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TW201829402A - Small molecule inhibitors of colony stimulating factor-1 receptor (csf-1r) and uses thereof - Google Patents

Small molecule inhibitors of colony stimulating factor-1 receptor (csf-1r) and uses thereof Download PDF

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TW201829402A
TW201829402A TW106145420A TW106145420A TW201829402A TW 201829402 A TW201829402 A TW 201829402A TW 106145420 A TW106145420 A TW 106145420A TW 106145420 A TW106145420 A TW 106145420A TW 201829402 A TW201829402 A TW 201829402A
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alkyl
independently selected
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heteroaryl
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菲利浦 瓊斯
芭芭拉 柯札可
傑森 克洛斯
傑森 布爾基
保羅 雷諾德
馬汀 崔恩伯雷
皮傑斯 曼達爾
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美商提薩羅有限公司
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Compounds of formula (I), which are useful as CSF-1R inhibitors, are provided. Also provided are pharmaceutical compositions and kits comprising said compounds, as well as methods and uses pertaining to said compounds.

Description

群落刺激因子1受體　(CSF-1R)之小分子抑制劑及其用途Small molecule inhibitor of community stimulating factor 1 receptor (CSF-1R) and use thereof

本發明係關於用作CSF-1R抑制劑之化合物，特定言之，本發明係關於用以治療諸如病症之具有有利活性及/或激酶選擇性之化合物。The present invention relates to compounds useful as CSF-1R inhibitors, and in particular, the present invention relates to compounds for the treatment of conditions such as disorders having beneficial activity and/or kinase selectivity.

CSF-1R (群落刺激因子-1受體)係III型跨膜受體蛋白酪胺酸激酶(RTK)，其包含含有五個重複Ig域之胞外域、單一跨膜域及由激酶嵌入域中斷之分裂細胞質激酶域。CSF-1R由c-fms (細胞貓麥克唐納肉瘤(cellular feline McDonough sarcoma))原癌基因編碼(Roussel等人，Nature. (1987) 325(6104):549-552)及其對單核巨噬細胞譜系之生長、分化及存活係至關重要的。此家族內之相關RTK包括幹細胞生長因子受體(c-KIT)、鰭狀細胞因子受體(FLT3)及血小板衍生之生長因子受體(PDGFR)。CSF-1R係由單核細胞、小神經膠質細胞、破骨細胞、蘭格漢氏細胞且於女性生殖道及胎盤中表現。 CSF-1R之天然配體係CSF，群落刺激因子(Robinson等人，Blood. (1969) 33(3):396-399)。CSF對CSF-1R之結合導致激酶域之受體二聚化及自磷酸化及導致下游傳訊途徑(諸如PI3K/AKT及Ras/MAPK傳訊途徑)之後續活化。CSF-1R傳訊已顯示會於免疫反應、骨重建及生殖系統中發揮生理作用。特定言之，CSF-1R之活化調節巨噬細胞、破骨細胞及小神經膠質細胞之增殖、分化及存活。此等細胞及CSF-1R傳訊途徑於炎性過程中亦發揮重要作用。CSF-1R敲除小鼠模型顯示出一系列範圍之表現型，其等包括經減少之巨噬細胞密度及小神經膠質細胞與破骨細胞之耗盡。 與CSF-1R各種不同角色一致，例如，在不同組織中，CSF-1R之功能不全係涉及許多疾病狀態，包括癌症、骨溶解及炎性失調症(諸如類風濕性關節炎及克羅恩氏病(Crohn’s disease))、腎同種異體移植排斥及肥胖症。例如，高CSF-1傳訊會導致高破骨細胞活性及骨損失，其導致炎性骨侵蝕及疾病(諸如關節炎)之進展。另外，CSF-1R及/或CSF-1之高表現或活化已於患有前列腺癌、卵巢癌、乳癌、胰臟癌及各種其他癌症之病患中經識別。CSF-1之過表現係與某些癌症(例如，乳癌、卵巢癌及前列腺癌之不良預後相關聯(Lin等人，J. Mammary Gland Biol. Neoplasia. (2002) 7(2):147-62)。此外，該CSF-1R傳訊途徑可驅動巨噬細胞向腫瘤微環境募集。亦認為此等腫瘤相關巨噬細胞(TAM)於促進腫瘤進展、轉移及血管生成中發揮作用(El-Gamal等人，Med. Res. Rev. (2013) 33(3):599-636；Bingle等人，J. Pathol. (2002) 196(3):254-65)。抑制CSF-1R傳訊已顯示可以腫瘤特異性方式減少TAM之數量且與經延長之存活相關(Strachan等人，Oncoimmunology (2013) 2(12):e26968)。TAM係腫瘤微環境中免疫逃避之重要驅動者及其等可藉由加強免疫抑制、血管生成及入侵有助於產生有利於腫瘤之環境。 CSF-1R抑制劑已被提出用於治療經CSF-1R介導之疾病，尤其癌症。據報導用小分子抑制劑或單株抗體阻斷CSF-1/CSF-1R傳訊在臨床前模型系統及最近在臨床中係有效的。然而，已知抑制劑中之許多已顯示為多靶抑制劑，其等針對其他III型RTK (諸如PDGFR、c-KIT及FLT)可具有顯著抑制活性。此外，已知抑制劑中之許多具有非最佳化活體內性質(例如，藥物動力學性質)及/或低抗CSF-1R活性。 仍需CSF-1R之抑制劑，尤其具有高效用、高選擇性及/或有利之活體內性質之抑制劑。CSF-1R (Communism Stimulating Factor-1 Receptor) is a type III transmembrane receptor protein tyrosine kinase (RTK), which comprises an extracellular domain containing five repetitive Ig domains, a single transmembrane domain, and disruption by the kinase insertion domain The dividing cytoplasmic kinase domain. CSF-1R is encoded by c-fms (cellular feline McDonough sarcoma) proto-oncogene (Roussel et al, Nature. (1987) 325 (6104): 549-552) and its The growth, differentiation, and survival of the phage lineage are critical. Related RTKs within this family include the stem cell growth factor receptor (c-KIT), the fin cytokine receptor (FLT3), and the platelet-derived growth factor receptor (PDGFR). CSF-1R is expressed by monocytes, microglia, osteoclasts, Langerhans cells and in the female reproductive tract and placenta. CSF-1R natural system CSF, community stimulating factor (Robinson et al, Blood. (1969) 33(3): 396-399). Binding of CSF to CSF-1R results in receptor dimerization and autophosphorylation of the kinase domain and subsequent activation of downstream signaling pathways such as the PI3K/AKT and Ras/MAPK signaling pathways. CSF-1R communication has been shown to play a physiological role in immune response, bone remodeling and the reproductive system. In particular, activation of CSF-1R regulates the proliferation, differentiation and survival of macrophages, osteoclasts and microglia. These cells and the CSF-1R signaling pathway also play an important role in the inflammatory process. The CSF-1R knockout mouse model shows a range of phenotypes including reduced macrophage density and depletion of microglia and osteoclasts. Consistent with the different roles of CSF-1R, for example, in different tissues, CSF-1R is not fully functional in many disease states, including cancer, osteolysis, and inflammatory disorders (such as rheumatoid arthritis and Crohn's). Crohn's disease), renal allograft rejection, and obesity. For example, high CSF-1 signaling can result in high osteoclast activity and bone loss, which leads to inflammatory bone erosion and progression of diseases such as arthritis. In addition, high performance or activation of CSF-1R and/or CSF-1 has been identified in patients with prostate cancer, ovarian cancer, breast cancer, pancreatic cancer, and various other cancers. Overexpression of CSF-1 is associated with poor cancer (eg, breast, ovarian, and prostate cancer) (Lin et al, J. Mammary Gland Biol. Neoplasia. (2002) 7(2): 147-62 In addition, the CSF-1R signaling pathway drives macrophages to recruit to the tumor microenvironment. These tumor-associated macrophages (TAMs) are also thought to play a role in promoting tumor progression, metastasis, and angiogenesis (El-Gamal et al). Man, Med. Res. Rev. (2013) 33(3): 599-636; Bingle et al., J. Pathol. (2002) 196(3): 254-65). Inhibition of CSF-1R signaling has been shown to be tumor Specific ways to reduce the number of TAM and correlate with prolonged survival (Strachan et al, Oncoimmunology (2013) 2(12):e26968). Important drivers of immune evasion in the TAM-based tumor microenvironment and their Immunosuppression, angiogenesis, and invasion contribute to a tumor-promoting environment. CSF-1R inhibitors have been proposed for the treatment of CSF-1R-mediated diseases, particularly cancer. Small molecule inhibitors or single plants have been reported. Antibody blocking CSF-1/CSF-1R signaling is effective in preclinical model systems and more recently in the clinic. However, it is known Many of the formulations have been shown to be multi-target inhibitors, which can have significant inhibitory activity against other type III RTKs, such as PDGFR, c-KIT and FLT. Furthermore, many of the known inhibitors have non-optimal activities. In vivo properties (eg, pharmacokinetic properties) and/or low resistance to CSF-1R activity. Inhibitors of CSF-1R are still required, particularly inhibitors of high potency, high selectivity and/or beneficial in vivo properties.

本發明者們已發現適用於作為CSF-1R之抑制劑之化合物之家族。此等化合物尤其適用於醫藥組合物及醫學治療中，其中CSF-1R之活性需經調整。 在第一態樣中，本發明提供由式(I)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中： A係5至10員雜芳基，其環原子由C、至少一個N及視需要O或S組成； n係0、1、2、3或4； m係0、1或2； X1 係選自NH、O、S、-CH=N-及-N=CH-； L表示直接鍵或其係基團-(CR6 R7 )p -，其中： p係1、2或3，及 各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素及羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R”)之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基； R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代； R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經取代； R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代；及 R4 及R5 係獨立地選自H及C1-3 -烷基， 或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在實施例中： R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；及/或 R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及/或 R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該烷基、醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re ) (其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，A係6員單環雜芳基。 在實施例中，n係1或2。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自鹵素、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中R8 及R9 係獨立地選自H、C1-4 -烷基及雜芳基， R10 及R10b 係獨立地選自H及C1-4 -烷基，且 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自Cl、Br及胺基或選自甲基胺基、-NHC(O)OCH3 、-NHC(O)CH3 、-NHC(O)NHCH3 、甲基、甲氧基、-NH-吡唑基、苯基及吡唑基，其各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。 在實施例中，m係1或2，及R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。 在實施例中，R3 係C1-8 -烷基，其視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、胺基磺醯基、磺醯基胺基及視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)。 在實施例中，R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，R3 係環己基，其經羥基取代及進一步視需要經1至3個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，R3 係二氫茚基(2,3-二氫-1H-茚基)，其視需要經1至4個獨立地選自以下之基團取代：羥基、視需要經羥基取代之C1-3 -烷基、F、Cl、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基)。 在實施例中，R4 及R5 皆係氫。 在實施例中，L係-(CR6 R7 )p -，其中p係1或2且其中各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素及羥基之基團取代。 在實施例中，存在之所有R6 及R7 基團係氫。 在實施例中，L表示直接鍵。 在實施例中，X1 係選自NH、O及S。 在實施例中，X1 係S。 在其他態樣及實施例中，本發明提供由式(II)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 Q1 、Q2 、Q3 及Q4 係獨立地選自N、CH及C(R1 )，其中該Q1 、Q2 、Q3 及Q4 中不少於一者且不多於兩者可表示N；及 n、m、X1 、L及R1 至R5 係如上文定義。 在其他態樣及實施例中，本發明提供由式(III)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 X2 係選自N、CH或C(R1 )； R11 及R12 係獨立地選自氫、鹵素、腈、-C(O)N(R13 R14 )、-N(R13 R14 )、-NHC(O)NR13 R14 、-NHC(O)OR15 、-NHC(O)R15b 、-C(O)R15b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR15 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R15 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， R15b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代；及 m、X1 、L及R2 至R5 係如上文定義。 在實施例中，R11 係選自氫、鹵素、腈、-C(O)N(R12 R13 )、C1-3 -烷基、羥基及-O(C1-3 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。 在實施例中，R12 係選自鹵素、C(O)N(R13 R14 )、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rh Ri )(其中Rh 及Ri 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rj (其中Rj 係選自羥基及胺基及鹵素)。 在實施例中，X2 係N。 在其他態樣及實施例中，本發明提供由式(IV)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 X3 係選自N、CH及CR1 ； n係0、1、2或3；及 m、X1 、L及R1 至R5 係如上文定義。 在其他態樣及實施例中，本發明提供由式(V)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 R16 及R17 係獨立地選自氫、鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及 其中n、X1 、X3 、L、R1 及R3 係如上文定義。 在實施例中，R16 及R17 係獨立地選自氫、鹵素、羥基、腈及視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代之-O(C1-4 -烷基)。 在其他態樣及實施例中，本發明提供由式(VI)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 R18 、R19 、R20 及R21 係獨立地選自氫、鹵素、腈、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 R24b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基， 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；及 其中m、X1 、L及R2 至R5 係如上文定義。 在實施例中，R18 係選自氫、鹵素、-NR22 R23 、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R22 及R23 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R24 及R24b 係獨立地選自H及C1-4 -烷基，且 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在實施例中，R20 係選自氫、鹵素、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在實施例中，R19 及R21 各獨立地係氫。 在其他態樣及實施例中，本發明提供由式(VII)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 q係0、1、2或3； R25 係獨立地選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 、R18 及R20 係如上文定義。 在其他態樣及實施例中，本發明提供由式(VIIa )或(VIIb )表徵之化合物， 或其醫藥上可接受之鹽或前藥，其中 m、q、X1 、R2 、R4 、R5 、R18 、R20 及R25 係如上文定義。 在其他態樣及實施例中，本發明提供由式(VIII)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 r係0、1、2或3； R26 係獨立地選自鹵素、羥基、腈、-N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 、R18 及R20 係如上文定義。 在其他態樣及實施例中，本發明提供由式(VIIIa )或(VIIIb )表徵之化合物， 或其醫藥上可接受之鹽或前藥，其中m、r、X1 、R2 、R4 、R5 、R18 、R20 及R26 係如上文定義。 在其他態樣及實施例中，本發明提供由式(IX)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 n係0、1或2； X4 係NH、O或S；及 m、X1 、L及R1 至R5 係如上文定義。 在其他態樣及實施例中，本發明提供由式(X)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 n係0、1或2； X5 係NH、O或S；及 m、X1 、L及R1 至R5 係如上文定義。 在其他態樣及實施例中，本發明提供由式(XI)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中n、m、X1 、L及R1 至R5 係如上文定義。 在其他態樣及實施例中，本發明提供由式(XII)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 R30 、R31 及R32 係獨立地選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt ) (其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；及 其中m、X1 、L及R2 至R5 係如上文定義。 在實施例中，R30 係選自氫、鹵素、-NR33 R34 、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R33 及R34 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R35 及R35b 係獨立地選自H及C1-4 -烷基，且 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在實施例中，R31 及R32 各獨立地係氫。 在其他態樣及實施例中，本發明提供由式(XIV)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中 s係0、1、2或3； R36 係獨立地選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 及R30 係如上文定義。 在其他態樣及實施例中，本發明提供由式(XV)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如上文定義。 在其他態樣及實施例中，本發明提供由式(XVa)或式(XVb)表徵之化合物， 或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如上文定義。 在其他態樣及實施例中，本發明提供由式(XVI)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如上文定義。 在其他態樣及實施例中，本發明提供由式(XIVa)或式(XIVb)表徵之化合物， 或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如上文定義。 在其他態樣及實施例中，本發明提供選自由以下組成之群之化合物： 化合物1：(1R,2R)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物2：(1S,2S)-2-({6-[(2-胺基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物3：(1R,2R)-2-[(6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物4：(1R,2R)-2-({6-[(3-溴吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物5：(1S,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物6：(1S,2S)-2-[(6-{[2-(甲基胺基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物7：N-環己基-6-(吡啶-4-基甲氧基)-1,3-苯并噻唑-2-胺 化合物8：N-環己基-6-(吡啶-3-基甲氧基)-1,3-苯并噻唑-2-胺 化合物9：N-環己基-6-(1,3-噻唑-4-基甲氧基)-1,3-苯并噻唑-2-胺 化合物10：N-環己基-6-(吡啶-2-基甲氧基)-1,3-苯并噻唑-2-胺 化合物11：N-環己基-6-(吡嗪-2-基甲氧基)-1,3-苯并噻唑-2-胺 化合物12：N-環己基-6-(嘧啶-4-基甲氧基)-1,3-苯并噻唑-2-胺 化合物13：N-環己基-6-(1,3-噻唑-2-基甲氧基)-1,3-苯并噻唑-2-胺 化合物14：N-環己基-6-(1,3-噻唑-5-基甲氧基)-1,3-苯并噻唑-2-胺 化合物15：6-[(2-胺基吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物16：6-[(6-氯吡嗪-2-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物17：6-[(5-氯吡啶-3-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物18：N-環己基-6-[(2-甲基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-胺 化合物19：4-({[2-(環己基胺基)-1,3-苯并噻唑-6-基]氧基}甲基)-N-甲基吡啶-2-甲醯胺 化合物20：N-環己基-6-[(3-甲基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-胺 化合物21：5-({[2-(環己基胺基)-1,3-苯并噻唑-6-基]氧基}甲基)-N-甲基吡啶-2-甲醯胺 化合物22：(1R,2R)-2-({6-[(2-胺基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物23：6-[(3-氯吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物24：(1R,2R)-2-({6-[(3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物25：(1S,2S)-2-({6-[(3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物26：N-環己基-6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-胺 化合物27：(1S,2S)-2-[(6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物28：(1R,2S)-1-({6-[(3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物29：(1R,2S)-1-({6-[(2-胺基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物30：(1S,2S)-2-({6-[(3-溴吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物31：6-[(3-溴吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物32：N-環己基-6-{[3-(1-甲基-1H-吡唑-4-基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-胺 化合物33：N-環己基-6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-胺 化合物34：(1R,2R)-2-({6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物35：(1S,2S)-2-({6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物36：(1R,2S)-1-({6-[(3-溴吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物37：(1R,2R)-2-{[6-({3-氯-1H-吡咯并[2,3-b]吡啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物38：(1R,2S)-1-[(6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-基)胺基]-2,3-二氫-1H-茚-2-醇 化合物39：6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物40：(1R,2S)-1-({6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物41：(1R,2S)-1-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物42：N-環己基-6-{[2-(甲基胺基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-胺 化合物43：(1R,2R)-2-[(6-{[2-(甲基胺基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物44：(1R,2R)-2-[(6-{[2-胺基-3-(三氟甲氧基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物45：(1S,2S)-2-[(6-{[2-胺基-3-(三氟甲氧基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物46：(1R,2R)-2-((6-((2-胺基-3-(三氟甲基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物47：(1S,2S)-2-((6-((2-胺基-3-(三氟甲基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物48：(1R,2R)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物49：(1S,2S)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物50：(1R,2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物51：(1S,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物52：N-[(1S,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己基]甲磺醯胺 化合物53：(2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)-4-甲基戊-1-醇 化合物54：(1S,2S)-2-((6-((2-胺基-3-氟吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物55：(1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4yl)甲氧基)苯并[d]噻唑-2-基胺基)環己醇 化合物56：(1S,2S)-2-{[4-甲氧基-6-({2-[(1-甲基-1H-吡唑-3-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物57：(1S,2S)-2-{[6-({2-[(2-羥乙基)胺基]嘧啶-4-基}甲氧基)-4-甲氧基-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物58：(1S,2S)-2-{[4-甲氧基-6-({2-[(1,2-噁唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物59：(1S,2S)-2-{[4-甲氧基-6-({2-[(1H-吡唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物60：(1S,2S)-2-{[4-甲氧基-6-({2-[(1-甲基-1H-1,2,3-三唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物61：6-((2-胺基嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物62：6-((2-胺基嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物63：6-((2-胺基嘧啶-4-基)甲氧基)-N-(4,4-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物64：N-(3,3-二氟環己基)-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-胺 化合物65：(1S,2S)-2-(6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-氟苯并[d]噻唑-2-基胺基)環己醇 化合物66：(1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物67：6-((2-胺基-3-氯吡啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物68：1-{4-[({2-[(3,3-二氟環己基)胺基]-4-甲氧基-1,3-苯并噻唑-6-基}氧基)甲基]吡啶-2-基}-3-甲脲 化合物69：(1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物70：(1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇 化合物71：N-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)乙醯胺 化合物72：N-(4-{[(2-{[(1R,2R)-2-羥基環己基]胺基}-4-甲氧基-1,3-苯并噻唑-6-基)氧基]甲基}吡啶-2-基)乙醯胺 化合物73：(1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇 化合物74：(1S,2S)-2-(6-((2-胺基-3-氟吡啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇 化合物75：(1S,2S)-2-({6-[(2-胺基吡啶-4-基)甲氧基]-7-氯-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物76：(1S,2S)-2-(7-氯-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇 化合物77：(1S,2S)-2-{[7-氯-4-甲氧基-6-({2-[(1-甲基-1H-1,2,3-三唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物78：(1S,2S)-2-{[7-氯-4-甲氧基-6-({2-[(1-甲基-1H-吡唑-3-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物79：4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基胺甲酸甲酯 化合物80：1-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)-3-甲脲 化合物81：(1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇 化合物82：(1S,2S)-2-{[4-甲氧基-6-({2-[(1-甲基-1H-吡唑-3-基)胺基]吡啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物83：(1S,2S)-2-{[4-甲氧基-6-({2-[(2-甲基嘧啶-4-基)胺基]吡啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物84：6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物85：(1R,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 及 化合物86：(1S,2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 及其醫藥上可接受之鹽及前藥。 在實施例中，該化合物針對CSF-1R具有小於200 nM之抑制活性(如以IC50 值量測呈現)。 在實施例中，該化合物對CSF-1R之選擇性比對PDGFRβ之選擇性高至少5倍之值及/或對CSF-1R之選擇性比對PDGFRα之選擇性高至少10倍之值及/或對CSF-1R之選擇性比對c-KIT之選擇性高至少20倍之值及/或對CSF-1R之選擇性比對FLT3之選擇性高至少200倍之值。 另一態樣提供包含本發明之化合物及至少一種醫藥上可接受之賦形劑之醫藥組合物。 在實施例中，該醫藥組合物包含選自由以下組成之群之另一活性劑：抗增殖劑、抗炎劑、抗血管生成劑、化學治療劑及免疫治療劑。 另一態樣提供本發明之化合物或本發明之醫藥組合物，其用於治療中。 另一態樣提供用於治療個體中經CSF-1R介導之疾病之方法，該方法包括向該個體投與有效量之本發明之化合物。 在實施例中，該經CSF-1R介導之疾病係選自癌症、骨失調症、炎性失調症及神經失調症。 在實施例中，該經CSF-1R介導之疾病係由以下表徵：CSF-1R之過表現、異常CSF-1R傳訊、CSF-1及/或IL-34之過表現及/或CSF-1R 基因中之突變。 在實施例中，該經CSF-1R介導之疾病係選自以下之癌症：乳癌、子宮頸癌、多形性神經膠質母細胞瘤(GBM)、肝細胞癌、何傑金氏淋巴瘤(Hodgkin’s lymphoma)、黑色素瘤、胰臟癌、色素沈著絨毛結節性滑膜炎(PVNS)、前列腺癌、卵巢癌、腱鞘巨細胞腫瘤(TGCT)、子宮內膜癌、多發性骨髓瘤、粒細胞白血病、骨癌、腎癌、腦癌及骨髓增生性失調症(MPD)。 在實施例中，該方法係用於治療經診斷為患有癌症或處於發展癌症之風險下之個體。 在實施例中，該經CSF-1R介導之疾病係選自以下之炎性失調症：牛皮癬性關節炎、關節炎、氣喘、甲狀腺炎、腎絲球腎炎、動脈粥樣硬化、牛皮癬、休格倫氏症候群(Sjogren’s syndrome)、類風濕性關節炎、全身性紅斑性狼瘡(SLE)、皮膚紅斑狼瘡、炎性腸疾病(包括克羅恩氏病(Crohn’s disease)及潰瘍性結腸炎(UC))、1型糖尿病、多發性硬化症及神經炎性病症(諸如HIV腦炎、阿茲海默症(Alzheimer’s disease)及ALS)。 在實施例中，該經CSF-1R介導之疾病係選自以下之骨失調症：骨質疏鬆症、骨關節炎、齒根骨膜炎、假體周圍骨質溶解及佩吉特氏病(Paget’s disease)。 在實施例中，該方法包括針對該經CSF-1R介導之疾病投與該化合物與另一治療干預之組合。 另一態樣提供用於如上文定義之方法中之本發明之化合物。 另一態樣提供根據本發明之化合物製造用於如上文定義之方法中之藥劑之用途。The inventors have found a family of compounds suitable for use as inhibitors of CSF-1R. These compounds are especially useful in pharmaceutical compositions and medical treatments where the activity of CSF-1R is adjusted. In a first aspect, the invention provides a compound characterized by formula (I), Or a pharmaceutically acceptable salt or prodrug thereof, wherein: A is a 5 to 10 membered heteroaryl group having a ring atom consisting of C, at least one N, and optionally O or S; n is 0, 1, 2, 3 Or 4; m series 0, 1 or 2; X 1 Is selected from the group consisting of NH, O, S, -CH=N- and -N=CH-; L represents a direct bond or a group thereof - (CR 6 R 7 ) p -, where: p is 1, 2 or 3, and each R 6 And each R 7 Are independently selected from hydrogen and C 1-4 An alkyl group, wherein each of the alkyl groups is optionally and independently substituted with 1 to 3 C, independently selected from halogen and hydroxy, optionally 1 to 3 halogens. 1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C 1-4 Substituted with a group of -alkyl), amidino, decylamino, sulfonyl, aminosulfonyl, sulfonylamino and -N(R'R"), wherein R ' And R ” Are independently selected from hydrogen and C 1-3 -alkyl; R 1 In each case independently selected from halogen, nitrile, -C(O)N(R 8 R 9 ), -N(R 8 R 9 ), -NHC(O)NR 8 R 9 ,-NHC(O)OR 10 , -NHC(O)R 10b , -C(O)R 10b , C 2-4 -醯基,C 2-4 - mercaptoamine, hydroxyl, -O(C 1-8 -alkyl), -C(O)OR 10 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 8 And R 9 The lines are independently selected from H, C 1-4 -alkyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 10 The lines are independently selected from H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R 10b The lines are independently selected from H, C 1-4 -alkyl, C 1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group , alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted; R 2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C 1-4 -alkyl and -O(C 1-4 -alkyl), wherein each alkyl group is optionally substituted; R 3 Is selected from C 1-8 -alkyl, C 2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group or a cycloalkenyl group a heterocycloalkenyl, aryl or heteroaryl group as desired; and R 4 And R 5 Lines are independently selected from H and C 1-3 -alkyl, or R 4 And R 5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In an embodiment: R 1 In each case independently selected from halogen, nitrile, -C(O)N(R 8 R 9 ), -N(R 8 R 9 ), -NHC(O)NR 8 R 9 ,-NHC(O)OR 10 , -NHC(O)R 10b , -C(O)R 10b , C 2-4 -醯基,C 2-4 - mercaptoamine, hydroxyl, -O(C 1-8 -alkyl), -C(O)OR 10 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 8 And R 9 The lines are independently selected from H, C 1-4 -alkyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 10 The lines are independently selected from H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R 10b The lines are independently selected from H, C 1-4 -alkyl, C 1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, and each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group Or an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group, optionally containing from 1 to 5 groups independently selected from the group consisting of Substitution: halogen, hydroxyl, -N (R a R b ) (where R a And R b Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R c (where R c Is selected from the group consisting of hydroxyl, amine and halogen; and/or R 2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C 1-4 -alkyl and -O(C 1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and/or R 3 Is selected from C 1-8 -alkyl, C 2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, wherein each of the alkyl group, a decyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R). d R e ) (where R d And R e Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 - mercaptoamine, -C(O)N(R f R g ) (where R f And R g Are independently selected from hydrogen and C 1-4 -alkyl or where R f And R g Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 - alkyl, aryl and heteroaryl. In the examples, A is a 6 membered monocyclic heteroaryl group. In an embodiment, n is 1 or 2. In an embodiment, R 1 In each case independently selected from halogen, nitrile, -C(O)N(R 8 R 9 ), -N(R 8 R 9 ), -NHC(O)NR 8 R 9 ,-NHC(O)OR 10 , -NHC(O)R 10b , -C(O)R 10b , C 2-4 -醯基,C 2-4 - mercaptoamine, hydroxyl, -O(C 1-8 -alkyl), -C(O)OR 10 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 8 , R 9 And R 10 Each line is independently selected from H, C 1-4 -alkyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 10b The lines are independently selected from H, C 1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( R a R b ) (where R a And R b Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R c (where R c It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R 1 In each case independently selected from halogen, -N(R 8 R 9 ), -NHC(O)NR 8 R 9 ,-NHC(O)OR 10 , -NHC(O)R 10b , -O(C 1-4 -alkyl), C 1-4 -alkyl, aryl and heteroaryl, wherein R 8 And R 9 The lines are independently selected from H, C 1-4 -alkyl and heteroaryl, R 10 And R 10b Lines are independently selected from H and C 1-4 An alkyl group, and wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R a R b ) (where R a And R b Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 1-4 -alkyl and (C 1-4 -alkyl)-R c (where R c It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R 1 In each case independently selected from Cl, Br and amine groups or selected from methylamino groups, -NHC(O)OCH 3 ,-NHC(O)CH 3 ,-NHC(O)NHCH 3 , methyl, methoxy, -NH-pyrazolyl, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C 1-3 -alkyl and -O(C 1-3 Substituted by a group of -alkyl). In an embodiment, m is 1 or 2, and R 2 Is selected from halogen, hydroxyl, nitrile, C 1-4 -alkyl and -O(C 1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. In an embodiment, R 3 Department C 1-8 An alkyl group which is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N (R) d R e ) (where R d And R e Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 -alkyl), aminosulfonyl, sulfonylamino and optionally substituted by hydroxyl or with 1 to 3 halogens -O(C 1-4 -alkyl). In an embodiment, R 3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aromatic The base or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R). d R e ) (where R d And R e Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 - mercaptoamine, -C(O)N(R f R g ) (where R f And R g Are independently selected from hydrogen and C 1-4 -alkyl or where R f And R g Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 - alkyl, aryl and heteroaryl. In an embodiment, R 3 a cyclohexyl group which is substituted by a hydroxy group and further optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R d R e ) (where R d And R e Are independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(R f R g ) (where R f And R g Are independently selected from hydrogen and C 1-3 -alkyl or where R f And R g Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens 1-4 -alkyl. In an embodiment, R 3 Is a dihydroindenyl group (2,3-dihydro-1H-indenyl) which is optionally substituted with 1 to 4 groups independently selected from the group consisting of a hydroxyl group, optionally substituted by a hydroxyl group. 1-3 -alkyl, F, Cl, nitrile, -N(R d R e ) (where R d And R e Are independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -C(O)N(R f R g ) (where R f And R g Are independently selected from hydrogen and C 1-3 -alkyl). In an embodiment, R 4 And R 5 All are hydrogen. In an embodiment, the L system - (CR 6 R 7 ) p - where p is 1 or 2 and each of the R 6 And each R 7 Are independently selected from hydrogen and C 1-4 An alkyl group, wherein each of the alkyl groups is optionally and independently substituted with 1 to 3 groups independently selected from a halogen and a hydroxyl group. In the embodiment, all Rs present 6 And R 7 The group is hydrogen. In an embodiment, L represents a direct bond. In an embodiment, X 1 It is selected from the group consisting of NH, O and S. In an embodiment, X 1 Department S. In other aspects and embodiments, the invention provides a compound characterized by formula (II), Or a pharmaceutically acceptable salt or prodrug thereof, wherein Q 1 , Q 2 , Q 3 And Q 4 Is independently selected from N, CH and C (R 1 ), where the Q 1 , Q 2 , Q 3 And Q 4 Not less than one and no more than two can represent N; and n, m, X 1 , L and R 1 To R 5 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (III), Or a pharmaceutically acceptable salt or prodrug thereof, wherein X 2 Is selected from N, CH or C (R 1 ); R 11 And R 12 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R 13 R 14 ), -N(R 13 R 14 ), -NHC(O)NR 13 R 14 ,-NHC(O)OR 15 , -NHC(O)R 15b , -C(O)R 15b , C 2-4 -醯基,C 2-4 - mercaptoamine, hydroxyl, -O(C 1-8 -alkyl), -C(O)OR 15 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 13 And R 14 The lines are independently selected from H, C 1-4 -alkyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 15 The lines are independently selected from H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R 15b The lines are independently selected from H, C 1-4 -alkyl, C 1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group , alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted; and m, X 1 , L and R 2 To R 5 Is as defined above. In an embodiment, R 11 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R 12 R 13 ), C 1-3 -alkyl, hydroxy and -O(C 1-3 -Alkyl), wherein each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. In an embodiment, R 12 Is selected from halogen, C(O)N(R 13 R 14 ), sulfonyl, C 1-4 -alkyl, C 2-4 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R 13 And R 14 The lines are independently selected from H, C 1-4 -alkyl, C 2-4 a fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R h R i ) (where R h And R i Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R j (where R j It is selected from the group consisting of hydroxyl and amine groups and halogens). In an embodiment, X 2 Department N. In other aspects and embodiments, the invention provides a compound characterized by formula (IV), Or a pharmaceutically acceptable salt or prodrug thereof, wherein X 3 Is selected from N, CH and CR 1 n system 0, 1, 2 or 3; and m, X 1 , L and R 1 To R 5 Is as defined above. In other aspects and embodiments, the invention provides compounds characterized by formula (V), Or a pharmaceutically acceptable salt or prodrug thereof, wherein R 16 And R 17 Is independently selected from the group consisting of hydrogen, halogen, hydroxyl, nitrile, C 1-4 -alkyl and -O(C 1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and n, X thereof 1 , X 3 , L, R 1 And R 3 Is as defined above. In an embodiment, R 16 And R 17 Is independently selected from the group consisting of hydrogen, halogen, hydroxy, nitrile, and -O(C), optionally substituted with one to three groups independently selected from the group consisting of halogen, hydroxy, and nitrile. 