )-C〇 -C3 烷基-Y、-N(R3 )-C(0)-C。-C3 烷基-C4 -C6 環烷基-、-N(R3)-C(S)-Cq-C3 烷基-C4-C6環烷基-、-N(R3)-C〇-C3 烷基-Y、 -N(R3)(R3a)、-N(R3)-CG-C3 烷基-C4-C6雜環基、-N(R3)-C2-C3烷 基-N(R3 )(R3 a )、-N(R3 )-C2 -C3 烷基-ORa ·、-N(R3 )-C〇 -C3 雜烷基 -Y、-N(R3 )-C(0)-〇-C〇 -C3 烷基-Y、-N(R3 )-C(S)-0-CQ -C3 烷基-Y、 134026-3 -85· 200916447 -n(r3)-s(o)2-c〇-c3 烷基-Υ、-N(R3)-C(O)-N(R3)-C0-C3 烷基-Υ、 -N(R3)-C(S)-N(R3)-C〇-C3 烷基-Υ、-N(R3)-c(o)-c〇-c3 烷基-c〇-c3 雜環基、-n(r3)-c(s)-cg-c3烷基-c〇-c3雜環基、-n(r3)-c(o)-C〇 -C3 烷基-C〇 -C3 雜環基-Y、-N(R3 )-C(S)-C〇 -C3 烷基-C〇 -C3 雜環 基-Y 及-N(R3 )-S(0)2 -N(R3 )-C〇 -C3 烷基-Y ; -C〇-C6烧基-C(S)-C〇-C3炫基-’其中當-C〇-C6烧基為C! -C3 烷基時，其係視情況被取代基取代，取代基選自包括 -N(R3)-C(〇)-CG-C3 烷基-Y、-N(R3)-C(S)-C〇-C3 烷基-Y、 v -C(0)-N(R3 )(R3 a)、-C⑸-N(R3 )(R3 a)、-C(0)-N(R3 )-C〇-C3 烷基-Y、 -C(S)-N(R3 )-C。-C3 烷基-Y、-N(R3 )-C(0)-C。-C3 烷基-C4 -C6 環烷基-、-N(R3)-C(S)-CG-C3烷基-C4-C6環烷基-、-N(R3)-C〇-C3烷基-Y、 -N(R3)(R3a)、-N(R3)-C〇-C3 烷基-(：4-(：6雜環基、-N(R3)-C2-C3 烷 基-N(R3)(R3a)、-N(R3)-C2-C3 烷基-〇Ra-、-N(R3)-C〇-C3 雜烷基 -Y、-N(R3)-C(0)-0-C〇-C3 烷基-Y、-N(R3)-C(S)-0-C〇-C3 烷基-Y、 -n(r3)-s(o)2-c〇-c3 烷基-Υ、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Υ、 t -N(R3 )-C(S)-N(R3 )-C0 -C3 烷基-Υ、-N(R3 )-C(O)-C0 -C3 烷基-C0 -C3 雜環基、-N(R3)-C ⑸-CG-C3 烷基-Q-Q 雜環基、-n(r3)-c(o)-c〇-c3 烷基-C〇-C3雜環基-Y ' -N(R3)-C(S)-Cq-C3烷基-C〇-C3 雜環 基-Y 及-N(R3 )-S(0)2 -N(R3 )-C〇 -C3 烷基-Y ; -C〇-C6烷基-，其中當-C〇-C6烷基為烷基時，其係視 情況被取代基取代，取代基選自包括-n(r3)-c(o)-cg-c3烷基 -Y、-N(R3)-C(0)-C〇-C3烷基-雜環基及-N(R3)-C(0)-C〇-C3烷基-環烷基； -C〇 -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當-C〇 -C3 烷基為 134026-3 -86- 200916447 q-c：3烷基時，其係視情況被取代基取代，取代基選自包括 -C(0)-N(R3)-C〇-C3 烷基-Y、-C(〇)-雜環基、_C(〇)_N(R3)(R3a)、 芳基-芳基、芳基-雜芳基、-雜芳基-芳基、雜芳基雜芳基、 雜芳基、雜環基-雜芳基及雜環基； -Q -c6烧基-雜烷基_c6烷基_c(0)_n(r3 )_c。a烷基·，其 中當-C〇 -C3烧基為Q -C：3烧基時，其係視情況被取代基取代， 取代基選自包括-C(O)-N(R3)-C0-C3烷基-Y、-c(0)_雜環基、 广 -c(0)-N(R3)(R3a)、芳基-芳基、芳基-雜芳基、-雜芳基-芳基、 ' 雜芳基-雜芳基、雜芳基、雜環基-雜芳基及雜環基； -C〇 -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當 _c〇 -C6 烷基為 c! -C6烧基時，其係視情況被取代基取代，取代基選自包括 -N(R7 )(R7 a) ' -N(R3 )(R3 a)、-N(R3 )-C(O)-C0 -C3 烧基-Y、-N(R3 )-C(0)-O-C。-C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-C。-C3 烷基-Y 及-N(R3 )-S(0)2 -C〇-C3 烷基-Y ; -C〇-C6烧基-雜芳基-C〇-C3烧基-，其中當-C0-C3烧基為 q-Cs烷基時，其係視情況被取代基取代，取代基選自包括 _C0-C3 烷基-N(R3)-C(0)-C〇-C3 烷基-N(R3)(R3a)、_N(R3)-C(0)-c0-c3 烷基-y、-n(r3)-c(o)-o-cq-c3 烷基-y、-n(r3)-c(o)- N(R3 )-C〇 -C3 烷基-Υ 及-N(R3 )-S(0)2 -C〇 -C3 烷基-Υ ; -C〇-C6烷基-芳基-C〇-C3烷基-，其中當-C0-C3烷基為Ci-q 烷基時，其係視情況被取代基取代，取代基選自包括-N(R3 )-C(0)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-Y、-n(r3)-c(o)-0-C〇 -C3 烷基-υ ' -N(R3 )-C(0)-N(R3 )-CG -C3 烷基-Υ 及-N(R3 )-S(0)2 -C〇-C3 烷基-Y ; 134026-3 -87- 200916447 -C〇-C6烷基-芳基-雜芳基-c0-c3烷基-，其中當-c〇-c3烷基 為(^-(:3烷基時，其係視情況被取代基取代，取代基選自包 括-n(r3)-c(o)-c〇-c3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-Y、 -N(R3)-C(0)-〇-Cq-C3 烷基-Y、-N(R3)-C(0)-N(R3)-C〇-C3 烷基-Y 及 -N(R3)-S(0)2-C〇-C3 烷基-Y ; -C〇-C6烷基-雜芳基-雜芳基-C〇-C3烷基-，其中當-C〇-C3烷 基為C】-C3炫基時，其係視情況被取代基取代，取代基選自 包括-N(R3KX〇)-C0-C3 烧基-Y、-N(R3)-C(O)-C0-C3 院基-Y、 -N(R3 )-C(0)-0-C。-C3 烷基-Y、-N(R3 )-C(0)-N(R3 )-C〇 -C3 烷基-Y 及 -N(R3)-S(0)2-C〇-C3 烷基-Y ; -C0-C6烧基-雜芳基-C0-C3烧基-，其中當-C0-C3烧基為 Q -C：3烧基時’其係視情況被取代基取代，取代基選自包括 -N(R3)-C(0)-C〇-C3 烷基-Y、-N(R3)-C(0)-C〇-C3 烷基-Y、 -N(R3 )-C(0)-0-CQ -C3 院基-Y、-N(R3 )-C(0)-N(R3 )-C〇 -C3 烧基-Y 及 -N(R3)-S(0)2-Cq-C3 烷基-γ; -c0 -Q 烷基-0-C(0)-N(R3 )-C0 -C3 烷基-’其中當 _c〇-C3 烷基為 C! -C3烧基時’其係視情況被基團取代，取代基選自 -C(0)-0Ra、-C(S)-ORa、-C(0)-N(R3 -C3 烷基、_C(S)_N(R3)_Ci_C3 烷基、-C(0)-N(R3)(R3a)-、-C(S)-N(R3)(R3a)_、_c(〇)_n(r3)_c〇_C3 烧基-芳基、-C(S)-N(R3)-C〇-C3 烧基-芳基、貌 基-雜 ^'基、-C(S)-N(R3 )-C〇 -C3 烧基-雜芳基、_c(0)-N(R3 )-C〇 -C3 院基-環烧基、-C(S)-N(R3 )-CG -C3烧基-環院基、七(〇)_雜環基、 -C(S)-雜環基、-C(0)-N(R3)-C〇-C3 烧基-Y、_(^s)-N(R3)-C〇-C3 院 基-Y、-C(0)-N(R3)-雜環基、-C(S)-N(R3)_雜環基、_c(〇)_n(r3)_ 134026-3 -88- 200916447 C〇 -C：3烷基-雜環烷基及_cxS)_N(R3 )_Cg _c3烷基-雜環烷基； -c0 -C：6 烧基-〇-C(S)-N(R3 )-C〇 -C3 烷基-，其中當-C〇 _c3 烷基為 Q -C：3烷基時’其係視情況被基團取代，取代基選自 -C(0)-0Ra、-C(S)-ORa、-C(0)-N(R3 )4 -C3 烷基、-C(S)-N(R3 -C3 烷基、-C(0)-N(R3)(R3a)-、-C⑸-N(R3)(R3a)-、-C(O)-N(R3)-C0-C3 烧基-方基、-C(S)-N(R3)-C〇-C3 炫基-芳基、-C(0)-N(R3)-C〇-C3 烧 基-雜芳基、-C(S)-N(R3)-C0-C3 烷基-雜芳基、-c(o)-n(r3)-c〇-c3 