1-4 -alkyl). In other aspects and embodiments, the invention provides compounds characterized by formula (VI), Or a pharmaceutically acceptable salt or prodrug thereof, wherein R 18 , R 19 , R 20 And R twenty one Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R twenty two R twenty three ), -N(R twenty two R twenty three ), -NHC(O)NR twenty two R twenty three ,-NHC(O)OR twenty four , -NHC(O)R 24b , -C(O)R 24b , C 2-4 -醯基,C 2-4 - mercaptoamine, hydroxyl, -O(C 1-8 -alkyl), -C(O)OR twenty four , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R twenty two And R twenty three The lines are independently selected from H, C 1-4 -alkyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R twenty four The lines are independently selected from H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and R 24b The lines are independently selected from H, C 1-4 -alkyl, C 1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, each of which is an indenyl group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkenyl group, an alkynyl group, The cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R). k R l ) (where R k And R l Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R m (where R m Is selected from the group consisting of hydroxyl, amine and halogen); and m, X therein 1 , L and R 2 To R 5 Is as defined above. In an embodiment, R 18 Is selected from hydrogen, halogen, -NR twenty two R twenty three ,-NHC(O)NR twenty two R twenty three ,-NHC(O)OR twenty four , -NHC(O)R 24b , C 2-4 - mercaptoamine, -O(C 1-4 -alkyl) and C 1-4 -alkyl, where R twenty two And R twenty three The lines are independently selected from H, C 1-4 -alkyl and heteroaryl, and wherein R twenty four And R 24b Lines are independently selected from H and C 1-4 -alkyl, and wherein each alkyl, mercaptoamine or heteroaryl is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R k R l ) (where R k And R l Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R m (where R m It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R 20 Is selected from hydrogen, halogen, -O (C 1-4 -alkyl), C 1-4 An alkyl group, an aryl group and a heteroaryl group, wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R k R l ) (where R k And R l Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R m (where R m It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R 19 And R twenty one Each is independently hydrogen. In other aspects and embodiments, the invention provides a compound characterized by formula (VII), Or a pharmaceutically acceptable salt or prodrug thereof, wherein q is 0, 1, 2 or 3; 25 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (R n R o ) (where R n And R o Are independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 - mercaptoamine, -C(O)N(R n R o ) (where R n And R o Are independently selected from hydrogen and C 1-3 -alkyl), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 -alkyl, aryl and heteroaryl; and m, X 1 , R 2 , R 4 , R 5 , R 18 And R 20 Is as defined above. In other aspects and embodiments, the invention provides a formula (VII) a ) or (VII b Characterized compound, Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, q, X 1 , R 2 , R 4 , R 5 , R 18 , R 20 And R 25 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (VIII), Or a pharmaceutically acceptable salt or prodrug thereof, wherein r is 0, 1, 2 or 3; 26 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (R q R r ) (where R q And R r Are independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 - mercaptoamine, -C(O)N(R q R r ) (where R q And R r Are independently selected from hydrogen and C 1-3 -alkyl), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 -alkyl, aryl and heteroaryl; and m, X 1 , R 2 , R 4 , R 5 , R 18 And R 20 Is as defined above. In other aspects and embodiments, the invention provides a formula (VIII) a ) or (VIII b Characterized compound, Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, r, X 1 , R 2 , R 4 , R 5 , R 18 , R 20 And R 26 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (IX), Or a pharmaceutically acceptable salt or prodrug thereof, wherein n is 0, 1 or 2; 4 NH, O or S; and m, X 1 , L and R 1 To R 5 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (X), Or a pharmaceutically acceptable salt or prodrug thereof, wherein n is 0, 1 or 2; 5 NH, O or S; and m, X 1 , L and R 1 To R 5 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (XI), Or a pharmaceutically acceptable salt or prodrug thereof, wherein n, m, X 1 , L and R 1 To R 5 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (XII), Or a pharmaceutically acceptable salt or prodrug thereof, wherein R 30 , R 31 And R 32 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R 33 R 34 ), -N(R 33 R 34 ), -NHC(O)NR 33 R 34 ,-NHC(O)OR 35 , -NHC(O)R 35b , -C(O)R 35b , C 2-4 -醯基,C 2-4 - mercaptoamine, hydroxyl, -O(C 1-8 -alkyl), -C(O)OR 35 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 33 And R 34 The lines are independently selected from H, C 1-4 -alkyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 35 The lines are independently selected from H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 35b The lines are independently selected from H, C 1-4 -alkyl, C 1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( R s R t ) (where R s And R t Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R u (where R u Is selected from the group consisting of hydroxyl, amine and halogen); and m, X therein 1 , L and R 2 To R 5 Is as defined above. In an embodiment, R 30 Is selected from hydrogen, halogen, -NR 33 R 34 ,-NHC(O)NR 33 R 34 ,-NHC(O)OR 35 , -NHC(O)R 35b , C 2-4 - mercaptoamine, -O(C 1-4 -alkyl) and C 1-4 -alkyl, where R 33 And R 34 The lines are independently selected from H, C 1-4 -alkyl and heteroaryl, and wherein R 35 And R 35b Lines are independently selected from H and C 1-4 -alkyl, and wherein each alkyl, mercaptoamine or heteroaryl is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R s R t ) (where R s And R t Are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R u (where R u It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R 31 And R 32 Each is independently hydrogen. In other aspects and embodiments, the invention provides compounds characterized by formula (XIV), Or a pharmaceutically acceptable salt or prodrug thereof, wherein s is 0, 1, 2 or 3; 36 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (R v R w ) (where R v And R w Are independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 - mercaptoamine, -C(O)N(R v R w ) (where R v And R w Are independently selected from hydrogen and C 1-3 -alkyl), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 1-4 -alkyl, aryl and heteroaryl; and m, X 1 , R 2 , R 4 , R 5 And R 30 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (XV), Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R 4 , R 5 , R 16 , R 17 , R 30 And R 36 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (XVa) or formula (XVb), Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R 4 , R 5 , R 16 , R 17 , R 30 And R 36 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by formula (XVI), Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R 4 , R 5 , R 16 To R 18 , R 20 And R 25 Is as defined above. In other aspects and embodiments, the invention provides a compound characterized by Formula (XIVa) or Formula (XIVb), Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R 4 , R 5 , R 16 To R 18 , R 20 And R 25 Is as defined above. In other aspects and embodiments, the invention provides a compound selected from the group consisting of: Compound 1: (1R, 2R)-2-((6-((2-Amino-3-chloropyridine-4-) Methoxy)benzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 2: (1S,2S)-2-({6-[(2-Aminopyridine-4) -yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 3: (1R, 2R)-2-[(6-{1H-pyrrolo[ 2,3-b]pyridin-4-ylmethoxy}-1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 4: (1R, 2R)-2-({ 6-[(3-Bromopyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 5: (1S, 2S)-2- ({6-[(2-Amino-3-chloropyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol compound 6: ( 1S,2S)-2-[(6-{[2-(methylamino)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-yl)amino]cyclohexene- 1-Alcohol Compound 7: N-Cyclohexyl-6-(pyridin-4-ylmethoxy)-1,3-benzothiazol-2-amine Compound 8: N-cyclohexyl-6-(pyridine-3- Methoxy)-1,3-benzothiazol-2-amine compound 9: N-cyclohexyl-6-(1,3-thiazol-4-ylmethoxy)-1,3-benzothiazole- 2-Amine Compound 10: N-Cyclohexyl-6-(pyridin-2-ylmethyl) Oxy)-1,3-benzothiazol-2-amine compound 11: N-cyclohexyl-6-(pyrazin-2-ylmethoxy)-1,3-benzothiazol-2-amine compound 12 :N-cyclohexyl-6-(pyrimidin-4-ylmethoxy)-1,3-benzothiazol-2-amine compound 13: N-cyclohexyl-6-(1,3-thiazol-2-yl Methoxy)-1,3-benzothiazol-2-amine compound 14: N-cyclohexyl-6-(1,3-thiazol-5-ylmethoxy)-1,3-benzothiazole-2 -amine compound 15: 6-[(2-aminopyridin-4-yl)methoxy]-N-cyclohexyl-1,3-benzothiazol-2-amine compound 16:6-[(6-chloro Pyrazin-2-yl)methoxy]-N-cyclohexyl-1,3-benzothiazol-2-amine compound 17:6-[(5-chloropyridin-3-yl)methoxy]-N -cyclohexyl-1,3-benzothiazol-2-amine compound 18: N-cyclohexyl-6-[(2-methylpyridin-4-yl)methoxy]-1,3-benzothiazole- 2-Amine Compound 19: 4-({[2-(Cyclohexylamino)-1,3-benzothiazol-6-yl]oxy}methyl)-N-methylpyridine-2-carboxamide Compound 20: N-cyclohexyl-6-[(3-methylpyridin-4-yl)methoxy]-1,3-benzothiazol-2-amine compound 21:5-({[2-(ring) Hexylamino)-1,3-benzothiazol-6-yl]oxy}methyl)-N-methylpyridine-2-carboxamide Compound 22: (1R, 2R)-2-({6- [(2-Aminopyridine-4 -yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol compound 23:6-[(3-chloropyridin-4-yl)methoxy]- N-cyclohexyl-1,3-benzothiazol-2-amine compound 24: (1R, 2R)-2-({6-[(3-chloropyridin-4-yl)methoxy]-1,3 -benzothiazol-2-yl}amino)cyclohexan-1-ol compound 25: (1S, 2S)-2-({6-[(3-chloropyridin-4-yl)methoxy]-1 , 3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 26: N-cyclohexyl-6-{1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy }-1,3-Benzothiazol-2-amine Compound 27: (1S,2S)-2-[(6-{1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy}- 1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 28: (1R, 2S)-1-({6-[(3-chloropyridin-4-yl)methoxy) ]-1,3-Benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 29: (1R, 2S)-1-({6-[(2) -aminopyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 30: (1S, 2S)-2-({6-[(3-Bromopyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol compound 31:6 -[(3-bromopyridin-4-yl)methoxy]-N-cyclohexyl-1,3-benzothiazol-2-amine Compound 32: N-cyclohexyl-6-{[3-(1- methyl- 1H-pyrazol-4-yl)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-amine Compound 33: N-cyclohexyl-6-[(3-phenylpyridine-4 -yl)methoxy]-1,3-benzothiazol-2-amine compound 34: (1R, 2R)-2-({6-[(3-phenylpyridin-4-yl)methoxy] -1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 35: (1S, 2S)-2-({6-[(3-phenylpyridin-4-yl)) Oxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 36: (1R, 2S)-1-({6-[(3-bromopyridin-4-yl) Methoxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 37: (1R, 2R)-2-{[6 -({3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 38: (1R,2S)-1-[(6-{1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy}-1,3-benzothiazol-2-yl)amine Compound]: 2-(3-amino-3-chloropyridin-4-yl)methoxy]-N-cyclohexyl-1, 3-benzothiazol-2-amine compound 40: (1R, 2S)-1-({6-[(3-phenylpyridin-4-yl)methoxy]-1,3-benzothiazole-2 -yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 41: (1R, 2S)-1-({6-[(2-amino-3-chloropyridine-4- Methoxy]-1,3-benzothiazide Zyridin-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 42: N-cyclohexyl-6-{[2-(methylamino)pyridin-4-yl] Methoxy}-1,3-benzothiazol-2-amine compound 43: (1R, 2R)-2-[(6-{[2-(methylamino)pyridin-4-yl]methoxy) }-1,3-Benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 44: (1R, 2R)-2-[(6-{[2-Amino-3-(trifluoro) Methoxy)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 45: (1S, 2S)-2-[(6 -{[2-Amino-3-(trifluoromethoxy)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol compound 46: (1R, 2R)-2-((6-((2-Amino-3-(trifluoromethyl)pyridin-4-yl)methoxy)benzo[d]thiazol-2-yl) Amino)cyclohexan-1-ol compound 47: (1S,2S)-2-((6-((2-amino-3-(trifluoromethyl)pyridin-4-yl)methoxy)benzene) And [d]thiazol-2-yl)amino)cyclohexan-1-ol compound 48: (1R, 2R)-2-((6-((2-amino-3-chloropyridin-4-yl))) Methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 49: (1S,2S)-2-((6-((2-amine) 3-chloropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 50: (1R, 2R)- 2-({6-[ (2-Amino-3-chloropyridin-4-yl)methoxy]-4-methoxy-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 51: (1S,2S)-2-({6-[(2-Amino-3-chloropyridin-4-yl)methoxy]-4-methoxy-1,3-benzothiazol-2-yl }Amino)cyclohexan-1-ol Compound 52: N-[(1S,2S)-2-({6-[(2-Amino-3-chloropyridin-4-yl)methoxy]-4 -Methoxy-1,3-benzothiazol-2-yl}amino)cyclohexyl]methanesulfonamide Compound 53: (2R)-2-({6-[(2-amino-3-chloro) Pyridin-4-yl)methoxy]-4-methoxy-1,3-benzothiazol-2-yl}amino)-4-methylpentan-1-ol Compound 54: (1S, 2S) -2-((6-((2-Amino-3-fluoropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexane- 1-Alcohol Compound 55: (1S, 2S)-2-(4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidine-4yl)methoxy) Benzo[d]thiazol-2-ylamino)cyclohexanol Compound 56: (1S,2S)-2-{[4-methoxy-6-({2-[(1-methyl-) 1H-pyrazol-3-yl)amino]pyrimidin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 57: (1S, 2S)-2-{[6-({2-[(2-hydroxyethyl)amino]pyrimidin-4-yl}methoxy)-4-methoxy-1,3-benzothiazole-2 -amino]cyclohexene-1- Alcohol compound 58: (1S, 2S)-2-{[4-methoxy-6-({2-[(1,2-oxazol-4-yl)amino]pyrimidin-4-yl}methoxy ))-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 59: (1S, 2S)-2-{[4-methoxy-6-({2-[ (1H-pyrazol-4-yl)amino]pyrimidin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 60: (1S , 2S)-2-{[4-methoxy-6-({2-[(1-methyl-1H-1,2,3-triazol-4-yl)amino]pyrimidin-4-yl }Methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 61: 6-((2-Aminopyrimidin-4-yl)methoxy)-N -(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine compound 62: 6-((2-aminopyrimidin-4-yl)methoxy)-N -(3,3-Difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine Compound 63: 6-((2-Aminopyrimidin-4-yl)methoxy)-N -(4,4-difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine compound 64: N-(3,3-difluorocyclohexyl)-4-methoxy-6 -((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[d]thiazole-2-amine Compound 65: (1S, 2S) 2-(6-((2-Amino-3-chloropyridin-4-yl)methoxy)-4-fluorobenzo[d]thiazol-2-ylamino)cyclohexanol compound 66: ( 1S , 2S)-2-((6-((2-Aminopyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1 - alcohol compound 67: 6-((2-amino-3-chloropyridin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d Thiazol-2-amine compound 68: 1-{4-[({2-[(3,3-difluorocyclohexyl))amino]-4-methoxy-1,3-benzothiazole-6- })oxy)methyl]pyridin-2-yl}-3-methylurea compound 69: (1S,2S)-2-((6-((2-aminopyrimidin-4-yl)methoxy)) -7-Chloro-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 70: (1S, 2S)-2-(6-((2-Amino) Pyrimidin-4-yl)methoxy)-7-fluoro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol compound 71: N-(4-((2-(( 1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-yl)acetamide Compound 72: N-( 4-{[(2-{[(1R,2R)-2-hydroxycyclohexyl]amino}-4-methoxy-1,3-benzothiazol-6-yl)oxy]methyl}pyridine 2-yl) acetamidine compound 73: (1S, 2S)-2-(6-((2-aminopyrimidin-4-yl)methoxy)-4-methoxy-7-methylbenzene And [d]thiazol-2-ylamino)cyclohexanol compound 74: (1S, 2S)-2-(6-((2-amino-3-fluoropyridin-4-yl)) Oxy)-7-chloro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol Compound 75: (1S,2S)-2-({6-[(2-amino) Pyridin-4-yl)methoxy]-7-chloro-4-methoxy-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 76: (1S, 2S) -2-(7-chloro-4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[ d]thiazol-2-ylamino)cyclohexanol compound 77: (1S,2S)-2-{[7-chloro-4-methoxy-6-({2-[(1-methyl-1H) -1,2,3-triazol-4-yl)amino]pyrimidin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol compound 78:(1S,2S)-2-{[7-Chloro-4-methoxy-6-({2-[(1-methyl-1H-pyrazol-3-yl)amino]pyrimidine-4 -yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol compound 79: 4-((2-((1S,2S)-2-hydroxycyclohexyl) Amino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-ylaminecarboxylic acid methyl ester compound 80: 1-(4-((2-((1S, 2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-yl)-3-methylurea compound 81: (1S, 2S)-2-(4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyridin-4-yl)methoxy)benzo[d] Thiazole-2 -ylamino)cyclohexanol compound 82: (1S,2S)-2-{[4-methoxy-6-({2-[(1-methyl-1H-pyrazol-3-yl))amine ]]pyridin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol compound 83: (1S, 2S)-2-{[4- Oxy-6-({2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino} Cyclohexan-1-ol Compound 84: 6-((2-Aminopyrimidin-4-yl)methoxy)-7-chloro-N-(3,3-difluorocyclohexyl)-4-methoxy Benzo[d]thiazol-2-amine Compound 85: (1R,2S)-2-({6-[(2-Amino-3-chloropyridin-4-yl)methoxy]-1,3- Benzothiazol-2-yl}amino)cyclohexan-1-ol and compound 86: (1S, 2R)-2-({6-[(2-amino-3-chloropyridin-4-yl)) Oxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol and pharmaceutically acceptable salts and prodrugs thereof. In an embodiment, the compound has an inhibitory activity against CSF-1R of less than 200 nM (eg, as an IC) 50 Value measurement is presented). In an embodiment, the compound has a selectivity for CSF-1R that is at least 5 times greater than the selectivity for PDGFRβ and/or a selectivity for CSF-1R that is at least 10 times greater than the selectivity for PDGFRα and/or Or the selectivity to CSF-1R is at least 20 times higher than the selectivity for c-KIT and/or the selectivity to CSF-1R is at least 200 times higher than the selectivity for FLT3. Another aspect provides a pharmaceutical composition comprising a compound of the invention and at least one pharmaceutically acceptable excipient. In an embodiment, the pharmaceutical composition comprises another active agent selected from the group consisting of an anti-proliferative, an anti-inflammatory, an anti-angiogenic, a chemotherapeutic, and an immunotherapeutic. In another aspect, a compound of the invention or a pharmaceutical composition of the invention is provided for use in therapy. Another aspect provides a method for treating a CSF-1R mediated disease in a subject, the method comprising administering to the individual an effective amount of a compound of the invention. In an embodiment, the CSF-1R mediated disease is selected from the group consisting of cancer, bone disorders, inflammatory disorders, and neurological disorders. In an embodiment, the CSF-1R mediated disease is characterized by overexpression of CSF-1R, abnormal CSF-1R signaling, overexpression of CSF-1 and/or IL-34, and/or CSF-1R Mutations in the gene. In an embodiment, the CSF-1R mediated disease is selected from the group consisting of breast cancer, cervical cancer, glioblastoma multiforme (GBM), hepatocellular carcinoma, Hodgkin's lymphoma ( Hodgkin's lymphoma), melanoma, pancreatic cancer, pigmented villonodular synovitis (PVNS), prostate cancer, ovarian cancer, giant cell tumor of the tendon sheath (TGCT), endometrial cancer, multiple myeloma, granulocytic leukemia , bone cancer, kidney cancer, brain cancer and myeloproliferative disorders (MPD). In an embodiment, the method is for treating an individual diagnosed with or at risk of developing cancer. In an embodiment, the CSF-1R mediated disease is selected from the group consisting of inflammatory disorders: psoriatic arthritis, arthritis, asthma, thyroiditis, glomerulonephritis, atherosclerosis, psoriasis, and rest. Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus (SLE), cutaneous lupus erythematosus, inflammatory bowel disease (including Crohn's disease and ulcerative colitis) )), type 1 diabetes, multiple sclerosis and neuroinflammatory conditions (such as HIV encephalitis, Alzheimer's disease and ALS). In an embodiment, the CSF-1R mediated disease is selected from the group consisting of osteoporosis, osteoarthritis, root periosteum, periprosthetic osteolysis, and Paget's disease. ). In an embodiment, the method comprises administering a combination of the compound and another therapeutic intervention for the CSF-1R mediated disease. Another aspect provides a compound of the invention for use in a method as defined above. Another aspect provides the use of a compound according to the invention for the manufacture of a medicament for use in a method as defined above.

儘管現將參考說明書及實例描述本發明之特定實施例，但應瞭解此等實施例係僅藉助於實例及僅說明可表示本發明之原理之應用之許多可能之特定實施例中之一小部分。考慮到本發明之益處，各種變化及修飾對彼等熟習此項技術者而言將為顯而易見的且如隨附申請專利範圍中進一步定義，認為該等變化及修飾係於本發明之精神及範圍內。定義 除非另有定義，否則本文使用之所有技術及科學術語具有與本發明所屬領域之一般技術者通常瞭解之含義相同之含義。儘管與彼等本文描述者類似或相同之任何方法及材料可用於實踐或測試本發明，但現已描述示例性方法、裝置及材料。本文引用之所有技術及專利公開案以全文引用之方式併入本文中。本文無任何內容可視為承認本發明因先前技術而無權提前公開此揭示內容。 除非另有指示，否則本發明之實務將採用於本發明之技術內之化學合成、組織培養、免疫學、分子生物學、微生物學、細胞生物學及重組DNA之習知技術。參見，例如，Michael R. Green及Joseph Sambrook, Molecular Cloning (第4版，Cold Spring Harbor Laboratory Press 2012)；系列Ausubel等人編，(2007) Current Protocols in Molecular Biology；系列Methods in Enzymology (Academic Press, Inc., N.Y.)；MacPherson等人，(1991) PCR 1: A Practical Approach (IRL Press at Oxford University Press)；MacPherson等人，(1995) PCR 2: A Practical Approach；Harlow及Lane編，(1999) Antibodies, A Laboratory Manual；Freshney (2005) Culture of Animal Cells: A Manual of Basic Technique，第5版；Gait編，(1984) Oligonucleotide Synthesis；美國專利案第4,683,195號；Hames及Higgins編，(1984) Nucleic Acid Hybridization；及Anderson (1999) Nucleic Acid Hybridization；Hames及Higgins編，(1984) Transcription and Translation；Immobilized Cells and Enzymes (IRL Press (1986))；Perbal (1984) A Practical Guide to Molecular Cloning；Miller及Calos編，(1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory)；Makrides編，(2003) Gene Transfer and Expression in Mammalian Cells；Mayer及Walker編，(1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press, London)；Herzenberg等人編，(1996) Weir’s Handbook of Experimental Immunology；Manipulating the Mouse Embryo: A Laboratory Manual，第3版，(Cold Spring Harbor Laboratory Press (2002))；Sohail (編) (2004) Gene Silencing by RNA Interference: Technology and Application (CRC Press)。 包括範圍之數值標識(例如，pH、溫度、時間、濃度、分子量等)係近似值，其等視需要以0.1或1.0之增量變化(+)或(-)。應瞭解，儘管不總是明確規定，但所有數值標識前皆有術語「約」。亦應瞭解，儘管不總是明確規定，但本文描述之所有試劑係僅示例性且此等試劑之相同物可為此項技術中已知。 如說明書及申請專利範圍中使用，除非內文另有明確規定，否則單數形式「一」、「一個」及「該」包括複數個參考物。例如，術語「細胞」包括複數個細胞，包括其混合物。除非另有明確規定或自內文顯而易見，否則如本文使用，術語「或」應瞭解為包括性的。本文使用之術語「包括」意指片語「包括但不限於」且可與片語「包括但不限於」交換使用。 如本文使用，術語「包含」旨在意指組合物及方法包括本文列舉之元件，但不排除其他元件。「基本上由……組成」當用以定義組合物及方法時，應意指排除就規定目的而言對組合具有任何基本意義之元件。因此，基本上由如本文定義之元件組成之組合物應不排除來自分離與純化方法之污染物及醫藥上可接受之載劑(諸如磷酸鹽緩衝鹽水、防腐劑及類似物)。「由……組成」應意指排除不止其他成分之痕量元素及用於投與本發明之組合物之實質性方法步驟或產生組合物或達成預期結果之方法步驟。由此等過渡術語中之各者定義之實施例係在本發明之範圍內。本文使用術語「包含」旨在包含及揭示其中術語「包含」由「基本上由……組成」或「由……組成」替換之相應表述。 「個體」、「個人」或「病患」在本文中可交換使用，及係指脊椎動物(諸如哺乳動物)。哺乳動物包括(但不限於)嚙齒動物、農場動物、體育競技動物、寵物及靈長類動物；例如鼠科、大鼠、兔、類人猿、牛、綿羊、豬、犬、貓、馬及人類。在一項實施例中，該等哺乳動物包括馬、狗及貓。在一較佳實施例中，該哺乳動物係人類。 「投與」在本文中被定義為以導致藥劑於個體體內之方式向該個體提供藥劑或含有該藥劑之組合物之方式。此投與可藉由任何途徑，包括(但不限於)經口、透皮(例如，藉由陰道、直腸或口腔黏膜)、藉由注射(例如，皮下、靜脈內、非經腸、腹膜內或CNS內)或藉由吸入(例如，經口或經鼻)。當然，醫藥製劑係藉由適用於各投與途徑之形式給定。 疾病之「治療」包括：(1)預防該疾病，即，使得該疾病之臨床症狀在可能易患該疾病但仍未經歷或顯示該疾病之症狀之病患中不發展；(2)抑制該疾病，即，阻止或減少該疾病或其臨床症狀之發展；及/或(3)減輕該疾病，即，使得該疾病或其臨床症狀消退。 術語「患有」當其涉及術語「治療」時係指已診斷患有或易患有該疾病之病患或個人。因為家族譜系中有疾病史或因為存在與該疾病相關聯之基因突變，病患亦可稱為「有風險患上」疾病。處於患有疾病之風險下之病患仍未發展該疾病之特徵性病狀中之所有或一些。 「有效量」或「治療有效量」係足以實現有利或所需結果之量。有效量可以一或多種投與、施用或劑量投與。此遞送係取決於許多變量，包括其中待使用個別劑量單位之時間週期、治療劑之生物利用率、投與途徑等。然而，應瞭解用於任何特定個體之本發明之治療劑之特定劑量濃度取決於各種因素，包括(例如)採用之特定化合物之活性、個體之年齡、體重、一般健康、性別及飲食、投與時間、排泄速率、藥物組合及治療中之特定失調症之嚴重性及投與形式。治療劑量通常可經滴定以最佳化安全性及效應。通常，來自活體外及/或活體內測試之劑量-效應關係最初可為用於病患投與之適當劑量提供有用之指導。一般而言，吾人將需投與有效達成與發現活體外有效之濃度一致之血清濃度之化合物之量。此等參數之測定亦係於本領域之技術中。此等考慮因素及有效調配物及投與程序為此項技術中熟知及係描述於標準參考書中。 如本文使用，術語「醫藥上可接受之賦形劑」包含標準醫藥賦形劑中之任何一者，包括載劑(諸如磷酸鹽緩衝鹽水溶液、水)及乳劑(諸如油/水或水/油乳液)及各種類型之潤濕劑。醫藥組合物亦可包括穩定劑及防腐劑。就載劑、穩定劑及佐劑之實例而言，參見Remington’s Pharmaceutical Sciences (第20版，Mack Publishing Co. 2000)。 如本文使用，術語「前藥」意指需在有機體內生物轉化(自發或酶促)以釋放活性藥物之親代藥物分子之藥理學衍生物。例如，前藥係本文描述之化合物之變體或衍生物，其等具有在某些代謝條件下可裂解之基團，其等當裂解時，變為本文描述之化合物(例如，式(I)化合物)。此等前藥當其等在生理條件下經溶劑分解或經酶促降解時，則其等活體內具有醫藥活性。取決於在有機體內釋放活性藥物所需之生物轉化步驟之數量及以前藥型形式存在之官能基之數量，本文之前藥化合物可稱為單一、雙重、三重等。前藥形式通常在哺乳動物有機體中提供溶解性、組織相容性或延遲釋放之優勢(Bundgard, Design of Prodrugs，第7至9頁，第21至24頁，Elsevier, Amsterdam 1985 and Silverman, 「The Organic Chemistry of Drug Design and Drug Action」，第352至401頁，Academic Press, San Diego, Calif., 1992)。 此項技術中通常已知的前藥包括熟知的酸衍生物，諸如，例如，藉由酸化合物與合適之醇反應製備之酯、藉由酸化合物與胺反應製備之醯胺、經反應以形成醯化鹼衍生物之鹼性基團等。其他前藥衍生物可與本文揭示之其他特徵組合以增強生物利用率。因此，熟習此項技術者將知曉具有(例如)游離胺基或羥基之本發明揭示之化合物中之某些可轉化為前藥。前藥亦包括具有共價結合至本文揭示之上述取代基中之任何一者之碳酸酯、胺甲酸酯、醯胺或烷基酯部分之化合物。 如本文使用，術語「醫藥上可接受之鹽」意指當前揭示之化合物之醫藥上可接受之酸加成鹽或醫藥上可接受之鹼加成鹽，其可經施用而無任何所得之實質性非所需之生物效應或與其中含有該鹽之醫藥組合物之任何其他組分產生之任何所得之有害相互作用。 如本文使用，術語「烷基」意指基本上由碳原子及相應數量之氫原子組成之飽和直鏈或分支鏈游離基。示例性烷基包括甲基、乙基、正丙基、異丙基、正丁基、異丁基等。考慮到本發明之益處，其他烷基將為熟習此項技術者顯而易見。術語「C1-3 -烷基」、「C4-8 -烷基」等具有相同含義，即，基本上由1至3 (或4或8)個碳原子及相應數量之氫原子組成之飽和直鏈或分支鏈游離基。 如本文使用，術語「烯基」意指基本上由碳原子及相應數量之氫原子組成之不飽和直鏈或分支鏈游離基，其中游離基包含至少一個碳碳雙鍵。示例性烯基包括乙烯基、丙-1-烯基、丙-2-烯基、異丙烯基、丁-1-烯基、2-甲基-丙-1-烯基、2-甲基-丙-2-烯基等。考慮到本發明之益處，其他烯基將為熟習此項技術者顯而易見。術語「C2-6 -烯基」具有相同含義，即，基本上由2至6個碳原子及相應數量之氫原子組成之不飽和直鏈或分支鏈游離基，其中游離基包含至少一個碳碳雙鍵。 如本文使用，術語「炔基」意指基本上由碳原子及相應數量之氫原子組成之不飽和直鏈或分支鏈游離基，其中游離基包含至少一個碳碳三鍵。示例性烯基包括乙炔基、丙-1-炔基、丙-2-炔基、丁-1-炔基、3-甲基-丁-1-炔基等。考慮到本發明之益處，其他炔基將為熟習此項技術者顯而易見。術語「C2-6 -炔基」具有相同含義，即，基本上由2至6個碳原子及相應數量之氫原子組成之不飽和直鏈或分支鏈游離基，其中游離基包含至少一個碳碳三鍵。 如本文使用，術語「碳環基」意指飽和、部分或完全不飽和或芳族游離基，其具有形成環之至少3至9個碳原子(即，環原子)。示例性碳環基包括環丙基、環丁基、環戊基、環己基、環己烯基及苯基。應瞭解碳環基可為單環或多環(例如，稠合、橋接或螺環系統)。在多環碳環基之情況下，存在其他環，例如，1、2、3或多個其他環，其等中之所有含有3至9個碳原子(即，環原子)。具有此等其他環之示例性碳環基包括雙環[3.1.0]己烷基、十氫萘基(雙環[4.4.0]癸烷基)、螺[5.5]十一烷基、八氫萘基及萘基。術語「環烷基」具有與飽和碳環基相關之相同含義。術語「環烯基」具有與不飽和碳環基相關之相同含義。術語「芳基」具有與芳族碳環基相關之相同含義。芳基之實例包括苯基與萘基及茚基與二氫茚基。 如本文使用，術語「雜環基」意指飽和、部分或完全不飽和或芳族游離基，其具有形成環之至少3至6個原子(即，環原子)，其中該等環原子中之1至5個係碳及剩餘1至5個環原子(即，雜環原子)係獨立地選自由以下組成之群：氮、硫及氧。示例性雜環基包括氮雜環丙基、吡咯啶基、哌啶基、嗎啉基、哌嗪基、吡咯基、吡啶基及咪唑基。在多環雜環基之情況下，存在其他環，例如，1、2、3或多個其他環，其等中之所有含有3至6個選自碳、氮、硫及氧之環原子。多環雜環包括稠合、橋接及螺環系統。具有此等其他環之示例性雜碳環基包括2-氮雜雙環[3.3.0]辛烷基、3,9-二氮雜螺[5.5]十一烷基、二氫吲哚基、苯并噻吩基及苯并噁唑基。術語「雜環烷基」具有與飽和雜環基相關之相同含義。示例性雜環烷基包括吡咯啶基、嗎啉基、哌啶基及哌嗪基。術語「雜環烯基」具有與不飽和雜環基相關之相同含義。示例性雜環烯基包括2,5-二氫-1H-吡咯基、2H-哌喃基、四氫-2H-噻喃-1,1-二側氧基(噻烷二側氧基)、四氫-2H-哌喃基及3,4-二氫-2H-哌喃基。術語「雜芳基」具有與芳族雜環基相關之相同含義。雜芳基通常含有6至10個環原子，及此等基團之實例包括單環基(諸如吡咯基、吡啶基、吡嗪基及噠嗪基)及多環基(諸如苯并呋喃基、苯并噻吩基、吲哚基、吡咯并吡啶基、喹啉基及喋啶基)。 如本文使用，術語「鹵基」及「鹵素」意指氟、氯、溴或碘。此等術語可交換使用及可為指鹵素游離基或鹵素原子本身。鑒於其中此術語係用於本發明中之內文，熟習此項技術者將易於可確定對該等術語之識別。 如本文使用，術語「氰基」、「腈類」及「腈」意指具有經由三鍵連接至氮原子之碳原子之游離基。腈基係經由其碳原子結合。 如本文使用，術語「醯基」意指具有至少一個碳-氧雙鍵之含碳游離基。醯基係經由碳-氧雙鍵之碳原子結合。 如本文使用，術語「羥基」意指OH基團，其係經由其氧原子結合。術語「硫基」意指SH基團，其係經由其硫原子結合。 如本文使用，術語「胺基」通常意指具有氮原子及1或2個氫原子之游離基。因此，術語「胺基」通常係指一級及二級胺。就此而言，如本文及隨附申請專利範圍中使用，三級胺係由通式RR† N-表示，其中R及R† 係可相同或不同之碳基。然而，本文可使用術語「胺基」以描述一級、二級及/或三級胺，及鑒於術語之內文，熟習此項技術者將易於可確定如何使用該術語。 如本文使用，術語「醯胺基」及「醯胺」通常意指具有直接結合至羰基(C=O)之氮原子之游離基。通常，術語旨在包含一級、二級及三級醯胺基。「醯胺基」及「醯胺」基係經由其等羰基碳原子結合。 如本文使用，術語「醯基胺基」意指含有至少一個碳-氧雙鍵之游離基，其具有結合至羰基碳之胺基。醯基胺基係經由胺基之氮原子結合。 如本文使用，術語「磺醯基」意指含有與氧原子參與兩個雙鍵之硫原子之游離基，即，其含有基團-S(=O)2 -。「磺醯基」係經由該硫原子結合。示例性磺醯基包括磺酸酯，例如，-S(O)2 OR，其中R係碳基，及烷基磺醯基，例如，-S(O)2 R，其中R係烷基。術語「胺基磺醯基」意指直接結合至如本文定義之胺基之磺醯基，例如，-S(O)2 NH2 。術語「磺醯基胺基」意指直接結合至如本文定義之磺醯基之胺基，例如，-NHS(O)2 CH3 。 對本文變量之任何定義中之化學基團之列表之列舉包括該變量作為任何單一基團或列舉基團之組合之定義。對針對本文之變量或態樣之實施例之列舉包括作為單一實施例或與任何其他實施例或其部分組合之實施例。 本文提供之組合物及方法可與本文提供之其他組合物及方法中之任何一者中之一或多者組合。 本文使用下列縮寫： ℃ =攝氏度1 H-NMR =質子核磁共振 ACN =乙腈 AcOH =乙酸 β-Me = 2-巰乙醇 BSA =牛血清白蛋白 BSTFA = N,O-雙(三甲基甲矽烷基)三氟乙醯胺 d4 -MeOD =氘化甲醇 d6 -DMSO =氘化二甲亞碸 DBU = 1,8-二氮雜雙環十一-7-烯 DCM =二氯甲烷 DIBAL =氫化二異丁基鋁 DIEA = N,N-二異丙基乙胺 DMA =二甲基乙醯胺 DMF =二甲基甲醯胺 DMSO =二甲亞碸 DPPA =疊氮磷酸二苯酯 DTT =二硫蘇糖醇 ES+ =電噴灑正離子化 EGTA =乙二醇-雙(β-胺基乙醚)-N,N,N',N'-四乙酸 ELISA =酶聯免疫吸附分析 Et2 O =乙醚 EtOAc =乙酸乙酯 FRET =螢光共振能量轉移 h =小時 HATU = 1-[雙(二甲基胺基)亞甲基]-1H-1,2,3-三唑并[4,5-b]吡啶鎓3-氧化物六氟磷酸鹽 HEPES = 4-(2-羥乙基)-1-哌嗪乙磺酸 HI FBS =熱滅活之胎牛血清 HPLC =高壓液相層析術 HRP =辣根過氧化物酶 Hz =赫茲 IPA =異丙醇 M =莫耳 mCPBA = 3-氯過氧苯甲酸 MeCN =乙腈 MHz =兆赫； min =分鐘 mL =毫升 MS =質譜分析 MW =微波 PBS =磷酸鹽緩衝鹽水 PMB =對甲氧基苄基 qPCR =定量聚合酶鏈反應 RPMI培養基=洛斯維派克紀念研究所培養基 rt / RT =室溫 Selectfluor = 1-氯甲基-4-氟-1,4-二氮雜雙環[2.2.2]辛烷雙(四氟硼酸鹽) tBuONO =亞硝酸第三丁酯 TFA =三氟乙酸 THF =四氫呋喃化合物 本發明係關於用作CSF-1R抑制劑之化合物。在一項態樣中，本發明提供由式(I)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中： A係5至10員雜芳基，其環原子由C、至少一個N及視需要O或S組成； n係0、1、2、3或4； m係0、1或2； X1 係選自NH、O、S、-CH=N-及-N=CH-； L 表示直接鍵或其係基團-(CR6 R7 )p -，其中： p 係1、2或3，及 各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素及羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基； R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4- 醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4- 醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代； R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經取代； R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代；及 R4 及R5 係獨立地選自H及C1-3 -烷基， 或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 烯基、C2-8 炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4- 醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4- 醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代。 在實施例中： R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；及/或 R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及/或 R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該烷基、醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中： R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4- 醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；及/或 R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及/或 R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該烷基、醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，A係選自5員單環雜芳基、6員單環雜芳基及9員雙環雜芳基。在一項實施例中，A係選自由以下組成之群：噻唑基、異噻唑基、噁唑基、異噁唑基、咪唑啉基、吡唑基、吡啶基、吡嗪基、嘧啶基、噠嗪基及吡咯并吡啶基。在另一實施例中，A係選自由以下組成之群：噻唑基、吡啶基、嘧啶基、吡嗪基及吡咯并吡啶基。在另一實施例中，A係選自由以下組成之群：吡啶基及嘧啶基。在一項實施例中，A係選自由以下組成之群：吡啶-4-基及嘧啶-4-基。 在實施例中，A係6員單環雜芳基，例如，吡啶基、嘧啶基或吡嗪基。在一項實施例中，A係吡啶基。在另一實施例中，A係嘧啶基。在其他實施例中，A係9員雙環雜芳基，例如，吡咯并吡啶基。在一項實施例中，A係1H-吡咯并[2,3-b]吡啶基。在其他實施例中，A係5員單環雜芳基，例如，噻唑基。 在實施例中，n係0、1、2或3。在其他實施例中，n係0、1或2。在其他實施例中，n係1、2或3。在其他實施例中，n係1或2。在其他實施例中，n係2或3。在其他實施例中，n係0。在其他實施例中，n係1。在其他實施例中，n係2。在其他實施例中，n係3。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R8 及R9 係各獨立地選自H及選自以下之視需要經取代之基團：C2-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基。在其他實施例中，R8 及R9 兩者皆不為甲基。在其他實施例中，在R8 及R9 中之一者為氫之情況下，另一者不為甲基。在其他實施例中，R1 不為-C(O)NH(CH3 )。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R8 及R9 係各獨立地選自H及選自以下之視需要經取代之基團：C2-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基。在其他實施例中，R8 及R9 兩者皆不為甲基。在其他實施例中，在R8 及R9 中之一者為氫之情況下，另一者不為甲基。在其他實施例中，R1 不為-C(O)NH(CH3 )。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C2-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C2-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-6 -炔基、環烷基、雜環烷基、芳基及雜芳基， 其中R8 、R9 及R10 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-6 -炔基、環烷基、雜環烷基、芳基及雜芳基， 其中R8 、R9 及R10 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中，R1 在各情況下係獨立地選自鹵素、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 其中R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 及R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 且 其中各該醯基胺基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中，R1 在各情況下係獨立地選自鹵素、-N(R8 R9 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 其中R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中，R1 在各情況下係獨立地選自鹵素、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中R8 及R9 係獨立地選自H、C1-4 -烷基及雜芳基， R10 及R10b 係獨立地選自H及C1-4 -烷基， 且 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中，R1 在各情況下係獨立地選自鹵素、-N(R8 R9 )、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中R8 及R9 係獨立地選自H及C1-4 -烷基，且 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中，R1 在各情況下係獨立地選自Cl、Br及胺基或選自甲基胺基、-NHC(O)OCH3 、 -NHC(O)CH3 、-NHC(O)NHCH3 、甲基、甲氧基、-NH-吡唑基、苯基及吡唑基，其各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。 在其他實施例中，R1 在各情況下係獨立地選自Cl、Br及胺基或選自甲基胺基、甲基、甲氧基、苯基及吡唑基，其各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。 在實施例中，存在至少一個R1 基團，其係選自鹵素。在一項實施例中，該鹵素係選自F、Cl及Br。在另一實施例中，該鹵素係選自Cl及Br。在另一實施例中，該鹵素係Cl。在另一實施例中，該鹵素係Br。在另一實施例中，該鹵素係F。在實施例中，存在至少一個R1 基團，其係選自-N(R8 R9 )，例如，NH2 或視需要經1至3個獨立地選自C1-4 -烷基及(C1-4 -烷基)-Rc 之基團取代之-NH-吡唑基，其中Rc 係選自羥基、胺基及鹵素。 在實施例中，n係1且R1 係-N(R8 R9 )，例如，NH2 。在實施例中，n係1且R1 係-N(R8 R9 )，例如，視需要經1至3個獨立地選自C1-4 -烷基及(C1-4 -烷基)-Rc 之基團取代之-NH-吡唑基，其中Rc 係選自羥基、胺基及鹵素。在實施例中，n係1且R1 係視需要經1至3個獨立地選自C1-4 -烷基之基團取代之-NH-吡唑-3-基或-NH-吡唑-4-基。在實施例中，n係1且R1 係Cl。在實施例中，n係1且R1 係Br。在實施例中，n係1且R1 係-NHC(O)OCH3 。在實施例中，n係1且R1 係-NHC(O)CH3 。在實施例中，n係1且R1 係-NHC(O)NHCH3 。在實施例中，n係1且R1 係甲基，其視需要經1至3個鹵素取代。在實施例中，n係1且R1 係視需要經甲基取代之吡唑基。在實施例中，n係1且R1 係視需要經1至3個鹵素取代之甲氧基。在實施例中，n係1且R1 係苯基，其視需要經1至3個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中，n係2，第一R1 係-N(R8 R9 )，例如，NH2 ，及第二R1 係選自鹵素、-O(C1-8 -烷基)及C1-3 -烷基，其中該烷基係視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。 在實施例中，n係2，第一R1 係-N(R8 R9 )，例如，NH2 ，及第二R1 係Cl。在實施例中，n係2，第一R1 係-N(R8 R9 )，例如，NH2 ，及第二R1 係-CF3 。在實施例中，n係2，第一R1 係-N(R8 R9 )，例如，NH2 ，及第二R1 係-OCF3 。在實施例中，n係2，第一R1 係-N(R8 R9 )，例如，NH2 ，及第二R1 係-OCHF2 。在一項實施例中，n係2，第一R1 係NH2 ，及第二R1 係Cl。 在實施例中，m係0或1。在其他實施例中，m係1或2。在其他實施例中，m係1。在其他實施例中，m係0。在其他實施例中，m係2。 在實施例中，R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素及羥基之基團取代。在其他實施例中，R2 在各情況下係獨立地選自鹵素、腈及視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-4 -烷基)。在其他實施例中，R2 在各情況下係獨立地選自鹵素及腈。在其他實施例中，R2 在各情況下係獨立地選自鹵素、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。在其他實施例中，R2 在各情況下係獨立地選自鹵素及視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-4 -烷基)。 在實施例中，m係1或2，及R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。在其他實施例中，m係1或2，及R2 係選自鹵素、腈及視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-4 -烷基)。在實施例中，m係1及R2 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-4 -烷基)。在其他實施例中，m係2及R2 係選自鹵素及-O(C1-4 -烷基)。在其他實施例中，m係2及R2 係選自C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。 在實施例中，R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在其他實施例中，各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至3個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，R3 係C1-8 -烷基，其視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、胺基磺醯基、磺醯基胺基及視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)。在其他實施例中，R3 係C1-6 -烷基，其視需要經1至3個獨立地選自以下之基團取代：鹵素、羥基、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、胺基磺醯基及磺醯基胺基。在其他實施例中，R3 係C1-5 -烷基，其視需要經1至3個獨立地選自鹵素、羥基及NH2 之基團取代。在其他實施例中，R3 係C1-5 -烷基，其視需要經1至3個獨立地選自鹵素及羥基之基團取代。在一項實施例中，R3 係4-甲基戊-1-醇。 在其他實施例中，R3 係選自環烷基、雜環烷基、環烯基及雜環烯基，其中各環烷基、雜環烷基、環烯基或雜環烯基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在其他實施例中，R3 係選自環烷基及雜環烷基，其中各環烷基或雜環烷基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在其他實施例中，R3 係選自環己基、苯基、四氫呋喃基、四氫吡喃基、四氫-2H-噻喃基-1、1-二側氧基、吡啶基、哌啶基或二氫茚基(2,3-二氫-1H-茚基)，其視需要經1至5個選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在其他實施例中，R3 係C3-8 -環烷基，其視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在一項實施例中，R3 係環己基，其視需要經1至4個獨立地選自以下之基團取代：羥基、視需要經羥基取代之C1-3- 烷基、F、Cl、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)及CONH2 。在另一實施例中，R3 係經羥基取代之環己基。在另一實施例中，R3 係經羥甲基取代之環己基。在另一實施例中，R3 係經兩個F取代之環己基。 在一項實施例中，R3 係經羥基及進一步視需要經1至3個獨立地選自以下之基團取代之環己基：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。在另一實施例中，R3 係經羥基及經氟取代之環己基。在另一實施例中，R3 係經羥基及經兩個F取代之環己基。在一項實施例中，該等兩個F原子係結合至該環己基之相同碳原子。 在其他實施例中，R3 係選自芳基或雜芳基，其中各芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在一項實施例中，R3 係二氫茚基(2,3-二氫-1H-茚基)，其視需要經1至4個獨立地選自以下之基團取代：羥基、視需要經羥基取代之C1-3 -烷基、F、Cl、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基)。在另一實施例中，R3 係經羥基取代之二氫茚基。在另一實施例中，R3 係經羥甲基取代之二氫茚基。 在一項實施例中，R3 係經羥基及進一步視需要經1至3個獨立地選自以下之基團取代之二氫茚基：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，R4 及R5 與居間的碳原子一起形成3至6員環烷基，例如，環丙基。在其他實施例中，R4 及R5 與居間的碳原子一起形成3至6員雜環烷基，例如，3至6員環烷氧基(諸如氧雜環丁烷基)。在其他實施例中，R4 及R5 中之一者係氫及另一者係選自C1-3 -烷基(例如，甲基)。在其他實施例中，R4 及R5 兩者均獨立地選自C1-3 -烷基(例如，其等均係甲基)。在一較佳實施例中，R4 及R5 皆係氫。 在實施例中，L係-(CR6 R7 )p -，其中p較佳係1或2 (尤其，其中p係1)且其中各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素(例如，氟)、羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基。 在實施例中，L係-(CR6 R7 )p -，其中p較佳係1或2 (尤其，其中p係1)且其中各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素(例如，氟)及羥基之基團取代。 在實施例中，結合至相同碳原子之R6 及R7 中之一者係氫及另一者係C1-4 烷基，其視需要經羥基取代。在其他實施例中，結合至相同碳原子之R6 及R7 中之一者係氫及另一者係甲基。在又其他實施例中，結合至相同碳原子之R6 及R7 中之一者係氫及另一者係羥甲基。在又其他實施例中，存在之所有R6 及R7 基團係氫。 在實施例中，L表示直接鍵。 在實施例中，X1 係選自NH、O及S。在其他實施例中，X1 係選自O及S。在一項實施例中，X1 係O。在另一實施例中，X1 係S。在實施例中，X1 係選自-CH=N-及-N=CH-。在一項實施例中，X1 係-CH=N-。在另一實施例中，X1 係-C=NH-。 在一項實施例中：A係6員單環雜芳基；n係0、1、2或3；m係0、1或2；X1 係選自NH、O或S；L表示直接鍵或其係基團-(CR6 R7 )p -，其中p係1或2及各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素、羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且其中R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在一項實施例中：A係9員雙環雜芳基；n係0、1、2或3；m係0、1或2；X1 係選自NH、O或S；L表示直接鍵或其係基團-(CR6 R7 )p -，其中p係1或2及各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素、羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且其中R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在另一實施例中：A係6員單環雜芳基；n係1或2；m係0、1或2；X1 係S；L表示直接鍵；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R8 及R9 係獨立地選自H、C1-4 -烷基及雜芳基，其中R10 及R10b 係獨立地選自H及C1-4 -烷基，且其中各該醯基、醯基胺基、烷基、烯基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素及羥基之基團取代；R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在另一實施例中：A係9員雙環雜芳基；n係1或2；m係0、1或2；X1 係S；L表示直接鍵；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R8 及R9 係獨立地選自H、C1-4 -烷基及雜芳基，其中R10 及R10b 係獨立地選自H及C1-4 -烷基，且其中各該醯基、醯基胺基、烷基、烯基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素及羥基之基團取代；R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在一項實施例中：A係6員單環雜芳基；n係0、1、2或3；m係0、1或2；X1 係選自NH、O或S；L表示直接鍵或其係基團-(CR6 R7 )p -，其中p係1或2及各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素、羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在一項實施例中：A係9員雙環雜芳基；n係0、1、2或3；m係0、1或2；X1 係選自NH、O或S；L表示直接鍵或其係基團-(CR6 R7 )p -，其中p係1或2及各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素、羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在另一實施例中：A係6員單環雜芳基；n係1或2；m係0、1或2；X1 係S；L表示直接鍵；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R8 及R9 係獨立地選自H及C1-4 -烷基，且其中各該醯基、醯基胺基、烷基、烯基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基，及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素及羥基之基團取代；R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在另一實施例中：A係9員雙環雜芳基；n係1或2；m係0、1或2；X1 係S；L表示直接鍵；R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R8 及R9 係獨立地選自H及C1-4 -烷基，且其中各該醯基、醯基胺基、烷基、烯基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基，及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素及羥基之基團取代；R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及R4 及R5 係獨立地選自H及C1-3 -烷基或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。 在一項實施例中，該化合物係由式(II)表徵，或其醫藥上可接受之鹽或前藥，其中 Q1 、Q2 、Q3 及Q4 係獨立地選自N、CH及C(R1 )，其中該Q1 、Q2 、Q3 及Q4 中不少於一者且不多於兩者可表示N；及 n、m、X1 、L及R1 至R5 係如本文定義。 在實施例中，Q1 係N及Q2 、Q3 及Q4 係CH或C(R1 )。在其他實施例中，Q1 及Q3 均係N及Q2 及Q4 均係CH或C(R1 )。在其他實施例中，Q1 及Q4 均係N及Q2 及Q3 均係CH或C(R1 )。在其他實施例中，Q2 及Q4 均係N及Q1 及Q3 均係CH或C(R1 )。在較佳實施例中，Q2 係N。在較佳實施例中，Q2 係N及Q1 、Q3 及Q4 係CH或C(R1 )。在其他較佳實施例中，Q2 及Q4 係N及Q1 及Q3 係CH或C(R1 )。 在另一實施例中，該化合物係由式(III)表徵，或其醫藥上可接受之鹽或前藥，其中 X2 係選自N、CH或C(R1 )； R11 及R12 係獨立地選自氫、鹵素、腈、-C(O)N(R13 R14 )、-N(R13 R14 )、-NHC(O)NR13 R14 、-NHC(O)OR15 、-NHC(O)R15b 、-C(O)R15b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR15 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R15 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， R15b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代；及 m、X1 、L及R2 至R5 係如本文定義。 在實施例中，R11 及R12 係獨立地選自氫、鹵素、腈、-C(O)N(R13 R14 )、-N(R13 R14 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR15 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R15 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代。 在實施例中，R11 及R12 係獨立地選自氫、鹵素、腈、-C(O)N(R13 R14 )、-N(R13 R14 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR15 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R15 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rh Ri )(其中Rh 及Ri 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rj (其中Rj 係選自羥基及胺基及鹵素)。 在實施例中，R11 係選自氫、鹵素、C(O)N(R13 R14 )、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rh Ri )(其中Rh 及Ri 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rj (其中Rj 係選自羥基及胺基及鹵素)。在實施例中，R11 不為氫。 在其他實施例中，R11 係選自氫、鹵素、腈、-C(O)N(R12 R13 )、C1-3 -烷基、羥基及-O(C1-3 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。在實施例中，R11 係氫。 在實施例中，R12 係選自氫、鹵素、腈、-N(R13 R14 )、-C(O)N(R13 R14 )、C1-4 -烷基、C2-4 -炔基、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-4 -烷基)、-C(O)OR15 、磺醯基及胺基磺醯基，其中 R13 及R14 係獨立地選自H及C1-3 -烷基， R15 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該烷基，炔基、醯基、醯基胺基、磺醯基、胺基磺醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至3個獨立地選自鹵素及C1-3 -烷基之基團取代。 在實施例中，R12 係選自鹵素、C(O)N(R13 R14 )、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rh Ri )(其中Rh 及Ri 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rj (其中Rj 係選自羥基及胺基及鹵素)。 在其他實施例中，R12 係氫。 在實施例中，X2 係N。在其他實施例中，X2 係CH或C(R1 )。在其他實施例中，X2 係CH。 在實施例中：L係-(CR6 R7 )p -，其中p係1及R6 及R7 中之一者係氫及另一者係視需要經羥基取代之C1-4 -烷基；及R3 係選自環烷基或雜芳基，其視需要經1至3個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)、NH2 、NHSO2 CH3 、SO2 CH3 及CONH2 之基團取代。 在其他實施例中，L表示直接鍵及R3 係選自環烷基或雜芳基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)、NH2 、NHSO2 CH3 、SO2 CH3 及CONH2 之基團取代。 在一項實施例中，L表示直接鍵；及R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在另一實施例中，L表示直接鍵；及R3 係經羥基取代及進一步視需要經1至3個獨立地選自視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。在一項實施例中，L表示直接鍵；及R3 係(2-羥基)環己基。 在另一實施例中，L表示直接鍵；及R3 係二氫茚基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)及CONH2 之基團取代。在一項實施例中，L表示直接鍵；及R3 係經羥基取代及進一步視需要經1至3個獨立地選自視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之二氫茚基。在一項實施例中，L表示直接鍵；及R3 係(1-羥基)二氫茚基或(2-羥基)二氫茚基。 在一項實施例中，該化合物係由式(IV)表徵，或其醫藥上可接受之鹽或前藥，其中 X3 係選自N、CH及CR1 ； n係0、1、2或3；及 m、X1 、L及R1 至R5 係如本文定義。 在實施例中，X3 係N。在其他實施例中，X3 係CH或CR1 。在較佳實施例中，X3 係CH。 在實施例中：X3 係N；n係0、1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在實施例中：X3 係N；n係0、1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中：X3 係CH；n係0、1、2或3；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基及雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中：X3 係CH；n係0、1、2或3；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基及雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中：X3 係N；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中：X3 係N；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中：X3 係CH；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在其他實施例中：X3 係CH；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。 在一項實施例中，該化合物係由式(V)表徵，或其醫藥上可接受之鹽或前藥，其中 R16 及R17 係獨立地選自氫、鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及 n、X1 、X3 、L、R1 及R3 係如本文定義。 在實施例中，R16 及R17 係獨立地選自氫、鹵素、羥基、腈及視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代之-O(C1-4 -烷基)。在其他實施例中，R16 及R17 係獨立地選自氫、鹵素及腈。在其他實施例中，R16 及R17 係獨立地選自鹵素及-O(C1-4 -烷基)。 在實施例中，R16 及R17 中之一者係氫及另一者係如本文定義。在實施例中，R16 係氫及R17 係如本文定義。在一項實施例中，R16 係氫及R17 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代。在其他實施例中，R17 係氫及R16 係如本文定義。在一項實施例中，R17 係氫及R16 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代。在其他實施例中，R16 及R17 皆係氫。 在實施例中，R16 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-3 -烷基)且R17 係氫。在實施例中，R16 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-3 -烷基)且R17 係鹵素。在實施例中，R16 係甲氧基且R17 係氫。在其他實施例中，R16 係乙氧基且R17 係氫。在實施例中，R16 係甲氧基且R17 係Cl。在實施例中，R16 係甲氧基且R17 係甲基。在實施例中，R16 係-OCF3 且R17 係甲基。 在實施例中：X3 係CH；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 、R9 及R10 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；X1 係選自NH、O或S；L亦表示直接鍵；R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在實施例中：X3 係CH；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 、R9 及R10 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；X1 係選自NH、O或S；L亦表示直接鍵；R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在實施例中：X3 係CH；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 、R9 及R10 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；X1 係選自NH、O或S；L亦表示直接鍵；R3 係二氫茚基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)及CONH2 之基團取代。 在實施例中：X3 係CH；n係1或2；及R1 在各情況下係獨立地選自鹵素、腈、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R8 、R9 及R10 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；X1 係選自NH、O或S；L亦表示直接鍵；R3 係二氫茚基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)及CONH2 之基團取代。 在一項實施例中，該化合物係由式(VI)表徵，或其醫藥上可接受之鹽或前藥，其中 R18 、R19 、R20 及R21 係獨立地選自氫、鹵素、腈、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 R24b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基， 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；及 其中m、X1 、L及R2 至R5 係如本文定義。 在實施例中，R18 、R19 、R20 及R21 係獨立地選自氫、鹵素、腈、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在實施例中，R18 係選自氫、鹵素、腈、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基,環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 R24b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在實施例中，R18 係選自氫、鹵素、腈、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R18 係選自氫、鹵素、腈、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 R24b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、雜環烯基、芳基及雜芳基， 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R18 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R18 係-C(O)N(R22 R23 )，其中R22 及R23 係獨立地選自H、C2-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基。 在實施例中，R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、雜環烯基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在實施例中，R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R18 係選自氫、鹵素、-NR22 R23 、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R22 及R23 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R24 及R24b 係獨立地選自H及C1-4 -烷基，且 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R18 係選自氫、鹵素、-NR22 R23 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R22 及R23 係獨立地選自H及C1-4 -烷基，且 其中各烷基或醯基胺基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R18 係選自NH2 及選自NH(CH3 )、視需要經甲基取代之NH-吡唑基、NHC(O)NHCH3 、NHC(O)OCH3 、NHC(O)CH3 及甲基，各視需要經1至3個鹵素取代。在其他實施例中，R18 係選自NH2 、NH(CH3 )及甲基，其視需要經1至3個鹵素取代。在其他實施例中，R18 係氫。在一項實施例中，R18 係選自NH2 及NHC(O)NHCH3 。 在實施例中，R19 係選自氫、鹵素、-NR22 R23 、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R22 及R23 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R24 及R24b 係獨立地選自H及C1-4 -烷基，且 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在實施例中，R19 係選自氫、鹵素、-NR22 R23 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R22 及R23 係獨立地選自H及C1-4 -烷基，及 其中各烷基或醯基胺基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R19 係選自NH2 及選自NH(CH3 )、視需要經C1-4 -烷基取代之NH-吡唑基、NHC(O)NHCH3 、NHC(O)OCH3 、NHC(O)CH3 及甲基，各視需要經1至3個鹵素取代。在其他實施例中，R19 係選自NH2 、NH(CH3 )及甲基，其視需要經1至3個鹵素取代。在其他實施例中，R19 係氫。在一項實施例中，R18 係選自NH2 及NHC(O)NHCH3 。 在實施例中，R19 係氫且R18 不為氫。 在實施例中，R20 係選自氫、鹵素、腈、-C(O)NR22 R23 、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基及雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R20 係選自氫、鹵素、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R20 係選自Cl、F、甲基、甲氧基、苯基及吡唑基，各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。在其他實施例中，R20 係氫。 在實施例中，R21 係選自氫、鹵素、-O(C1-8 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。 在其他實施例中，R21 係選自Cl、F、甲基、甲氧基、苯基及吡唑基，各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。在其他實施例中，R21 係氫。 在實施例中，R19 及R21 各獨立地係氫(或氘)。 在一項實施例中，R18 係-N(R22 R23 )，例如，NH2 ；R20 係鹵素，例如，Cl、F或Br；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係-N(R22 R23 )，例如，NH2 ；R20 係-O(C1-3 -烷基)，例如，甲氧基，其視需要經1至3個鹵素取代；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係-N(R22 R23 )，例如，NH2 ；R20 係C1-3 -烷基，例如，甲基，其視需要經1至3個鹵素取代；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH2 ；R20 係Cl；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH2 ；R20 係F；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH2 ；R20 係Br；及R19 及R21 各獨立地係氫(或氘)。 在一項實施例中，R20 係視需要經取代之苯基；及R18 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R20 係視需要經取代之吡唑基；R18 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R20 係鹵素，例如，Cl或Br；及R18 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R20 係C1-3 -烷基，例如，甲基，其視需要經1至3個鹵素取代；及R18 、R19 及R21 各獨立地係氫(或氘)。 在一項實施例中，R18 係NH2 、NH(CH3 )、視需要經C1-4 -烷基取代之NH-吡唑基、NHC(O)NHCH3 、NHC(O)OCH3 或NHC(O)CH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。在一項實施例中，R18 係NH2 或NH(CH3 )；及R19 、R20 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係C1-3 -烷基，例如，甲基，其視需要經1至3個鹵素取代；及R19 、R20 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH2 ；及R20 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH-吡唑基，其視需要經C1-4 -烷基取代；及R20 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NHC(O)NR22 R23 ，例如，NHC(O)NHCH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NHC(O)OR24 ，例如，NHC(O)OCH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NHC(O)R24b ，例如，NHC(O)CH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。 在實施例中：L係-(CR6 R7 )p -，其中p係1及R6 及R7 中之一者係氫及另一者係視需要經羥基取代之C1-4 -烷基；及R3 係選自環烷基或雜芳基，其視需要經1至3個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)、NH2 、NHSO2 CH3 、SO2 CH3 及CONH2 之基團取代。 在其他實施例中：L表示直接鍵；及R3 係選自環烷基或雜芳基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)、NH2 、NHSO2 CH3 、SO2 CH3 及CONH2 之基團取代。 在一項實施例中：L表示直接鍵；及R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在另一實施例中：L表示直接鍵；及R3 係經羥基取代及進一步視需要經1至3個獨立地選自視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。在一項實施例中：L表示直接鍵；及R3 係(2-羥基)環己基。 在一項實施例中：L表示直接鍵；及R3 係二氫茚基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)及CONH2 之基團取代。 在另一實施例中：L表示直接鍵；及R3 係經羥基取代及進一步視需要經1至3個獨立地選自視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之二氫茚基。在一項實施例中：L表示直接鍵；及R3 係(1-羥基)二氫茚基或(2-羥基)二氫茚基。 在一項實施例中，該化合物係由式(VII)表徵，或其醫藥上可接受之鹽或前藥，其中 q係0、1、2或3； R25 係獨立地選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 、R18 及R20 係如本文定義。 在實施例中，q係0、1或2。在其他實施例中，q係1、2或3。在其他實施例中，q係1或2。在其他實施例中，q係0。在其他實施例中，q係1。在其他實施例中，q係2。 在實施例中，各R25 係獨立地選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，R25 係獨立地選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，R25 係結合至環己烷環之碳原子，其結合至羥基之氧原子。在一項實施例中，結合至環己烷環之碳原子(其結合至羥基之氧原子)之R25 基團係選自C1-3 -烷基，例如，甲基。 在實施例中，q係1及R25 係選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，q係2及各R25 係獨立地選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，q係2，第一R25 係羥基，及第二R25 係選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在另一實施例中，R18 係NH2 ；R20 係Cl；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH2 ；R20 係F；及R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH2 ；R20 係Br；及R19 及R21 各獨立地係氫(或氘)。 在另一實施例中，R18 係NH2 及R20 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH(CH3 )；及R20 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NH-吡唑基，其視需要經C1-4 -烷基取代；及R20 、R19 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NHC(O)NHCH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NHC(O)OCH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。在另一實施例中，R18 係NHC(O)CH3 ；及R19 、R20 及R21 各獨立地係氫(或氘)。 在一項實施例中，該化合物係由式(VIIa )表徵，或其醫藥上可接受之鹽或前藥，其中m、q、X1 、R2 、R4 、R5 、R18 、R20 及R25 係如本文定義。 由式(VIIa )表徵式化合物可尤其證實對CSF-1R比對其他激酶(諸如c-KIT、PDGFRα、PDGFRβ及/或FLT-3)具有良好之選擇性及對CSF-1R之良好抑制活性。 在另一實施例中，該化合物係由式(VIIb )表徵，或其醫藥上可接受之鹽或前藥，其中m、q、X1 、R2 、R4 、R5 、R18 、R20 及R25 係如本文定義。 在另一實施例中，該化合物係由式(VIIc )表徵，或其醫藥上可接受之鹽或前藥，其中m、q、X1 、R2 、R4 、R5 、R18 、R20 及R25 係如本文定義。 在另一實施例中，該化合物係由式(VIId )表徵，或其醫藥上可接受之鹽或前藥，其中m、q、X1 、R2 、R4 、R5 、R18 、R20 及R25 係如本文定義。 由式(VIIb )、式(VIIc )及式(VIId )表徵之化合物可尤其證實對CSF-1R之良好抑制活性。 在實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R24b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S、O或NH。 在實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S、O或NH。 在其他實施例中：R18 係選自氫、鹵素、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R24b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S、O或NH。 在其他實施例中：R18 係選自氫、鹵素、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S、O或NH。 在其他實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R24b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S。 在其他實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S。 在其他實施例中：R18 係選自氫、鹵素、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R24b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S。 在其他實施例中：R18 係選自氫、鹵素、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S。 在一項實施例中，該化合物係由式(VIII)表徵，或其醫藥上可接受之鹽或前藥，其中 r係0、1、2或3； R26 係獨立地選自鹵素、羥基、腈、-N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 、R18 及R20 係如本文定義。 在實施例中，r係0、1或2。在其他實施例中，r係1、2或3。在其他實施例中，r係1或2。在其他實施例中，r係0。在其他實施例中，r係1。在其他實施例中，r係2。 在實施例中，各R26 係獨立地選自鹵素、羥基、腈、-N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-4 -烷基或其中Rq 及Rr 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，R26 係獨立地選自鹵素、羥基、腈、-N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，各R26 係結合至茚烷部分內之飽和碳原子。在其他實施例中，各R26 係結合至茚烷部分內之不飽和碳原子。在其他實施例中，至少一個R26 係結合至茚烷部分內之飽和碳原子及至少一個R26 係結合至茚烷部分內之不飽和碳原子。 在一項實施例中，該化合物係由式(VIIIa )表徵，或其醫藥上可接受之鹽或前藥，其中m、r、X1 、R2 、R4 、R5 、R18 、R20 及R26 係如本文定義。 在一項實施例中，該化合物係由式(VIIIb )表徵，或其醫藥上可接受之鹽或前藥，其中m、r、X1 、R2 、R4 、R5 、R18 、R20 及R26 係如本文定義。 由式(VIII)，尤其由式(VIIIa )表徵之化合物可尤其證實對CSF-1R之良好抑制活性且亦可顯示對CSF-1R比對其他激酶(諸如c-KIT、PDGFRα、PDGFRβ及/或FLT-3)尤其高之選擇性。 在實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S、O或NH。 在其他實施例中：R18 係選自氫、鹵素、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S、O或NH。 在其他實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S。 在其他實施例中：R18 係選自氫、鹵素、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)；及X1 係S。 在一項實施例中，該化合物係由式(IX)表徵，或其醫藥上可接受之鹽或前藥，其中 n係0、1或2； X4 係NH、O或S；及 m、X1 、L及R1 至R5 係如本文定義。 在實施例中，X4 係O或S。在一項實施例中，X4 係S。 在實施例中：n係1；R1 係選自鹵素、-C(O)N(R8 R9 )(其中R8 及R9 係獨立地選自H及C1-4 -烷基)、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基及胺基及鹵素)；R4 及R5 係獨立地選自氫；m係0、1或2；R2 係獨立地選自鹵素、羥基、腈、-O(C1-4 -烷基)及C1-4 -烷基，其中該烷基係視需要經1至3個獨立地選自鹵素之基團取代；X1 係S；L表示直接鍵；及R3 係選自環烷基、雜環烷基、芳基或雜芳基，其中各環烷基、雜環烷基、芳基及雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中：n係1；R1 係選自鹵素、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基及胺基及鹵素)；R4 及R5 係獨立地選自氫；m係0、1或2；R2 係獨立地選自鹵素、羥基、腈、-O(C1-4 -烷基)及C1-4 -烷基， 其中該烷基係視需要經1至3個獨立地選自鹵素之基團取代；X1 係S；L表示直接鍵；及R3 係選自環烷基、雜環烷基、芳基或雜芳基，其中各環烷基、雜環烷基、芳基及雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在一項實施例中，該化合物係由式(X)表徵，或其醫藥上可接受之鹽或前藥，其中 n係0、1或2； X5 係NH、O或S；及 m、X1 、L及R1 至R5 係如本文定義。 在實施例中，X5 係O或S。在一項實施例中，X5 係S。 在實施例中：n係1；R1 係選自鹵素、-C(O)N(R8 R9 )(其中R8 及R9 係獨立地選自H及C1-4 -烷基)，磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基及胺基及鹵素)；R4 及R5 係獨立地選自氫；m係0、1或2；R2 係獨立地選自鹵素、羥基、腈、-O(C1-4 -烷基)及C1-4 -烷基， 其中該烷基係視需要經1至3個獨立地選自鹵素之基團取代；X1 係S；L表示直接鍵；及R3 係選自環烷基、雜環烷基、芳基或雜芳基，其中各環烷基、雜環烷基、芳基及雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中：n係1；R1 係選自鹵素、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基及胺基及鹵素)；R4 及R5 係獨立地選自氫；m係0、1或2；R2 係獨立地選自鹵素、羥基、腈、-O(C1-4 -烷基)及C1-4 -烷基，其中該烷基係視需要經1至3個獨立地選自鹵素之基團取代；X1 係S；L表示直接鍵；及R3 係選自環烷基、雜環烷基、芳基或雜芳基，其中各環烷基、雜環烷基、芳基及雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在一項實施例中，該化合物係由式(XI)表徵，或其醫藥上可接受之鹽或前藥，其中n、m、X1 、L及R1 至R5 係如本文定義。 在實施例中：n係1或2；R1 係選自鹵素、-C(O)N(R8 R9 )(其中R8 及R9 係獨立地選自H及C1-4 -烷基)，磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基及胺基及鹵素)；R4 及R5 係獨立地選自氫；m係0、1或2；R2 係獨立地選自鹵素、羥基、腈、-O(C1-4 -烷基)及C1-4 -烷基，其中該烷基係視需要經1至3個獨立地選自鹵素之基團取代；X1 係S；L表示直接鍵；及R3 係選自環烷基、雜環烷基、芳基或雜芳基，其中各環烷基、雜環烷基、芳基及雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中：n係1或2；R1 係選自鹵素、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基及胺基及鹵素)；R4 及R5 係獨立地選自氫；m係0、1或2；R2 係獨立地選自鹵素、羥基、腈、-O(C1-4 -烷基)及C1-4 -烷基，其中該烷基係視需要經1至3個獨立地選自鹵素之基團取代；X1 係S；L表示直接鍵；及R3 係選自環烷基、雜環烷基、芳基或雜芳基，其中各環烷基、雜環烷基、芳基及雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在一項實施例中，該化合物係由式(XII)表徵，或其醫藥上可接受之鹽或前藥，其中 R30 、R31 及R32 係獨立地選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；及 其中m、X1 、L及R2 至R5 係如本文定義。 在實施例中，R30 、R31 及R32 係獨立地選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在實施例中，R30 係選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基, 環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在實施例中，R30 係選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R30 係選自氫、鹵素、腈、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R30 係選自氫、鹵素、腈、-N(R33 R34 )、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R30 係-C(O)N(R33 R34 )，其中R33 及R34 係獨立地選自H、C2-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基。 在實施例中，R30 係選自氫、鹵素、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-4 -烷基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在實施例中，R30 係選自氫、鹵素、-C(O)N(R33 R34 )、-N(R33 R34 )、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-4 -烷基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R30 係選自氫、鹵素、-NR33 R34 、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R33 及R34 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R35 及R35b 係獨立地選自H及C1-4 -烷基，及 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R30 係選自氫、鹵素、-NR33 R34 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R33 及R34 係獨立地選自H、C1-4 -烷基及雜芳基，及 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R30 係選自NH2 、NH(CH3 )、NHCH2 CH2 OH、視需要經C1-4 -烷基取代之NH-吡唑基、視需要經C1-4 -烷基取代之NH-異噁唑基、視需要經C1-4 -烷基取代之NH-三唑基及甲基(其視需要經1至3個鹵素取代)。在其他實施例中，R30 係選自NH2 、NH(CH3 )及甲基(其視需要經1至3個鹵素取代)。 在實施例中，R31 係選自氫、鹵素、腈、-C(O)NR33 R34 、-N(R33 R34 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 其中R33 及R34 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基及雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R31 係選自氫、鹵素、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(RsRt)(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R31 係選自Cl、F、甲基、甲氧基、苯基及吡唑基，各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。在其他實施例中，R31 係氫。 在實施例中，R32 係選自氫、鹵素、腈、-C(O)NR33 R34 、-N(R33 R34 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基， 其中R33 及R34 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基及雜環烷基、芳基及雜芳基，且 其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R32 係選自氫、鹵素、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。 在其他實施例中，R32 係選自Cl、F、甲基、甲氧基、苯基及吡唑基，各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。在其他實施例中，R31 係氫。 在實施例中，R31 及R32 各獨立地係氫(或氘)。 在一項實施例中，R30 係NH2 、NH(CH3 )、NHCH2 CH2 OH、視需要經C1-4 -烷基取代之NH-吡唑基、視需要經C1-4 -烷基取代之NH-異噁唑基或視需要經C1-4 -烷基取代之NH-三唑基；及R31 及R32 各獨立地係氫(或氘)。在一項實施例中，R30 係NH2 或視需要經C1-4 -烷基取代之NH-吡唑基；及R31 及R32 各獨立地係氫(或氘)。在一項實施例中，R30 係NH2 或NH(CH3 )；及R31 及R32 各 獨立地係氫(或氘)。 在另一實施例中，R30 係NH2 及R31 及R32 各獨立地係氫(或氘)。在另一實施例中，R30 係NH(CH3 )；及R31 及R32 各獨立地係氫(或氘)。在另一實施例中，R30 係NH-吡唑基，其視需要經C1-4 -烷基取代；及R31 及R32 各獨立地係氫(或氘)。在另一實施例中，R30 係NHCH2 CH2 OH；及R31 及R32 各獨立地係氫(或氘)。在另一實施例中，R30 係NH-三唑基，其視需要經C1-4 -烷基取代；及R31 及R32 各獨立地係氫(或氘)。在另一實施例中，R30 係NH-異噁唑基，其視需要經C1-4 -烷基取代；及R31 及R32 各獨立地係氫(或氘)。 在實施例中：L係-(CR6 R7 )p -，其中p係1及R6 及R7 中之一者係氫及另一者係視需要經羥基取代之C1-4 -烷基；及R3 係選自環烷基或雜芳基，其視需要經1至3個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)、NH2 、NHSO2 CH3 、SO2 CH3 及CONH2 之基團取代。 在其他實施例中：L表示直接鍵；及R3 係選自環烷基或雜芳基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)、NH2 、NHSO2 CH3 、SO2 CH3 及CONH2 之基團取代。 在一項實施例中：L表示直接鍵；及R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在另一實施例中：L表示直接鍵；及R3 係經羥基取代及進一步視需要經1至3個獨立地選自視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。在一項實施例中：L表示直接鍵；及R3 係(2-羥基)環己基。 在一項實施例中：L表示直接鍵；及R3 係二氫茚基，其視需要經1至4個獨立地選自羥基、視需要經鹵素或羥基取代之C1-3 -烷基、F、Cl、-O(C1-4 -烷基)及CONH2 之基團取代。 在另一實施例中：L表示直接鍵；及R3 係經羥基取代及進一步視需要經1至3個獨立地選自視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之二氫茚基。在一項實施例中：L表示直接鍵；及R3 係(1-羥基)二氫茚基或(2-羥基)二氫茚基。 在一項實施例中，該化合物係由式(XIII)表徵，或其醫藥上可接受之鹽或前藥，其中 X1 、L、R3 、R4 、R5 、R16 、R17 及R30 係如本文定義。 在實施例中：R30 係選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R16 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-3 -烷基)及R17 係氫或鹵素；X1 係選自NH、O或S；L表示直接鍵；R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在實施例中：R30 係選自鹵素、腈、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R16 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-3 -烷基)及R17 係氫或鹵素；X1 係選自NH、O或S；L表示直接鍵；R3 係視需要經1至4個獨立地選自羥基、視需要經羥基取代之C1-3 -烷基、Cl、-O(C1-4 -烷基)及CONH2 之基團取代之環己基。 在另一實施例中，R16 係甲氧基且R17 係氫。在另一實施例中，R16 係甲氧基且R17 係Cl。在另一實施例中，R16 係甲氧基且R17 係甲基。 在一項實施例中，該化合物係由式(XIV)表徵，或其醫藥上可接受之鹽或前藥，其中 s係0、1、2或3； R36 係獨立地選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 及R30 係如本文定義。 在實施例中，s係0、1或2。在其他實施例中，s係1、2或3。在其他實施例中，s係1或2。在其他實施例中，s係0。