烷基-環烷基、-C(S)-N(R3 )-CQ -C3烷基-環烷基、-C(o)-雜環基、 -c(s)-雜環基、-c(o)-n(r3)-c〇-c3烷基-Y、-C⑸-n(r3kvc3烷 基-Y、-C(0)-N(R3)-雜環基、-C(s)-N(R3)-雜環基、-C(0)-N(R3)_ c〇-c3烷基-雜環烷基及-C⑸-N(R3)-CG-C3烷基-雜環烷基；及 -q -C3烷基-N(R3 )-(:(0)-(^ -C7烷基-’其中q -C3烷基係視情 況被-C(0)N(R3 )-(：! -C3烷基-A1 a取代’且Q -C7烷基係視情況 被取代基取代，取代基選自包括-N(R3 )-(:(0)-04 -C3烷基 -A1 b、_N(R3 烷基-A1 b、-MRq-Sah-CVQ 烷基-N(R3)-C(0)-CG-C3 alkyl-Y,_N(R3)-C(s)-CQ-C3 alkyl-Y, -C(0)-N(R3)-C〇 -C3 alkyl-Y, -C(S)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(0)-CQ-C3 alkyl-C4-C6 cycloalkyl -, -N(R3)-C(S)-CG-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C. -C3 alkyl-Y, -N(R3)(R3a), -N(R3)-C. -C3 alkyl-C4 -C6 heterocyclyl, -N(R3)-C2 -C3 alkyl-N(R3)(R3 a), -N(R3)-C2 -C3 alkyl-ORa, -N( R3 )-C〇-C3 炫基-C〇-C3 miscellaneous group-Y,-N(R3)-C(0)-0·C0-C3 alkyl-Y, NKRq-CXSKKVCg alkyl-Y,- N(R3)-S(0)2-C〇-C3 alkyl-Y,-N(R3)-C(O)-N(R3)-C0-C3 alkyl-Y,-N(R3)- C(5)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-C( S)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-C(0)-C〇-C3 alkyl-C〇-c3 heterocyclic group-Y, -N(R3 )-C(5)-C. -C3 burnt base-C. -C3 Heterocyclyl-Y and _N(R3)-S(〇)2 - 134026-3 -84- 200916447 N(R3)-C〇-C3 alkyl-oxime; -c〇-c6 alkyl-n (r3)-c(s)-c〇-c3 alkyl-, wherein -C〇-C3 alkyl is Q-c3 alkyl, which is optionally substituted with a substituent selected from the group consisting of -n(r3 )-c(o)-c〇-c3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, -C(O)-N(R3)-Cg-C3 Alkyl-Y, -C(S)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-c4-C6 cycloalkyl- , -N(R3)-C(5)-CQ-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y, -N(R3)(R3a), -N( R3)-C〇-C3 alkyl-C4-C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2-C3 alkyl ( ORa, -n(r3)-c〇-c3 alkyl-C〇-C3 heteroalkyl-Y, -n(r3)-c(o)-oc〇-c3 alkyl-y, -n(r3) -c(5)-〇-cG-c3 alkyl-y, -n(r3)-s(o)2-cg-c3 alkyl•Y,-N(R3)-C(0)-N(R3)-C 〇-C3 alkyl-Y, -n(r3)-c(s)-n(r3)-c〇-c3 alkyl-y, -n(r3)-c(o)-c〇-c3 alkyl -c〇-c3 heterocyclic group, -n(r3)-c(s)-C〇-C3 alkyl-C〇-C3 heterocyclic group, -N(R3)-(:(0)-(:〇 -C3 alkyl-C〇-C3 heterocyclyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-CVC3 heterocycle -Y and -n(r3)-s(o)2-n(r3)-c〇-c3 alkyl-Y; -c0-c6 alkyl-c(o)-c〇-c3 alkyl-, wherein When the -C0-C6 alkyl group is a q-c3f^ alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y. , -N(R3)-C(S)-C〇-C3 alkyl-Y, -C(0)-N(R3)(R3a), -C(S)-N(R3)(R3a),- C(O)-N(R3)-C0-C3 alkyl-Y, -C(5)-N(R3)-C〇-C3 alkyl-Y, -N(R3)-C(0)-C.-C3 Alkyl-C4 -C6 cycloalkyl-, -N(R3)-C(S)-Cq-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl-Y -N(R3)(R3a), -N(R3)-CG-C3 alkyl-C4-C6 heterocyclic group, -N(R3)-C2-C3 alkyl-N(R3)(R3a), -N(R3)-C2 -C3 alkyl-ORa ·, -N(R3)-C〇-C3 heteroalkyl-Y, -N(R3)-C(0)-〇-C〇-C3 alkyl -Y, -N(R3)-C(S)-0-CQ-C3 alkyl-Y, 134026-3 -85· 200916447 -n(r3)-s(o)2-c〇-c3 alkyl- Υ, -N(R3)-C(O)-N(R3)-C0-C3 alkyl-oxime, -N(R3)-C(S)-N(R3)-C〇-C3 alkyl-oxime , -N(R3)-c(o)-c〇-c3 alkyl-c〇-c3 heterocyclic group, -n(r3)-c(s)-cg-c3 alkyl-c〇-c3 heterocyclic ring , -n(r3)-c(o)-C〇-C3 alkyl-C〇-C3 heterocyclyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-C 〇-C3 heterocyclyl-Y and -N(R3)-S(0)2 -N(R3)-C〇-C3 alkyl-Y; -C〇-C6 alkyl-C(S)-C〇 -C3 炫-' wherein when -C〇-C6 alkyl is C!-C3 alkyl, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(〇)-CG -C3 alkyl-Y, -N(R3)-C(S)-C〇-C3 alkyl-Y, v-C(0)-N(R3)(R3 a), -C(5)-N(R3) (R3 a), -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(S)-N(R3)-C. -C3 alkyl-Y, -N(R3)-C(0)-C. -C3 alkyl-C4 -C6 cycloalkyl-, -N(R3)-C(S)-CG-C3 alkyl-C4-C6 cycloalkyl-, -N(R3)-C〇-C3 alkyl -Y, -N(R3)(R3a), -N(R3)-C〇-C3 alkyl-(:4-(:6heterocyclyl, -N(R3)-C2-C3 alkyl-N ( R3)(R3a), -N(R3)-C2-C3 alkyl-〇Ra-, -N(R3)-C〇-C3 heteroalkyl-Y, -N(R3)-C(0)-0 -C〇-C3 alkyl-Y, -N(R3)-C(S)-0-C〇-C3 alkyl-Y, -n(r3)-s(o)2-c〇-c3 alkyl -Υ, -N(R3)-C(0)-N(R3)-C〇-C3 alkyl-oxime, t-N(R3)-C(S)-N(R3)-C0-C3 alkyl -Υ, -N(R3)-C(O)-C0-C3 alkyl-C0-C3 heterocyclic group, -N(R3)-C(5)-CG-C3 alkyl-QQ heterocyclic group, -n( R3)-c(o)-c〇-c3 alkyl-C〇-C3 