在其他實施例中，s係1。在其他實施例中，s係2。 在實施例中，各R36 係獨立地選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-4 -烷基或其中Rv 及Rw 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，R36 係獨立地選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，R36 係結合至環己烷環之碳原子，其係結合至羥基之氧原子。在一項實施例中，結合至環己烷環之碳原子(其係結合至羥基之氧原子)之R36 基團係選自C1-3 -烷基(例如，甲基)。 在實施例中，s係1及R36 係選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，s係2及各R36 係獨立地選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在實施例中，s係2，第一R36 係羥基及第二R36 係選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、磺醯基、胺基磺醯基、磺醯基胺基及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。 在一項實施例中，該化合物係由式(XIVa )表徵，或其醫藥上可接受之鹽或前藥，其中m、s、X1 、R2 、R4 、R5 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XIVb )表徵，或其醫藥上可接受之鹽或前藥，其中m、s、X1 、R2 、R4 、R5 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XIVc )表徵，或其醫藥上可接受之鹽或前藥，其中m、s、X1 、R2 、R4 、R5 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XIVd )表徵，或其醫藥上可接受之鹽或前藥，其中m、s、X1 、R2 、R4 、R5 、R30 及R36 係如本文定義。 在實施例中：R30 係選自氫、鹵素、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R33 至R35 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R4 及R5 係獨立地選自H及C1-3 -烷基；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S、O或NH。 在其他實施例中：R30 係選自氫、鹵素、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R33 至R35 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S、O或NH。 在其他實施例中：R30 係選自氫、鹵素、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R33 至R35 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S。 在其他實施例中：R30 係選自氫、鹵素、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R33 至R35 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；m係0或1；R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代；及X1 係S。 在一項實施例中，該化合物係由式(XV)表徵，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如本文定義。 在實施例中，R30 係選自氫、鹵素、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基胺基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基及C1-8 -烷基，其中R33 至R35 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；R16 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-4 -烷基)；R17 係選自H、F、Cl及CH3 ；s係0或1；R36 係選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中，R30 係-N(R33 R34 )，其中R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；R16 係甲氧基；R17 係H；及s係0。 在一項實施例中，該化合物係由式(XVa)表徵，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XVb)表徵，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XVc)表徵，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XVd)表徵，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如本文定義。 在一項實施例中，該化合物係由式(XVI)表徵，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如本文定義。 在實施例中：R18 係選自氫、鹵素、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基及C1-4 -烷基，其中R22 至R24 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中R24b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫、鹵素、腈、-N(R22 R23 )、C2-4 -醯基胺基、-O(C1-4 -烷基)、磺醯基、胺基磺醯基、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，其中R22 及R23 係獨立地選自氫、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R4 及R5 各獨立地係H；R16 係視需要經1至3個獨立地選自鹵素之基團取代之-O(C1-4 -烷基)；R17 係選自H、F、Cl及CH3 ；q係0或1；及R25 係選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。 在實施例中：R18 係選自-N(R22 R23 )及-NHC(O)NR22 R23 ，其中R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該醯基、烷基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；R20 係選自氫及鹵素；R4 及R5 各獨立地係H；R16 係甲氧基；R17 係H；及q係0。 在一項實施例中，該化合物係由式(XVIa )表徵，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如本文定義。 在另一實施例中，該化合物係由式(XVIb )表徵，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如本文定義。 在另一實施例中，該化合物係由式(XVIc )表徵，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如本文定義。 在另一實施例中，該化合物係由式(XVId )表徵，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如本文定義。 在一項態樣中，該化合物係選自由化合物1至86組成之群： 或其醫藥上可接受之鹽或前藥。 在一項實施例中，該化合物係選自由以下組成之群：化合物1至49或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、5、6、7、12、13、15、17、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45及46；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、5、6、15、17、19、20、22、23、24、25、26、27、28、29、30、31、32、34、35、36、37、38、39、40、41、42、44、45及46；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、5、20、23、24、25、26、27、28、29、30、31、35、36、37、38、39、41、44、45及46；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、3、5、25、26、27、30、36、37、38、39及41；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、3、5、25、26、27、30、36、37、38、39、41、50、51、53、54、55、56、58、59、60、61、62、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85及86；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、5、37、38、41、55、58、59、64、65、69、74、75、76、77、78、79、81、82、83、84、85及86；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、5、6、20、23、24、25、26、27、28、29、30、31、32、35、36、37、38、39、40、41、42、43、44及45；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、5、24、25、26、27、28、29、30、31、35、36、37、38、39、44及45；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、5、27、30及41；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、5、27、30、38、41、54、55、56、58、59、60、61、62、64、65、66、68、69、71、72、73、74、76、77、78、79、80、81、82、83、84、85及86；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物5、55、58、59、60、64、65、69、74、76、77、78、79、80、81、82、83及84；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物59、55、76、79、64、82、71、72、60、56、69、73、58、80及77；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、15、20、24、25、26、30、35、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、15、20、24、25、35及36；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、24、25及36；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、20、24、25、26、27、30、35、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物3、4、24、25、35、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物4、24、25、35及36；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、4、20、24、25、30、35、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物2、4、24、25、30、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物2、4、25、36及38；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、3、4、20、24、25、30、35、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物1、2、4、24、25、36及38；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物2、24、25及36；或其醫藥上可接受之鹽或前藥。 在另一實施例中，該化合物係選自由以下組成之群：化合物2、4、24、25、36、50、54、55、56、66、69、70、72、73及84；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物3、4、24、25、35、36、38、50、51、54、55、56、66、69、70、72、73及84；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物36、54、55、66、69、70、72及73；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物2、36、50、54、55、56、66、69、70、72、73及84；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物36、54、55、66、69、70、72及73；或其醫藥上可接受之鹽或前藥。在另一實施例中，該化合物係選自由以下組成之群：化合物50、51、54、55、56、66、69、70、72、73及84；或其醫藥上可接受之鹽或前藥。 本發明之化合物可用作激酶抑制劑。特定言之，本發明之化合物可用作CSF-1R之抑制劑。用於測定化合物抗CSF-1R (例如，抗小鼠或人類CSF-1R或其具有蛋白激酶活性之片段)之抑制活性之分析係為此項技術中已知及亦列舉於下列實例中。下文列舉之活性值可(例如)根據如下列實例中列舉之分析測定。 在實施例中，本發明之化合物具有以下之IC50 值(例如，在無細胞分析中抗CSF-1R之抑制活性)：小於1.5 μM、小於750 nM、小於500 nM、小於400 nM、小於300 nM、小於200 nM、小於150 nM、小於100 nM、小於75 nM、小於50 nM、小於40 nM、小於30 nM、小於25 nM、小於20 nM、小於15 nM、小於10 nM或小於5 nM。在其他實施例中，本發明之化合物具有以下之IC50 值(例如，在無細胞分析中抗CSF-1R之抑制活性)：小於4 nM、小於3 nM、小於2 nM或小於1 nM。 在實施例中，本發明之化合物具有以下之IC50 值(例如，在基於細胞之分析中抗CSF-1R之抑制活性)：小於10 μM、小於5 μM、小於2 μM、小於1 μM、小於750 nM、小於500 nM、小於400 nM、小於300 nM、小於200 nM、小於150 nM、小於100 nM或小於75 nM。在其他實施例中，本發明之化合物具有以下之IC50 值(例如，在基於細胞之分析中抗CSF-1R之抑制活性)：小於65 nM、小於40 nM、小於30 nM或小於20 nM。 本發明之化合物可對CSF-1R比對其他激酶(例如，c-KIT、PDGFRα、PDGFRβ及/或FLT3)更具選擇性。特定言之，本發明之化合物可選擇性抑制CSF-1R之活性而非其他激酶(例如，c-KIT、PDGFRα、PDGFRβ及/或FLT3)之活性。用於測定相化合物對CSF-1R而非對其他激酶之選擇性之分析係為此項技術中已知。用於測定化合物對CSF-1R而非對其他激酶之選擇性之分析之實例亦列舉於下列實例中。下文列舉之選擇性值可(例如)根據下列實例中列舉之分析測定。 在實施例中，本發明之化合物對CSF-1R之選擇性係對另一激酶之選擇性之以下倍數之值：至少10倍、至少11倍、至少12倍、至少13倍、至少14倍、至少15倍、至少16倍、至少17倍、至少18倍、至少19倍、至少20倍、至少25倍、至少30倍、至少35倍、至少40倍、至少45倍、至少50倍、至少55倍、至少60倍、至少65倍、至少70倍、至少75倍、至少80倍、至少85倍、至少90倍、至少95倍、至少100倍、至少150倍、至少200倍、至少250倍、至少300倍、至少350倍、至少400倍、至少450倍、至少500倍、至少1000倍、至少1500倍、至少2000倍或至少5000倍。「選擇性」意指導致該另一激酶之50%最大抑制(IC50 )之化合物之濃度係至少比導致CSF-1R之50%最大抑制之化合物之濃度大規定係數。因此，對CSF-1R具有10 nM之IC50 值及對另一激酶具有200 nM之IC50 值之化合物對CSF-1R之選擇性係對該另一激酶之選擇性之20倍之值。 在實施例中，本發明之化合物對CSF-1R之選擇性係對PDGFRβ之選擇性之以下倍數之值：至少2倍、至少2.5倍、至少5倍、至少10倍、至少15倍、至少20倍、至少25倍、至少30倍或至少40倍。 在實施例中，本發明之化合物對CSF-1R之選擇性係對PDGFRα之選擇性之至少5倍、至少10倍、至少15倍、至少20倍、至少30倍、至少40倍、至少50倍、至少60倍、至少70倍、至少80倍、至少90倍、至少100倍、至少150倍、至少200倍或至少250倍之值。 在實施例中，本發明之化合物對CSF-1R之選擇性係對c-KIT之選擇性之至少15倍、至少20倍、至少30倍、至少40倍、至少50倍、至少100倍、至少200倍、至少300倍、至少400倍、至少500倍、至少1000倍、至少2000倍、至少3000倍、至少4000倍或至少5000倍之值。 在實施例中，本發明之化合物對CSF-1R之選擇性係對FLT3之選擇性之至少50倍、至少100倍、至少200倍、至少500倍、至少1000倍、至少1500倍、至少2000倍、至少3000倍、至少4000倍或至少5000倍之值。鹽 本發明揭示本質上呈鹼性之化合物通常可與各種無機及/或有機酸形成各種不同之鹽。儘管此等鹽對於向動物及人類投與而言通常係醫藥上可接受，但在實務上通常需要首先將化合物自呈醫藥上不可接受之鹽之反應混合物分離及然後藉由用鹼性試劑處理將後者簡單地轉化回至游離鹼化合物，及接著將該游離鹼轉化為醫藥上可接受之酸加成鹽。鹼性化合物之酸加成鹽可使用習知技術容易地製備，例如，藉由用大體上當量之所選礦物或有機酸於水性溶劑介質或合適之有機溶劑(諸如，例如，甲醇或乙醇)中處理鹼化合物。一經小心蒸發溶劑，即獲得所需固體鹽。帶正電之本發明揭示之化合物(例如，含有季銨)亦可與各種無機酸及/或有機酸之陰離子組分形成鹽。 可用以製備化合物之醫藥上可接受之鹽之酸係彼等可形成無毒酸加成鹽者，例如，含有藥理上可接受之陰離子之鹽，諸如氯化物、溴化物、碘化物、硝酸鹽、硫酸鹽或硫酸氫鹽、磷酸鹽或酸式磷酸鹽、乙酸鹽、乳酸鹽、檸檬酸鹽或酸式檸檬酸鹽、酒石酸鹽或酒石酸氫鹽、琥珀酸鹽、蘋果酸鹽、馬來酸鹽、富馬酸鹽、葡糖酸鹽、蔗糖鹽、苯甲酸鹽、甲磺酸鹽及雙羥萘酸鹽[即，1,1'-亞甲基-雙-(2-羥基-3-萘甲酸鹽)]鹽。 本發明揭示本質上呈酸性之化合物(例如，含有羧酸或四唑部分之化合物)通常可與各種無機及/或有機鹼形成各種不同之鹽。儘管此等鹽對於向動物及人類投與而言通常係醫藥上可接受，但在實務上通常需要首先將化合物自呈醫藥上不可接受之鹽之反應混合物分離及然後藉由用酸性試劑處理將後者簡單地轉化回至游離酸化合物，及接著將該游離酸轉化為醫藥上可接受之鹼加成鹽。此等鹼加成鹽可使用使用習知技術容易地製備，例如，藉由用含有所需藥理上可接受之陽離子之水溶液處理相應之酸性化合物，及然後將所得溶液蒸發至乾燥，例如，在減壓下。或者，鹼加成鹽亦可藉由將酸性化合物之低碳數鏈烷醇溶液及所需鹼金屬醇鹽混合在一起，及然後以與之前相同之方式將所得溶液蒸發至乾燥製備。在任一情況下，可使用試劑之化學計量量以確保反應之完整性及所需固體鹽之最大產物產率。 可用以製備化合物之醫藥上可接受之鹼加成鹽之鹼係彼等可形成無毒鹼加成鹽者，例如，含有藥理上可接受之陽離子之鹽，諸如鹼金屬陽離子(例如，鉀及鈉)、鹼土金屬陽離子(例如，鈣及鎂)、銨或其他水溶性胺加成鹽(諸如N-甲基葡糖胺(葡甲胺)、低碳數鏈烷醇銨及有機胺之其他此等鹼)。前藥 根據本發明使用之醫藥上可接受之前藥係CSF-1R抑制劑之衍生物，例如，由式(I)表徵之化合物，其等可活體內轉化為本文描述之化合物。前藥(其等可本身具有一些活性)當其等(例如)在生理學條件下經歷溶劑分解或通過酶促降解時可變為活體內完全醫藥上活性。用於製備如本文描述之化合物之前藥之方法將為熟習此項技術者基於本發明而顯而易見。立體化學 本發明揭示之化合物之立體異構體(例如，順式及反式異構體)及所有光學異構體(例如，R-及S-對映體)及此等異構體之外消旋、非對映異構及其他混合物係在本發明之範圍內。 例如，在基團R3 含有一或多個對掌性碳原子之情況下，本發明之化合物可主要作為單一對映體(或非對映體)存在，或作為異構體之混合物(例如，對映體或非對映體)存在。 在實施例中，本發明之化合物係作為外消旋混合物存在，例如，該等R-及S-異構體(或所有對映體或非對映體)係以近似相等之量存在。在其他實施例中，本發明之化合物係作為異構體之混合物存在，其中一種對映體(或非對映體)係以對映異構過量至少約5%、10%、25%、40%、70%、80%、90%、95%、97%、98%或99% (例如，約100%)存在。 用於製備經對映異構富集及/或對映異構純化合物之方法將為熟習此項技術者基於本發明而顯而易見。此等方法之實例包括化學拆分(例如，結晶)及對掌性層析術。 本發明揭示之化合物可以數種互變異構形式存在，包括烯醇與亞胺形式，及酮與烯胺形式及幾何異構體與其混合物。互變異構體作為溶解於溶液中之互變異構體之混合物存在。在固體形式中，通常一種互變異構體占主導。儘管可描述一種互變異構體，但所有互變異構體係在本發明之範圍內。 在化合物由指示立體化學資訊之結構式表徵之情況下，本發明延伸至由該結構式表徵之該等化合物中之一或多種之混合物。因此，在實施例中，本發明提供由式(VIIa )及(VIIb )表徵之化合物或其一或多種之醫藥上可接受之鹽或前藥之混合物。在其他實施例中，本發明提供由式(VIIIa )及(VIIIb )表徵之化合物或其一或多種之醫藥上可接受之鹽或前藥之混合物。其他形式 本文描述之化合物之醫藥上可接受之水合物、溶劑合物、多晶型物等亦係在本發明之範圍內。如本文描述之化合物可呈非晶型形式及/或呈一或多種結晶形式。 同位素標記化合物亦係在本發明之範圍內。如本文使用，「同位素標記化合物」係指本發明揭示之化合物，其包括各如本文描述之醫藥鹽及其前藥，其中一或多個原子係經具有不同於自然界中通常發現之原子質量或質量數之原子質量或質量數之原子置換。可併入本發明揭示之化合物內之同位素之實例包括包括氫、碳、氮、氧、磷、氟及氯之同位素(諸如，分別2 H、3 H、13 C、14 C、15 N、18 O、17 O、31 P、32 P、35 S、18 F及36 Cl)。氘化化合物(例如，具有一或多個氫原子經氘置換之本發明之化合物)較佳。醫藥組合物 本發明提供醫藥組合物，其等包含至少一種本發明之化合物(例如，由式(I)表徵之化合物)及至少一種醫藥上可接受之賦形劑(例如，用於根據本文揭示之方法使用)。 醫藥上可接受之賦形劑可為此項技術中已知的任何此賦形劑，其包括彼等描述(例如)於Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro編，1985)中者。本發明揭示之化合物之醫藥組合物可藉由此項技術中已知的習知方式製備，其等包括(例如)將至少一種本發明揭示之化合物與醫藥上可接受之賦形劑混合。 本發明之醫藥組合物或劑型可包括藥劑及另一載劑，例如，化合物或組合物，惰性或活性，諸如可偵測之藥劑、標誌物、佐劑、稀釋劑、黏合劑、穩定劑、緩衝劑、鹽、親脂性溶劑、防腐劑、佐劑或類似物。載劑亦包括醫藥賦形劑及添加劑，例如，蛋白質、肽、胺基酸、脂質及碳水化合物(例如，糖，包括單醣、二、三、四及寡醣；衍生糖(諸如醛醣醇、醛醣酸、酯化糖及類似物)；及多醣或糖聚合物)，其等可單獨或組合存在，包含單獨或以重量或體積計之1至99.99%之組合。示例性蛋白賦形劑包括血清白蛋白諸如人類血清白蛋白(HSA)、重組人類白蛋白(rHA)、明膠、酪蛋白及類似物。典型胺基酸/抗體組分(其等亦可發揮緩衝能力)包括丙胺酸、甘胺酸、精胺酸、甜菜鹼、組胺酸、麩胺酸、天冬胺酸、半胱胺酸、離胺酸、白胺酸、異白胺酸、纈胺酸、甲硫胺酸、苯基丙胺酸、阿斯巴甜及類似物。碳水化合物賦形劑亦旨在本發明之範圍內，其等之實例包括(但不限於)單醣(諸如果糖、麥芽糖、半乳糖、葡萄糖、D-甘露糖、山梨糖及類似物)；二醣(諸如乳糖、蔗糖、海藻糖、纖維雙醣及類似物)；多醣(諸如棉子糖、松三糖、麥芽糊精、聚葡萄糖、澱粉及類似物)；及醛醣醇(諸如甘露醇、木糖醇、麥芽糖醇、乳糖醇、木糖醇山梨糖醇(山梨醇)及肌醇)。 可使用之載劑包括緩衝劑或pH調節劑；通常，該緩衝劑係製備自有機酸或鹼之鹽。典型緩衝劑包括有機酸鹽(諸如檸檬酸、抗壞血酸、葡萄糖酸、碳酸、酒石酸、琥珀酸、乙酸或酞酸之鹽)；Tris、鹽酸氨丁三醇或磷酸鹽緩衝劑。額外之載劑包括聚合物賦形劑/添加劑，諸如聚乙烯吡咯啶酮、聚蔗糖(聚合糖)、葡聚糖(例如，環糊精(諸如2-羥基丙基-β-環糊精))、聚乙二醇、調味劑、抗菌劑、甜味劑、抗氧化劑、抗靜電劑、表面活性劑(例如，聚山梨酯(諸如「TWEEN 20」及「TWEEN 80」))、脂質(例如，磷脂、脂肪酸)、類固醇(例如，膽固醇)及螯合劑(例如，EDTA)。 本發明亦提供醫藥組合物及包含該等組合物之套組，其等含有至少一種如本文描述之化合物(例如，由式(I)表徵之化合物)及至少一種另一醫藥活性劑。此等醫藥組合物及套組可經調適以容許該化合物及另一活性劑之同時、接續及/或分別投與。例如，該化合物及另一活性劑可調配於不同劑型中，例如，調配於不同錠劑、膠囊、凍乾物或液體中，或其等可調配於相同劑型中，例如，調配於相同錠劑、膠囊、凍乾物或液體中。在該化合物及另一活性劑係調配於相同劑型中之情況下，該化合物及另一活性劑可大體上存在於混合物中，例如，於錠劑之核內，或其等可大體上存在於劑型之獨立區內，例如，存在於相同錠劑之不同層內。 本發明之另一態樣提供醫藥組合物，其包含：(i)如本文描述之化合物，例如，由式(I)表徵之化合物；(ii)另一活性劑；及(iii)醫藥上可接受之賦形劑。 本發明之另一態樣提供套組，其包含：(i)如本文描述之化合物，例如，由式(I)表徵之化合物；(ii)針對在治療中使用該化合物之使用說明，例如，用於如本文描述之方法中；及(iii)視需要另一活性劑。 在實施例中，該另一活性劑係抗增殖劑、抗炎劑、抗血管生成劑、化學治療劑或免疫治療劑。 醫藥組合物可經調配以便於提供其中之活性成分之緩慢、延長或控制之釋放，使用例如呈變化比例之羥丙基甲基纖維素以提供所需之釋放曲線，使用其他聚合物基質、脂質體及/或微球。該等醫藥組合物亦可視需要含有遮光劑且可為於胃腸道之某一部位中視需要以延遲之方式(例如藉由使用腸溶包衣)僅(或優先地)釋放該(等)活性成分之組合物。嵌入組合物之實例包括聚合物質及蠟。該活性成分亦可呈微囊封形式，視需要，與此項技術中熟知的一或多種醫藥上可接受之載劑、賦形劑或稀釋劑一起(參見，例如Remington’s)。本發明揭示之化合物可根據一般技術者熟知的方法加以調配以持續釋放。此等調配物之實例可參見美國專利案第3,119,742；3,492,397；3,538,214；4,060,598及4,173,626號。化學合成 下文顯示說明性合成方案(方案I)以用於製備由式(I)表徵之化合物，其中基團R4 及R5 均係氫：方案I 在方案I之步驟(i)中，化合物A (其可購買獲得或根據熟習此項技術者已知的一般合成方法製備)係經由親核芳族取代與經取代之胺反應以產生中間物B。在步驟(ii)中，甲氧基之去保護(例如，使用BBr3 )產生中間物C。在步驟(iii)中，攜載具有結合至其之離去基「LG」之碳原子之環基A (其可視需要經保護，例如，視需要經取代)參與親核取代或偶合反應以產生目標化合物D。 方案I可經改變以獲得如本文揭示之其他化合物。例如，在環基A於目標化合物D中係經烷基、烯基、炔基或(雜)芳基(即，R1 )取代之情況下，該目標化合物可在方案I之步驟(iii)中使用經取代之環基R1 -A-C(R4 R5 )-LG獲得。或者，該目標化合物可使用環基A-C(R4 R5 )-LG製備，其係經鹵化物或擬鹵化物(例如，三氟甲磺酸酯或烷氧基)於環上待經R1 取代之位置處取代。此產生相應之產物D’，其可然後(a)在鈴木反應中與有機硼物質(例如，R1 -B(OH)2 )偶合；(b)在根岸反應中與有機鋅物質(例如，(R1 )2 Zn)偶合；或(例如) (c)在薗頭反應中與炔烴偶合。經偶合之產物可視需要經進一步反應(例如，還原)以產生所需最終產物。此等步驟係闡述於下文方案II及III中：方案II 在方案II中，基團「Y」係鹵化物或擬鹵化物(例如，三氟甲磺酸酯或烷氧基)。在適用於鈴木、根岸或薗頭反應之條件下之偶合產生產物D，其中R1 係通常含有至少一個碳碳雙鍵或三鍵之基團。R1 基團中之不飽和鍵可經還原，例如，如方案III中闡述，其中化合物D係經催化氫化以產生相應之產物。方案III 藉助於另一實例，下文顯示說明性合成方案(方案IV)以用於製備式(I)苯并噻唑化合物，其等包含R2 基團(諸如-O(C1-4 -烷基)或鹵素)，使用-OMe作為示例性R2 基團闡述：方案IV 在方案IV中，烷氧基硝基苯衍生物E (其可獲得自商業來源或製備自(例如)相應之鹵化前驅物)係(例如)藉由在步驟(iv)中用還原劑(諸如阮內鎳(Raney-Ni)及肼)處理，接著在步驟(v)中環化(例如，使用KSCN及CuSO4 )轉化為相應之烷氧基胺基苯并噻唑衍生物F。化合物F可然後(例如)藉由用t-BuONO及CuBr2 處理轉化為溴苯并噻唑中間物G。使G與基團H2 N-L-R3 反應(例如，如方案I之步驟(i)中描述)產生化合物H，其可然後經去保護以產生相應之芳基醇I (例如，使用TFA)。產物J可藉由使I與含有「環A」之基團反應獲得，例如，如方案I之步驟(iii)中顯示。應瞭解「環A」加成可在添加基團NH2 -L-R3 之前進行，在該情況下反應(viii)及(ix)可在反應(vii)前進行。亦應瞭解中間物(諸如G)可於苯并噻唑環上經額外之R2 基團取代以便於產生相應之經取代之產物。藉助於實例，於乙腈中用selectfluor處理G可產生7-氟衍生物，其可然後通過反應方案以提供7-氟-4-甲氧基苯并噻唑產物。 藉助於又另一實例，下文顯示說明性合成方案(方案V)以用於製備式(I)苯并噻唑化合物，其等包含R2 基團(諸如-O(C1-4 -烷基)或鹵素)，使用-OMe作為示例性R2 基團闡述：方案V 在方案V中，含有「環A」之部分係在苯并噻唑環形成前引入。在步驟(x)中，含有「環A」之化合物K係與經取代之對硝基苯酚偶合，例如，使用Cs2 CO3 ，以形成中間物L。然後將此化合物還原至相應之苯胺M (例如，使用氫在Pt-C觸媒之存在下)，及進一步反應以形成經取代之硫脲化合物N (例如，藉由與二(1H-咪唑-1-基)甲硫酮反應及然後與NH2 -L-R3 反應)。化合物N係然後經環化以形成相應之苯并噻唑O (例如，使用BSTFA及三溴化苄基三甲基銨)。應瞭解產物O可經進一步處理，例如，於R1 處經取代或去保護，以產生其他式(I)化合物。通常在此等反應中，R4 及R5 中之一者或兩者係氫。亦應瞭解可使用除溴甲基衍生物外之K之鹵化衍生物，例如，氯甲基衍生物。 藉助於又另一實例，下文顯示說明性合成方案(方案VI)以用於製備式(I)苯并噻唑化合物，其等包含R2 基團，諸如-O(C1-4 -烷基)或鹵素，使用-OMe闡述為示例性R2 基團：方案VI 在方案VI中，使視需要經取代之鄰甲氧基苯胺前驅物P溴化(例如，使用於溶液中之Br2 )以產生化合物Q，然後將其轉化為相應之苯并噻唑化合物R及然後S (例如，如描述於方案IV之步驟(v)及(vi)中)。此中間物可然後與NH2 -L-R3 反應以產生化合物T (例如，如描述於方案I之步驟(i)中)。相應之硼酸鹽U之形成(例如，使用雙(頻哪醇)二硼與PCy3 及Pd2 (dba)3 )及接著水解(例如，使用過氧化氫)產生羥基苯并噻唑化合物V。產物O可藉由使V與含有「環A」之基團反應(例如，如方案I之步驟(iii)中顯示)獲得。 用於製備根據本發明之化合物之其他方法將為熟習此項技術者基於其等對本申請案之共同常識及內容(特定言之，下文之實例)而顯而易見。醫學適應症 本文描述之化合物及含有其之醫藥組合物係適用於治療中，特定言之適用於個體中經CSF-1R介導之失調症之治療性治療中。待根據本文描述之方法治療之個體包括脊椎動物(諸如哺乳動物)。在較佳實施例中，該哺乳動物係人類病患。 本發明提供用於治療個體中經CSF-1R介導之疾病之方法，該方法包括向該個體投與有效量之如本文定義之化合物，例如，由式(I)表徵之化合物。本發明亦提供如本文定義之化合物，例如，由式(I)表徵之化合物，其用於治療個體中經CSF-1R介導之疾病之方法中。本發明進一步提供如本文定義之化合物(例如，由式(I)表徵之化合物)於製造用於治療個體中經CSF-1R介導之疾病之方法之藥劑之用途。 CSF-1R及其配體已涉及許多疾病狀態，其等包括癌症；骨失調症(諸如骨質溶解)；炎性失調症(諸如類風濕性關節炎、動脈粥樣硬化及炎性腸疾病)；及神經失調症(諸如阿茲海默症(Alzheimer’s disease)、ALS及腦損傷)。 在實施例中，經CSF-1R介導之疾病係選自癌症、骨失調症、炎性失調症及神經失調症。 CSF-1R可以許多方法介導疾病之發展及/或進展，其等包括：異常傳訊、CSF-1R之過表現、CSF-1R 基因突變、其配體CSF-1及IL-34之過表現及/或通過其在巨噬細胞、小神經膠質細胞及破骨細胞之發展及進展中所發揮之作用。 在實施例中，經CSF-1R介導之疾病係由CSF-1R之過表現表徵。在實施例中，該經CSF-1R介導之疾病係由異常CSF-1R傳訊表徵。在實施例中，該經CSF-1R介導之疾病係由CSF-1及/或IL-34之過表現表徵。在實施例中，該經CSF-1R介導之疾病係由CSF-1R 基因中之突變表徵。 癌症 CSF-1R及其配體CSF-1之過表現發生於顯著數量之癌症類型中，例如於腱鞘巨細胞腫瘤、乳癌、卵巢癌、前列腺癌及子宮內膜癌中。CSF-1R及CSF-1之濃度係與腫瘤進展、細胞侵襲及預後不良相關。在非轉移性乳癌中，CSF-1R表現與下降之整體存活患者相關聯(Kluger等人，Clin. Cancer Res. (2004) 10(1,Pt.1):173-7)。CSF-1R於腫瘤基質細胞而非癌細胞本身中之高表現程度可為何傑金氏淋巴瘤中較低存活率之標誌(Koh等人，Am. J. Clin. Pathol. (2014) 141(4):573-83)。CSF-1之高表現程度亦據報導與各種癌症類型(包括乳癌、卵巢癌及前列腺癌)中之較高組織學腫瘤分級、轉移及預後不良相關聯(Lin等人，同上)。特定言之，CSF-1之高全身濃度係與晚期轉移性癌症相關聯，例如患有前列腺癌轉移至骨之男性及患有進展轉移性乳癌之女性。 巨噬細胞分化及增殖係取決於CSF-1R傳訊途徑，且募集向腫瘤環境係藉由包括CSF-1之趨化介素所驅動。一經募集至腫瘤微環境，腫瘤相關巨噬細胞(tumor associated macrophage；TAM)即釋放促血管生成因子、用以入侵之重要蛋白酶及涉及腫瘤細胞之生長及運動之其他生長因子。 TAM係與許多癌症相關聯，且高量TAM係與血管生成及惡性進展相關。特定言之，大量TAM已經識別為數種癌症類型(包括乳癌、前列腺癌、卵巢癌、子宮頸癌、胰臟癌及何傑金氏淋巴瘤)中之不良預後因素(Bingle等人，2002，同上；Pollard等人，Nat. Rev. Cancer. (2004) 4(1):71-78)。各種臨床前模型中TAM數量之減小已經證實為與延長之存活率相關。 CSF-1R傳訊之抑制據報導在各種癌症模型(諸如胃腸道間質瘤、乳癌、骨肉瘤、肺癌及前列腺癌之模型)中會減少血管生成、減少惡性細胞之生長、改善預後、預防或減少腫瘤進展及減小TAM之數量(Pyonteck等人，Nat. Med. (2013) 19(10):1264-1272；Strachan等人，2013，同上；Laoui等人，Front. Immunol. (2014) 5:a.489)。 因此，在一項實施例中，經CSF-1R介導之疾病係癌症。在實施例中，該癌症係與高量的腫瘤相關巨噬細胞(TAM)相關聯。在實施例中，該癌症係與CSF-1R及/或CSF-1之過表現相關聯。在實施例中，該癌症係與CSF-1R突變相關聯。用於評估TAM、CSF-1R、CSF-1及CSF-1R 突變之方法係如本文描述及/或為熟習此項技術者已知。 在一項實施例中，該癌症係選自乳癌、子宮頸癌、多形性神經膠質母細胞瘤(GBM)、肝細胞癌、何傑金氏淋巴瘤、黑色素瘤、胰臟癌、色素沈著絨毛結節性滑膜炎(PVNS)、前列腺癌、卵巢癌、腱鞘巨細胞腫瘤(TGCT)、子宮內膜癌、多發性骨髓瘤、粒細胞白血病、骨癌、腎癌、腦癌及骨髓增生性失調症(MPD)。 在實施例中，如本文揭示之化合物之投與可治療經診斷為患有癌症或處於發展癌症之風險下之個體。在實施例中，投與如本文揭示之化合物可改善預後、減少血管生成、減小腫瘤相關巨噬細胞(TAM)之數量、減少惡性細胞之生長及/或預防或減少腫瘤進展。 炎性疾病 CSF-1R之過表現與許多炎性失調症相關聯，例如，類風濕性關節炎、動脈粥樣硬化、克羅恩氏病、炎性腸疾病、類肉瘤病、腎小球性腎炎、同種異體移植排斥及動脈粥樣硬化。 巨噬細胞在慢性炎症中發揮關鍵作用，且此等細胞的數量增加係與疾病嚴重性相關。該等巨噬細胞係促炎細胞介素(諸如TNFα及IL-1b)之重要來源，其等可於不同細胞類型中誘發CSF-1表現。此有助於單核細胞募集、分化及增殖及進一步TNFα及IL-1b表現，其導致可有助於驅動慢性炎症之正反饋循環。 類風濕性關節炎係由巨噬細胞於結締組織及滑液中之聚集所引起之炎性自體免疫疾病。經CSF-1R/CSF-1介導之傳訊已表明有助於巨噬細胞增殖及滲透至滑膜組織內。CSF-1R之抑制可減少疾病進展、減少對骨及軟骨之破壞及減小存在於患有由膠原誘發之關節炎之病患之關節中之巨噬細胞之數量。 增加數量之腎巨噬細胞及高濃度之CSF-1係與由免疫介導之腎炎之數種形式(諸如狼瘡性腎炎)相關聯。減小之肌酐清除率係與高腎CSF-1濃度相關。在狼瘡性腎炎小鼠模型中，CSF-1R抗體減少於腎炎之位點處之巨噬細胞募集及增殖。 小神經膠質細胞在中樞神經系統內之免疫反應中發揮重要作用及被視為在調節與腦疾病相關聯之神經炎性反應中發揮作用。CSF-1R傳訊對小神經膠質細胞於成人腦中之增殖及存活而言係重要的，及CSF-1R敲除小鼠缺乏小神經膠質細胞。小神經膠質細胞之增殖及活化係數種神經炎性疾病之特點，其等包括實驗性自體免疫性腦脊髓炎(EAE)、HIV腦炎、神經退行性病症(諸如阿茲海默症及ALS)、中風及腦損傷。增加之小神經膠質細胞增殖與增加之CSF-1R上調相關及在一些情況下與疾病嚴重性相關。CSF-1據報導促進阿茲海默症及ALS中之炎症。在阿茲海默症之小鼠模型中，用CSF-1R抑制劑治療據報導可阻斷小神經膠質細胞增殖、耗盡小神經膠質細胞群體及促進抗炎型態之轉移(Luo等人，J. Exp. Med. (2013) 210(1):157-72；Dagher等人，J. Neuroinflammation (2015) 12:139；Olmos-Alonso等人，Brain (2016) 139(Pt.3):891-907)。 因此，在一項實施例中，經CSF-1R介導之疾病係炎性失調症。在實施例中，該炎性失調症係與高量之巨噬細胞或小神經膠質細胞相關聯。在實施例中，該炎性失調症係與高表現之CSF-1R及/或CSF-1相關聯。在實施例中，該炎性失調症係選自牛皮癬性關節炎、關節炎、氣喘、甲狀腺炎、腎絲球腎炎、動脈粥樣硬化、牛皮癬、休格倫氏症候群、類風濕性關節炎、全身性紅斑性狼瘡(SLE)、皮膚紅斑狼瘡、炎性腸疾病(包括克羅恩氏病及潰瘍性結腸炎(UC))、1型糖尿病、多發性硬化症及神經炎性病症(諸如HIV腦炎、阿茲海默症及ALS)。 骨疾病 破骨細胞係可再吸收骨之造血來源之多核細胞，及在數種骨骼疾病(包括骨質疏鬆症、炎性骨質溶解及骨質侵蝕)中發揮關鍵作用。破骨細胞數量之增加及破骨細胞-成骨細胞數量之失衡會導致異常高的骨再吸收速率。 CSF-1及CSF-1R在破骨細胞存活率及分化中發揮重要作用。據報導，在CSF-1中具有單點突變之小鼠具有經減小數量的破骨細胞及經發展之骨硬化症；同時移除破骨細胞培養物中的CSF-1會導致破骨細胞凋亡。骨質疏鬆症係一種骨疾病，其係因成骨細胞減損及具經增加之破骨細胞依賴性骨再吸收所造成的。據報導，用抗-CSF-1抗體治療骨質疏鬆症小鼠模型可保護骨密度及抑制骨再吸收(Sauter等人，J. Leukoc. Biol. (2014) 96(2):265–274)。佩吉特氏病係與增加之骨轉換相關聯之骨代謝失調症。突變已於許多基因(包括CSF-1 )中經識別，該等突變係與使個體易於患佩吉特氏病之破骨細胞功能之調節相關聯。CSF-1亦在齒根骨膜炎(一種與骨再吸收相關聯之牙齒炎性疾病)之發病機制中發揮潛在作用(Rabello等人，Biochem. Biophys. Comm. (2006) 3(1):791-796)。研究亦已顯示CSF-1R之抑制有助於骨保護。例如，使用CSF-1R之抑制劑之治療據報導抑制破骨細胞培養物、大鼠顱頂及大鼠胎長骨中之骨退化(Conway等人，Proc. Natl. Acad. Sci. USA (2005) 102(44):16078-16083)。 因此，在一項實施例中，經CSF-1R介導之疾病係選自骨質疏鬆症、骨關節炎、齒根骨膜炎、假體周圍骨質溶解及佩吉特氏病之骨失調症。 組合治療 在實施例中，如本文揭示之經CSF-1R介導之疾病之治療係藉由投與本發明之化合物與用於該經CSF-1R介導之疾病之另一治療干預之組合達成。其他治療干預可在投與本發明之化合物之前、期間及/或之後進行。 在實施例中，其他治療干預包括投與如本文揭示之醫藥藥劑，尤其抗增殖劑、抗炎劑、抗血管生成劑、化學治療劑或免疫治療劑。在實施例中，其他治療干預係過繼性t細胞轉移。在其他實施例中，其他治療干預係放射治療。投與及劑量 本發明揭示之化合物可調配為用於經口、經頰、非經腸(例如，靜脈內、腹膜內、肌內或皮下)、局部、直腸或鼻內投與或以適用於藉由吸入或吹入投與之形式之醫藥組合物。在一項實施例中，化合物或醫藥組合物係經調配以用於全身投與，例如，經由非經腸途徑。在另一實施例中，化合物或醫藥組合物係經調配以用於經口投與，例如，以固體形式。此等投與模式及用於製備適當之醫藥組合物之方法係描述(例如)於Gibaldi’s Drug Delivery Systems in Pharmaceutical Care (第1版，American Society of 15 Health-System Pharmacists 2007)中。 在用於經口投與之固體劑型(例如，膠囊、錠劑、藥丸、糖衣錠、粉末、顆粒及類似物)中，活性成分係與一或多種醫藥上可接受之載劑、賦形劑或稀釋劑(諸如檸檬酸鈉或磷酸二鈣)及/或下列中之任何一者混合：(1)填料或填充劑，諸如澱粉、乳糖、蔗糖、葡萄糖、甘露醇、微晶纖維素、磷酸鈣及/或矽酸；(2)黏合劑，諸如，例如，羧甲基纖維素、海藻酸鹽、明膠、預膠化玉米澱粉、聚乙烯吡咯啶酮、羥丙基甲基纖維素、蔗糖及/或阿拉伯膠；(3)濕潤劑，諸如甘油；(4)崩解劑，諸如瓊脂-瓊脂、碳酸鈣、羥乙酸澱粉鈉、馬鈴薯或木薯澱粉、海藻酸、某些矽酸鹽及碳酸鈉；(5)溶液阻滯劑，諸如石蠟；(6)吸收促進劑，諸如季銨化合物；(7)潤濕劑，諸如，例如，月桂硫酸鈉、乙醯乙醇及甘油單硬脂酸酯；(8)吸收劑，諸如高嶺土及膨潤土；(9)潤滑劑，諸如滑石、二氧化矽、硬脂酸鈣、硬脂酸鎂、固體聚乙二醇、月桂硫酸鈉及其混合物；及(10)著色劑。在膠囊、錠劑及藥丸之情況下，醫藥組合物亦可包含緩衝劑。相似類型之固體組合物亦可於經軟質及硬質填充之明膠膠囊中使用填料及賦形劑(諸如乳糖或牛奶糖)及高分子量聚乙二醇及類似物製備。 錠劑可視需要與一或多種輔助成分一起壓縮或模製製得。經壓縮之錠劑可使用黏合劑(例如，明膠或羥丙基甲基纖維素)、潤滑劑、惰性稀釋劑、防腐劑、崩解劑(例如，羥乙酸澱粉鈉或交聯羧甲基纖維素鈉)、表面活性劑及/或分散劑製備。模製錠劑可藉由在合適之機器中模製用惰性液體稀釋劑潤濕之粉狀活性成分之混合物製得。錠劑及其他固體劑型(諸如糖衣錠、膠囊、藥丸及顆粒)可視需要經刻痕或用包衣及外殼(諸如此項技術中熟知的腸溶包衣及其他包衣)製備。 在實施例中，醫藥組合物可以固體形式經口投與。活性成分之用於經口投與之液體劑型包括醫藥上可接受之乳劑、微乳劑、溶液、懸浮液、糖漿及酏劑。用於經口投與之液體製劑可呈現為在使用前以水或其他合適之載體構成之乾燥產品。除活性成分外，液體劑型可含有此項技術中常用之惰性稀釋劑，諸如，例如，水或其他溶劑、增溶劑及乳化劑，諸如乙醇、異丙醇、碳酸乙酯、乙酸乙酯、苄醇、苯甲酸苄酯、丙二醇、1,3-丁二醇、油(例如，棉籽油、花生油、玉米油、胚芽油、橄欖油、蓖麻油及芝麻油)、甘油、四氫呋喃醇、聚乙二醇及山梨糖醇之脂肪酸酯及其混合物。除惰性稀釋劑外，液體醫藥組合物可包括佐劑，諸如潤濕劑、乳化劑及懸浮劑、甜味劑、調味劑、著色劑、芳香劑及防腐劑及類似物。除活性成分外，懸浮液亦可含有懸浮劑，諸如(但不限於)乙氧基化異硬脂醇、聚氧乙烯山梨糖醇及脫水山梨醇酯、微晶纖維素、偏氫氧化鋁、膨潤土、瓊脂-瓊脂及黃蓍膠及其混合物。合適之液體製劑可使用醫藥上可接受之添加劑，諸如懸浮劑(例如，山梨糖醇糖漿、甲基纖維素或氫化食用脂肪)；乳化劑(例如，卵磷脂或阿拉伯膠)；非水性載體(例如，杏仁油、油性酯或乙醇)及/或防腐劑(例如，對羥基苯甲酸甲酯或丙酯或山梨酸)藉由習知方式製備。活性成分亦可作為推注、舐劑或糊劑投與。 就經頰投與而言，組合物可採取以習知方式調配之錠劑或口含錠之形式。 在實施例中，醫藥組合物係藉由非經口方式投與，諸如藉由局部施用、透皮施用、注射及類似方式。在相關實施例中，該等醫藥組合物係藉由注射、輸注或移植(例如，靜脈內、肌內、動脈內、皮下及類似方式)非經腸投與。 本發明揭示之化合物可經調配以用於藉由注射(包括使用習知導管插入術或輸注)非經腸投與。用於注射之調配物可以單位劑型呈現例如於安瓿或於多劑量容器中並添加防腐劑。組合物可採取諸如於油或水性載體中之懸浮液、溶液或乳液之形式，及可含有調配劑(諸如熟習此項技術者認可之懸浮液、穩定劑及/或分散劑)。或者，活性成分可以在使用前用合適之載體(例如，無菌無熱原水)重構之粉末形式。 醫藥組合物可以無菌注射劑之形式。該等醫藥組合物可藉由(例如)過濾保留細菌之過濾器或藉由以可在使用前立即溶解於無菌水或一些其他無菌可注射介質中之無菌固體組合物之形式併入滅菌劑加以殺菌。為製備此組合物，將活性成分溶解於或懸浮於非經腸可接受之液體載體中。示例性載體及溶劑包括(但不限於)水；藉由添加適當量之鹽酸、氫氧化鈉或合適之緩衝劑調整至合適pH之水；1,3-丁二醇；林格氏溶液及等滲氯化鈉溶液。該醫藥組合物亦可含有一或多種防腐劑(例如，對羥基苯甲酸甲酯、對羥基苯甲酸乙酯或對羥基苯甲酸正丙酯)。為改善溶解性，可添加溶解增強劑或增溶劑或溶劑可含有10至60% w/w之丙二醇或類似物。 醫藥組合物可含有一或多種醫藥上可接受之無菌等滲水溶液或非水溶液、分散液、懸浮液或乳液或無菌粉末，該等無菌粉末可僅在使用前重構為無菌可注射溶液或分散液。此等醫藥組合物可含有抗氧化劑；緩衝劑；抑菌劑；溶質(其使調配物與預期接受者之血液等滲)；懸浮劑；增稠劑；防腐劑及類似物。 合適之水性及非水性載劑(其等可用於本發明之醫藥組合物中)之實例包括水、乙醇、多元醇(諸如甘油、丙二醇、聚乙二醇及類似物)及其合適之混合物、植物油(諸如橄欖油)及可注射有機酯(諸如油酸乙酯)。適當之流動性可(例如)藉由使用包衣材料(諸如卵磷脂)；在分散液之情況下藉由維持所需粒度；及藉由使用表面活性劑維持。在一些實施例中，為延長活性成分之效應，需減慢化合物自皮下或肌內注射之吸收。此可藉由使用具有較差水溶性之結晶或非晶型材料之液體懸浮液達成。活性成分之吸收速率則取決於其分解速率，其進一步可取決於結晶大小及結晶形式。或者，非經腸投與之活性成分之延遲吸收係藉由將化合物溶解或懸浮於油載體中達成。另外，可注射醫藥形式之經延長之吸收可藉由內含延遲吸收之藥劑(諸如單硬脂酸鋁及明膠)實現。 控釋非經腸組合物可以水性懸浮液、微球、微膠囊、磁性微球、油溶液、油懸浮液、乳劑之形式，或活性成分可併入生物相容性載劑、脂質體、奈米顆粒、移植物或輸注裝置內。用於製備微球及/或微膠囊之材料包括(但不限於)生物可降解/生物可蝕解聚合物，諸如聚乳酸、聚(氰基丙烯酸異丁酯)、聚(2-羥乙基-L-麩醯胺酸)及聚(乳酸)。在調配控釋非經腸調配物時可使用之生物相容性載劑包括碳水化合物(諸如聚葡萄糖)、蛋白質(諸如白蛋白、脂蛋白或抗體)。用於移植物之材料可為非生物可降解(例如，聚二甲基矽氧烷)或生物可降解(諸如，例如聚(己內酯)、聚(乳酸)、聚(乙醇酸)或聚(原酸酯))。 就局部投與而言，本發明揭示之化合物可調配為軟膏或霜劑。本發明揭示之化合物亦可調配於直腸組合物中，諸如栓劑或保留灌腸劑，例如，含有習知栓劑基質(諸如可可油或其他甘油酯)。 就鼻內投與或藉由吸入之投與而言，本發明揭示之化合物可自泵噴霧容器以由病患擠壓或泵送之溶液或懸浮液之形式或自加壓容器或霧化器呈氣溶膠噴霧呈現及使用合適之推進劑(例如，二氯二氟甲烷、三氯氟甲烷、二氯四氟乙烷、二氧化碳或其他合適之氣體)而便利地遞送。在加壓氣溶膠之情況下，劑量單位可藉由提供閥門以遞送計量量測定。加壓容器或噴霧器可含有本發明揭示之化合物之溶液或懸浮液。用於吸入器或吹入器中之膠囊及含藥卡式管(例如，製得自明膠)可經調配以含有本發明揭示之化合物及合適之粉末基質(諸如乳糖或澱粉)之粉末混合物。 通常，本文描述之藥劑及組合物係以足以抑制接受該藥劑或組合物之個體中之CSF-1R之有效量或數量投與。通常，該劑量可基於(例如)年齡、身體狀況、體重、性別、飲食、投與時間及其他臨床因素進行調整。該有效量亦可取決於投與模式(例如，靜脈內注射相比於經口投與)及組合物之性質(例如，迅速分解相比於緩釋組合物)而變化。有效量之判定係在熟習此項技術者之能力內。通常，用於向個體投與之有效量係在約0.1至1000 mg/kg之範圍內。 在其他態樣中，本發明提供如本文描述用於治療中(例如，用於如本文定義之方法中)之劑型或醫藥組合物。 本文已進行一般描述，提供下列非限制性實例以進一步闡述本發明。 實例實例 1 至 49 ： 化學合成 實例1：(1R,2R)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇標題化合物係根據下列合成方案合成：步驟1： 在60℃下將2,3-二氯異菸鹼酸(960 mg, 5.00 mmol)及BH3 •THF (1.0 M, 25 mL, 25當量)之混合物加熱4小時。在冷卻至室溫後，添加MeOH (5 mL)，及在減壓下移除揮發物。反應混合物係用水(50 mL)稀釋及用DCM (50 mL x 3)萃取。經組合之有機相係用鹽水(100 mL)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈白色固體之(2,3-二氯吡啶-4-基)甲醇(400 mg, 45%)。MS (ES+) C6 H5 Cl2 NO要求值：178，實測值：179 [M+H]+ 。1 H NMR (500 MHz, d6 -DMSO) δ 8.38 (d, J = 5 Hz, 1H), 7.58 (d, J = 5 Hz, 1H), 5.85-5.75 (br s, 1 H), 4.61 (s, 2H)。 步驟2： 在150℃下將(2,3-二氯吡啶-4-基)甲醇(200 mg, 1.12 mmol)及(4-甲氧基苯基)甲胺(1.0 mL, 7.65 mmol, 6.8當量)之混合物加熱4小時。濃縮該反應混合物。殘餘物係藉由質量觸發之製備型HPLC (移動相：A = 0.1% TFA/H2 O，B = 0.1% TFA/MeCN；梯度：B = 10 - 90%；12 min；管柱：C18)純化以產生呈白色固體之(3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲醇(200 mg, 64%)。MS (ES+) C14 H15 ClN2 O2 要求值：278，實測值：279 [M+H]+ 。1 H NMR (500 MHz, d6 -DMSO) δ 7.93 (d, J = 5.5 Hz, 1H), 7.23 (d, J = 9 Hz, 2H), 6.85 (d, J = 9 Hz, 2H), 6.78 (d, J = 5.5 Hz, 1H), 4.53 (s, 2H), 4.50 (s, 2H), 3.70 (s, 3H)。 步驟3： 在室溫下將3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲醇(50 mg, 0.18 mmol)及SOCl2 (2.0 mL, 27 mmol)於DCM (2 mL)中之混合物攪拌2小時。在減壓下移除揮發物以產生呈黃色固體之3-氯-4-(氯甲基)-N-(4-甲氧基苄基)吡啶-2-胺(50 mg, 94%)。MS (ES+) C14 H14 Cl2 N2 O要求值：297，實測值：298 [M+H]+ 。1 H NMR (500 MHz, d6 -DMSO) δ 7.96 (d, J = 5.5 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 5.5 Hz, 1H), 4.76 (s, 2H), 4.60 (s, 2H), 3.71 (s, 3H)。 步驟4： 在110℃下將2-溴-6-甲氧基苯并[d]噻唑(3.00 g, 12.3 mmol)及(1R,2R)-2-胺基環己醇(4.25 g, 36.9 mmol)之混合物加熱6小時。使該反應冷卻至室溫，用水(30 mL)稀釋，及用EtOAc (3 × 30 mL)萃取。經組合之有機萃取物係於Na2 SO4 上乾燥及濃縮以產生呈棕色固體之(1R,2R)-2-((6-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇(3.5 g, 88%)。MS (ES+) C14 H18 N2 O2 S要求值：278，實測值：279 [M+H]+ 。1 H NMR (500 MHz, CDCl3 ) δ 7.37 (d, J = 11 Hz, 1H), 7.03 (d, J = 3.5 Hz, 1H), 6.84 (dd, J = 11, 3.5 Hz, 1H), 6.27 (bs, 1H), 3.78 (s, 3H), 3.4-3.35 (m, 2H), 2.12-2.01 (m, 2H), 1.70-1.65 (m, 2H), 1.38-1.16 (m, 4H)。 步驟5： 在0℃下向2-(6-甲氧基苯并[d]噻唑-2-基胺基)環己醇(3.00 g, 10.8 mmol)於DCM (30 mL)中之溶液中緩慢添加三溴化硼(5.4 g, 21 mmol)。在室溫下將所得混合物攪拌3小時。該反應混合物然後用冰水(20 mL)，接著用飽和NaHCO3 (10 mL)緩慢稀釋。所得沈澱係經過濾及收集以產生呈淺棕色固體之2-(((1R,2R)-2-羥基環己基)胺基)苯并[d]噻唑-6-醇(2.6 g, 90%)。MS (ES+) C13 H16 N2 O2 S要求值：264，實測值：265 [M+H]+ 。1 H NMR (500 MHz, d4 -MeOD) δ 7.12 (d, J = 9 Hz, 1H), 6.89 (d, J = 2 Hz, 1H), 6.62 (dd, J = 9, 2 Hz, 1H), 3.50-3.41 (m, 1H), 3.31-3.36 (m, 1H), 2.10-2.03 (m, 1H), 1.98-1.93 (m, 1H), 1.70-1.59 (m, 2H), 1.36-1.17 (m, 4H)。 步驟6： 在80℃下將3-氯-4-(氯甲基)-N-(4-甲氧基苄基)吡啶-2-胺(50 mg, 0.17 mmol)、2-((1R,2R)-2-羥基環己基胺基)苯并[d]噻唑-6-醇(45 mg, 0.17 mmol)及Cs2 CO3 (110 mg, 0.34 mmol)於DMF (2 mL)中之混合物攪拌3小時。在減壓下移除揮發物。殘餘物係藉由製備型HPLC (移動相：A = 0.1% TFA/H2 O，B = 0.1% TFA/MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之(1R,2R)-2-(6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇(30 mg, 34%)。MS (ES+) C27 H29 ClN4 O3 S要求值：524，實測值：525 [M+H]+ 。 步驟7： 在室溫下將(1R,2R)-2-(6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇(30 mg, 0.06 mmol)於TFA (2 mL)中之混合物攪拌8小時。在減壓下移除揮發物。殘餘物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之(1R,2R)-2-(6-((2-胺基-3-氯吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇(5 mg, 21%)。MS (ES+) C19 H21 ClN4 O2 S要求值：404，實測值：405 [M+H]+ 。1 H NMR (500 MHz, d6 -DMSO) δ 7.90 (d, J = 5.0 Hz, 1H), 7.72 (d, J = 7.5 Hz, 1H), 7.36 (d, J = 2.5 Hz, 1H), 7.26 (d, J = 8.5 Hz, 1H), 6.88 (dd, J = 8.5, 2.5 Hz, 1H), 6.72 (d, J = 5.0 Hz, 1H), 6.31 (s, 2H), 5.07 (s, 2H), 4.73 (d, J = 5.5 Hz, 1H), 3.52~3.48 (m, 1H), 3.36~3.31 (m, 1H), 2.06~2.04 (m, 1H), 1.89~1.86 (m, 1H), 1.64 – 1.60 (m, 2H), 1.29 – 1.17 (m, 4H)。 表1中之下列實例係類似於實例1製備。 表1： 實例 50 至 86 ： 化學合成 實例50：(1R,2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇之合成標題化合物係根據下列合成方案合成：步驟1： 在0℃下向苯基甲醇(41.0 g, 380 mmol)於DMF (500 ml)中之溶液添加NaH (9.60 g, 399 mmol)。將該反應混合物攪拌0.5小時，然後添加4-氟-2-甲氧基-1-硝基苯(50.0 g, 292 mmol)。在室溫下將該混合物攪拌1小時。該反應係用水(500 mL)中止，過濾及在減壓下濃縮以產生呈黃色固體之4-(苄氧基)-2-甲氧基-1-硝基苯(75 g, 99%)。LC-MS (ES+) C14 H13 NO4 要求值：259，實測值：260 (M+H)+ 。 步驟2： 在0℃下向4-(苄氧基)-2-甲氧基-1-硝基苯(75.0 g, 290 mmol)於MeOH (800 mL)中之溶液添加阮內鎳(3.0 g)，接著滴加N2 H4 .H2 O (44.0 g, 870 mmol)。在室溫下將該混合物攪拌整夜。該反應混合物係由飽和NH4 OH (200ml)中止及用EtOAc (100 mL x 2)萃取。有機層係經乾燥，過濾及在減壓下濃縮以產生呈黃色液體之4-(苄氧基)-2-甲氧基苯胺(56 g, 84 %)。LC-MS (ES+) C14 H15 NO2 要求值：229，實測值：230 (M+H)+ 。 步驟3： 向於4-(苄氧基)-2-甲氧基苯胺(28.0 g, 0.122 mol)於甲醇(600ml)中之溶液添加KSCN (59.3g, 0.611 mol)，接著添加無水CuSO4 (195g, 1.22 mol)。在90℃下將該混合物攪拌整夜及在減壓下濃縮。將殘餘物溶解於DCM (500ml)中，過濾沈澱及濾餅係用二氯甲烷(100 mL x 2)清洗。經組合之有機層係用飽和NH4 OH (500 mL)清洗。水層係用二氯甲烷萃取。在減壓下濃縮經組合之有機層。殘餘物係藉由矽膠矽膠層析術(50%至100% EtOAc於石油醚中)純化以產生呈黑色固體之6-(苄氧基)-4-甲氧基苯并[d]噻唑-2-胺(13 g, 37%)。LC-MS (ES+) C15 H14 N2 O2 S要求值：286，實測值：287 (M+H)+ 。 步驟4： 在0℃下向6-(苄氧基)-4-甲氧基苯并[d]噻唑-2-胺(22.0 g, 0.077 mol)於乙腈(100 mL)中之懸浮液添加t-BuONO (11.8 g, 0.110 mol)。將該混合物攪拌30分鐘，然後添加CuBr2 (10.3 g, 0.046 mol)。在室溫下將該反應再攪拌2小時。添加水，過濾沈澱及用EtOAc萃取濾液。經組合之有機層係用水、稀飽和NH4 OH、鹽水清洗及在減壓下濃縮。殘餘物係藉由矽膠層析術(10% EtOAc於石油醚中)純化以產生呈灰白色固體之6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(8.0 g, 30%)。LC-MS (ES+) C15 H12 BrNO2 S要求值：349，實測值：350 (M+H)+ 。 步驟5： 在110℃下將6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(3.50 g, 10.0 mmol)、(1R, 2R)-2-胺基環己醇(3.45 g, 30.0 mmol)及DIPEA (5.16 g, 40.0 mmol)於DMF (10 mmol)中之混合物加熱48小時。將該反應冷卻至室溫，用水(30 mL)稀釋，及用EtOAc (3 × 30 mL)萃取。經組合之有機萃取物係由水(100 ml)、鹽水(100 ml)清洗，於Na2 SO4 上乾燥及經濃縮以產生呈棕色固體之(1R,2R)-2-(6-(苄氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(3.8 g, 100%，粗)。MS (ES+) C21 H24 N2 O3 S要求值：384，實測值：385 [M+H]+ 。 步驟6： 在65℃下將(1R,2R)-2-(6-(苄氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(1152 mg, 3.0 mmol)於TFA (10 mL)中之溶液加熱48小時。移除溶劑，反應混合物係由飽和NaHCO3 緩慢稀釋及用EtOAc (3 × 50 mL)萃取。經組合之有機萃取物係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥及濃縮以產生呈棕色固體之2-((1R,2R)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(882 mg, 100%，粗)。MS (ES+) C14 H18 N2 O3 S要求值：294，實測值：295 [M+H]+ 。 步驟7： 在80℃下將3-氯-4-(氯甲基)-N-(4-甲氧基苄基)吡啶-2-胺(實例1，步驟3；202 mg, 0.68 mmol)、2-((1R,2R)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(200 mg, 0.68 mmol)及Cs2 CO3 (443 mg, 1.36 mmol)於DMF (2 mL)中之混合物攪拌3小時。該混合物係由水(30 ml)稀釋及用EtOAc (3 × 30 mL)萃取。經組合之有機相係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥及濃縮以產生呈棕色固體之(1R,2R)-2-(6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(300 mg, 79%，粗)。MS (ES+) C28 H31 ClN4 O4 S要求值：554，實測值：555 [M+H]+ 。 步驟8： 在室溫下將(1R,2R)-2-(6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(300 mg, 0.54 mmol)於TFA (2 mL)中之混合物攪拌8小時。在減壓下移除揮發物。殘餘物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之(1R,2R)-2-(6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(19 mg, 8%)。MS (ES+) C20 H23 ClN4 O3 S要求值：434，實測值：435 [M+H]+ 。1 H NMR (500 MHz, DMSO) δ 8.50 (s, 1H), 7.95 (d, J = 5.4 Hz, 1H), 7.04 (s, 1H), 6.85 (d, J = 5.5 Hz, 1H), 6.69 (s, 1H), 5.14 (s, 2H), 3.88 (s, 3H), 3.60 (d, J = 11.0 Hz, 1H), 3.32 (dd, J = 17.5, 11.8 Hz, 1H), 2.01 (d, J = 13.0 Hz, 1H), 1.89 (d, J = 8.9 Hz, 1H), 1.70 – 1.56 (m, 2H), 1.42 – 0.92 (m, 4H)。 表2中之下列實例係類似於實例50製備。 表2： 實例54：(1S,2S)-2-((6-((2-胺基-3-氟吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇標題化合物係根據下列合成方案合成：步驟1： 在0℃下向2-氯-3-氟異菸鹼酸(5.0 g, 28 mmol)及4-甲基嗎啉(3.8 mL, 7.0 mmol)於無水THF (150 mL)中之溶液中滴加氯甲酸異丁酯(4.5 mL, 34 mmol)及攪拌1小時。反應混合物係用THF (50 mL)稀釋及濾過矽藻土。將濾液冷卻至0℃，添加NaBH4 (1.0 g, 28 mmol)，及將所得混合物攪拌30分鐘。反應混合物係用10 % KHSO4 (5 mL)中止。在減壓下移除揮發物及反應混合物係用EtOAc (200 mL)稀釋。分離各層及有機層係用水(50 mL)，接著用飽和NaHCO3 (2 x 50 mL)清洗，於MgSO4 上乾燥，過濾及在減壓下濃縮。殘餘物係用5:1己烷-醚(50 mL)研磨。所得固體係經過濾及收集以產生(2-氯-3-氟吡啶-4-基)甲醇(3.7 g, 80%)。MS (ES+) C6 H5 ClFNO要求值：161，實測值：162 [M+H]+ 。 步驟2： 向(2-氯-3-氟吡啶-4-基)甲醇(1.0 g, 6.2 mmol)於DCM (25 mL)中之溶液中滴加三溴化磷(0.70 mL, 7.4 mmol)及在0℃下將所得混合物攪拌2小時，然後在室溫下攪拌整夜。反應混合物係用DCM (20 mL)稀釋及用10% NaHCO3 (5 mL)清洗。分離各層，及有機層係用鹽水(5 mL)清洗，於MgSO4 上乾燥，過濾及在減壓下濃縮以產生呈淡黃色固體之4-(溴甲基)-2-氯-3-氟吡啶(1.1 g, 79%)。MS (ES+) C6 H4 BrClFN要求值：223，實測值：224, 226 [M+H]+ 。 步驟3： 向3-甲氧基-4-硝基苯酚(0.750 g, 4.46 mmol)及4-(溴甲基)-2-氯-3-氟吡啶(1.0 g, 4.4 mmol)於1:1 DMF/THF (10 mL)中之溶液添加Cs2 CO3 (2.2 g, 6.7 mmol)及在室溫下將所得混合物攪拌20小時。