heterocyclyl-Y '-N(R3)-C(S)-Cq-C3 alkyl-C〇-C3 heterocyclic group- Y and -N(R3)-S(0)2 -N(R3)-C〇-C3 alkyl-Y; -C〇-C6 alkyl-, wherein when -C〇-C6 alkyl is alkyl , which is optionally substituted by a substituent selected from the group consisting of -n(r3)-c(o)-cg-c3alkyl-Y, -N(R3)-C(0)-C〇-C3 -heterocyclyl and -N(R3)-C(0)-C〇-C3 alkyl-cycloalkyl; -C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 Alkyl-, wherein when -C〇-C3 alkyl is 134026-3 -86- 200916447 qc:3 alkyl , which is optionally substituted by a substituent selected from the group consisting of -C(0)-N(R3)-C〇-C3 alkyl-Y, -C(〇)-heterocyclyl, _C(〇)_N (R3) (R3a), aryl-aryl, aryl-heteroaryl, -heteroaryl-aryl, heteroarylheteroaryl,heteroaryl,heterocyclyl-heteroaryl and heterocyclic -Q-c6alkyl-heteroalkyl-c6alkyl_c(0)_n(r3)_c.aalkyl-, wherein when the -C〇-C3 alkyl group is a Q-C:3 alkyl group, It is optionally substituted by a substituent selected from the group consisting of -C(O)-N(R3)-C0-C3 alkyl-Y, -c(0)-heterocyclyl, and broad-c(0)- N(R3)(R3a), aryl-aryl, aryl-heteroaryl, -heteroaryl-aryl, 'heteroaryl-heteroaryl,heteroaryl,heterocyclyl-heteroaryl and Heterocyclic group; -C〇-C6 alkyl-C(0)-N(R3)-C〇-C3 alkyl-, wherein when _c〇-C6 alkyl is c!-C6 alkyl, the system Substituted by a substituent, the substituent is selected from the group consisting of -N(R7)(R7 a) ' -N(R3 )(R3 a), -N(R3 )-C(O)-C0 -C3 alkyl-Y , -N(R3 )-C(0)-OC. -C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C. -C3 alkyl-Y and -N(R3)-S(0)2 -C〇-C3 alkyl-Y; -C〇-C6 alkyl-heteroaryl-C〇-C3 alkyl-, wherein When the -C0-C3 alkyl group is a q-Cs alkyl group, it is optionally substituted with a substituent selected from the group consisting of _C0-C3 alkyl-N(R3)-C(0)-C〇-C3 alkane. -N(R3)(R3a), _N(R3)-C(0)-c0-c3 alkyl-y, -n(r3)-c(o)-o-cq-c3 alkyl-y,- n(r3)-c(o)- N(R3)-C〇-C3 alkyl-Υ and -N(R3)-S(0)2 -C〇-C3 alkyl-Υ; -C〇-C6 An alkyl-aryl-C〇-C3 alkyl- group, wherein when the -C0-C3 alkyl group is a Ci-q alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)- C(0)-C〇-C3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkyl-Y, -n(r3)-c(o)-0-C〇- C3 alkyl-υ '-N(R3)-C(0)-N(R3)-CG-C3 alkyl-Υ and -N(R3)-S(0)2 -C〇-C3 alkyl-Y ; 134026-3 -87- 200916447 -C〇-C6 alkyl-aryl-heteroaryl-c0-c3 alkyl-, wherein when -c〇-c3 alkyl is (^-(:3 alkyl, It is optionally substituted with a substituent selected from the group consisting of -n(r3)-c(o)-c〇-c3 alkyl-Y, -N(R3)-C(0)-C〇-C3 alkane -Y, -N(R3)-C(0)-〇-Cq-C3 alkyl-Y, -N(R3)-C(0)-N(R3)-C〇-C3 alkyl- Y and -N(R3)-S(0)2-C〇-C3 alkyl-Y; -C〇-C6 alkyl-heteroaryl-heteroaryl-C〇-C3 alkyl-, wherein - When the C〇-C3 alkyl group is a C-C3 leukoyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3KX〇)-C0-C3 alkyl-Y, -N(R3)- C(O)-C0-C3 Institute-Y, -N(R3)-C(0)-0-C.-C3 Alkyl-Y, -N(R3)-C(0)-N(R3) -C〇-C3 alkyl-Y and -N(R3)-S(0)2-C〇-C3 alkyl-Y; -C0-C6 alkyl-heteroaryl-C0-C3 alkyl-, wherein When the -C0-C3 alkyl group is a Q-C:3 alkyl group, it is optionally substituted with a substituent selected from the group consisting of -N(R3)-C(0)-C〇-C3 alkyl-Y. , -N(R3)-C(0)-C〇-C3 Alkyl-Y, -N(R3)-C(0)-0-CQ-C3 Institute-Y,-N(R3)-C( 0)-N(R3)-C〇-C3 alkyl-Y and -N(R3)-S(0)2-Cq-C3 alkyl-γ; -c0 -Q alkyl-0-C(0) -N(R3)-C0-C3 alkyl-' wherein when _c〇-C3 alkyl is C!-C3 alkyl, it is optionally substituted by a group selected from -C(0)- 0Ra, -C(S)-ORa, -C(0)-N(R3 - C3 alkyl, _C(S)_N(R3)_Ci_C3 alkyl, -C(0)-N(R3)(R3a)- , -C(S)-N(R3)(R3a)_, _c(〇)_n(r3)_c〇_C3 alkyl-aryl, -C(S)-N(R3)-C〇-C3 Ji-fang Base, morphine-hetero-', -C(S)-N(R3)-C〇-C3 alkyl-heteroaryl, _c(0)-N(R3)-C〇-C3 yard-ring Anthracenyl, -C(S)-N(R3)-CG-C3 alkyl-ring-based, hepta-(hetero)-heterocyclyl, -C(S)-heterocyclyl, -C(0)-N (R3)-C〇-C3 alkyl-Y, _(^s)-N(R3)-C〇-C3 Institute-Y, -C(0)-N(R3)-heterocyclyl, -C (S)-N(R3)_heterocyclyl, _c(〇)_n(r3)_ 134026-3 -88- 200916447 C〇-C: 3 alkyl-heterocycloalkyl and _cxS)_N(R3) _Cg _c3 alkyl-heterocycloalkyl; -c0 -C:6 alkyl-indole-C(S)-N(R3)-C〇-C3 alkyl-, wherein -C〇_c3 alkyl is Q -C: 3 alkyl group when it is optionally substituted by a group selected from -C(0)-0Ra, -C(S)-ORa, -C(0)-N(R3)4 -C3 Alkyl, -C(S)-N(R3-C3 alkyl, -C(0)-N(R3)(R3a)-, -C(5)-N(R3)(R3a)-, -C(O)- N(R3)-C0-C3 alkyl-aryl, -C(S)-N(R3)-C〇-C3 leu-aryl, -C(0)-N(R3)-C〇-C3 Pyridyl-heteroaryl, -C(S)-N(R3)-C0-C3 alkyl-heteroaryl, -c(o)-n(r3)-c〇-c3 alkyl-cycloalkyl, -C(S)-N(R3)-CQ-C3 alkyl-cycloalkyl, -C(o)-heterocyclyl, -c(s)-heterocyclyl, -c(o)-n(r3 )-c〇-c3 alkyl-Y, -C(5)-n(r3kvc3 alkyl- Y, -C(0)-N(R3)-heterocyclyl, -C(s)-N(R3)-heterocyclyl, -C(0)-N(R3)_c〇-c3 alkyl- Heterocycloalkyl and -C(5)-N(R3)-CG-C3 alkyl-heterocycloalkyl; and -q-C3 alkyl-N(R3)-(:(0)-(^-C7 alkyl- 'wherein the q-C3 alkyl group is optionally substituted by -C(0)N(R3)-(:!-C3alkyl-A1a' and the Q-C7 alkyl group is optionally substituted by a substituent, the substituent is selected Included from -N(R3)-(:(0)-04 -C3 alkyl-A1 b, _N(R3 alkyl-A1 b, -MRq-Sah-CVQ alkyl -八113、-叫113)-5(0)2-1^(113)-(：1-(：3烷基-八113、-叫113)-(：(0)-：^(113)-Ci -C3 烷基-A1 b 及-N(R3 )-S(0)2 -N(R3 -C3 烷基-A1 b ; Z係選自包括- eight 113, - 113) -5 (0) 2-1 ^ (113) - (: 1-(: 3 alkyl - eight 113, - called 113) - (: (0) -: ^ (113) -Ci -C3 alkyl-A1 b and -N(R3 )-S(0)2 -N(R3 -C3 alkyl-A1 b ; Z series selected from 視情況經取代之 ^ ρ3Replaced as appropriate ^ ρ3 βΤ a0&gt;A、^^(CH2)〇_3,βΤ a0&gt;A,^^(CH2)〇_3, (CH2)〇-3 134026-3 -89- 200916447(CH2)〇-3 134026-3 -89- 200916447 200916447200916447 其中各A係獨立為氮、-CH=或-C(R4)=，其中可以有〇 2或3個氮；且 D為 c Rc Ra Rc w、c^M、Rb Ί—w、 ,Rh X 或 X 63.如請求項i之化合物，豆中 ^ T '、 —卜 W、/Rh X D為 w為氮； RC 為-H ; X為s ; Rh為-q-Ce烷基或烷基-苯基，其中該烷基與苯基 係視情況獨立經取代； Z為視情況經取之-C3-C8烷基-; L為'ΜΗΚΧΟ)-。烷基-，其中Q烷基係被-N(H)-C(0)-0-Ci_C6燒基-笨基或烷基取代；且 為^'基-雜方基-或雜方基_，其每一個係視情況經取 代。 、” 64.如睛求項63之化合物，其中γ為苯基，唑基、噻唑或咪唑 65‘如清求項63之化合物，其中Ζ為-C4烷基-。 66.如請求項1之化合物，其中 I r ^Rh D為 5 · 134026-3 -91 · 200916447 w為氮； Rc 為·Η ; X為S ; R為-q-c：6烧基或-CpC^烷基_苯基，其中該烷基與笨基 係視情況獨立經取代； Z為視情況經取之_c3_C8烷基_ ; L為-C〗烷基-，被選自包括_N(H)_c(〇)_〇_CrC6烷基_苯基、 N(H)-C(〇)-〇_Cl _c6 院基、_NH c(〇)雜環基 a &amp; 烷基及 NHC(0)-Cl-C6烧基_S(Vci-C6烷基之取代基取代；且 Y為雜芳基-，其係視情況經取代。67· 士 β求項66之化合物，其中γ為視情況經取代之苯并味 68. 如明求項66之化合物，其中γ為被初2或⑽_Νη2取代之 本弁味。坐。 69. 如請求項66之化合物 70. 如請求項1之化合物 其中Ζ為-c4烷基-。 其中 Ra ! .Μ、 C II X Rb W Rc 為氮； 4 -H ; Μ為氮； 把為Η ; 妒為笨基或c]-c6烷基； 134026-3 92· 200916447 z為視情況經取之-C3-C8烷基_ ; L 為-NO^-CCCO-Ci 烷基-，其中 q 烷基係被 _N(H)-C(0)-0-q-Ce烷基-苯基取代；且 Y為芳基-雜芳基-’其係視情況經取代。 71. 如請求項1之化合物，其中 Rc Ra D為 k ; W為氮； Rc 為-Η ; X為S ; M為氮； Ra 為 Η ; Rb為笨基或心-心烷基； z為視情況經取之-c3 -c8烷基-; L 為烷基-，被 ^(11)-(:(0)-0-(^ -C6 烷基-苯基、-N(H)-C(0)-◦-Ci-C：6烷基及烷基-SCVCi-q烷基取代；且 γ為視情況經取代之苯并咪唑。 72. 如請求項71之化合物，其中z為_C4烷基_。 73·如凊求項71之化合物，其中Y係被-c(o)-nh2取代。 74. 如请求項71之化合物，其中γ係進一步選自視情況經取代 之芳基-雜芳基。 75. —種式（ΙΙΠ)化合物： Y-L-D (III) 或其Ν-氧化物、水合物、溶劑合物、藥學上可接受之鹽、 134026-3 •93- 200916447 前體藥物或複合物’或其外消旋或呈比例混合物、非 對映異構物或對掌異構物，其中 D係選自包括 -卜Ν、Ν'與如 h ; Y Rb s S S Rb與Rh係獨立選自包括_Ci 6烷基、_c“。芳基及_C7 i6烷基 芳基； L係選自包括_c〇-6次烷基_、_c〇3次烷基_N(H)_c(〇)_c〇_6次烷 基-’視情況被0-3個R4取代； y係選自包括視情況經取代之_c6 i〇芳基與視情況經取代 之-5-10員雜芳基； R4係選自包括-N(H)-C(0)-R3 與 _N(H)-C(0)-〇-R3 ;且 r3係選自包括視情況經取代之_Ci 6烷基、_Ci 6雜烷基、 m員雜環基及_c7_16烷基芳基。 _ζ—ΝΗ Ν ^ \/\ Rb 76.如請求項75之化合物，其中d為 ; 。Wherein each A is independently nitrogen, -CH= or -C(R4)=, wherein there may be 2 or 3 nitrogens; and D is c Rc Ra Rc w, c^M, Rb Ί—w, , Rh X Or X 63. The compound of claim i, in the bean ^ T ', -Bu W, /Rh XD is w is nitrogen; RC is -H; X is s; Rh is -q-Ce alkyl or alkyl- Phenyl, wherein the alkyl group and the phenyl group are independently substituted; Z is optionally taken as -C3-C8 alkyl-; L is 'ΜΗΚΧΟ'-. Alkyl-, wherein the Q alkyl group is substituted by -N(H)-C(0)-0-Ci_C6 alkyl-phenyl or alkyl; and is a 'hetero-hetero- or heteroaryl _, Each of them is replaced as appropriate. 64. The compound of claim 63, wherein γ is phenyl, azolyl, thiazole or imidazole 65', such as the compound of claim 63, wherein hydrazine is -C4 alkyl-. 