向該反應混合物添加冰冷水(20 mL)，攪拌10分鐘，及於布氏漏斗上過濾。固體係用冷水(10 mL)清洗及在真空下乾燥2小時以提供呈灰白色固體之2-氯-3-氟-4-((3-甲氧基-4-硝基苯氧基)甲基)吡啶(1.34 g, 96%)。MS (ES+) C13 H10 ClFN2 O4 要求值：312，實測值：313 [M+H]+ 。 步驟4： 在反應容器中裝入2-氯-3-氟-4-((3-甲氧基-4-硝基苯氧基)甲基)吡啶(1.3 g, 15 mmol)、10% Pt-C (130 mg)及5:1 THF/MeOH (24 mL)。懸浮液係經N2 脫氣1分鐘及用H2 淨化1分鐘。在H2 之氣氛下在20 PSI下將反應混合物攪拌1小時。該反應混合物係用N2 淨化，濾過矽藻土，及在減壓下濃縮以產生呈淡黃色粉末之4-((2-氯-3-氟吡啶-4-基)甲氧基)-2-甲氧基苯胺(1.1 g, 94%)。MS (ES+) C13 H12 ClFN2 O2 要求值：282，實測值：283 [M+H]+ 。 步驟5： 向4-((2-氯-3-氟吡啶-4-基)甲氧基)-2-甲氧基苯胺(1.1 g, 3.9 mmol)於DCM (60 mL)中之溶液添加二(1H-咪唑-1-基)甲硫酮(0.97 g, 5.5 mmol)及在室溫下將所得混合物攪拌3小時。向此溶液添加(1S,2S)-2-胺基環己醇(0.9 g, 7.8 mmol)及在室溫下將所得混合物攪拌3小時。在減壓下移除揮發物。殘餘物係經由矽膠層析術(20至80% EtOAc於己烷中)純化以產生呈灰白色粉末之1-(4-((2-氯-3-氟吡啶-4-基)甲氧基)-2-甲氧基苯基)-3-((1S,2S)-2-羥基環己基)硫脲(1.59 g, 93%)。MS (ES+) C20 H23 ClFN3 O3 S要求值：439，實測值：440 [M+H]+ 。 步驟6： 向1-(4-((2-氯-3-氟吡啶-4-基)甲氧基)-2-甲氧基苯基)-3-((1S,2S)-2-羥基環己基)硫脲(0.90 g, 2.1 mmol)於DCM (80 mL)中之溶液添加BSTFA (1.1 mL, 4.1 mmol)及攪拌10分鐘。然後添加固體三溴化苄基三甲基銨(0.80 g, 2.1 mmol)。10分鐘後，將飽和NaHCO3 (30 mL)添加至反應混合物內及攪拌5分鐘。反應混合物係用DCM (20 mL)稀釋及分離各層。有機層係用飽和NaHCO3 (30 mL)，接著用10% Na2 S2 O3 水溶液(20 mL)清洗，於MgSO4 上乾燥，過濾及在減壓下濃縮。殘餘物係用1:2醚/己烷(30 mL)研磨及所得固體係通過布氏漏斗過濾，用1:1醚/己烷(10 mL)沖洗，在真空下乾燥。將(1S,2S)-2-((6-((2-氯-3-氟吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己醇分離為灰白色粉末(810 mg, 90%)。MS (ES+) C19 H21 ClN4 O3 S要求值：437，實測值：438 [M+H]+ 。 步驟7： 乙醯胺(0.221 g, 3.73 mmol)、(1S,2S)-2-((6-((2-氯-3-氟吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己醇(1.09 g, 2.49 mmol)及Cs2 CO3 (1.62 g, 4.98 mmol)於二噁烷(12 mL)中之懸浮液係用N2 脫氣2分鐘。添加Pd2 (dba)3 (0.057 g, 0.062 mmol)及Xantphos (0.072 g, 0.12 mmol)及該混合物係再用N2 脫氣2分鐘。將該反應混合物加熱至100℃及攪拌5小時。該反應混合物係用DCM (20 mL)稀釋及用水(20 mL)清洗。分離各層，及水層係用DCM (2 x 10 mL)萃取，於MgSO4 上乾燥，過濾及在減壓下濃縮。殘餘物係經由矽膠層析術(0至100 % EtOAc於己烷中w/ 10% MeOH)純化以產生呈淺棕色泡沫固體之N-(3-氟-4-(((2-(((1S,2S)-2-羥基環己基)胺基)-4-甲氧基苯并[d]噻唑-6-基)氧基)甲基)吡啶-2-基)乙醯胺(320 mg, 28%)。MS (ES+) C22 H25 FN4 O4 S要求值：460，實測值：461 [M+H]+ 。 步驟8： 向N-(3-氟-4-(((2-(((1S,2S)-2-羥基環己基)胺基)-4-甲氧基苯并[d]噻唑-6-基)氧基)甲基)吡啶-2-基)乙醯胺(68 mg, 0.15 mmol)於MeOH (0.74 mL)中之溶液添加於二噁烷中之HCl (185 µl, 0.738 mmol, 4M)及在60℃下將所得混合物攪拌2小時。濃縮該反應混合物。殘餘物係用Et2 O (2 x 2 mL)研磨，小心移除濾液，及在真空下乾燥固體以提供呈灰白色蓬鬆固體之(1S,2S)-2-((6-((2-胺基-3-氟吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇(65 mg, 97%, HCl 鹽)。MS (ES+) C20 H23 FN4 O3 S要求值：418，實測值：419 [M+H]+ ；1 H NMR (600 MHz, DMSO-d6 ) δ 9.36 (br s, 1H), 8.00 (br s, 2H), 7.84 (d, J = 6.2 Hz, 1H), 7.13 (d, J = 2.3 Hz, 1H), 6.91 (t, J = 5.7 Hz, 1H), 6.79 (s, 1H), 5.26 (s, 2H), 3.92 (s, 3H), 3.76 – 3.67 (m, 1H), 3.37 – 3.31 (m, 1H), 2.02 – 1.95 (m, 1H), 1.95 – 1.86 (m, 1H), 1.68 – 1.64 (m, 2H), 1.33 – 1.20 (m, 4H)。 實例55：(1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：將(1S,2S)-2-((6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己醇(實例66，步驟5) (4.0 g, 9.5 mmol)、1-甲基-1H-吡唑-4-胺(1.84 g, 19 mmol)、DIPEA (2.45 g, 19 mmol)於DMA (30 mL)中之混合物加熱至120℃，歷時10小時。將水(100 ml)添加至該混合物內及其係用EtOAc (100 mL × 3)萃取。經組合之EtOAc相係用鹽水清洗，於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係經由矽膠層析術(0至10% MeOH於DCM中)純化以產生呈棕色油之粗產物(2.45 g)。然後該粗產物係藉由逆相HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 0 - 100%；20 min；管柱：C18)純化以產生呈棕色固體之(1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇(1.4 mg, 31%)。MS (ES+) C23 H27 N7 O3 S要求值：481，實測值：482 [M+H]+ 。1 H NMR (500 MHz, MeOD) δ 8.37 (d, J = 5 Hz, 1H),7.94 (s, 1H),7.56 (s, 1 H), 6.86-6.91 (m, 2 H), 6.64 (d, J = 2 Hz, 1H), 5.08 (s, 2H), 3.93 (s, 3H), 3.85 (s, 3H), 3.57-3.62 (m, 1H), 3.39-3.43 (m, 1H), 2.14-2.16 (m, 1H), 2.03-2.05 (m, 1H), 1.72-1.79(m, 2H), 1.24-1.43 (m, 4H)。 表3中之下列實例係類似於實例55製備。 表3： 實例61及62：6-((2-胺基嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺標題化合物係根據下列合成方案合成：步驟1： 在65℃下將6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(實例50，步驟4) (700 mg, 1.80 mmol)於TFA (10 mL)中之混合物攪拌16小時。該反應混合物係經濃縮，藉由飽和NaHCO3 (50 ml)稀釋及用EtOAc (50 ml × 3)萃取。經組合之有機層係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黃色固體之2-溴-4-甲氧基苯并[d]噻唑-6-醇(520 mg, 100%)。MS (ES+) C8 H6 BrNO2 S要求值：259, 261，實測值：262[M+H]+。 步驟2： 向2-溴-4-甲氧基苯并[d]噻唑-6-醇(520 mg, 2.00 mmol)及甲磺酸(2-胺基嘧啶-4-基)甲酯(406 mg, 2.00 mmol)之溶液添加於DMF (10 mL)中之Cs2 CO3 (1.9 g, 6.0 mmol)。在室溫下將反應混合物攪拌2小時。該反應混合物係用水(50 ml)稀釋及用EtOAc (50 ml × 3)萃取。經組合之有機層係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黃色固體之4-((2-溴-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)嘧啶-2-胺(400 mg, 54%)。MS (ES+) C13 H11 BrN4 O2 S要求值：366，實測值：367[M+H]+ 。 步驟3： 向4-((2-溴-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)嘧啶-2-胺(367 mg, 1.00 mmol)及3,3-二氟環己胺鹽酸鹽(516 mg, 3.00 mmol)之溶液添加於DMF (5 mL)中之DIPEA (774 mg, 6.00 mmol)。在140℃下將反應混合物攪拌16小時。該反應混合物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之6-((2-胺基嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(48 mg, 11%)。MS (ES+) C19 H21 F2 N5 O2 S要求值：421，實測值：422[M+H]+ 。 最終產物係藉由對掌性層析術[移動相：EtOH (1%甲醇氨)管柱：纖維素-SC 4.6 × 100 mm 5 μm]分離以產生兩種異構物。呈白色固體之異構物1 (化合物60) (5.9 mg)。MS (ES+) C19 H21 F2 N5 O2 S要求值：421，實測值：422[M+H]+；1 H NMR (500 MHz, MeOD) δ 8.25 (d, J = 5.1 Hz, 1H), 6.83 (dd, J = 6.2, 3.7 Hz, 2H), 6.62 (d, J = 2.2 Hz, 1H), 4.96 (s, 2H), 4.10 – 3.98 (m, 1H), 3.97 – 3.88 (m, 3H), 2.51 – 2.39 (m, 1H), 2.20 – 2.11 (m, 1H), 2.09 – 1.99 (m, 1H), 1.75 (ddd, J = 37.7, 24.5, 11.3 Hz, 3H), 1.38 – 1.24 (m, 2H)；呈白色固體之異構物2 (化合物61) (6.8 mg)。MS (ES+) C19 H21 F2 N5 O2 S要求值：421，實測值：422[M+H]+；1 H NMR (500 MHz, MeOD) δ 8.25 (d, J = 5.1 Hz, 1H), 6.83 (dd, J = 6.2, 3.7 Hz, 2H), 6.62 (d, J = 2.3 Hz, 1H), 4.96 (s, 2H), 4.09 – 3.97 (m, 1H), 3.95 – 3.89 (m, 3H), 2.46 (dd, J = 19.1, 10.9 Hz, 1H), 2.15 (dd, J = 10.9, 7.5 Hz, 1H), 2.05 (dd, J = 21.9, 11.1 Hz, 1H), 1.85。 表4中之下列實例係類似於實例61及62製備。 表4： 實例64：N-(3,3-二氟環己基)-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-胺標題化合物係根據下列合成方案合成：步驟1： 將6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(實例50，步驟4) (300 mg, 0.86 mmol)、3,3-二氟環己胺鹽酸鹽(296 mg, 1.72 mmol)及DIPEA (222 mg, 1.72 mmol)於NMP (1 ml)中之混合物加熱至180℃，歷時4小時。添加飽和NH4 Cl溶液(100 ml)，及該混合物係用EtOAc (50 mL × 3)萃取。經組合之有機相係用鹽水清洗，於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(50% EtOAc於石油醚中)純化以產生呈黃色固體之6-(苄氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(130 mg, 37%)。MS (ESI+) C21 H22 F2 N2 O2 S要求值：404，實測值：405[M+H]+ 。 步驟2： 在55℃下將6-(苄氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(130 mg, 0.32 mmol)於TFA (3 ml)中之混合物攪拌2小時。蒸發TFA及將殘餘物溶解於EtOAc (100 mL)中。有機層係用飽和NaHCO3 清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黃色油之2-(3,3-二氟環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(90 mg, 89%)。MS (ESI+) C14 H16 F2 N2 O2 S要求值：314，實測值：315 [M+H]+ 。 步驟3： 在80℃下將2-(3,3-二氟環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(90 mg, 0.29 mmol)、2-氯-4-(氯甲基)嘧啶(57 mg, 0.35 mmol)及Cs2 CO3 (189 mg, 0.58 mmol)於DMF (5 ml)中之混合物攪拌3小時。在減壓下移除揮發物。殘餘物係藉由矽膠層析術(10% EtOAc於石油醚中)純化以產生呈黃色固體之6-((2-氯嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(60 mg, 43%)。MS (ESI+) C19 H19 ClF2 N4 O2 S要求值：440，實測值：441 [M+H]+ 。 步驟4： 在110℃下將6-((2-氯嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(60 mg, 0.14 mmol)、1-甲基-1H-吡唑-4-胺(23 mg, 0.17 mmol)及TsOH.H2 O (12 mg, 0.07 mmol)於二噁烷(2 ml)中之混合物攪拌16小時。該混合物係用EtOAc稀釋，用飽和NaHCO3 清洗，及於Na2 SO4 上乾燥。濃縮經組合之有機層及殘餘物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之N-(3,3-二氟環己基)-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-胺(3 mg, 5%)。MS (ES+) C22 H25 N7 O3 S要求值：501，實測值：502 [M+H]+ 。1 H NMR (500 MHz, d6-DMSO) δ 9.51 (s, 1H), 8.40 (d, J = 5 Hz, 1H), 7.78 - 7.88 (m, 2H),7.46 (s, 1 H), 6.98 (s, 1 H), 6.81 (d, J = 5 Hz, 1H), 6.61 (d, J = 2 Hz, 1H), 5.04 (s, 2H), 3.89 (s, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 3.26 (s, 1H), 1.97 - 2.01 (m, 2H), 1.72 - 1.84 (m, 3H), 1.43 - 1.50 (m, 1H), 1.21 - 1.33 (m, 1H)。 實例65：(1S,2S)-2-(6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-氟苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：步驟1： 向2-氟-4-甲氧基苯胺(3.0 g, 21 mmol)於HOAc (50 mL)中之溶液添加KSCN (8.2 g, 85 mmol)。將反應混合物冷卻至0℃及滴加Br2 (4.6 g, 25 mmol)。在室溫下將該反應混合物攪拌4小時。用飽和NH4 OH將該反應混合物之pH調整至pH = 7。該混合物係用EtOAc (3 × 80 mL)萃取，經組合之有機層係於Na2 SO4 上乾燥及在減壓下濃縮。殘餘物係藉由矽膠層析術(30% EtOAc於PE中)純化以產生4-氟-6-甲氧基苯并[d]噻唑-2-胺(2.1 g, 50%)。MS (ES+) C8 H7 FN2 OS要求值：198，實測值：199 [M+H]+ 。 步驟2： 將4-氟-6-甲氧基苯并[d]噻唑-2-胺(1.3 g, 5.8 mmol)於MeCN (40 mL)中之溶液冷卻至-5℃。緩慢滴加CuBr2 (1.3 g, 5.8 mmol)及t BuONO (0.67 mg, 5.80 mmol)。在0至5℃下將該反應攪拌30分鐘。將反應混合物加熱至40℃及攪拌6小時。過濾該反應混合物。濾液係用1 N HCl溶液清洗，於Na2 SO4 上乾燥，過濾及在減壓下濃縮以產生2-溴-4-氟-6-甲氧基苯并[d]噻唑(1.2 g, 70%)。MS (ESI+) C8 H5 BrFNOS要求值：261，實測值：262 [M+H]+ 。 步驟3： 將2-溴-4-氟-6-甲氧基苯并[d]噻唑(300 mg, 1.15 mmol)、(1S,2S)-2-胺基環己醇(297 mg, 2.30 mmol)及DIPEA (397 mg, 3.45 mmol)於DMA (10 ml)中之混合物加熱至100℃，歷時整夜。添加飽和NH4 Cl溶液(80 ml)，該混合物係用EtOAc (3 x 10 mL)萃取。經組合之有機層係於Na2 SO4 上乾燥，過濾及在減壓下濃縮。殘餘物係藉由矽膠層析術(30% EtOAc於PE中)純化以產生呈棕色固體之(1S,2S)-2-(4-氟-6-甲氧基苯并[d]噻唑-2-基胺基)環己醇(236 mg, 43%)。MS (ESI+) C14 H17 FN2 O2 S要求值：296，實測值：297 [M+H]+ 。 步驟4： 將(1S,2S)-2-(4-氟-6-甲氧基苯并[d]噻唑-2-基胺基)環己醇(490 mg, 1.64 mmol)於DCM (10 ml)中之溶液冷卻至0℃及添加BBr3 (4 ml, 17%)，在室溫下將所得溶液攪拌整夜。添加飽和NH4 Cl溶液，過濾懸浮液，及收集固體以提供4-氟-2-((1S,2S)-2-羥基環己基胺基)苯并[d]噻唑-6-醇(360 mg, 77%)。MS (ESI+) C13 H15 FN2 O2 S要求值：282，實測值：283 [M+H]+ 。 步驟5： 在80℃下將4-氟-2-((1S,2S)-2-羥基環己基胺基)苯并[d]噻唑-6-醇(80 mg, 0.28 mmol)、3-氯-4-(氯甲基)-N-(4-甲氧基苄基)吡啶-2-胺(實例1，步驟3；116 mg, 0.34 mmol)及Cs2 CO3 (183 mg, 0.56 mmol)於DMF (5 ml)中之混合物攪拌整夜。在減壓下移除揮發物及殘餘物係藉由矽膠層析術(50% EtOAc於石油醚中)純化以產生呈黃色固體之(1S,2S)-2-(6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-4-氟苯并[d]噻唑-2-基胺基)環己醇(82 mg, 54%)。MS (ESI+) C27 H28 ClFN4 O3 S要求值：542，實測值：543 [M+H]+ 。 步驟6： 在室溫下將(1S,2S)-2-(6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-4-氟苯并[d]噻唑-2-基胺基)環己醇(82 mg, 0.15 mmol)於TFA (3 mL)中之混合物攪拌整夜。在減壓下移除揮發物。殘餘物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之(1S,2S)-2-(6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-氟苯并[d]噻唑-2-基胺基)環己醇(19.4 mg, 31%)。MS (ES+) C19 H20 ClFN4 O2 S要求值：422，實測值：423 [M+H]+ 。1 H NMR (500 MHz, d6-DMSO) δ 7.9-7.95(m, 2H),7.24 (d, J = 2.5 Hz, 1H), 6.84-6.87 (m, 1H), 6.71 (d, J = 5 Hz, 1H), 6.34 (s, 2H), 5.08(s, 2H), 4.75 (d, J = 5 Hz, 1H), 3.49-3.52 (m, 1H), 2.03-2.07 (m, 1H), 1.86-1.89 (m, 1H), 1.61-1.65 (m, 2H), 1.17-1.30 (m, 4H)。 實例66：(1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇標題化合物係根據下列合成方案合成：步驟1： 向2-氯-4-甲基嘧啶(5.0 g, 39 mmol)於CCl4 (100 ml)中之溶液添加NCS (7.8 g, 58 mmol)及AIBN (0.64 g, 3.9 mmol)及在回流下將所得混合物加熱18小時。容許將反應混合物冷卻至室溫。使該反應混合物濾過矽藻土墊，及在減壓下濃縮濾液。殘餘物係經由矽膠層析術(10至40% EtOAc於己烷中)純化以產生呈澄清油之2-氯-4-(氯甲基)嘧啶(3.1 g, 49%)。MS (ES+) C5 H4 Cl2 N2 要求值：162，實測值：163 [M+H]+ 。 步驟2： 向3-甲氧基-4-硝基苯酚(2.83 g, 16.7 mmol)及2-氯-4-(氯甲基)嘧啶(3.0 g, 18 mmol)於DMF (16 ml)中之溶液添加K2 CO3 (2.8 g, 20 mmol)及在室溫下將所得混合物攪拌20小時。添加冰冷水(30 ml)及將該混合物攪拌10分鐘後，於布氏漏斗上過濾。固體係用冷水(10 mL)清洗及在真空下乾燥2小時以產生呈淡棕色固體之2-氯-4-((3-甲氧基-4-硝基苯氧基)甲基)嘧啶(4.6 g, 93%)。MS (ES+) C12 H10 ClN3 O4 要求值：295，實測值：296 [M+H]+ 。 步驟3： 在反應容器中裝入2-氯-4-((3-甲氧基-4-硝基苯氧基)甲基)嘧啶(4.6 g, 15.6 mmol)、10% Pt-C (460 mg, 0.12 mmol)及THF-MeOH (5:1, 60 ml)。懸浮液係經N2 脫氣3分鐘及經H2 淨化3分鐘。在H2 之氣氛下在1 atm下將反應混合物攪拌2小時。該反應混合物係用N2 淨化，濾過矽藻土，及在減壓下濃縮以產生呈淡黃色粉末之4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯胺(4.0 g, 97%)。MS (ES+) C12 H12 ClN3 O2 要求值：265，實測值：266 [M+H]+ 。 步驟4： 向4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯胺(4.0 g, 15 mmol)於DCM (200 ml)中之溶液添加二(1H-咪唑-1-基)甲硫酮(3.2 g, 18 mmol)及在室溫下將所得混合物攪拌4小時。添加(1S,2S)-2-胺基環己醇(3.5 g, 30 mmol)及在室溫下將所得混合物攪拌3小時。在減壓下移除揮發物。殘餘物係經由矽膠層析術(25至100% EtOAc於己烷中)純化以產生呈白色之1-(4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯基)-3-((1S,2S)-2-羥基環己基)硫脲(6.1 g, 96%)。MS (ES+) C19 H23 ClN4 O3 S要求值：422，實測值：423 [M+H]+ 。 步驟5： 向1-(4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯基)-3-((1S,2S)-2-羥基環己基)硫脲(1.0 g, 2.3 mmol)於DCM (100 ml)中之溶液添加BSTFA (1.3 ml, 4.7 mmol)及將所得溶液攪拌5分鐘。將固體三溴化苄基三甲基銨(0.92 g, 2.3 mmol)添加至先前反應混合物內。20分鐘後，添加飽和NaHCO3 (30 ml)及將反應混合物攪拌5分鐘。將雙相混合物轉移至具有額外之20 ml DCM及分離各層之分液漏斗。有機層係用飽和NaHCO3 水溶液(30 ml)，接著用10% Na2 S2 O3 水溶液(1 x 20 ml)清洗，於MgSO4 上乾燥，過濾，及在減壓下濃縮。殘餘物係用1:2醚/己烷(30 ml)研磨及所得固體係通過布氏漏斗過濾。在用1:1醚/己烷(10 ml)沖洗後，收集呈灰白色粉末(945 mg, 95%)之(1S,2S)-2-((6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇(0.945 g, 95%)。MS (ES+) C19 H21 ClN4 O3 S要求值：420，實測值：421 [M+H]+ 。 步驟6： 在微波小瓶中裝入(1S,2S)-2-((6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己醇(300 mg, 0.71 mmol)及氨(7 M於MeOH中，2.0 mL)。將該小瓶密封及在微波反應器中將反應混合物加熱至120℃，歷時4小時。在減壓下移除揮發物。殘餘物係藉由逆相製備型HPLC (移動相：A = 0.1% TFA/H2 O，B = 0.1% TFA/MeCN；梯度：B = 10 - 90%；20 min；管柱：C18)純化以產生呈灰白色粉末之作為TFA鹽(182 mg, 64%)之(1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇。MS (ES+) C19 H23 N5 O3 S要求值：401，實測值：402 [M+H]+ ；1 H NMR (600 MHz, DMSO-d6 ) δ 8.23 (d, J = 5.0 Hz, 1H), 7.60 (d, J = 7.5 Hz, 1H), 6.90 (d, J = 2.4 Hz, 1H), 6.70 – 6.58 (m, 3H), 6.55 (d, J = 2.4 Hz, 1H), 4.90 (s, 2H), 4.75 (d, J = 4.9 Hz, 1H), 3.82 (s, 3H), 3.54 – 3.45 (m, 1H), 3.37 – 3.32 (m, 1H), 2.10 – 1.98 (m, 1H), 1.91 – 1.83 (m, 1H), 1.69 – 1.51 (m, 2H), 1.35 – 1.10 (m, 4H)。 實例67：6-((2-胺基-3-氯吡啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺標題化合物係根據下列合成方案合成：步驟1： 向6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(實例50，步驟4) (3.0 g, 8.5 mmol)於DMF (20 mL)中之溶液添加NaSMe (1.2 g, 17 mmol)。在室溫下將該反應攪拌16小時。該反應混合物係用水(100 ml)稀釋及用Et2 O (100 ml × 3)萃取。經組合之有機層係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黃色油之6-(苄氧基)-4-甲氧基-2-(甲硫基)苯并[d]噻唑(2.7 g, 100%)。MS (ES+) C16 H15 NO2 S2 要求值：317，實測值：318 [M+H]+。 步驟2： 在65℃下將6-(苄氧基)-4-甲氧基-2-(甲硫基)苯并[d]噻唑(2.7 g, 8.5 mmol)於TFA (20 ml)中之混合物攪拌16小時。在減壓下移除溶劑。添加飽和NaHCO3 (50 ml)及該混合物係用EtOAc (50 ml × 3)萃取。經組合之有機層係用鹽水(100 mL)清洗，於Na2 SO4 上乾燥，過濾及濃縮以提供呈棕色油之4-甲氧基-2-(甲硫基)苯并[d]噻唑-6-醇(1.9 g, 100%)。MS (ES+) C9 H9 NO2 S2 要求值：227，實測值：228[M+H]+。 步驟3： 在80℃下將4-甲氧基-2-(甲硫基)苯并[d]噻唑-6-醇(1.8 g, 8.0 mmol)、3-氯-4-(氯甲基)-N-(4-甲氧基苄基)吡啶-2-胺(2.4 g, 8.0 mmol)及Cs2 CO3 (7.8 g, 24 mmol)於DMF (20 mL)中之混合物攪拌2小時。該反應混合物係用水(100 ml)稀釋，用Et2 O (100 ml)及EtOAc (50 ml × 3)萃取。經組合之有機相係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈白色固體之3-氯-4-((4-甲氧基-2-(甲硫基)苯并[d]噻唑-6-基氧基)甲基)-N-(4-甲氧基苄基)吡啶-2-胺(2.1 g, 53%)。MS (ES+) C23 H22 ClN3 O3 S2 要求值：487，實測值：488[M+H]+。 步驟4： 在0℃下向3-氯-4-((4-甲氧基-2-(甲硫基)苯并[d]噻唑-6-基氧基)甲基)-N-(4-甲氧基苄基)吡啶-2-胺(2.0 g, 4.1 mmol)於DCM (100 mL)中之溶液添加m-CPBA (834 mg, 4.1 mmol)。在室溫下將該反應混合物攪拌2小時。該混合物係用飽和Na2 S2 O3 (100 ml)、飽和NaHCO3 (100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈白色固體之3-氯-4-((4-甲氧基-2-(甲基亞磺醯基)苯并[d]噻唑-6-基氧基)甲基)-N-(4-甲氧基苄基)吡啶-2-胺(2.1 g, 97%)。MS (ES+) C23 H22 ClN3 O4 S2 要求值：503，實測值：504[M+H]+。 步驟5： 在140℃下將3-氯-4-((4-甲氧基-2-(甲基亞磺醯基)苯并[d]噻唑-6-基氧基)甲基)-N-(4-甲氧基苄基)吡啶-2-胺(50 mg, 0.1 mmol)及3,3-二氟環己胺(135 mg, 1 mmol)之混合物攪拌6小時。該反應混合物係用水(50 ml)稀釋及用EtOAc (50 ml × 3)萃取。經組合之有機層係用水(100 ml)及鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黃色固體之6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(50 mg, 87%)。MS (ES+) C28 H29 ClF2 N4 O3 S要求值：574，實測值：575[M+H]+。 步驟6： 在室溫下將6-((3-氯-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(50 mg, 0.09 mmol)於TFA (5 mL)中之混合物攪拌8小時。該反應混合物係藉由製備型HPLC (移動相：A = 10 mM碳酸氫銨/H2 O，B =乙腈；梯度：B = 60%-95%於18 min內；管柱：Welch Xtimate® C18, 10 μm, 21.2 mm x 250 mm)純化以產生呈白色固體之6-((2-胺基-3-氯吡啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(5.0 mg, 12%)。MS (ES+) C20 H21 ClF2 N4 O2 S要求值：454，實測值：455[M+H]+；1 H NMR (500 MHz, DMSO) δ 8.01 – 7.86 (m, 3H), 6.98 (d, J = 2.3 Hz, 1H), 6.75 (d, J = 5.0 Hz, 1H), 6.58 (d, J = 2.3 Hz, 1H), 6.33 (s, 2H), 5.07 (s, 2H), 3.94 (d, J = 5.7 Hz, 2H), 3.83 (s, 3H), 2.61 (d, J = 4.6 Hz, 3H)。 實例69：(1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇標題化合物係根據下列合成方案合成：步驟1： 在0℃下向3-甲氧基-4-硝基苯酚(1.0 g, 5.9 mmol)之溶液添加N-琥珀醯亞胺氯(0.868 g, 6.50 mmol)，及在50℃下將所得混合物攪拌2小時。該反應混合物係用EtOAc (20 mL)稀釋及用水(2 x 20 mL)清洗。分離各層，及有機層係用飽和NaCl (10 mL)清洗，於MgSO4 上乾燥，過濾及在減壓下濃縮以提供呈黃色固體之2-氯-5-甲氧基-4-硝基苯酚(1.2 g, ~100%)。MS (ES+) C7 H6 ClNO4 要求值：203，實測值：204 [M+H]+ 。 步驟2： 向K2 CO3 (0.758 g, 5.48 mmol)及2-氯-5-甲氧基-4-硝基苯酚(0.93 g, 4.5 mmol)於DMF (4.57 ml)中之懸浮液添加2-氯-4-(氯甲基)嘧啶(0.89 g, 5.4 mmol)及在50℃下將所得混合物攪拌15小時。該反應係用水(15 mL)稀釋，攪拌5分鐘，及於布氏漏斗上過濾。固體係用水(2 x 10 mL)清洗。乾燥後，分離呈棕色固體之2-氯-4-((2-氯-5-甲氧基-4-硝基苯氧基)甲基)嘧啶(1.31 g, 83%)。MS (ES+) C12 H9 Cl2 N3 O4 要求值：329，實測值：330 [M+H]+。 步驟3： 在N2 之氣氛下在反應容器中裝入10% Pt-C (0.80 g, 0.20 mmol)、2-氯-4-((2-氯-5-甲氧基-4-硝基苯氧基)甲基)嘧啶(1.3 g, 4.1 mmol)及THF (41 ml)。懸浮液係經N2 脫氣2分鐘及經H2 淨化2分鐘。在H2 之氣氛下在1 atm下將反應混合物攪拌2小時。該反應混合物係經N2 淨化，濾過矽藻土，及在減壓下經濃縮以提供呈橙棕色非晶型材料之5-氯-4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯胺(1.2 g, 99%)。MS (ES+) C12 H11 Cl2 N3 O2 要求值：299，實測值：300 [M+H]+。 步驟4： 向5-氯-4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯胺(1.2 g, 4.0 mmol)於DCM (20 ml)中之溶液添加二(1H-咪唑-1-基)甲硫酮(0.78 g, 4.4 mmol)及在室溫下將所得混合物攪拌1小時。添加(1S,2S)-2-胺基環己醇(0.92 g, 8.0 mmol)及在室溫下將黃棕色混合物再攪拌1小時。在減壓下移除揮發物。該反應混合物係用EtOAc (30 mL)稀釋及用水(2 x 20 mL)清洗。分離各層，及有機層係用飽和NaHCO3 (10 mL)清洗，於MgSO4 上乾燥，過濾及在減壓下濃縮以產生呈細小淺棕色固體之1-(5-氯-4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯基)-3-((1S,2S)-2-羥基環己基)硫脲(1.8 g, 90%)。MS (ES+) C19 H22 Cl2 N4 O3 S要求值：456，實測值：457 [M+H]+ 。 步驟5： 向1-(5-氯-4-((2-氯嘧啶-4-基)甲氧基)-2-甲氧基苯基)-3-((1S,2S)-2-羥基環己基)硫脲(1.8 g, 3.5 mmol)於DCM (30 ml)中之溶液添加(Z)-2,2,2-三氟-N-(三甲基甲矽烷基)乙醯亞胺酸三甲基甲矽烷基酯(1.88 ml, 7.08 mmol)及在室溫下將所得混合物攪拌5分鐘。然後作為於DCM (15 ml)中之溶液添加苄基三甲基三溴化銨(1.38 g, 3.54 mmol)。15分鐘後，該反應混合物係用飽和NaHCO3 (10 mL)、水(20 mL)及飽和Na2 S2 O4 (5 mL)稀釋。將所得混合物攪拌5分鐘，分離各層，及有機層係於MgSO4 上乾燥，過濾及在減壓下濃縮。殘餘物係用1:1 Et2 O/己烷(20 mL)研磨。所得固體係通過布氏漏斗過濾，用1:1 Et2 O/己烷(10 mL)沖洗，及收集分離之呈淺棕色固體之(1S,2S)-2-((7-氯-6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇(1.60 g, 94%)。MS (ES+) C19 H20 Cl2 N4 O3 S要求值：454，實測值：455 [M+H]+ 。 步驟6： 在微波小瓶中裝入於MeOH (7.0 ml, 49 mmol, 7M)中之(1S,2S)-2-((7-氯-6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己醇(0.90 g, 2.0 mmol)及NH3 。將該小瓶密封及在微波反應器中將該反應混合物加熱至120℃，歷時3小時。在減壓下移除揮發物。殘餘物係用水(15 mL)稀釋，在50℃下攪拌10分鐘，及於布氏漏斗上收集固體。乾燥後，殘餘物係藉由逆相HPLC (移動相：A = 0.1% NH4 OH/H2 O，B = 0.1% NH4 OH/ MeCN；梯度：B = 0 - 100%；20 min；管柱：C18)純化以提供呈淺棕色固體之(1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇(620 mg, 72%)。MS (ES+) C19 H22 ClN5 O3 S要求值：435，實測值：436 [M+H]+ ；1 H NMR (600 MHz, DMSO-d6 ) δ 8.27 (d, J = 5.0 Hz, 1H), 7.89 (d, J = 7.7 Hz, 1H), 6.79 (s, 1H), 6.74 (d, J = 4.9 Hz, 1H), 6.67 (s, 2H), 5.04 (s, 2H), 4.75 (d, J = 5.1 Hz, 1H), 3.85 (s, 3H), 3.53 – 3.46 (m, 1H), 3.36 – 3.32 (m, 1H), 2.09 – 1.99 (m, 1H), 1.92 – 1.84 (m, 1H), 1.69 – 1.56 (m, 2H), 1.31 – 1.16 (m, 4H)。 實例70：(1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：步驟1： 在80℃下將6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(實例50，步驟4) (750 mg, 2.15 mmol)、Selectfluor (835 mg, 2.36 mmol)於CH3 CN (50 ml)中之混合物攪拌整夜。添加飽和NaCl (100 mL)。反應混合物係用EtOAc (3 × 50 mL)萃取，經組合之有機層係於Na2 SO4 上乾燥，過濾及在減壓下濃縮。殘餘物係藉由矽膠層析術(10% EtOAc於PE中)純化以提供呈黃色固體之6-(苄氧基)-2-溴-7-氟-4-甲氧基苯并[d]噻唑(300 mg, 38%)。MS (ESI+) C15 H11 BrFNO2 S要求值：367，實測值：368 [M+H]+ 。 步驟2： 在120℃下將混合物6-(苄氧基)-2-溴-7-氟-4-甲氧基苯并[d]噻唑(300 mg, 0.810 mmol)及(1S,2S)-2-胺基環己醇(234 mg, 2.03 mmol)攪拌6小時。將該混合物分配至EtOAc與水之間。乾燥及濃縮有機層。殘餘物係藉由矽膠矽膠層析術(0至50 % EtOAc於PE中)純化以提供呈固體(250 mg, 76%)之(1S,2S)-2-(6-(苄氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇。MS (ES+) C21 H23 ClN2 O3 S要求值：402，實測值：403[M+H]+。 步驟3： 在55℃下將(1S,2S)-2-(6-(苄氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(90 mg, 0.22 mmol)於5 mL TFA中之混合物攪拌2小時。移除溶劑，反應混合物係由飽和NaHCO3 (50 ml)稀釋，用EtOAc (50 ml × 3)萃取。經組合之有機層係用水(100 ml)、鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黑色固體之7-氟-2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(70 mg, 100%)。MS (ES+) C14 H17 FN2 O3 S要求值：312，實測值：313[M+H]+ 。 步驟4： 在80℃下將7-氟-2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(70 mg, 0.22 mmol)、2-氯-4-(氯甲基)嘧啶(37 mg, 0.22 mmol)及Cs2 CO3 (216 mg, 0.66 mmol)於DMF (2 mL)中之混合物攪拌2小時。反應混合物係用水(50 mL)稀釋及用EtOAc (3 x 50 mL)萃取。經組合之有機層係用水(100 ml)、鹽水(100 ml)清洗，於Na2 SO4 上乾燥，過濾及濃縮以產生呈黃色固體之(1S,2S)-2-(6-((2-氯嘧啶-4-基)甲氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(96 mg, 100%)。MS (ES+) C19 H20 ClFN4 O3 S要求值：438，實測值：439[M+H]+ 。 步驟5： 在100℃下將於NH4 OH (2 ml)中之(1S,2S)-2-(6-((2-氯嘧啶-4-基)甲氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(60 mg, 0.14 mmol)攪拌1小時。反應混合物係藉由製備型HPLC (移動相：A = 10 mM碳酸氫銨/H2 O，B =乙腈；梯度：B = 60%-95%於18 min內；管柱：Welch Xtimate® C18, 10 μm, 21.2 mm x 250 mm)純化以產生呈白色固體之(1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(5.0 mg, 8%)。MS (ES+) C19 H22 FN5 O3 S要求值：419，實測值：420 [M+H]+；1 H NMR (500 MHz, MeOD) δ 8.35 (d, J = 5.9 Hz, 1H), 7.14 (d, J = 5.9 Hz, 1H), 6.87 (d, J = 6.8 Hz, 1H), 5.20 (s, 2H), 3.96 (s, 3H), 3.69 (dt, J = 11.7, 4.2 Hz, 1H), 3.46 (dt, J = 13.0, 4.8 Hz, 1H), 2.11 (dd, J = 47.6, 15.4 Hz, 2H), 1.84 – 1.73 (m, 2H), 1.41 (dt, J = 24.5, 15.1 Hz, 4H)。 實例71：N-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)乙醯胺標題化合物係根據下列合成方案合成：在80℃下將2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(如針對實例50，步驟1至6描述製備) (20 mg, 0.068 mmol)、N-(4-(氯甲基)吡啶-2-基)乙醯胺(15 mg, 0.082 mmol)及Cs2 CO3 (44 mg, 0.136 mmol)於DMF (3 ml)中之混合物攪拌整夜。在減壓下移除揮發物及殘餘物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以產生呈白色固體之N-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)乙醯胺(9 mg, 30%)。MS (ES+) C22 H26 N4 O4 S要求值：442，實測值：443 [M+H]+ 。1 H NMR (500 MHz, d6-DMSO) δ 10.51 (s, 1H), 8.29 (d, J = 5 Hz, 1H), 8.16 (s, 1H),7.61 (d, J = 7.5 Hz, 1H), 7.13 (d, J = 4 Hz, 1H), 6.93 (s, 1H), 6.55 (s, 1H), 5.12 (s, 2H), 4.76 (d, J = 5.5 Hz, 1H), 3.81 (s, 3H), 3.43 - 3.49 (m, 1H), 2.08 (s, 3H), 2.02 - 2.05 (m, 1H), 1.86 - 1.90 (m, 1H), 1.60 - 1.64 (m, 2H), 1.18 - 1.30 (m, 4H)。 表5中之下列實例係類似於實例71製備。 表5： 實例73：(1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：步驟1： 在0℃下向4-溴-2-甲氧基-5-甲基苯胺(10 g, 73.0 mmol)於DCM (200 mL)中之溶液滴加Br2 (11.7 g, 73.0 mmol)，歷時10分鐘。在室溫下將反應混合物攪拌整夜。該反應係在0℃下用NaHCO3 水溶液(200 mL)中止，該混合物係用EtOAc (3 × 200 mL)萃取及用鹽水(200 mL)清洗。該混合物係於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(0%至20%，EtOAc於石油醚中)純化以產生呈黃色固體之4-溴-2-甲氧基-5-甲基苯胺(8.0 g, 50%)。MS (ES+) C8 H10 BrNO，要求值：215，實測值：216 [M+H]+。 步驟2： 向4-溴-2-甲氧基-5-甲基苯胺(4.0 g, 18 mmol)於MeOH (200 mL)中之溶液添加KSCN (3.6 g, 37 mmol)及CuSO4 (14.9 g, 93 mmol)。在80℃下將反應混合物攪拌整夜。該反應混合物係用NH3 水溶液(7M, 200 mL)中止，用EtOAc (3 × 200 mL)萃取及用鹽水(200 mL)清洗。該反應混合物係於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(0%至10% MeOH於DCM中)純化以產生呈黃色固體之6-溴-4-甲氧基-7-甲基苯并[d]噻唑-2-胺(2.0 g, 39.5%)。MS (ES+) C9 H9 BrN2 OS，要求值：272，實測值：274 [M+H]+ 。 步驟3： 在0℃下將亞硝酸第三丁酯(754 mg, 7.32 mmol)滴加至CuBr2 (3.2 g, 14 mmol)及6-溴-4-甲氧基-7-甲基苯并[d]噻唑-2-胺(2.0 g, 7.32 mmol)於CH3 CN (20 mL)中之混合物。在室溫下將該混合物攪拌16小時。該反應混合物係用水稀釋及用EtOAc萃取。有機層係經乾燥及濃縮以提供呈米黃色固體之2,6-二溴-4-甲氧基-7-甲基苯并[d]噻唑(2.1 g, 89.3%)。MS (ES+) C9 H7 Br2 NOS要求值：335，實測值：336, 338 [M+H]+ 。 步驟4： 在130℃下將2,6-二溴-4-甲氧基-7-甲基苯并[d]噻唑(1.5 g, 4.45 mmol)及(1S,2S)-2-胺基環己醇(768 mg, 6.67 mmol)之混合物攪拌1小時。將該混合物分配至EtOAc與水之間。乾燥及濃縮有機層。粗殘餘物係藉由矽膠矽膠層析術(10%至50%，EtOAc於石油醚中)純化以提供呈棕色固體(800 mg, 48.4%)之(1S,2S)-2-(6-溴-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇。MS (ES+) C15 H19 BrN2 O2 S要求值：370，實測值：370, 372 [M+H]+ 。 步驟5： 在100℃下將(1S,2S)-2-(6-溴-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇(500 mg, 1.35 mmol)、4,4,4',4',5,5,5',5'-八甲基-2,2'-雙1,3,2-二氧雜硼烷) (513 mg, 2.02 mmol)、KOAc (265 mg, 2.70 mmol)、PCy3 (37 mg, 0.13 mmol)及Pd2 (dba)3 (137 mg, 0.135 mmol)於5 mL 1,4-二噁烷中之混合物攪拌16小時。該反應混合物係經過濾及藉由矽膠矽膠層析術(10%至50% EtOAc於石油醚中)純化以提供呈棕色固體之(1S,2S)-2-(4-甲氧基-7-甲基-6-(4,4,5,5-四甲基-1,3,2-二氧雜硼烷-2-基)苯并[d]噻唑-2-基胺基)環己醇(500 mg, 88.6%)。MS (ES+) C21 H31 BN2 O4 S要求值：418，實測值：419 [M+H]+ 。 步驟6： 在0℃下將H2 O2 (30滴)滴加至(1S,2S)-2-(4-甲氧基-7-甲基-6-(4,4,5,5-四甲基-1,3,2-二氧雜硼烷-2-基)苯并[d]噻唑-2-基胺基)環己醇(500 mg, 1.20 mmol)於MeOH (12 mL)中之溶液。在0℃下將反應混合物攪拌20分鐘，用EtOAc稀釋，用水、鹽水清洗，乾燥及在減壓下濃縮。殘餘物係經由矽膠層析術(0%至10%，MeOH於DCM中)純化以產生呈棕色固體之2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基-7-甲基苯并[d]噻唑-6-醇(250 mg, 67%)。MS (ES+) C15 H20 N2 O3 S，要求值：308，實測值：309 [M+H]+ 。 步驟7： 在室溫下向2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基-7-甲基苯并[d]噻唑-6-醇(100 mg, 0.325 mmol)及2-氯-4-(氯甲基)嘧啶(52 mg, 0.32 mmol)於DMF (1 mL)中之溶液添加Cs2 CO3 (211 mg, 0.650 mmol)。然後在80℃下將該反應攪拌2小時。該反應係用水(5 mL)中止，用EtOAc (3 × 5 mL)萃取，用鹽水(5 mL)清洗，於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(0至20% EtOAc於石油醚中)純化以產生呈白色固體之(1S,2S)-2-(6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇(20 mg, 14.3%)。MS (ES+) C20 H23 ClN4 O3 S要求值：434，實測值：434, 436 [M+H]+ 。 步驟8： 在100℃下將(1S,2S)-2-(6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇(20 mg, 0.046 mmol)於NH4 OH (0.5 mL)中之溶液攪拌整夜。該反應混合物係藉由製備型HPLC (移動相：A = 10 mM碳酸氫銨/H2 O，B =乙腈；梯度：B = 60%-95%於18 min內；管柱：Welch Xtimate® C18, 10 μm, 21.2 mm x 250 mm)純化以提供呈白色固體之((1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇(5 mg, 26%)。MS (ES+) C21 H26 N4 O3 S要求值：415，實測值：416 [M+H]+。1 H NMR (500 MHz, MeOD) δ 8.42 – 8.16 (m, 1H), 7.02 – 6.80 (m, 1H), 6.62 (s, 1H), 5.00 (s, 2H), 3.90 (s, 3H), 3.70 – 3.54 (m, 1H), 3.51 – 3.39 (m, 1H), 2.30 (s, 3H), 2.20 – 2.12 (m, 1H), 2.09 – 1.95 (m, 1H), 1.89 – 1.61 (m, 2H), 1.49 – 1.21 (m, 5H)。 實例74：(1S,2S)-2-(6-((2-胺基-3-氟吡啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：步驟1： 在室溫下向6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(實例50，步驟4) (0.5 g, 1.4 mmol)於NMP (5 mL)中之溶液添加NCS (0.17 g, 2.8 mmol)。在50℃下將該混合物攪拌2小時。所得混合物係用水(10 mL)稀釋及用EtOAc (3 × 10 mL)萃取。經組合之有機層係用鹽水(10 mL)清洗，於Na2 SO4 上乾燥，過濾及在減壓下濃縮。殘餘物係藉由矽膠層析術(EtOAc於石油醚中，10-20%)純化以產生呈白色固體(0.4 g, 74%)之6-(苄氧基)-2-溴-7-氯-4-甲氧基苯并[d]噻唑。MS (ES+) C15 H11 BrClNO2 S要求值：383，實測值：384[M+H]+ 。 步驟2： 在室溫下向6-(苄氧基)-2-溴-7-氯-4-甲氧基苯并[d]噻唑(0.2 g , 0.5 mmol)於DMA (5 mL)中之溶液添加(1S,2S)-2-胺基環己醇(0.12 g, 1 mmol)及DIPA (0.65 g, 5.0 mmol)。在90℃下將該混合物攪拌整夜。所得混合物係用H2 O (10 mL)稀釋及用EtOAc (3 × 10 mL)萃取。經組合之有機層係用鹽水(10 mL)清洗，於Na2 SO4 上乾燥，過濾及在減壓下濃縮。殘餘物係藉由矽膠矽膠層析術(30-50% EtOAc於石油醚中)純化以產生呈黃色固體(0.2 g, 95%)之(1S,2S)-2-(6-(苄氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇。MS (ES+) C21 H23 ClN2 O3 S要求值：418，實測值：419[M+H]+ 。 步驟3： 在50℃下將(1S,2S)-2-(6-(苄氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基胺基)-環己醇(0.20 g, 0.48 mmol)於TFA (2 mL)中之溶液加熱3小時。冷卻至室溫後，該混合物係用飽和NaHCO3 中和及用EtOAc (3 × 10 mL)萃取。經組合之有機層係用鹽水(10 mL)清洗，於Na2 SO4 上乾燥，過濾及在減壓下濃縮以提供呈黃色固體(90 mg, 60%)之7-氯-2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇。MS (ES+) C14 H17 ClN2 O3 S要求值：328，實測值：329 [M+H]+ 。 步驟4： 在室溫下向7-氯-2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(90 mg, 0.27 mmol)於DMF (3 mL)中之溶液添加4-(氯甲基)-3-氟-N-(4-甲氧基苄基)吡啶-2-胺(92 mg, 0.33 mmol)及Cs2 CO3 (0.18 g, 0.54 mmol)。在100℃下將該混合物攪拌整夜。所得混合物係用水(10 mL)稀釋及用EtOAc (3 × 10 mL)萃取。經組合之有機層係用鹽水(10 mL)清洗，於Na2 SO4 上乾燥，過濾及在減壓下濃縮以提供呈黃色固體(50 mg, 33%)之(1S,2S)-2-(7-氯-6-((3-氟-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇。MS (ES+) C28 H30 ClFN4 O4 S要求值：572，實測值：573 [M+H]+ 。 步驟5： 在室溫下將(1S,2S)-2-(7-氯-6-((3-氟-2-(4-甲氧基苄基胺基)吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(50 mg, 0.09 mmol)於TFA (2 mL)中之溶液攪拌整夜。該混合物係用NaHCO3 水溶液中和及用EtOAc (3 × 10 mL)萃取。經組合之有機層係用鹽水(10 mL)清洗，於Na2 SO4 上乾燥，過濾及在減壓下濃縮以提供粗產物，其係藉由製備型HPLC (移動相：A = 0.01% TFA/H2 O，B = MeCN；梯度：B = 5% - 95%於8 min內；管柱：XBridge C18, 5 μm, 30 mm × 150 mm)純化以產生呈白色固體(17.3 mg, 44%)之(1S,2S)-2-(6-((2-胺基-3-氟吡啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇。MS (ES+) C20 H22 ClFN4 O3 S要求值：452，實測值：453 [M+H]+；1 H NMR (400 MHz, DMSO) δ 7.90 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 4.0 Hz, 1H), 6.85 (s, 1H), 6.69 (t, J = 4.0 Hz, 1H), 6.24 (s, 2H), 5.21 (s, 2H), 4.75 (d, J = 4.0 Hz, 1H), 3.87 (s, 3H), 2.03 (d, J = 4.0 Hz, 1H), 1.87 (d, J = 4.0 Hz, 1H), 1.63 (t, J = 12.0 Hz, 2H), 1.24 (m, 6H)。 表6中之下列實例係類似於實例74製備。 表6： 實例76：(1S,2S)-2-(7-氯-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：在110℃下將(1S,2S)-2-(7-氯-6-((2-氯嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(實例74，步驟5) (60 mg, 0.13 mmol)、1-甲基-1H-吡唑-4-胺(21 mg, 0.15 mmol)及TsOH.H2 O (11 mg, 0.065 mmol)於二噁烷(2 ml)中之混合物攪拌整夜。該混合物係用EtOAc (5 mL)稀釋，用飽和NaHCO3 清洗，及於Na2 SO4 上乾燥。濃縮經組合之有機層。殘餘物係藉由製備型HPLC (移動相：A = 0.1% NH4 HCO3 /H2 O，B = MeCN；梯度：B = 5 - 95%；12 min；管柱：C18)純化以提供呈白色固體之(1S,2S)-2-(7-氯-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇(3.5 mg, 5%)。MS (ES+) C23 H26 ClN7 O3 S要求值：515，實測值：516 [M+H]+ 。1 H NMR (500 MHz, d6-DMSO) δ 9.51 (s, 1H), 8.44 (d, J = 4.5 Hz, 1H),7.89 (d, J = 9.5 Hz, 2H),7.48 (s, 1 H), 6.83 - 6.89 (m, 2H), 5.17 (s, 2H), 4.17 (d, J = 5.5 Hz, 1H), 3.77 (s, 3H), 3.49 (s, 3H), 2.02 - 2.08 (m, 1H), 1.86 - 1.89 (m, 1H), 1.60 - 1.65 (m, 2H), 1.19 - 1.30 (m, 4H)。 表7中之下列實例係類似於實例76製備。 表7： 實例79：4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基胺甲酸甲酯標題化合物係根據下列合成方案合成：步驟1： 在55℃下將4-(氯甲基)吡啶-2-基胺甲酸第三丁酯(700 mg, 2.88 mmol)於HCl-二噁烷(4M, 5 mL)中之溶液攪拌2小時。在減壓下濃縮反應混合物以產生4-(氯甲基)吡啶-2-胺，其無需進一步純化即可用於下一步驟中。MS (ES+) C6 H7 ClN2 要求值：142，實測值：143[M+H]+ 。 步驟2： 向4-(氯甲基)吡啶-2-胺(300 mg, 2.1 mmol)於DCM (8 mL)中之溶液添加Et3 N (637 mg, 6.3 mmol)及氯甲酸甲酯(199 mg, 2.1 mmol)。在室溫下將所得混合物攪拌16小時。該反應混合物係用水(10 mL)清洗，用DCM (15 mL × 3)萃取。經組合之有機層係於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(0至70 % EtOAc於PE中)純化以產生呈白色固體之4-(氯甲基)吡啶-2-基胺甲酸甲酯(120 mg, 28%)。MS (ES+) C8 H9 ClN2 O2 要求值：200，實測值：201[M+H]+ 。 步驟3： 向4-(氯甲基)吡啶-2-基胺甲酸甲酯(100 mg, 0.5 mmol)及2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(如實例50，步驟1至6中描述製備) (138 mg, 0.47 mmol)於DMF (3 mL)中之溶液添加K2 CO3 (130 mg, 0.94 mmol)。在90℃下將該反應混合物攪拌3小時。該混合物係藉由質量觸發之製備型HPLC (移動相：A = 10 M NH4 HCO3 /H2 O，B = MeCN；梯度：B = 40-70%；8.5 min；管柱：C18)過濾及純化以產生呈白色固體之4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基胺甲酸甲酯(18 mg, 9%)。MS (ES+) C22 H26 N4 O5 S要求值：458，實測值：459 [M+H]+ 。1 H NMR (500MHz, DMSO) δ 10.23 (s, 1H), 8.25 (d, J = 5.0 Hz, 1H), 7.94 (s, 1H), 7.63 (d, J = 7.5 Hz,1H), 7.10 (d, J = 5.1 Hz, 1H), 6.94 (d, J = 2.3 Hz, 1H), 6.56 (d, J = 2.3 Hz, 1H), 5.13 (s, 2H), 4.78 (d, J = 5.0 Hz, 1H), 3.83 (s, 3H), 3.67 (s, 3H), 3.50 (s, 1H), 2.03 (d, J = 13.1 Hz, 1H), 1.86 (s, 1H), 1.63 (s, 2H),1.31 - 1.16 (m, 5H)。 實例80：1-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)-3-甲脲標題化合物係根據下列合成方案合成：步驟1： 在55℃下將4-(氯甲基)吡啶-2-基胺甲酸第三丁酯(400 mg, 1.65 mmol)於HCl-二噁烷(4M, 3 mL)中之溶液攪拌2小時。濃縮反應混合物以產生4-(氯甲基)吡啶-2-胺。殘餘物無需進一步純化即可用於下一步驟中。MS (ES+) C6 H7 ClN2 要求值：142，實測值：143[M+H]+ 。 步驟2： 向4-(氯甲基)吡啶-2-胺(300 mg, 2.1 mmol)於DCM (8 mL)中之溶液添加Et3 N (4 mL)及甲基胺基甲醯氯(589 mg, 6.3 mmol)。在室溫下將所得混合物攪拌整夜。該反應混合物係用水(10 mL)清洗及用DCM (15 mL × 3)萃取。有機層係於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(0-95% EtOAc於石油醚中)純化以產生呈白色固體之1-(4-(氯甲基)吡啶-2-基)-3-甲脲(55 mg, 13%)。MS (ES+) C8 H10 ClN3 O要求值：199，實測值：200[M+H]+ 。 步驟3： 向1-(4-(氯甲基)吡啶-2-基)-3-甲脲(50 mg, 0.25 mmol)及2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(如實例50，步驟1至6中描述製備) (74 mg, 0.25 mmol)於DMF (1 mL)中之溶液添加K2 CO3 (69 mg, 0.5 mmol)。在90℃下將反應混合物攪拌3小時。該混合物係藉由質量觸發之製備型HPLC (移動相：A = 10 M NH4 HCO3 /H2 O，B = MeCN；梯度：B = 30-60%；9.5min；管柱：C18)過濾及純化以產生呈白色固體之1-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)-3-甲脲(27 mg, 24%)。MS (ES+) C22 H27 N5 O4 S要求值：457，實測值：458 [M+H]+ 。1 H NMR (500MHz, DMSO) δ 9.29 (s, 1H), 8.27 - 8.01 (m, 2H), 7.62 (d, J = 7.5 Hz, 1H), 7.39 (s, 1H), 6.95 (dd, J = 21.8, 3.5 Hz, 2H), 6.55 (d, J = 1.9 Hz, 1H), 5.07 (s, 2H), 4.77 (d, J = 4.9 Hz, 1H), 3.83 (s, 3H), 3.51 (s, 1H), 2.73 (d, J = 4.5 Hz, 3H), 2.02 (s, 1H), 1.86 (s, 1H), 1.63 (s, 2H), 1.32 - 1.12 (m, 5H)。 表8中之下列實例係類似於實例80製備。 表8： 實例81：(1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇標題化合物係根據下列合成方案合成：步驟1： 在0℃下向(2-溴吡啶-4-基)甲醇(1.0 g, 5.3 mmol)及DIPEA (2.06 g, 15.9 mmol)於DCM (20 mL)中之溶液添加MsCl (640 mg, 5.6 mmol)。將所得混合物升溫至室溫及攪拌2小時。該混合物係用DCM (10 mL)稀釋及用飽和水性NH4 Cl (20 mL)，飽和水性Na2 CO3 (20 mL)及鹽水(10 mL)清洗。