66. a compound wherein I r ^Rh D is 5 · 134026-3 -91 · 200916447 w is nitrogen; Rc is ·Η; X is S; R is -qc: 6 alkyl or -CpC^alkyl-phenyl, wherein The alkyl group and the stupid group are independently substituted as appropriate; Z is optionally taken as _c3_C8 alkyl group; L is -C alkyl group-, and is selected from the group consisting of _N(H)_c(〇)_〇 _CrC6alkyl-phenyl, N(H)-C(〇)-〇_Cl _c6, _NH c(〇)heterocyclyl a &amp; alkyl and NHC(0)-Cl-C6 alkyl _ S (substituted with a substituent of a Vci-C6 alkyl group; and Y is a heteroaryl group, which is optionally substituted. 67. A compound of the formula 66, wherein γ is optionally substituted benzoin 68. The compound of claim 66, wherein γ is the odor of the original 2 or (10) Ν 2 η 。 。. 69. The compound of claim 66. The compound of claim 1 wherein hydrazine is -c4 alkyl-. Ra ! .Μ, C II X Rb W Rc is nitrogen; 4 -H ; Μ is nitrogen; 把 is Η ; 妒 is stupid or c]- C6 alkyl; 134026-3 92· 200916447 z is optionally taken as -C3-C8 alkyl _ ; L is -NO^-CCCO-Ci alkyl-, wherein q alkyl is _N(H)- C(0)-0-q-Cealkyl-phenyl substituted; and Y is aryl-heteroaryl-', which is optionally substituted. 71. The compound of claim 1, wherein Rc Ra D is k W is nitrogen; Rc is -Η; X is S; M is nitrogen; Ra is Η; Rb is stupid or cardio-alkyl; z is taken as appropriate - c3 - c8 alkyl -; Alkyl-, is (11)-(:(0)-0-(^-C6 alkyl-phenyl, -N(H)-C(0)-◦-Ci-C:6 alkyl and alkane And the gamma is an optionally substituted benzimidazole. 72. The compound of claim 71, wherein z is _C4 alkyl-. 73. The compound of claim 71, wherein Y is substituted by -c(o)-nh2. 74. The compound of claim 71, wherein the gamma is further selected from optionally substituted aryl-heteroaryl. 75. Formula (ΙΙΠ) compound: YLD (III) or its oxime-oxide, hydrate, solvate, pharmaceutically acceptable salt, 134026-3 •93- 200916447 prodrug or complex' or its racemization Or in a proportional mixture, diastereomer or para-isomer, wherein D is selected from the group consisting of -Bu, Ν' and as H; Y Rb s SS Rb and Rh are independently selected from the group consisting of _Ci 6 alkane Base, _c". Aryl and _C7 i6 alkylaryl; L is selected from the group consisting of _c〇-6-alkyl-, _c〇3 alkyl-N(H)_c(〇)_c〇_6-alkyl-' Optionally substituted by 0-3 R4; y is selected from the group consisting of optionally substituted _c6 i〇 aryl and optionally substituted 5- to 10-membered heteroaryl; R4 is selected from the group consisting of -N(H -C(0)-R3 and _N(H)-C(0)-〇-R3; and r3 is selected from the group consisting of optionally substituted _Ci 6 alkyl, _Ci 6 heteroalkyl, m-membered a cyclic group and a _c7_16 alkylaryl group. _ζ—ΝΗ Ν ^ \/\ Rb 76. The compound of claim 75, wherein d is ; Rh 77.如請求項75之化合物，其中〇為 ；。 盘、月长員1之化合物，其中選自包括視情況經取代之芳基 與視it况經取代之雜芳基之取代基係本身進一步視情況 代基取代，取代基選自包括_〇_Ci %烷基-烷氧基、 _CF3、-0-芳基、院氧基、-nh-C(0)_Ci_C6絲、_ 素、c「c6 134026-3 -94- 200916447 烷基、-〇-⑽基取代之烷基）及-〇_烷基_N(烷基）2。 士吻求項1之化合物，其中γ係進一步選自雜環基。 8〇.如請求項1之化合物，其中 L為-C〇-Q烷基-C(0)-N(R3)-(：〇必烷基_，其中當c〇_c3烷基 為^&lt;：3烷基時，此Ci_C3烷基係視情況被芳基、雜芳基、1 雜芳基-芳基、-芳基-雜芳基、-芳基_芳基或雜芳基-雜芳基 取代，其中各雜芳基或芳基部份基團係視情況經取代；且 r γ為芳基或雜芳基，其每一個係視情況經取代。 81. 如請求項1之化合物，其中 L 為-C0 -C6 烧基-〇-C0 烧基-C(0)-N(R3 )-C〇 -C3 烧基 _，其中 田c〇-C3烷基為c] -C：3烷基時，此q -C3烷基係視情況被_雜芳 基-芳基、-雜芳基-雜芳基、雜芳基、_雜芳基雜環基取代， 其中各雜芳基與芳基部份基團係視情況經取代；且 γ為視情況經取代之芳基。 82. 如請求項1之化合物，其中當c〇_C3烷基為Q_c3烷基時，此 L 烷基係視情況被-雜芳基-芳基、-雜芳基-雜芳基、雜 芳基、-雜芳基-雜環基取代，其中各雜芳基與芳基部份基 團係進一步視情況被1至3個視情況經取代之芳基、烷氧 基、-N(烷基h、鹵素、烷基、經稠合之雜環基、-CF3、視 情況經取代之雜環基、-Oq -c6烷基-N(烷基）2、-oq -C6烷 基-NH2及-NH-芳基取代。 83·如請求項1之化合物，其中 L 為-C0 -C6 烷基-C(0)-N(R3 )-C〇 -C3 烷基-，其中當 C〇 _c3 烷基 為C! -C3烷基時’此q -C3烷基係視情況被-C(0)-N(R3 )-C。-C3 134026-3 -95- 200916447 烷基-雜芳基、-c⑼-N(r3KvC3烷基_芳基取代，其中各雜 芳基或芳基部份基團係視情況經取代；且 Y為Η、視情況經取代之苦其十^ 方暴次視情況經取代之雜環 84‘如請求項i之化合物’其中丫為視情況經取代之雜芳基。 85. 如請求们之化合物，其中γ為視情況經取代之芳基或視 情況經取代之雜芳基，其中各雜芳基或芳基部份基團係視 情況破1或2個獨立經選擇之函素、垸基或烧氧基取代。 86. 如請求項1-5中任一項之化合物，其中 告L為、C0 A烷基-〇-C0 -C!烷基（(〇)_N(R3 ) c〇 烷基，其中 田Cq-c3烷基為Cl_c3烷基時，此Ci_c3烷基係視情況被 -C(0)-N(R3)_C()_C3 院基 _雜環基或 _c(〇)_n(r3)_c〇_C3 烧基 _芳基 取代’其中各雜環基或芳基部份基團係視情況經取代；且 ‘.、、視情況經取代之芳基或視情況經取代之雜芳基。 :求項1之化合物，其_ γ為視情況經取代之芳基。Rh 77. The compound of claim 75, wherein 〇 is ; a compound of the platoon, the member of the present invention, wherein the substituent is selected from the group consisting of an optionally substituted aryl group and a substituted heteroaryl group, and the substituent itself is further substituted with a substituent selected from the group consisting of _〇_ Ci % alkyl-alkoxy, _CF3,-0-aryl, alkoxy, -nh-C(0)_Ci_C6 silk, _ 素, c "c6 134026-3 -94- 200916447 alkyl, -〇- (10) a base-substituted alkyl group) and a hydrazine-alkyl group-N-alkyl group. The compound of claim 1, wherein the γ-ray is further selected from the group consisting of a heterocyclic group. L is -C〇-Qalkyl-C(0)-N(R3)-(: 〇 烷基 alkyl_, wherein when c〇_c3 alkyl is ^&lt;:3 alkyl, this Ci_C3 alkyl Substituted by aryl, heteroaryl, 1 heteroaryl-aryl, -aryl-heteroaryl, -aryl-aryl or heteroaryl-heteroaryl, wherein each heteroaryl or aryl The radical moiety is optionally substituted; and r γ is aryl or heteroaryl, each of which is optionally substituted. 81. The compound of claim 1 wherein L is -C0 -C6 alkyl - 〇-C0 alkyl-C(0)-N(R3)-C〇-C3 alkyl group, wherein the field c〇-C3 alkyl is c]-C:3 alkane In this case, the q-C3 alkyl group is optionally substituted by a heteroaryl-aryl group, a heteroaryl-heteroaryl group, a heteroaryl group or a heteroaryl group, wherein each heteroaryl group and aryl group are substituted. A part of the group is optionally substituted; and γ is an optionally substituted aryl group. 82. The compound of claim 1, wherein when the c〇_C3 alkyl group is a Q_c3 alkyl group, the L alkyl group is The case is substituted by a -heteroaryl-aryl, -heteroaryl-heteroaryl,heteroaryl,heteroaryl-heterocyclyl group, wherein each heteroaryl group and the aryl moiety group are further 1 to 3 optionally substituted aryl, alkoxy, -N (alkyl h, halogen, alkyl, fused heterocyclic group, -CF3, optionally substituted heterocyclic group, -Oq -c6alkyl-N(alkyl)2, -oq-C6alkyl-NH2 and -NH-aryl substituted. 83. The compound of claim 1, wherein L is -C0 -C6 alkyl-C(0 -N(R3)-C〇-C3 alkyl-, wherein when C〇_c3 alkyl is C!-C3 alkyl, this q-C3 alkyl group is optionally taken as -C(0)-N ( R3)-C.-C3 134026-3 -95- 200916447 Alkyl-heteroaryl, -c(9)-N (r3KvC3 alkyl-aryl substitution, wherein each heteroaryl or aryl moiety The group is substituted as the case may be; and Y is Η, as the case may be substituted, and the substituted heterocyclic ring 84' is as the compound of claim i', where hydrazine is substituted as appropriate 85. A compound of claimant, wherein γ is optionally substituted aryl or optionally substituted heteroaryl, wherein each heteroaryl or aryl moiety is interrupted by 1 or 2 Individually selected elements, thiol or alkoxy substituted. The compound of any one of claims 1 to 5, wherein L is C0 A alkyl-〇-C0-C! alkyl ((〇)_N(R3) c〇 alkyl, wherein Tian Cq- When the c3 alkyl group is a Cl_c3 alkyl group, the Ci_c3 alkyl group is optionally taken as -C(0)-N(R3)_C()_C3)-heterocyclyl or _c(〇)_n(r3)_c〇_ C3 alkyl-aryl substituted wherein each heterocyclyl or aryl moiety is optionally substituted; and '., optionally substituted aryl or optionally substituted heteroaryl. The compound of Item 1, wherein _ γ is an optionally substituted aryl group. 88·如晴求項86之化合物，其中_c(0)娜3 )_c〇 _c3烧基雜環基為 _e(c〇~N(R3 )-c0 -C3 烧基-雜芳基。 89.如Π月求項1之化合物，其中Y-L-為苯基-CH2-0-C(0)-NH-。 % β I項1之化合物，其中 告為 C〇 -C6 烷基 _0_C〇 _C1 烷基-C(0)-N(R3 )-C0 -c3 烷基 _，其中 ^基為Ci_c3院基時，此烧基係視情況被 (〇) N(R3)'c〇-C3 烷基-雜芳基或-C(O)-N(R3)-C0-C3 烷基-芳基 代，里+ 如 獨立 ^ 各雜芳基或芳基部份基團係視情況被1至3個 代基取代’取代基選自包括鹵素、_〇H…、烧 134026-3 -96- 200916447 基、-C(0)-OH、-C(0)-0-烷基、-C(0)-NH-視情況經取代之芳基、 -C(0)-NH-視情況經取代之雜芳基、-C(0)-NH-烷基-Ο-烷基、 -C(0)-NH-烷基-雜環基、-烷基-視情況經取代之芳基、烷氧 基、視情況經取代之芳基、視情況經取代之雜芳基。 91. 如請求項1之化合物，其中選自包括-C(0)-NH-視情況經取 代之芳基、-C(0)-NH-視情況經取代之雜芳基、-烷基-視情況 經取代之芳基、視情況經取代之芳基及視情況經取代之雜 芳基之取代基係視情況被1或2個獨立經選擇之取代基取 代，取代基選自包括_素、烷氧基、烷基、-0-芳基、-NH-C(O)-烷基、酮基、-CN、雜環基、-0-鹵基取代之烷基、-CF3&amp;-0-烧基-Ο-烧基。 92. 