該混合物係於Na2 SO4 上乾燥，過濾及濃縮。殘餘物係藉由矽膠層析術(0至50% EtOAc於PE中)純化以產生呈淺紅色固體之甲磺酸2-溴吡啶-4-基)甲酯(1.2 g, 85%)。MS (ES+) C7 H8 BrNO3 S要求值：265，實測值：266 [M+H]+ 。 步驟2： 向甲磺酸(2-溴吡啶-4-基)甲酯(300 mg, 1.13 mmol)及2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(如針對實例50，步驟1至6中描述製備) (332 mg, 1.13 mmol)於DMF (4 mL)中之溶液添加Cs2 CO3 (736 mg, 2.26 mmol)。在80℃下將所得混合物攪拌20分鐘。該反應混合物係藉由質量觸發之製備型HPLC (移動相：A = 10 M NH4 HCO3 /H2 O，B = MeCN；梯度：B = 40-70%；10.85 min；管柱：C18)過濾及純化以產生呈白色固體之(1S,2S)-2-(6-((2-溴吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(185 mg, 35%)。MS (ES+) C20 H22 BrN3 O3 S要求值：463，實測值：464[M+H]+ 。 步驟3： 在壓力管中，將1-甲基吡唑-4-胺HCl (21 mg, 0.16 mmol)、(1S,2S)-2-(6-((2-溴吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇(60 mg, 0.13 mmol)、RuPhos Pd G4 (11 mg, 0.013 mmol)、RuPhos (6 mg, 0.013 mmol)及Cs2 CO3 (127 mg, 0.39 mmol)溶解於1,4-二噁烷(2 mL)中。將管密封及用N2 淨化。在85℃下將反應混合物攪拌3小時。LCMS監測該反應。該混合物係藉由質量觸發之製備型HPLC (移動相：A = 10 M NH4 HCO3 /H2 O，B = MeCN；梯度：B = 30-60%；10.0 min；管柱：C18)過濾及純化以產生呈白色固體之(1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇(5 mg, 9%)。MS (ES+) C24 H28 N6 O3 S要求值：480，實測值：481[M+H]+ 。1 H NMR (500MHz, DMSO) δ 8.81 (s, 1H), 8.07 (d, J = 5.3 Hz, 1H), 7.91 (s, 1H), 7.61 (d, J = 7.5 Hz, 1H), 7.37 (s, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.70 (s, 1H), 6.65 (d, J = 5.3 Hz, 1H), 6.54 (d, J = 2.2 Hz, 1H), 5.02 (s, 2H), 4.77 (d, J = 5.0 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.51 (s, 1H), 2.02 (s, 1H), 1.87 (d, J = 11.2 Hz, 1H), 1.63 (t, J = 10.8 Hz, 2H), 1.23 (s, 5H)。 表9中之下列實例係類似於實例81製備。 表9： 實例84：6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺標題化合物係根據下列合成方案合成：步驟1： 在50℃下在氬下將6-(苄氧基)-2-溴-4-甲氧基苯并[d]噻唑(實例50，步驟4) (750 mg, 2.14 mmol)及NCS (570 mg, 4.29 mmol)於NMP (10 mL)中之混合物攪拌3小時。添加水及該混合物係用EtOAc (3 x 5 mL)萃取。有機層係用鹽水清洗，乾燥及在減壓下濃縮以提供呈棕色固體之6-(苄氧基)-2-溴-7-氯-4-甲氧基苯并[d]噻唑。MS (ES+) C15 H11 BrClNO2 S要求值：383，實測值：384, 386 [M+H]+ 。 步驟2： 在180℃下將6-(苄氧基)-2-溴-7-氯-4-甲氧基苯并[d]噻唑(160 mg, 0.41 mmol)及3,3-二氟環己胺鹽酸鹽(140 mg, 0.82 mmol)於DIPEA (20滴)及NMP (20滴)中之混合物攪拌4小時。該反應混合物係用水稀釋及用EtOAc (3 × 10 mL)萃取。經組合之有機層係於Na2 SO4 上乾燥及濃縮。殘餘物係經由矽膠層析術(0%至10% EtOAc於石油醚中)純化以產生呈黃色油之6-(苄氧基)-7-氯-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(100 mg, 54.9%)。MS (ES+) C21 H21 ClF2 N2 O2 S，要求值：438，實測值：439[M+H]+ 。 步驟3： 在65℃下將6-(苄氧基)-7-氯-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(100 mg, 0.23 mmol)於TFA (3 mL)中之溶液攪拌16小時。蒸發TFA，殘餘物係用水稀釋及用EtOAc萃取。經組合之有機層係用飽和NaHCO3 溶液清洗，於Na2 SO4 上乾燥及濃縮以提供呈棕色油之7-氯-2-(3,3-二氟環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(100 mg，粗)。MS (ES+) C14 H15 ClF2 N2 O2 S要求值：348，實測值：349[M+H]+ 。 步驟4： 在室溫下將甲磺酸(2-胺基嘧啶-4-基)甲酯(52 mg, 0.26 mmol)、7-氯-2-(3,3-二氟環己基胺基)-4-甲氧基苯并[d]噻唑-6-醇(90 mg, 0.26 mmol)及Cs2 CO3 (2168 mg, 0.52 mmol)於DMF (1 mL)中之混合物攪拌2小時。該反應混合物係藉由製備型HPLC (移動相：A = 0.01% TFA/H2 O，B = MeCN；梯度：B = 60% - 95%於18 min內；管柱：Venusil CBP C18 (L) C18, 10 μm, 21.2 mm x 250 mm, Cat. NO. :VX902520-L)純化以產生呈白色固體之6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺(20 mg, 15%)。MS (ES+) C19 H20 ClF2 N5 O2 S，要求值：455，實測值：456[M+H]+；1 H NMR (500 MHz, DMSO) δ 8.32 (d, J = 5.2 Hz, 1H), 8.08 (d, J = 7.5 Hz, 1H), 7.08 (s, 2H), 6.83 (s, 2H), 5.10 (s, 2H), 3.95 – 3.90 (m, 1H), 3.87 (s, 3H), 2.46 – 2.42 (m, 1H), 2.05 – 1.96 (m, 2H), 1.87 – 1.72 (m, 3H), 1.52 – 1.45 (m, 1H), 1.39 – 1.29 (m, 1H)。 實例85及86： 表10中之下列實例係類似於實例1製備： 表10： 實例 87 ： CSF-1R 競爭性結合分析 結合至CSF-1R之化合物係藉由基於FRET之競爭性結合分析(LanthaScreen® Eu激酶結合分析；Invitrogen)量測。Alexa Fluor®結合物示蹤劑第236號(cat no. PV5592)對經His標誌之hCSF1R (aa538-910)之結合係藉由添加經Eu標記之抗-His抗體偵測。示蹤劑及抗體對CSF1R之結合導致高度FRET，而用激酶抑制劑取代示蹤劑導致FRET之損失。His-CSF1R (5 µl)係用5 µl遞增化合物濃度於反應緩衝劑(50 mM HEPES [pH 7.5], 10 mM MgCl2 , 1 mM EGTA, 0.003% Tween 20)中培養20分鐘，然後與5 µl抗體混合及在室溫下培養90分鐘。CSF1R、示蹤劑及抗-His抗體之最終濃度分別係3 nM、10 nM及2 nM。在平板閱讀器(激發：320 nm；發射：615 nm)中跟隨FRET信號。劑量-反應曲線係使用IC50 回歸曲線擬合(GeneData Screener)分析。 下表11總結CSF-1R競爭性結合分析之結果，其中各化合物之IC50 值如下指示：(A)小於50 nM；(B) 50 nM至200 nM；(C) 200 nM至500 nM；(D) 500 nM至1.5 µM；及(E) ＞1.5 µM。 表11：CSF-1R競爭性結合分析 實例 88 ： mCSF 依賴性細胞增殖分析 將M-NFS-60細胞(ATCC – CRL-1838)重懸浮於含有10 ng/mL重組小鼠m-CSF (R&D Systems – 416-ML-010)之培養基(RPMI-1640, GlutaMax Supplement, HEPES – Gibco 72400-047)中。然後將細胞平鋪於384孔板(5000個細胞/孔，35 μL/孔)上，及在37℃，5% CO2 下培養整夜。將DMSO (對照)或遞增濃度之化合物稀釋於培養基中，添加至384孔板(5 μL/孔，最終DMSO濃度為0.5%)，及細胞用化合物在37℃，5% CO2 下培養72小時。然後藉由添加35 μL之CellTiter-Glo 2.0 (Promega, G9243)使用製造商之建議書量測細胞存活率。細胞係用CellTiter-Glo 2.0在室溫下培養10分鐘，及然後由Envision平板閱讀器讀取發光。劑量-反應曲線係使用IC50 回歸曲線擬合(GeneData Screener)分析。曲線係經標準化至無抑制劑之高對照及具有1 µM十字孢鹼之低對照。 下表12總結mCSF依賴性細胞增殖分析之結果，其中各化合物之IC50 值如下指示：(A)小於1 µM；(B) 1 µM至2 µM；(C) 2 µM至5 µM；(D) 5 µM至10 µM；(E)大於10 µM。 表12：mCSF依賴性細胞增殖分析 實例 89 ： 激酶抑制之選擇性 評估本發明之化合物對CSF-1R之選擇性高於對激酶c-Kit、FLT3、PDGFRα及PDGFRβ之選擇性。 就CSF-1R、FLT3、c-KIT、PDGFRα及PDGFRβ激酶分析而言，於衍生自BL21菌株之大腸桿菌宿主中製備經激酶標誌之T7噬菌體菌株。大腸桿菌生長至對數階段，用T7噬菌體感染及在32℃下振盪培養直至細胞溶解。將溶解產物離心及過濾以移除細胞碎片。塗覆鏈黴親和素之磁珠係用生物素化小分子配體在室溫下處理30分鐘以產生用於激酶分析之親和樹脂。經配體處理之珠係用過量生物素阻斷及用阻斷緩衝劑(SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT)清洗以移除未結合之配體及減少非特異性結合。結合反應係藉由在1x結合緩衝劑(20% SeaBlock, 0.17x PBS, 0.05% Tween 20, 6 mM DTT)中組合激酶、經配體處理之親和珠及測試化合物以進行組裝。將測試化合物製備為於100% DMSO中之111X儲備液。Kd值係使用具有三個DMSO對照點之11點，3倍化合物稀釋系列測定。用於Kd量測之所有化合物係藉由聲傳遞分配(非接觸分配)於100% DMSO中。然後將化合物直接稀釋至分析中使得DMSO之最終濃度係0.9%。所有反應係於聚丙烯384孔板中進行。各係0.02 ml之最終體積。該等分析板係在室溫下振盪培養1小時及親和珠係用清洗緩衝劑(1x PBS, 0.05% Tween 20)清洗。然後將該等珠重懸浮於溶析緩衝劑(1x PBS, 0.05% Tween 20, 0.5 μM非生物素化親和配體)中及在室溫下振盪培養30分鐘。溶析物中之激酶濃度係藉由qPCR量測。 化合物處理 各測試化合物之11點3倍連續稀釋係以100x最終測試濃度製備於100% DMSO中及接著在分析中稀釋至1x (最終DMSO濃度= 1%)。大多數Kd值係使用化合物最高濃度= 30,000 nM測定。若測定之初始Kd係＜ 0.5 nM (測試之最低濃度)，則以起始自較低最高濃度之連續稀釋重複量測。記錄為40,000 nM之Kd值指示該Kd係經測定為＞30,000 nM。 結合常數(Kd) 結合常數係以標準劑量-反應曲線使用Hill等式計算： 反應=背景+ 信號-背景 1 + (KdHill斜率/劑量Hill斜率) 將該Hill斜率設定至-1。 曲線係使用非線性最小二乘擬合以Levenberg-Marquardt演算法進行擬合。 下表13總結選擇性分析之結果，其中針對c-Kit、FLT3、PDGFRα及PDGFRβ量測之Kd值係相對於針對CSF-1R之Kd值給定。 各化合物對CSF-1R相對於c-Kit之選擇性係如下給定：(A) ＞ 50倍；(B) 10至50倍；(C) 5至10倍；及(D)小於5倍更具選擇性。各化合物對CSF-1R相對於FLT3之選擇性係如下給定：(A) ＞ 500倍；(B) 200至500倍；(C) 100至200倍；及(D)小於100倍更具選擇性。各化合物對CSF-1R相對於PDGFRα之選擇性係如下給定：(A) ＞ 15倍；(B) 10至15倍；(C) 5至10倍；及(D)小於5倍更具選擇性。各化合物對CSF-1R相對於PDGFRβ之選擇性係如下給定：(A) ＞ 10倍；(B) 2.5至10倍；(C) 1.5至2.5倍；及(D)小於1.5倍更具選擇性。 表13：化合物之激酶選擇性 實例 90 ： CSF-1R 細胞靶接合分析 將THP-1細胞重懸浮於含有10% HI FBS及0.1% β-Me之RPMI培養基(無酚紅)中，及然後平鋪於96孔TC板(125 µl, 250K個細胞/孔)。該等細胞係在37℃，5% CO2 下培養20小時，接著添加0.1% DMSO (對照)或變化濃度之CSF-1R抑制劑。在37℃下培養30分鐘後，該等細胞係用50 ng/mL人類MCSF (Sigma M6518)處理5分鐘，及然後添加至125 µl細胞溶解緩衝劑(R&D Systems SAMPLE稀釋劑CONC 2)。在室溫下培養45分鐘後，經酪胺酸磷酸化之CSF-1R係藉由夾心ELISA (R&D Systems DYC3268)，遵循製造商之方案進行評估。簡而言之，將Nunc-Immuno MaxiSorp板(Sigma 9410)用抗人類CSF-1R塗覆，阻斷，及在室溫下結合至100 µL THP-1細胞溶解物，歷時2小時。清洗後，將經HRP標記之抗二氧磷基酪胺酸添加至板及在室溫下再培養2小時。清洗後，誘發ELISA信號及分別藉由1-步驟Ultra TMB-ELISA受質溶液(Life Technologies 34028)及2 N硫酸中止。於BioTek Neo平板閱讀器上量測於450 nm及540 nm下之吸光度，及將ELISA信號計算為Ab450nm -Ab540nm 。 標準劑量反應曲線係由使用可變斜率模型藉由Genedata Screener軟體擬合： 信號=信號陰性對照 + (信號DMSO 對照 -信號陰性對照 )/(1+(IC50 /劑量)^Hill斜率) 等式中僅信號及劑量作為已知值處理。 下表14總結細胞靶接合分析之結果，其中各化合物之IC50 值係如下指示：(A)小於250 nM；(B) 250 nM至500 nM；(C) 500 nM至1 µM；(D) 1 µM至2 µM；(E)大於2 µM。 表14：細胞靶接合分析 本文引用之所有專利案、公開申請案及參考文獻之教義係以全文引用之方式併入本文中。 儘管本發明已引用其示例性實施例特別性地表明及描述，但熟習此項技術者會瞭解，對本發明其中形式及細節作出各種變化並不會悖離隨附申請專利範圍包含之本發明之精神及範圍。While the invention has been described with respect to the specific embodiments of the embodiments of the embodiments of the invention . In view of the benefits of the present invention, various changes and modifications will be apparent to those skilled in the art and are further defined in the scope of the appended claims. Inside.definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning meaning meaning Exemplary methods, devices, and materials have been described, although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All of the technical and patent publications cited herein are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention Unless otherwise indicated, the practice of the present invention will employ the techniques of chemical synthesis, tissue culture, immunology, molecular biology, microbiology, cell biology, and recombinant DNA within the teachings of the present invention. See, for example, Michael R. Green and Joseph Sambrook, Molecular Cloning (4th edition, Cold Spring Harbor Laboratory Press 2012); Series Ausubel et al., (2007) Current Protocols in Molecular Biology; Series Methods in Enzymology (Academic Press, Inc., NY); MacPherson et al., (1991) PCR 1: A Practical Approach (IRL Press at Oxford University Press); MacPherson et al., (1995) PCR 2: A Practical Approach; Harlow and Lane, ed., (1999) Antibodies, A Laboratory Manual; Freshney (2005) Culture of Animal Cells: A Manual of Basic Technique, 5th Edition; Gait, 1984, Oligonucleotide Synthesis; US Patent No. 4,683,195; Hames and Higgins, 1984, Nucleic Acid Hybridization; and Anderson (1999) Nucleic Acid Hybridization; edited by Hames and Higgins, (1984) Transcription and Translation; Immobilized Cells and Enzymes (IRL Press (1986)); Perbal (1984) A Practical Guide to Molecular Cloning; Miller and Calos Edit, (1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory) Makrides, (2003) Gene Transfer and Expression in Mammalian Cells; Mayer and Walker, eds. (1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press, London); Herzenberg et al., (1996) Weir's Handbook of Experimental Immunology Manipulating the Mouse Embryo: A Laboratory Manual, 3rd edition, (Cold Spring Harbor Laboratory Press (2002)); Sohail (ed.) (2004) Gene Silencing by RNA Interference: Technology and Application (CRC Press). Numerical values including ranges (eg, pH, temperature, time, concentration, molecular weight, etc.) are approximate values that are optionally varied (+) or (-) in increments of 0.1 or 1.0. It should be understood that although not always explicitly stated, all numerical values are preceded by the term "about." It should also be understood that, although not always explicitly stated, all of the reagents described herein are exemplary only and the equivalents of such reagents are known in the art. As used in the specification and claims, the singular forms "", "," For example, the term "cell" includes a plurality of cells, including mixtures thereof. The term "or" as used herein shall be understood to be inclusive unless otherwise expressly stated or apparent from the context. The term "comprising" as used herein means the phrase "including but not limited to" and may be used interchangeably with the phrase "including but not limited to". As used herein, the term "comprising" is intended to mean that the compositions and methods include the elements recited herein, but do not exclude other elements. "Consisting essentially of" when used to define a composition and method, shall mean excluding elements that have any fundamental meaning to the combination for the purposes specified. Thus, compositions consisting essentially of the elements as defined herein should not exclude contaminants from the separation and purification methods and pharmaceutically acceptable carriers such as phosphate buffered saline, preservatives and the like. "Consisting of" shall mean a method step of excluding more trace elements of the other ingredients and substantial method steps or compositions for producing the compositions or achieving the desired results. Embodiments defined by each of these transition terms are within the scope of the invention. The term "comprising" is used herein to encompass and disclose the corresponding expression in which the term "comprising" is replaced by "consisting essentially of" or "consisting of." "Individual", "individual" or "patient" are used interchangeably herein and refer to a vertebrate (such as a mammal). Mammals include, but are not limited to, rodents, farm animals, sports animals, pets, and primates; for example, murine, rat, rabbit, apes, cows, sheep, pigs, dogs, cats, horses, and humans. In one embodiment, the mammals include horses, dogs, and cats. In a preferred embodiment, the mammal is a human. "Administration" is defined herein as the manner in which a pharmaceutical agent or a composition containing the pharmaceutical agent is provided to the individual in a manner that results in the pharmaceutical agent being administered to the individual. This administration can be by any means including, but not limited to, oral, transdermal (eg, by vaginal, rectal or oral mucosa), by injection (eg, subcutaneous, intravenous, parenteral, intraperitoneal) Or within the CNS) or by inhalation (eg, oral or nasal). Of course, pharmaceutical preparations are given in a form suitable for each route of administration. "Treatment" of a disease includes: (1) preventing the disease, that is, causing the clinical symptoms of the disease to not develop in a patient who may be susceptible to the disease but has not experienced or manifested the symptoms of the disease; (2) inhibiting the disease The disease, ie, prevents or reduces the progression of the disease or its clinical symptoms; and/or (3) alleviates the disease, ie, causes the disease or its clinical symptoms to subside. The term "dose" when it refers to the term "treatment" refers to a patient or individual who has been diagnosed or susceptible to the disease. Because of a history of disease in the family lineage or because of a genetic mutation associated with the disease, the patient may also be referred to as a "risk-prone" disease. A patient at risk of developing a disease has not yet developed all or some of the characteristic conditions of the disease. An "effective amount" or "therapeutically effective amount" is an amount sufficient to achieve a desired or desired result. An effective amount can be administered, administered or dosed in one or more amounts. This delivery depends on a number of variables, including the time period in which the individual dosage unit is to be used, the bioavailability of the therapeutic agent, the route of administration, and the like. However, it is to be understood that the particular dosage concentration of the therapeutic agent of the present invention for any particular individual will depend on a variety of factors including, for example, the activity of the particular compound employed, the age, weight, general health, sex and diet, Time, excretion rate, drug combination, and the severity of the particular disorder in the treatment and the form of administration. The therapeutic dose can usually be titrated to optimize safety and efficacy. In general, dose-response relationships from in vitro and/or in vivo testing may initially provide useful guidance for the appropriate dosage for administration to a patient. In general, we will be required to administer an amount effective to achieve a serum concentration consistent with the concentration effective in vitro. The determination of these parameters is also within the skill of the art. These considerations, as well as effective formulations and administration procedures, are well known in the art and are described in standard reference books. As used herein, the term "pharmaceutically acceptable excipient" encompasses any of the standard pharmaceutical excipients, including carriers (such as phosphate buffered saline, water) and emulsions (such as oil/water or water/). Oil emulsion) and various types of wetting agents. Pharmaceutical compositions may also include stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see Remington&apos;s Pharmaceutical Sciences (20th Edition, Mack Publishing Co. 2000). As used herein, the term "prodrug" means a pharmacological derivative of a parent drug molecule that is required to be biotransformed (spontaneously or enzymatically) in an organism to release the active drug. For example, a prodrug is a variant or derivative of a compound described herein, which has a group that is cleavable under certain metabolic conditions, which, when cleaved, becomes a compound described herein (eg, formula (I) Compound). Such prodrugs have medicinal activity in vivo when they are solvolyzed or enzymatically degraded under physiological conditions. The prodrug compounds herein may be referred to as single, double, triple, etc., depending on the number of biotransformation steps required to release the active drug in the organism and the amount of functional groups present in the prior form. Prodrug forms often provide solubility, histocompatibility or delayed release advantages in mammalian organisms (Bundgard, Design of Prodrugs, pp. 7-9, pages 21-24, Elsevier, Amsterdam 1985 and Silverman, "The Organic Chemistry of Drug Design and Drug Action", pp. 352-401, Academic Press, San Diego, Calif., 1992). Prodrugs generally known in the art include well-known acid derivatives such as, for example, esters prepared by reacting an acid compound with a suitable alcohol, decylamine prepared by reacting an acid compound with an amine, reacted to form a basic group such as a hydrazine base derivative. Other prodrug derivatives can be combined with other features disclosed herein to enhance bioavailability. Thus, those skilled in the art will recognize that certain of the compounds disclosed herein having, for example, a free amine group or a hydroxyl group can be converted to a prodrug. Prodrugs also include compounds having a carbonate, carbamate, decylamine or alkyl ester moiety covalently bonded to any of the above-described substituents disclosed herein. The term "pharmaceutically acceptable salt," as used herein, means a pharmaceutically acceptable acid addition salt or a pharmaceutically acceptable base addition salt of a compound disclosed herein, which can be administered without any substantial substance. An undesired biological effect or any resulting deleterious interaction with any other component of the pharmaceutical composition in which the salt is contained. As used herein, the term "alkyl" refers to a saturated straight or branched chain radical consisting essentially of a carbon atom and a corresponding number of hydrogen atoms. Exemplary alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and the like. Other alkyl groups will be apparent to those skilled in the art in view of the benefit of this invention. The term "C1-3 -alkyl", "C4-8 -Alkyl" and the like have the same meaning, that is, a saturated straight or branched chain radical consisting essentially of 1 to 3 (or 4 or 8) carbon atoms and a corresponding number of hydrogen atoms. As used herein, the term "alkenyl" means an unsaturated straight or branched chain radical consisting essentially of a carbon atom and a corresponding number of hydrogen atoms, wherein the radical comprises at least one carbon-carbon double bond. Exemplary alkenyl groups include ethenyl, prop-1-enyl, prop-2-enyl, isopropenyl, but-1-enyl, 2-methyl-prop-1-enyl, 2-methyl- Prop-2-enyl and the like. Other alkenyl groups will be apparent to those skilled in the art in view of the benefit of this invention. The term "C2-6 "Alkenyl" has the same meaning, that is, an unsaturated straight or branched chain radical consisting essentially of 2 to 6 carbon atoms and a corresponding number of hydrogen atoms, wherein the radical comprises at least one carbon-carbon double bond. As used herein, the term "alkynyl" means an unsaturated straight or branched chain radical consisting essentially of a carbon atom and a corresponding number of hydrogen atoms, wherein the radical comprises at least one carbon-carbon triple bond. Exemplary alkenyl groups include ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, 3-methyl-but-1-ynyl, and the like. Other alkynyl groups will be apparent to those skilled in the art in view of the benefits of the present invention. The term "C2-6 An alkynyl group has the same meaning, that is, an unsaturated straight or branched chain radical consisting essentially of 2 to 6 carbon atoms and a corresponding number of hydrogen atoms, wherein the radical comprises at least one carbon-carbon triple bond. As used herein, the term "carbocyclyl" means a saturated, partially or fully unsaturated or aromatic radical having at least 3 to 9 carbon atoms (ie, ring atoms) forming a ring. Exemplary carbocyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, and phenyl. It will be appreciated that the carbocyclic group can be monocyclic or polycyclic (eg, fused, bridged or spiro ring systems). In the case of a polycyclic carbocyclic group, there are other rings, for example, 1, 2, 3 or a plurality of other rings, all of which contain 3 to 9 carbon atoms (i.e., ring atoms). Exemplary carbocyclic groups having such other rings include bicyclo[3.1.0]hexyl, decahydronaphthyl (bicyclo[4.4.0]decyl), spiro[5.5]undecyl, octahydronaphthalene. Base and naphthyl. The term "cycloalkyl" has the same meaning as that associated with a saturated carbocyclic group. The term "cycloalkenyl" has the same meaning as that associated with an unsaturated carbocyclic group. The term "aryl" has the same meaning as that associated with an aromatic carbocyclic group. Examples of the aryl group include a phenyl group and a naphthyl group and an anthracenyl group and an indanyl group. As used herein, the term "heterocyclyl" means a saturated, partially or fully unsaturated or aromatic radical having at least 3 to 6 atoms (ie, ring atoms) forming a ring, wherein the ring atoms are The 1 to 5 carbon atoms and the remaining 1 to 5 ring atoms (i.e., heterocyclic atoms) are independently selected from the group consisting of nitrogen, sulfur, and oxygen. Exemplary heterocyclic groups include azacyclopropyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, pyrrolyl, pyridyl and imidazolyl. In the case of a polycyclic heterocyclic group, there are other rings, for example, 1, 2, 3 or a plurality of other rings, all of which contain 3 to 6 ring atoms selected from the group consisting of carbon, nitrogen, sulfur and oxygen. Polycyclic heterocycles include fused, bridged, and spiro ring systems. Exemplary heterocarbocyclyl groups having such other rings include 2-azabicyclo[3.3.0]octyl, 3,9-diazaspiro[5.5]undecyl, indanyl, benzene And thienyl and benzoxazolyl. The term "heterocycloalkyl" has the same meaning as that associated with a saturated heterocyclic group. Exemplary heterocycloalkyl groups include pyrrolidinyl, morpholinyl, piperidinyl, and piperazinyl. The term "heterocyclenyl" has the same meaning as that associated with an unsaturated heterocyclic group. Exemplary heterocycloalkenyl groups include 2,5-dihydro-1H-pyrrolyl, 2H-piperidyl, tetrahydro-2H-thiopyran-1,1-di-oxyl (thiane di-oxy), Tetrahydro-2H-piperidyl and 3,4-dihydro-2H-pyranyl. The term "heteroaryl" has the same meaning as that associated with an aromatic heterocyclic group. The heteroaryl group usually has 6 to 10 ring atoms, and examples of such groups include monocyclic groups (such as pyrrolyl, pyridyl, pyrazinyl and pyridazinyl) and polycyclic groups (such as benzofuranyl, Benzothiophenyl, fluorenyl, pyrrolopyridyl, quinolyl and acridinyl). As used herein, the terms "halo" and "halogen" mean fluoro, chloro, bromo or iodo. These terms are used interchangeably and may refer to a halogen radical or a halogen atom itself. In view of the fact that this term is used in the context of the present invention, those skilled in the art will readily be able to determine the identification of such terms. As used herein, the terms "cyano", "nitrile" and "nitrile" mean a radical having a carbon atom attached to a nitrogen atom via a triple bond. The nitrile group is bonded via its carbon atom. As used herein, the term "mercapto" refers to a carbon-containing radical having at least one carbon-oxygen double bond. The fluorenyl group is bonded via a carbon atom of a carbon-oxygen double bond. As used herein, the term "hydroxy" means an OH group that is bonded via its oxygen atom. The term "thio" means an SH group which is bonded via its sulfur atom. As used herein, the term "amino" generally refers to a radical having a nitrogen atom and one or two hydrogen atoms. Thus, the term "amine group" generally refers to primary and secondary amines. In this regard, as used herein and in the accompanying claims, the tertiary amine is derived from the general formula RR.† N-represents, where R and R† The same or different carbon groups. However, the term "amine group" may be used herein to describe a primary, secondary, and/or tertiary amine, and in light of the terminology, those skilled in the art will readily be able to determine how to use the term. As used herein, the terms "amylamine" and "guanamine" generally mean a radical having a nitrogen atom bonded directly to a carbonyl group (C=O). Generally, the term is intended to include primary, secondary, and tertiary guanamine groups. The "amylamine" and "guanamine" groups are bonded via their carbonyl carbon atoms. As used herein, the term "mercaptoamine" means a radical containing at least one carbon-oxygen double bond having an amine group bonded to a carbonyl carbon. The mercaptoamine group is bonded via a nitrogen atom of an amine group. As used herein, the term "sulfonyl" means a radical containing a sulfur atom that participates in two double bonds with an oxygen atom, ie, it contains a group -S(=O)2 -. The "sulfonyl group" is bonded via the sulfur atom. Exemplary sulfonyl groups include sulfonate esters, for example, -S(O)2 OR, wherein R is a carbon group, and alkylsulfonyl, for example, -S(O)2 R, wherein R is an alkyl group. The term "aminosulfonyl" means a sulfonyl group bonded directly to an amine group as defined herein, for example, -S(O)2 NH2 . The term "sulfonylamino" means an amine group bonded directly to a sulfonyl group, as defined herein, for example, -NHS(O)2 CH3 . The listing of a list of chemical groups in any definition of a variable herein includes the definition of the variable as any single group or combination of enumerated groups. The listing of the embodiments of the variables or aspects herein is to be construed as a single embodiment or in combination with any other embodiments or portions thereof. The compositions and methods provided herein can be combined with one or more of any of the other compositions and methods provided herein. This article uses the following abbreviations: °C = degrees Celsius1 H-NMR = proton nuclear magnetic resonance ACN = acetonitrile AcOH = acetic acid β-Me = 2-巯 ethanol BSA = bovine serum albumin BSTFA = N, O-bis(trimethylformamidinyl) trifluoroacetamide d4 -MeOD = hydrogenated methanol d6 -DMSO = deuterated dimethyl hydrazine DBU = 1,8-diazabicyclo undec-7-ene DCM = dichloromethane DIBAL = diisobutylaluminum hydride DIEA = N,N-diisopropylethylamine DMA = dimethylacetamide DMF = dimethylformamide DMSO = dimethyl hydrazine DPPA = diphenyl azide DTT = dithiothreitol ES+ = electrospray positive ionization EGTA = ethylene glycol - bis (β-aminoethyl ether) - N, N, N', N' - tetraacetic acid ELISA = enzyme-linked immunosorbent assay Et2 O = ether EtOAc = ethyl acetate FRET = fluorescence resonance energy transfer h = hour HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4, 5-b]pyridinium-3-oxide hexafluorophosphate HEPES = 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid HI FBS = heat-inactivated fetal bovine serum HPLC = high pressure liquid chromatography HRP = horseradish peroxidase Hz = Hertz IPA = isopropanol M = mol mCPBA = 3-chloroperoxybenzoic acid MeCN = acetonitrile MHz = megahertz; min = minute mL = ml MS = mass spectrometry MW = microwave PBS = phosphate buffered saline PMB = p-methoxybenzyl qPCR = quantitative polymerase chain reaction RPMI medium = Los Angeles Park Memorial Institute medium rt / RT = room temperature Selectfluor = 1-chloromethyl-4-fluoro-1 , 4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate) tBuONO = butyl nitrite TFA = trifluoroacetic acid THF = tetrahydrofuranCompound This invention relates to compounds useful as CSF-1R inhibitors. In one aspect, the invention provides a compound characterized by formula (I),Or a pharmaceutically acceptable salt or prodrug thereof, wherein: A is a 5 to 10 membered heteroaryl group having a ring atom consisting of C, at least one N, and optionally O or S; n is 0, 1, 2, 3 Or 4; m series 0, 1 or 2; X1 Is selected from the group consisting of NH, O, S, -CH=N- and -N=CH-; L represents a direct bond or a group thereof - (CR6 R7 )p -, where: p is 1, 2 or 3, and each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each of the alkyl groups is optionally and independently substituted with 1 to 3 C, independently selected from halogen and hydroxy, optionally 1 to 3 halogens.1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C1-4 -alkyl), aminyl, mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -N (R'R” Replaced by the group, where R' And R” Are independently selected from hydrogen and C1-3 -alkyl; R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4- Mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4- Mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group , alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted; R3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group or a cycloalkenyl group a heterocycloalkenyl, aryl or heteroaryl group as desired; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl, or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 Alkenyl, C2-8 Alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4- Mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4- An anthracenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group, The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl groups are optionally substituted. In an embodiment: R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, and each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group Or an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group, optionally containing from 1 to 5 groups independently selected from the group consisting of Substitution: halogen, hydroxyl, -N (Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; and/or R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and/or R3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, wherein each of the alkyl group, a decyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment: R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4- Mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a fluorenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group Or an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group, optionally containing from 1 to 5 groups independently selected from the group consisting of Substitution: halogen, hydroxyl, -N (Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; and/or R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and/or R3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, wherein each of the alkyl group, a decyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment, the A is selected from the group consisting of a 5-membered monocyclic heteroaryl group, a 6-membered monocyclic heteroaryl group, and a 9-membered bicyclic heteroaryl group. In one embodiment, the A line is selected from the group consisting of thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolinyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, Pyridazinyl and pyrrolopyridinyl. In another embodiment, the A is selected from the group consisting of thiazolyl, pyridyl, pyrimidinyl, pyrazinyl, and pyrrolopyridinyl. In another embodiment, the A line is selected from the group consisting of pyridyl and pyrimidinyl. In one embodiment, the A line is selected from the group consisting of pyridin-4-yl and pyrimidin-4-yl. In an embodiment, A is a 6 membered monocyclic heteroaryl group, for example, pyridinyl, pyrimidinyl or pyrazinyl. In one embodiment, the A is pyridyl. In another embodiment, the A is a pyrimidinyl group. In other embodiments, the A is a 9 membered bicyclic heteroaryl group, for example, a pyrrolopyridinyl group. In one embodiment, the A is 1H-pyrrolo[2,3-b]pyridinyl. In other embodiments, the A is a 5-membered monocyclic heteroaryl group, for example, a thiazolyl group. In an embodiment, n is 0, 1, 2 or 3. In other embodiments, n is 0, 1, or 2. In other embodiments, n is 1, 2 or 3. In other embodiments, n is 1 or 2. In other embodiments, n is 2 or 3. In other embodiments, n is 0. In other embodiments, n is 1. In other embodiments, n is 2. In other embodiments, n is 3. In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 Each line is independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R8 And R9 Each of which is independently selected from H and a group selected from the group consisting of: C2-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl. In other embodiments, R8 And R9 Neither is methyl. In other embodiments, in R8 And R9 In the case where one is hydrogen, the other is not methyl. In other embodiments, R1 Not -C(O)NH(CH3 ). In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 Each line is independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R8 And R9 Each of which is independently selected from H and a group selected from the group consisting of: C2-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl. In other embodiments, R8 And R9 Neither is methyl. In other embodiments, in R8 And R9 In the case where one is hydrogen, the other is not methyl. In other embodiments, R1 Not -C(O)NH(CH3 ). In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 Each line is independently selected from H, C2-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 Each line is independently selected from H, C2-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 Each line is independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkenyl group, an alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 Each line is independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-6 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 , R9 And R10 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).a Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-6 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 , R9 And R10 The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).a Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R1 In each case independently selected from halogen, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 And R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, alkyl group, cycloalkyl group, heterocycloalkyl group, aryl group or heteroaryl group is as needed Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R1 In each case independently selected from halogen, -N(R8 R9 ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 a fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group, and wherein each of the mercaptoamine, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl is as desired Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R1 In each case independently selected from halogen, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -O(C1-4 -alkyl), C1-4 -alkyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl and heteroaryl, R10 And R10b Lines are independently selected from H and C1-4 An alkyl group, and wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R1 In each case independently selected from halogen, -N(R8 R9 ), -O(C1-4 -alkyl), C1-4 -alkyl, aryl and heteroaryl, wherein R8 And R9 Lines are independently selected from H and C1-4 An alkyl group, and wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R1 In each case independently selected from Cl, Br and amine groups or selected from methylamino groups, -NHC(O)OCH3 , -NHC(O)CH3 ,-NHC(O)NHCH3 , methyl, methoxy, -NH-pyrazolyl, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C1-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In other embodiments, R1 In each case, it is independently selected from the group consisting of Cl, Br and an amine group or selected from the group consisting of methylamino, methyl, methoxy, phenyl and pyrazolyl, each of which is optionally independently selected from 1 to 3 Halogen, C1-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In an embodiment, there is at least one R1 a group selected from the group consisting of halogens. In one embodiment, the halogen is selected from the group consisting of F, Cl, and Br. In another embodiment, the halogen is selected from the group consisting of Cl and Br. In another embodiment, the halogen is Cl. In another embodiment, the halogen is Br. In another embodiment, the halogen is F. In an embodiment, there is at least one R1 a group selected from -N(R8 R9 ), for example, NH2 Or 1 to 3 independently selected from C as needed1-4 -alkyl and (C1-4 -alkyl)-Rc Substituted by -NH-pyrazolyl, wherein Rc It is selected from the group consisting of hydroxyl, amine and halogen. In an embodiment, n is 1 and R1 Department-N(R8 R9 ), for example, NH2 . In an embodiment, n is 1 and R1 Department-N(R8 R9 ), for example, 1 to 3 independently selected from C as needed1-4 -alkyl and (C1-4 -alkyl)-Rc Substituted by -NH-pyrazolyl, wherein Rc It is selected from the group consisting of hydroxyl, amine and halogen. In an embodiment, n is 1 and R1 Depending on the need, 1 to 3 are independently selected from C1-4 -NH-pyrazol-3-yl or -NH-pyrazol-4-yl substituted with an alkyl group. In an embodiment, n is 1 and R1 Line Cl. In an embodiment, n is 1 and R1 Department Br. In an embodiment, n is 1 and R1 Department-NHC(O)OCH3 . In an embodiment, n is 1 and R1 Department-NHC(O)CH3 . In an embodiment, n is 1 and R1 Department-NHC(O)NHCH3 . In an embodiment, n is 1 and R1 A methyl group which is optionally substituted with 1 to 3 halogens. In an embodiment, n is 1 and R1 The pyrazolyl group which is substituted with a methyl group is required. In an embodiment, n is 1 and R1 The methoxy group which is substituted with 1 to 3 halogens is required. In an embodiment, n is 1 and R1 a phenyl group which is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, n is 2, the first R1 Department-N(R8 R9 ), for example, NH2 And the second R1 Is selected from halogen, -O (C1-8 -alkyl) and C1-3 An alkyl group, wherein the alkyl group is optionally selected from the group consisting of halogen, C, and 1 to 31-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In an embodiment, n is 2, the first R1 Department-N(R8 R9 ), for example, NH2 And the second R1 Line Cl. In an embodiment, n is 2, the first R1 Department-N(R8 R9 ), for example, NH2 And the second R1 Department-CF3 . In an embodiment, n is 2, the first R1 Department-N(R8 R9 ), for example, NH2 And the second R1 Department-OCF3 . In an embodiment, n is 2, the first R1 Department-N(R8 R9 ), for example, NH2 And the second R1 Department-OCHF2 . In one embodiment, n is 2, the first R1 NH2 And the second R1 Line Cl. In an embodiment, m is 0 or 1. In other embodiments, m is 1 or 2. In other embodiments, m is 1. In other embodiments, m is 0. In other embodiments, m is 2. In an embodiment, R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with from 1 to 3 groups independently selected from the group consisting of halogen and hydroxy. In other embodiments, R2 In each case independently selected from the group consisting of halogen, nitrile and, optionally, 1 to 3 groups independently selected from halogens -O(C1-4 -alkyl). In other embodiments, R2 In each case, it is independently selected from the group consisting of halogen and nitrile. In other embodiments, R2 In each case independently selected from halogen, C1-4 -alkyl and -O(C1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. In other embodiments, R2 In each case independently selected from halogen and optionally substituted by 1 to 3 groups independently selected from halogens.1-4 -alkyl). In an embodiment, m is 1 or 2, and R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. In other embodiments, m is 1 or 2, and R2 Is selected from the group consisting of halogen, nitrile and -O(C) substituted with 1 to 3 groups independently selected from halogen1-4 -alkyl). In an embodiment, m is 1 and R2 -O(C) substituted with 1 to 3 groups independently selected from halogen1-4 -alkyl). In other embodiments, m is 2 and R2 Is selected from halogen and -O (C1-4 -alkyl). In other embodiments, m is 2 and R2 Is selected from C1-4 -alkyl and -O(C1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. In an embodiment, R3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aromatic The base or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In other embodiments, each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl groups is optionally substituted with from 1 to 3 groups independently selected from the group consisting of: Halogen, hydroxyl, nitrile, -N(Rd Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, R3 Department C1-8 An alkyl group which is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N (R)d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), aminosulfonyl, sulfonylamino and optionally substituted by hydroxyl or with 1 to 3 halogens -O(C1-4 -alkyl). In other embodiments, R3 Department C1-6 An alkyl group which is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, -N(Rd Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), aminosulfonyl and sulfonylamino. In other embodiments, R3 Department C1-5 An alkyl group which is optionally selected from the group consisting of halogen, hydroxyl and NH by 1 to 32 Replaced by the group. In other embodiments, R3 Department C1-5 An alkyl group which is optionally substituted with 1 to 3 groups independently selected from a halogen and a hydroxyl group. In one embodiment, R3 4-methylpentan-1-ol. In other embodiments, R3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl and heterocycloalkenyl, wherein each cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocycloalkenyl group is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxyl, nitrile, -N(Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In other embodiments, R3 It is selected from the group consisting of cycloalkyl and heterocycloalkyl, wherein each cycloalkyl or heterocycloalkyl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In other embodiments, R3 Is selected from cyclohexyl, phenyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydro-2H-thiopyranyl-1, 1-dioxy, pyridyl, piperidinyl or dihydroindenyl (2, 3-Dihydro-1H-indenyl), which is optionally substituted with 1 to 5 groups selected from the group consisting of halogen, hydroxy, nitrile, -N(R)d Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In other embodiments, R3 Department C3-8 a cycloalkyl group which is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In one embodiment, R3 a cyclohexyl group which is optionally substituted with 1 to 4 groups independently selected from the group consisting of a hydroxyl group, optionally substituted by a hydroxyl group.1-3- Alkyl, F, Cl, optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl) and CONH2 . In another embodiment, R3 It is a cyclohexyl group substituted by a hydroxyl group. In another embodiment, R3 It is a cyclohexyl group substituted with a hydroxymethyl group. In another embodiment, R3 It is a cyclohexyl group substituted by two F. In one embodiment, R3 A cyclohexyl group substituted with a hydroxyl group and further optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N (R)d Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In another embodiment, R3 It is a cyclohexyl group substituted with a hydroxyl group and a fluorine. In another embodiment, R3 It is a cyclohexyl group substituted with a hydroxyl group and substituted with two F groups. In one embodiment, the two F atomic systems are bonded to the same carbon atom of the cyclohexyl group. In other embodiments, R3 Is selected from an aryl or heteroaryl group, wherein each aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In one embodiment, R3 Is a dihydroindenyl group (2,3-dihydro-1H-indenyl) which is optionally substituted with 1 to 4 groups independently selected from the group consisting of a hydroxyl group, optionally substituted by a hydroxyl group.1-3 -alkyl, F, Cl, nitrile, -N(Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl). In another embodiment, R3 It is a hydroxy-substituted dihydroindenyl group. In another embodiment, R3 It is a hydroxymethyl substituted dihydroindenyl group. In one embodiment, R3 a dihydroindenyl group substituted with a hydroxyl group and further optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N (R)d Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, R4 And R5 Together with the intervening carbon atoms, a 3 to 6 membered cycloalkyl group is formed, for example, a cyclopropyl group. In other embodiments, R4 And R5 Together with the intervening carbon atoms, a 3 to 6 membered heterocycloalkyl group is formed, for example, a 3 to 6 membered cycloalkoxy group (such as an oxetane group). In other embodiments, R4 And R5 One of them is hydrogen and the other is from C1-3 - an alkyl group (for example, a methyl group). In other embodiments, R4 And R5 Both are independently selected from C1-3 - an alkyl group (for example, all of which are methyl groups). In a preferred embodiment, R4 And R5 All are hydrogen. In an embodiment, the L system - (CR6 R7 )p - where p is preferably 1 or 2 (especially where p is 1) and wherein each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each alkyl group is optionally and independently substituted with 1 to 3 C independently substituted with halogen (e.g., fluorine), hydroxyl group, optionally 1 to 3 halogens.1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C1-4 -alkyl), aminyl, mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -N (R'R” Replaced by the group, where R' And R” Are independently selected from hydrogen and C1-3 -alkyl. In an embodiment, the L system - (CR6 R7 )p - where p is preferably 1 or 2 (especially where p is 1) and wherein each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each of the alkyl groups is optionally and independently substituted with 1 to 3 groups independently selected from halogen (e.g., fluorine) and a hydroxyl group. In an embodiment, R is bonded to the same carbon atom6 And R7 One of them is hydrogen and the other is C1-4 An alkyl group which is optionally substituted with a hydroxy group. In other embodiments, R is bonded to the same carbon atom6 And R7 One of them is hydrogen and the other is methyl. In still other embodiments, R is bonded to the same carbon atom6 And R7 One of them is hydrogen and the other is hydroxymethyl. In still other embodiments, all R are present6 And R7 The group is hydrogen. In an embodiment, L represents a direct bond. In an embodiment, X1 It is selected from the group consisting of NH, O and S. In other embodiments, X1 It is selected from O and S. In one embodiment, X1 Department O. In another embodiment, X1 Department S. In an embodiment, X1 It is selected from -CH=N- and -N=CH-. In one embodiment, X1 -CH=N-. In another embodiment, X1 Department -C=NH-. In one embodiment: A is a 6 membered monocyclic heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2;1 Is selected from NH, O or S; L represents a direct bond or a group thereof - (CR6 R7 )p - where p is 1 or 2 and each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each alkyl group is optionally and independently substituted with 1 to 3 C independently selected from the group consisting of halogen, hydroxy, and optionally 1 to 3 halogens.1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C1-4 -alkyl), aminyl, mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -N (R'R” Replaced by the group, where R' And R” Are independently selected from hydrogen and C1-3 -alkyl; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, and wherein R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile;3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group or a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In one embodiment: A is a 9 membered bicyclic heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2;1 Is selected from NH, O or S; L represents a direct bond or a group thereof - (CR6 R7 )p - where p is 1 or 2 and each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each alkyl group is optionally and independently substituted with 1 to 3 C independently selected from the group consisting of halogen, hydroxy, and optionally 1 to 3 halogens.1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C1-4 -alkyl), aminyl, mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -N (R'R” Replaced by the group, where R' And R” Are independently selected from hydrogen and C1-3 -alkyl; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, and wherein R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile;3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group or a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In another embodiment: A is a 6 membered monocyclic heteroaryl; n is 1 or 2; m is 0, 1 or 2;1 Line S; L means direct key; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl and heteroaryl, wherein R10 And R10b Lines are independently selected from H and C1-4 -alkyl, and wherein each of the fluorenyl, decylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen and hydroxy; R3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aromatic The base or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In another embodiment: A-line 9-membered bicyclic heteroaryl; n-line 1 or 2; m-system 0, 1 or 2;1 Line S; L means direct key; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl and heteroaryl, wherein R10 And R10b Lines are independently selected from H and C1-4 -alkyl, and wherein each of the fluorenyl, decylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen and hydroxy; R3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aromatic The base or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In one embodiment: A is a 6 membered monocyclic heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2;1 Is selected from NH, O or S; L represents a direct bond or a group thereof - (CR6 R7 )p - where p is 1 or 2 and each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each alkyl group is optionally and independently substituted with 1 to 3 C independently selected from the group consisting of halogen, hydroxy, and optionally 1 to 3 halogens.1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C1-4 -alkyl), aminyl, mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -N (R'R” Replaced by the group, where R' And R” Are independently selected from hydrogen and C1-3 -alkyl; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group Or an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group, optionally containing from 1 to 5 groups independently selected from the group consisting of Substitution: halogen, hydroxyl, -N (Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile;3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group or a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In one embodiment: A is a 9 membered bicyclic heteroaryl; n is 0, 1, 2 or 3; m is 0, 1 or 2;1 Is selected from NH, O or S; L represents a direct bond or a group thereof - (CR6 R7 )p - where p is 1 or 2 and each R6 And each R7 Are independently selected from hydrogen and C1-4 An alkyl group, wherein each alkyl group is optionally and independently substituted with 1 to 3 C independently selected from the group consisting of halogen, hydroxy, and optionally 1 to 3 halogens.1-4 -Alkyl, optionally substituted with 1 to 3 halogens -O(C1-4 -alkyl), aminyl, mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino and -N (R'R” Replaced by the group, where R' And R” Are independently selected from hydrogen and C1-3 -alkyl; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group Or an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group, optionally containing from 1 to 5 groups independently selected from the group consisting of Substitution: halogen, hydroxyl, -N (Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile;3 Is selected from C1-8 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group or a cycloalkenyl group The heterocyclenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In another embodiment: A is a 6 membered monocyclic heteroaryl; n is 1 or 2; m is 0, 1 or 2;1 Line S; L means direct key; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 And R9 Lines are independently selected from H and C1-4 -alkyl, and wherein each of the fluorenyl, decylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl, and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen and hydroxy; R3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aromatic The base or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In another embodiment: A-line 9-membered bicyclic heteroaryl; n-line 1 or 2; m-system 0, 1 or 2;1 Line S; L means direct key; R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R8 And R9 Lines are independently selected from H and C1-4 -alkyl, and wherein each of the fluorenyl, decylamino, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C1-4 -alkyl, and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen; R2 In each case independently selected from the group consisting of halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen and hydroxy; R3 Is selected from the group consisting of cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein each of the cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aromatic The base or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R).d Re ) (where Rd And Re Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and R4 And R5 Lines are independently selected from H and C1-3 -alkyl or R4 And R5 Together with the intervening carbon atom, a 3 to 6 membered cycloalkyl or heterocycloalkyl group is formed which is optionally substituted with one or more halogen atoms. In one embodiment, the compound is characterized by formula (II),Or a pharmaceutically acceptable salt or prodrug thereof, wherein Q1 , Q2 , Q3 And Q4 Is independently selected from N, CH and C (R1 ), where the Q1 , Q2 , Q3 And Q4 Not less than one and no more than two can represent N; and n, m, X1 , L and R1 To R5 Is as defined herein. In an embodiment, Q1 Department N and Q2 , Q3 And Q4 Department CH or C (R1 ). In other embodiments, Q1 And Q3 Both N and Q2 And Q4 Both are CH or C (R1 ). In other embodiments, Q1 And Q4 Both N and Q2 And Q3 Both are CH or C (R1 ). In other embodiments, Q2 And Q4 Both N and Q1 And Q3 Both are CH or C (R1 ). In a preferred embodiment, Q2 Department N. In a preferred embodiment, Q2 Department N and Q1 , Q3 And Q4 Department CH or C (R1 ). In other preferred embodiments, Q2 And Q4 Department N and Q1 And Q3 Department CH or C (R1 ). In another embodiment, the compound is characterized by formula (III),Or a pharmaceutically acceptable salt or prodrug thereof, wherein X2 Is selected from N, CH or C (R1 ); R11 And R12 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R13 R14 ), -N(R13 R14 ), -NHC(O)NR13 R14 ,-NHC(O)OR15 , -NHC(O)R15b , -C(O)R15b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR15 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R13 And R14 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R15 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R15b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group , alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl is optionally substituted; and m, X1 , L and R2 To R5 Is as defined herein. In an embodiment, R11 And R12 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R13 R14 ), -N(R13 R14 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR15 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R13 And R14 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R15 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group An alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted. In an embodiment, R11 And R12 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R13 R14 ), -N(R13 R14 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR15 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R13 And R14 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R15 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a nonylcycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group, The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted by 1 to 5 groups independently selected from the group consisting of :halogen, hydroxyl, -N(Rh Ri ) (where Rh And Ri Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rj (where Rj It is selected from the group consisting of hydroxyl and amine groups and halogens). In an embodiment, R11 Is selected from hydrogen, halogen, C(O)N(R13 R14 ), sulfonyl, C1-4 -alkyl, C2-4 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R13 And R14 The lines are independently selected from H, C1-4 -alkyl, C2-4 a fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rh Ri ) (where Rh And Ri Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rj (where Rj It is selected from the group consisting of hydroxyl and amine groups and halogens). In an embodiment, R11 Not hydrogen. In other embodiments, R11 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R12 R13 ), C1-3 -alkyl, hydroxy and -O(C1-3 -Alkyl), wherein each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. In an embodiment, R11 Hydrogen. In an embodiment, R12 Is selected from hydrogen, halogen, nitrile, -N (R13 R14 ), -C(O)N(R13 R14 ), C1-4 -alkyl, C2-4 -alkynyl, C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-4 -alkyl), -C(O)OR15 , sulfonyl and aminosulfonyl, wherein R13 And R14 Lines are independently selected from H and C1-3 -alkyl, R15 The lines are independently selected from H, C1-4 -alkyl, C1-4 Alkenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, and wherein each of the alkyl, alkynyl, decyl, decylamino, sulfonyl Aminosulfonyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl is optionally selected from halogen and C, optionally from 1 to 31-3 - an alkyl group substituted. In an embodiment, R12 Is selected from halogen, C(O)N(R13 R14 ), sulfonyl, C1-4 -alkyl, C2-4 - alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R13 And R14 The lines are independently selected from H, C1-4 -alkyl, C2-4 a fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rh Ri ) (where Rh And Ri Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rj (where Rj It is selected from the group consisting of hydroxyl and amine groups and halogens). In other embodiments, R12 Hydrogen. In an embodiment, X2 Department N. In other embodiments, X2 Department CH or C (R1 ). In other embodiments, X2 Department CH. In an embodiment: L-system - (CR6 R7 )p - where p is 1 and R6 And R7 One of them is hydrogen and the other is a C that needs to be replaced by a hydroxyl group.1-4 -alkyl; and R3 Is selected from a cycloalkyl or heteroaryl group, optionally containing 1 to 3 C, independently selected from a hydroxyl group, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl), NH2 NHSO2 CH3 , SO2 CH3 And CONH2 Replaced by the group. In other embodiments, L represents a direct key and R3 Is selected from cycloalkyl or heteroaryl, optionally substituted by 1 to 4 C, optionally substituted by halogen or hydroxy, optionally with a hydroxyl group1-3 -alkyl, F, Cl, -O (C1-4 -alkyl), NH2 NHSO2 CH3 , SO2 CH3 And CONH2 Replaced by the group. In one embodiment, L represents a direct bond; and R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In another embodiment, L represents a direct key; and R3 Substituted by a hydroxy group and further optionally 1 to 3 C, optionally substituted by a hydroxy group, as desired1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In one embodiment, L represents a direct bond; and R3 (2-hydroxy)cyclohexyl. In another embodiment, L represents a direct key; and R3 Is a dihydroindenyl group which is optionally substituted with 1 to 4 C, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl) and CONH2 Replaced by the group. In one embodiment, L represents a direct bond; and R3 Substituted by a hydroxy group and further optionally 1 to 3 C, optionally substituted by a hydroxy group, as desired1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted with a