如請求項1之化合物，其中L為苯基-CH2 -O-CCCO-NH-C! -C3烷 基-，其中q -C3烷基係被-C(0)-NH-嘧唑基取代，其中噻唑 基係視情況經取代。 93. 如請求項1之化合物，其中 L為苯基-CH2 -O-CCCO-NH-q -C3烷基-，其中C! -C3烷基係被 -C(0)-NH-嘍唑基取代，其中嘧唑基係視情況被1或2個獨立 經選擇之取代基取代，取代基選自包括視情況經取代之芳 基、烷基、-C(0)-0-烷基' -C(0)-0H、-C(0)-NH-視情況經取代 之芳基、-C(0)-NH-視情況經取代之雜芳基、-C(0)-NH-烷基-0-烷基、-C(0)-NH-烷基-雜環基、稠合之視情況經取代之環烷 基、稠合之視情況經取代之雜環基及稠合之視情況經取代 之芳基。 94. 如請求項1-5中任一項之化合物，其中 134026-3 -97- 200916447 L 為-C0 -C6 烷基-N(R3 )_C(0)_N(R3 )_C〇 &amp; 烷基 _，其中當 c『c3 烷基為q 烷基時，此Cl Α烷基係視情況被_c(〇)_n(r3 )_ C0-C3烷基-雜芳基-芳基、烷基_雜芳基或 -C(0)-N(R3 )-C〇 -C3烷基-芳基取代，其中各雜芳基或芳基部份 基團係視情況經取代；且 Y為視情況經取代之芳基、視情況經取代之雜環基或視 情況經取代之環烷基。 95·如請求項丨之化合物’ 為視情況經取代之雜芳基。 96. 如請求項1之化合物，其中 L為-C0-C6烧基-O-C0-C成基七(〇)_雕3&gt;Cq_C3烧基…直中 當Q-C3烧基為Cl-C3院基時，此Ci_C3烧基係視情：被 -C(〇)娜3)-㈣烧基-雜芳基、侧.喊KVC成基·芳其、-C(0)-N(R3^ 雜方基.雜m〇_3Kvc3烧基-芳f芳基及 -C(〇)_N(R3 )-C〇-C3 烷基-芳基.雜关 W 雜方基取代，其中各雜芳基或 方基部份基團係視情況經取代且 〆Y為Η。 97. 如請求項！之化合物，其中w為〇。 98. 如$求項1之化合物，其中 -口c r Ms Rb 备 為結構 Η ΗN'c，N、Rb ,Μ 如請求項98之化合物，Α中 ，， r X 為結構100.如請求項 114、17、39 W 、 46 、 48 、 50 、 52 Rb 1—N c/NH: li S 54、56 134026-3 -98- 200916447 58、60及62中任一項之化合物 S—/CH3 S ° 其中88. A compound according to item 86, wherein _c(0)na3)_c〇_c3 alkylidylheterocyclyl is _e(c〇~N(R3)-c0-C3 alkyl-heteroaryl. 89. The compound of claim 1, wherein YL- is phenyl-CH2-0-C(0)-NH-. % β I, the compound of item 1, wherein C 〇-C6 alkyl _0_C〇 _C1 alkyl-C(0)-N(R3)-C0-c3 alkyl_, wherein when the base is a Ci_c3, the base is optionally (〇) N(R3)'c〇-C3 Alkyl-heteroaryl or -C(O)-N(R3)-C0-C3 alkyl-aryl, +1 as independent ^ each heteroaryl or aryl moiety is optionally 1 The three substituted substituents are selected from the group consisting of halogen, 〇H..., 134026-3 -96-200916447, -C(0)-OH, -C(0)-0-alkyl, -C( 0) -NH- optionally substituted aryl, -C(0)-NH- optionally substituted heteroaryl, -C(0)-NH-alkyl-oxime-alkyl, -C(0 -NH-alkyl-heterocyclyl, -alkyl-optionally substituted aryl, alkoxy, optionally substituted aryl, optionally substituted heteroaryl. 91. a compound selected from the group consisting of -C(0)-NH- optionally substituted aryl, -C(0)-NH- Substituents of heteroaryl, -alkyl-optionally substituted aryl, optionally substituted aryl and optionally substituted heteroaryl are optionally taken by 1 or 2 independently selected substituents. Substituted, the substituent is selected from the group consisting of _, alkoxy, alkyl, -O-aryl, -NH-C(O)-alkyl, keto, -CN, heterocyclyl,-0-halo Alkyl, -CF3&amp;-0-alkyl-oxime-alkyl. 92. The compound of claim 1, wherein L is phenyl-CH2-O-CCCO-NH-C!-C3 alkyl-, wherein The q-C3 alkyl group is substituted by -C(0)-NH-pyrazolyl, wherein the thiazolyl group is optionally substituted. 93. The compound of claim 1, wherein L is phenyl-CH2-O-CCCO- NH-q-C3 alkyl-, wherein the C!-C3 alkyl group is substituted by -C(0)-NH-carbazolyl, wherein the pyrazolyl is optionally substituted by one or two independently selected substituents a substituent selected from the group consisting of an optionally substituted aryl group, an alkyl group, -C(0)-0-alkyl'-C(0)-0H, -C(0)-NH-, optionally substituted a group, -C(0)-NH- optionally substituted heteroaryl, -C(0)-NH-alkyl-0-alkyl, -C(0)-NH-alkyl-heterocyclyl, Substituted cycloalkyl group a fused, optionally substituted heterocyclic group and a fused aryl group optionally substituted. The compound according to any one of claims 1 to 5, wherein 134026-3 -97- 200916447 L is -C0 -C6 alkyl-N(R3)_C(0)_N(R3)_C〇&amp;alkyl _, wherein when c "c3 alkyl is q alkyl, this Cl Α alkyl is optionally taken as _c(〇)_n(r3)_C0-C3 alkyl-heteroaryl-aryl, alkyl_ a heteroaryl or -C(0)-N(R3)-C〇-C3 alkyl-aryl group wherein each heteroaryl or aryl moiety is optionally substituted; and Y is optionally Substituted aryl, optionally substituted heterocyclic or optionally substituted cycloalkyl. 95. The compound of claim ’ is a heteroaryl group optionally substituted. 96. The compound of claim 1, wherein L is -C0-C6 alkyl-O-C0-C-based seven (〇)_雕3&gt; Cq_C3 alkyl... straight-line when Q-C3 alkyl is Cl-C3 In the case of the base, the Ci_C3 base is as follows: by -C(〇)na 3)-(tetra)alkyl-heteroaryl, side. shouting KVC into base ·fang,-C(0)-N(R3^ Heterocyclyl.hetero m〇_3Kvc3 alkyl-arylfaryl and -C(〇)_N(R3)-C〇-C3 alkyl-aryl.Hybrid W heteroaryl group, wherein each heteroaryl group Or the radical moiety is replaced by the case and 〆Y is Η. 97. The compound of the claim!, where w is 〇. 98. For the compound of claim 1, wherein - port cr Ms Rb is prepared as Structure ΗN'c, N, Rb, Μ as in the compound of claim 98, Α,, r X is the structure 100. as claimed in items 114, 17, 39 W, 46, 48, 50, 52 Rb 1 - N c /NH: li S 54,56 134026-3 -98- 200916447 Compound S-/CH3 S ° of any of 58, 60 and 62 為結構 胤-種組合物，其包含如請求項i之化合物及藥學上可接受 之載劑。 肌-種抑制組織蛋白I乙醯化酶活性之活體外方法，此方法 包括使組織蛋白去乙醯化酶或包含此組織蛋白去乙醯化 酶之細胞，與抑制有效量之如請求項丨之化合物接觸。 103. —種抑制組織蛋白去乙醯化酶活性之活 、 广万法，此方法 包括使組織蛋白去乙醯化酶或包含此組織蛋白去乙醯化 酶之細胞，與抑制有效量之如請求項1〇1之組合物接觸。 說-種如請求項i之化合物製造藥劑之用途，該藥劑係用於 治療對組織蛋白去乙醯化酶活性之抑制劑具回應性之疾 病。 ’、 劑之用途，該藥劑係用 性之抑制劑具回應性之 1〇5. —種如請求項1〇1之组合物製造藥 於治療對組織蛋白去乙醯化酶活 疾病。 娜一種如請求項1之化合物製造藥劑之用途，該藥劑係用於 治療·蛋白質所媒介之疾病或病症，選自包括腦癌、乳 癌、口腸癌、肝癌、脾臟癌、睪丸癌及甲狀腺癌。 1〇7.—種如請求項1之化合物 ,Α ςτρτ ^ I I樂幻之用达，该樂劑係用於 ’口 '、 白質所媒介之疾病或病症，選自包括與老 關聯之病症、由 皮下知肪之失去及經降低之骨礦物質 134026-3 •99- 200916447 於 與 於 於 心 1〇8.種如叫求項i之化合物製造藥劑之用途，該藥劑係用 /口療SIRT蛋白質所媒介之疾病或病症，選自包括第I型 第II型糖尿病。 種士叫求項1之化合物製造藥劑之用途，該藥劑係用 治療肥胖。 110.種如凊求項1之化合物製造藥劑之用途，該藥劑係用 治療SIRT蛋白f所媒介之疾病或病症，選自包括發炎、 臟衰竭、：全；p A f、 京退化、aids及適應生熱作用。 134026-3 -100- 200916447 七、指定代表圖： (一) 本案指定代表圖為：（無） (二) 本代表圖之元件符號簡單說明: 八、本案若有化學式時，請揭示最能顯示發明特徵的化學式： Y——L—Z—D (I) 134026-1It is a structural composition comprising the compound of claim i and a pharmaceutically acceptable carrier. An in vitro method for inhibiting the activity of a tissue protein I acetylated enzyme, the method comprising: deactivating a tissue protein to an acetamylase or a cell comprising the tissue protein deacetylase, and inhibiting an effective amount as claimed. The compound is in contact. 103. A method for inhibiting the activity of tissue protein deacetylase, the method comprising: degrading a tissue protein to an acetamylase or a cell comprising the tissue protein to an acetamylase, and inhibiting the effective amount The composition of claim 1〇1 is contacted. The use of a compound as claimed in claim i for the treatment of a disease responsive to an inhibitor of tissue protein deacetylase activity. The use of the agent, the inhibitor of the drug system is responsive. The composition of claim 1 is manufactured to treat a tissue protein deacetylase active disease. A use for the manufacture of a medicament according to claim 1, which is for use in the treatment of a disease or a condition mediated by a protein, including brain cancer, breast cancer, oral cancer, liver cancer, spleen cancer, testicular cancer and thyroid cancer. . 1〇7.—A compound of claim 1, Α ςτρτ ^ II, which is used for diseases or conditions mediated by 'mouth' or white matter, and is selected from the group consisting of diseases associated with the old, Loss of subcutaneous fat and reduced bone minerals 134026-3 •99- 200916447 The use of a compound for the manufacture of a compound such as the compound of the formula i. The disease or condition mediated by the protein is selected from the group consisting of type I type II diabetes. The use of the compound of claim 1 for the manufacture of a medicament for the treatment of obesity. 110. The use of a medicament for the manufacture of a compound according to claim 1, wherein the medicament is a disease or condition mediated by the SIRT protein f, selected from the group consisting of inflammation, visceral failure, total: p A f , Beijing degeneration, aids and Adapt to the heat effect. 134026-3 -100- 200916447 VII. Designation of representative drawings: (1) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please reveal the best display. Chemical formula of the invention: Y——L—Z—D (I) 134026-1
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