dihydroindenyl group. In one embodiment, L represents a direct bond; and R3 It is a (1-hydroxy) dihydroindenyl group or a (2-hydroxy) indanyl group. In one embodiment, the compound is characterized by formula (IV),Or a pharmaceutically acceptable salt or prodrug thereof, wherein X3 Is selected from N, CH and CR1 n series 0, 1, 2 or 3; and m, X1 , L and R1 To R5 Is as defined herein. In an embodiment, X3 Department N. In other embodiments, X3 CH or CR1 . In a preferred embodiment, X3 Department CH. In an embodiment: X3 N; n is 0, 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment: X3 N; n is 0, 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments: X3 Line CH; n series 0, 1, 2 or 3; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl and heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments: X3 Line CH; n series 0, 1, 2 or 3; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl and heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group, The cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).a Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments: X3 N; n is 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments: X3 N; n is 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments: X3 Line CH; n series 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments: X3 Line CH; n series 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 And R9 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R10 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc It is selected from the group consisting of hydroxyl, amine and halogen). In one embodiment, the compound is characterized by formula (V),Or a pharmaceutically acceptable salt or prodrug thereof, wherein R16 And R17 Is independently selected from the group consisting of hydrogen, halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and n, X1 , X3 , L, R1 And R3 Is as defined herein. In an embodiment, R16 And R17 Is independently selected from the group consisting of hydrogen, halogen, hydroxy, nitrile, and -O(C), optionally substituted with one to three groups independently selected from the group consisting of halogen, hydroxy, and nitrile.1-4 -alkyl). In other embodiments, R16 And R17 The lines are independently selected from the group consisting of hydrogen, halogen, and nitrile. In other embodiments, R16 And R17 Is independently selected from halogen and -O (C1-4 -alkyl). In an embodiment, R16 And R17 One of them is hydrogen and the other is as defined herein. In an embodiment, R16 Hydrogen and R17 Is as defined herein. In one embodiment, R16 Hydrogen and R17 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with from 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile. In other embodiments, R17 Hydrogen and R16 Is as defined herein. In one embodiment, R17 Hydrogen and R16 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -Alkyl), wherein each of the alkyl groups is optionally substituted with from 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile. In other embodiments, R16 And R17 All are hydrogen. In an embodiment, R16 -O(C) substituted with 1 to 3 groups independently selected from halogen1-3 -alkyl) and R17 Hydrogen. In an embodiment, R16 -O(C) substituted with 1 to 3 groups independently selected from halogen1-3 -alkyl) and R17 Halogen. In an embodiment, R16 Methoxy and R17 Hydrogen. In other embodiments, R16 Ethoxy and R17 Hydrogen. In an embodiment, R16 Methoxy and R17 Line Cl. In an embodiment, R16 Methoxy and R17 Is a methyl group. In an embodiment, R16 Department-OCF3 And R17 Is a methyl group. In an embodiment: X3 Line CH; n series 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen); X1 Is selected from NH, O or S; L also means direct bond; R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In an embodiment: X3 Line CH; n series 1 or 2; and R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen); X1 Is selected from NH, O or S; L also means direct bond; R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In an embodiment: X3 Line CH; n series 1 or 2; and R1 In each case independently selected from halogen, nitrile, -C(O)N(R8 R9 ), -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen); X1 Is selected from NH, O or S; L also means direct bond; R3 Is a dihydroindenyl group which is optionally substituted with 1 to 4 C, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl) and CONH2 Replaced by the group. In an embodiment: X3 Line CH; n series 1 or 2; and R1 In each case independently selected from halogen, nitrile, -N(R8 R9 ), -NHC(O)NR8 R9 ,-NHC(O)OR10 , -NHC(O)R10b , -C(O)R10b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR10 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R8 , R9 And R10 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R10b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, amino sulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl, amine and halogen); X1 Is selected from NH, O or S; L also means direct bond; R3 Is a dihydroindenyl group which is optionally substituted with 1 to 4 C, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl) and CONH2 Replaced by the group. In one embodiment, the compound is characterized by formula (VI),Or a pharmaceutically acceptable salt or prodrug thereof, wherein R18 , R19 , R20 And Rtwenty one Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and R24b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, each of which is an indenyl group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkenyl group, an alkynyl group, The cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; and wherein m and X1 , L and R2 To R5 Is as defined herein. In an embodiment, R18 , R19 , R20 And Rtwenty one Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R18 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and R24b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine sulfonyl group, The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted by 1 to 5 groups independently selected from the group consisting of :halogen, hydroxyl, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R18 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R18 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and R24b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, each of which is a mercapto group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkene group The base, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy , -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R18 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R18 Department-C(O)N(Rtwenty two Rtwenty three ), where Rtwenty two And Rtwenty three The lines are independently selected from H, C2-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl. In an embodiment, R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R24b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, The cycloalkyl, heterocycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R18 Is selected from hydrogen, halogen, -NRtwenty two Rtwenty three ,-NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl) and C1-4 -alkyl, where Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl and heteroaryl, and wherein Rtwenty four And R24b Lines are independently selected from H and C1-4 An alkyl group, and wherein each alkyl group, mercaptoamino group or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R18 Is selected from hydrogen, halogen, -NRtwenty two Rtwenty three , C2-4 - mercaptoamine, -O(C1-4 -alkyl) and C1-4 -alkyl, where Rtwenty two And Rtwenty three Lines are independently selected from H and C1-4 -alkyl, and wherein each alkyl or mercaptoamine group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R18 Lined from NH2 And selected from NH (CH)3 ), NH-pyrazolyl, NHC(O)NHCH substituted by methyl group as needed3 , NHC(O)OCH3 , NHC(O)CH3 And methyl groups, each of which is optionally substituted with 1 to 3 halogens. In other embodiments, R18 Lined from NH2 , NH (CH3 And a methyl group, which is optionally substituted with 1 to 3 halogens. In other embodiments, R18 Hydrogen. In one embodiment, R18 Lined from NH2 And NHC(O)NHCH3 . In an embodiment, R19 Is selected from hydrogen, halogen, -NRtwenty two Rtwenty three ,-NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl) and C1-4 -alkyl, where Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl and heteroaryl, and wherein Rtwenty four And R24b Lines are independently selected from H and C1-4 An alkyl group, and wherein each alkyl group, mercaptoamino group or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R19 Is selected from hydrogen, halogen, -NRtwenty two Rtwenty three , C2-4 - mercaptoamine, -O(C1-4 -alkyl) and C1-4 -alkyl, where Rtwenty two And Rtwenty three Lines are independently selected from H and C1-4 -alkyl, and wherein each alkyl or mercaptoamine group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R19 Lined from NH2 And selected from NH (CH)3 ), as needed1-4 -Alkyl substituted NH-pyrazolyl, NHC(O)NHCH3 , NHC(O)OCH3 , NHC(O)CH3 And methyl groups, each of which is optionally substituted with 1 to 3 halogens. In other embodiments, R19 Lined from NH2 , NH (CH3 And a methyl group, which is optionally substituted with 1 to 3 halogens. In other embodiments, R19 Hydrogen. In one embodiment, R18 Lined from NH2 And NHC(O)NHCH3 . In an embodiment, R19 Hydrogen and R18 Not hydrogen. In an embodiment, R20 Is selected from hydrogen, halogen, nitrile, -C(O)NRtwenty two Rtwenty three , -N(Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl and heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R20 Is selected from hydrogen, halogen, -O (C1-4 -alkyl), C1-4 An alkyl group, an aryl group and a heteroaryl group, wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R20 Is selected from the group consisting of Cl, F, methyl, methoxy, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C1-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In other embodiments, R20 Hydrogen. In an embodiment, Rtwenty one Is selected from hydrogen, halogen, -O (C1-8 -alkyl), C1-4 An alkyl group, an aryl group and a heteroaryl group, wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, Rtwenty one Is selected from the group consisting of Cl, F, methyl, methoxy, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C1-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In other embodiments, Rtwenty one Hydrogen. In an embodiment, R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In one embodiment, R18 Department-N(Rtwenty two Rtwenty three ), for example, NH2 ;R20 Halogen, for example, Cl, F or Br; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department-N(Rtwenty two Rtwenty three ), for example, NH2 ;R20 Department-O(C1-3 -alkyl), for example, methoxy, which is optionally substituted with 1 to 3 halogens; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department-N(Rtwenty two Rtwenty three ), for example, NH2 ;R20 Department C1-3 An alkyl group, for example, a methyl group, which is optionally substituted with 1 to 3 halogens; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 ;R20 Department Cl; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 ;R20 Department F; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 ;R20 Department Br; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In one embodiment, R20 Substituting a substituted phenyl group; and R18 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R20 Respectively substituted pyrazolyl; R18 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R20 Halogen, for example, Cl or Br; and R18 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R20 Department C1-3 An alkyl group, for example, a methyl group, which is optionally substituted with 1 to 3 halogens; and R18 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In one embodiment, R18 NH2 , NH (CH3 ), as needed1-4 -Alkyl substituted NH-pyrazolyl, NHC(O)NHCH3 , NHC(O)OCH3 Or NHC(O)CH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In one embodiment, R18 NH2 Or NH (CH3 ); and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department C1-3 An alkyl group, for example, a methyl group, which is optionally substituted with 1 to 3 halogens; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 ; and R20 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Is NH-pyrazolyl, which is optionally C1-4 -alkyl substitution; and R20 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department NHC(O)NRtwenty two Rtwenty three , for example, NHC(O)NHCH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department NHC(O)ORtwenty four , for example, NHC(O)OCH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NHC(O)R24b , for example, NHC(O)CH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In an embodiment: L-system - (CR6 R7 )p - where p is 1 and R6 And R7 One of them is hydrogen and the other is a C that needs to be replaced by a hydroxyl group.1-4 -alkyl; and R3 Is selected from a cycloalkyl or heteroaryl group, optionally containing 1 to 3 C, independently selected from a hydroxyl group, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl), NH2 NHSO2 CH3 , SO2 CH3 And CONH2 Replaced by the group. In other embodiments: L represents a direct key; and R3 Is selected from cycloalkyl or heteroaryl, optionally substituted by 1 to 4 C, optionally substituted by halogen or hydroxy, optionally with a hydroxyl group1-3 -alkyl, F, Cl, -O (C1-4 -alkyl), NH2 NHSO2 CH3 , SO2 CH3 And CONH2 Replaced by the group. In one embodiment: L represents a direct bond; and R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In another embodiment: L represents a direct key; and R3 Substituted by a hydroxy group and further optionally 1 to 3 C, optionally substituted by a hydroxy group, as desired1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In one embodiment: L represents a direct bond; and R3 (2-hydroxy)cyclohexyl. In one embodiment: L represents a direct bond; and R3 Is a dihydroindenyl group which is optionally substituted with 1 to 4 C, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl) and CONH2 Replaced by the group. In another embodiment: L represents a direct key; and R3 Substituted by a hydroxy group and further optionally 1 to 3 C, optionally substituted by a hydroxy group, as desired1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted with a dihydroindenyl group. In one embodiment: L represents a direct bond; and R3 It is a (1-hydroxy) dihydroindenyl group or a (2-hydroxy) indanyl group. In one embodiment, the compound is characterized by formula (VII),Or a pharmaceutically acceptable salt or prodrug thereof, wherein q is 0, 1, 2 or 3;25 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and m, X1 , R2 , R4 , R5 , R18 And R20 Is as defined herein. In an embodiment, q is 0, 1 or 2. In other embodiments, q is 1, 2 or 3. In other embodiments, q is 1 or 2. In other embodiments, q is 0. In other embodiments, q is 1. In other embodiments, q is 2. In an embodiment, each R25 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-4 -alkyl or where Rf And Rg Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment, R25 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, R25 It is bonded to a carbon atom of a cyclohexane ring which is bonded to an oxygen atom of a hydroxyl group. In one embodiment, the carbon bonded to the carbon atom of the cyclohexane ring (which is bonded to the oxygen atom of the hydroxyl group)25 The group is selected from C1-3 - alkyl, for example, methyl. In the embodiment, q series 1 and R25 Is selected from halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In the embodiment, q system 2 and each R25 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, q is 2, the first R25 Hydroxyl group, and second R25 Is selected from halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In another embodiment, R18 NH2 ;R20 Department Cl; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 ;R20 Department F; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 ;R20 Department Br; and R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 NH2 And R20 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department NH (CH3 ); and R20 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Is NH-pyrazolyl, which is optionally C1-4 -alkyl substitution; and R20 , R19 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department NHC(O)NHCH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department NHC(O)OCH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In another embodiment, R18 Department NHC(O)CH3 ; and R19 , R20 And Rtwenty one Each is independently hydrogen (or hydrazine). In one embodiment, the compound is of formula (VII)a Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, q, X1 , R2 , R4 , R5 , R18 , R20 And R25 Is as defined herein. By formula (VIIa The compound of the formula can in particular prove to have good selectivity for CSF-1R over other kinases such as c-KIT, PDGFRα, PDGFRβ and/or FLT-3 and good inhibitory activity against CSF-1R. In another embodiment, the compound is of formula (VII)b Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, q, X1 , R2 , R4 , R5 , R18 , R20 And R25 Is as defined herein. In another embodiment, the compound is of formula (VII)c Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, q, X1 , R2 , R4 , R5 , R18 , R20 And R25 Is as defined herein. In another embodiment, the compound is of formula (VII)d Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, q, X1 , R2 , R4 , R5 , R18 , R20 And R25 Is as defined herein. By formula (VIIb ), formula (VIIc ) and formula (VIId The compound characterized can particularly demonstrate good inhibitory activity against CSF-1R. In an embodiment: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R24b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group A heterocycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Is S, O or NH. In an embodiment: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Is S, O or NH. In other embodiments: R18 Is selected from hydrogen, halogen, -N (Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R24b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Is S, O or NH. In other embodiments: R18 Is selected from hydrogen, halogen, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Is S, O or NH. In other embodiments: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R24b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Department S. In other embodiments: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Department S. In other embodiments: R18 Is selected from hydrogen, halogen, -N (Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R24b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Department S. In other embodiments: R18 Is selected from hydrogen, halogen, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Department S. In one embodiment, the compound is characterized by formula (VIII),Or a pharmaceutically acceptable salt or prodrug thereof, wherein r is 0, 1, 2 or 3;26 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rq Rr ) (where Rq And Rr Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rq Rr ) (where Rq And Rr Are independently selected from hydrogen and C1-3 -alkyl), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and m, X1 , R2 , R4 , R5 , R18 And R20 Is as defined herein. In an embodiment, r is 0, 1 or 2. In other embodiments, r is 1, 2 or 3. In other embodiments, r is 1 or 2. In other embodiments, r is 0. In other embodiments, r is 1. In other embodiments, r is 2. In an embodiment, each R26 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rq Rr ) (where Rq And Rr Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rq Rr ) (where Rq And Rr Are independently selected from hydrogen and C1-4 -alkyl or where Rq And Rr Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment, R26 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rq Rr ) (where Rq And Rr Are independently selected from hydrogen and C1-3 -A, optionally substituted by hydroxyl or by 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rq Rr ) (where Rq And Rr Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, each R26 It is bonded to a saturated carbon atom in the decane moiety. In other embodiments, each R26 It is bonded to an unsaturated carbon atom in the decane moiety. In other embodiments, at least one R26 Is bonded to a saturated carbon atom in the decane moiety and at least one R26 It is bonded to an unsaturated carbon atom in the decane moiety. In one embodiment, the compound is of formula (VIII)a Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, r, X1 , R2 , R4 , R5 , R18 , R20 And R26 Is as defined herein. In one embodiment, the compound is of formula (VIII)b Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, r, X1 , R2 , R4 , R5 , R18 , R20 And R26 Is as defined herein. From formula (VIII), especially from formula (VIII)a The characterized compounds may in particular demonstrate good inhibitory activity against CSF-1R and may also show particularly high selectivity for CSF-1R over other kinases such as c-KIT, PDGFRα, PDGFRβ and/or FLT-3. In an embodiment: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Is S, O or NH. In other embodiments: R18 Is selected from hydrogen, halogen, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Is S, O or NH. In other embodiments: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Department S. In other embodiments: R18 Is selected from hydrogen, halogen, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, a cycloalkyl group, a heterocycloalkyl group The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group, heterocyclic ring The alkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl); and X1 Department S. In one embodiment, the compound is characterized by formula (IX),Or a pharmaceutically acceptable salt or prodrug thereof, wherein n is 0, 1 or 2;4 NH, O or S; and m, X1 , L and R1 To R5 Is as defined herein. In an embodiment, X4 Is O or S. In one embodiment, X4 Department S. In an embodiment: n is 1; R1 Is selected from halogen, -C(O)N(R8 R9 ) (where R8 And R9 Lines are independently selected from H and C1-4 -alkyl), sulfonyl, C1-4 -alkyl, C2-4 Alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl and amine groups and halogens; R4 And R5 Is independently selected from hydrogen; m is 0, 1 or 2; R2 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -O (C1-4 -alkyl) and C1-4 An alkyl group, wherein the alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; X1 Line S; L means direct key; and R3 Is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, wherein each cycloalkyl group, heterocycloalkyl group, aryl group and heteroaryl group are optionally selected from 1 to 5 independently selected from the following Group substitution: halogen, hydroxyl, nitrile, -N (Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment: n is 1; R1 Is selected from halogen, sulfonyl, C1-4 -alkyl, C2-4 Alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl and amine groups and halogens; R4 And R5 Is independently selected from hydrogen; m is 0, 1 or 2; R2 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -O (C1-4 -alkyl) and C1-4 -alkyl, Wherein the alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; X1 Line S; L means direct key; and R3 Is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, wherein each cycloalkyl group, heterocycloalkyl group, aryl group and heteroaryl group are optionally selected from 1 to 5 independently selected from the following Group substitution: halogen, hydroxyl, nitrile, -N (Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In one embodiment, the compound is characterized by formula (X),Or a pharmaceutically acceptable salt or prodrug thereof, wherein n is 0, 1 or 2;5 NH, O or S; and m, X1 , L and R1 To R5 Is as defined herein. In an embodiment, X5 Is O or S. In one embodiment, X5 Department S. In an embodiment: n is 1; R1 Is selected from halogen, -C(O)N(R8 R9 ) (where R8 And R9 Lines are independently selected from H and C1-4 -alkyl), sulfonyl, C1-4 -alkyl, C2-4 Alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl and amine groups and halogens; R4 And R5 Is independently selected from hydrogen; m is 0, 1 or 2; R2 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -O (C1-4 -alkyl) and C1-4 -alkyl, Wherein the alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; X1 Line S; L means direct key; and R3 Is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, wherein each cycloalkyl group, heterocycloalkyl group, aryl group and heteroaryl group are optionally selected from 1 to 5 independently selected from the following Group substitution: halogen, hydroxyl, nitrile, -N (Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment: n is 1; R1 Is selected from halogen, sulfonyl, C1-4 -alkyl, C2-4 Alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl and amine groups and halogens; R4 And R5 Is independently selected from hydrogen; m is 0, 1 or 2; R2 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -O (C1-4 -alkyl) and C1-4 An alkyl group, wherein the alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; X1 Line S; L means direct key; and R3 Is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, wherein each cycloalkyl group, heterocycloalkyl group, aryl group and heteroaryl group are optionally selected from 1 to 5 independently selected from the following Group substitution: halogen, hydroxyl, nitrile, -N (Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In one embodiment, the compound is characterized by formula (XI),Or a pharmaceutically acceptable salt or prodrug thereof, wherein n, m, X1 , L and R1 To R5 Is as defined herein. In an embodiment: n is 1 or 2; R1 Is selected from halogen, -C(O)N(R8 R9 ) (where R8 And R9 Lines are independently selected from H and C1-4 -alkyl), sulfonyl, C1-4 -alkyl, C2-4 Alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl and amine groups and halogens; R4 And R5 Is independently selected from hydrogen; m is 0, 1 or 2; R2 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -O (C1-4 -alkyl) and C1-4 An alkyl group, wherein the alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; X1 Line S; L means direct key; and R3 Is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, wherein each cycloalkyl group, heterocycloalkyl group, aryl group and heteroaryl group are optionally selected from 1 to 5 independently selected from the following Group substitution: halogen, hydroxyl, nitrile, -N (Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment: n is 1 or 2; R1 Is selected from halogen, sulfonyl, C1-4 -alkyl, C2-4 Alkynyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl Substituted by 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Ra Rb ) (where Ra And Rb Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rc (where Rc Is selected from the group consisting of hydroxyl and amine groups and halogens; R4 And R5 Is independently selected from hydrogen; m is 0, 1 or 2; R2 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -O (C1-4 -alkyl) and C1-4 An alkyl group, wherein the alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; X1 Line S; L means direct key; and R3 Is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group, wherein each cycloalkyl group, heterocycloalkyl group, aryl group and heteroaryl group are optionally selected from 1 to 5 independently selected from the following Group substitution: halogen, hydroxyl, nitrile, -N (Rd Re ) (where Rd And Re Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino, -C(O)N(Rf Rg ) (where Rf And Rg Are independently selected from hydrogen and C1-3 -alkyl or where Rf And Rg Forming a 4 to 7 membered heterocyclic group together with an intermediate nitrogen atom) and optionally substituted by an amine group or a hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In one embodiment, the compound is characterized by formula (XII),Or a pharmaceutically acceptable salt or prodrug thereof, wherein R30 , R31 And R32 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R33 R34 ), -N(R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; and wherein m and X1 , L and R2 To R5 Is as defined herein. In an embodiment, R30 , R31 And R32 Is independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R33 R34 ), -N(R33 R34 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R30 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R33 R34 ), -N(R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R30 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R33 R34 ), -N(R33 R34 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R30 Is selected from hydrogen, halogen, nitrile, -N (R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R30 Is selected from hydrogen, halogen, nitrile, -N (R33 R34 ), C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R30 Department-C(O)N(R33 R34 ), where R33 And R34 The lines are independently selected from H, C2-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl. In an embodiment, R30 Is selected from hydrogen, halogen, -C(O)N(R33 R34 ), -N(R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-4 -alkyl, where R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 Alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, alkenyl, cycloalkyl, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In an embodiment, R30 Is selected from hydrogen, halogen, -C(O)N(R33 R34 ), -N(R33 R34 ), C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-4 -alkyl, where R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and each of the mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R30 Is selected from hydrogen, halogen, -NR33 R34 ,-NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , C2-4 - mercaptoamine, -O(C1-4 -alkyl) and C1-4 -alkyl, where R33 And R34 The lines are independently selected from H, C1-4 -alkyl and heteroaryl, and wherein R35 And R35b Lines are independently selected from H and C1-4 -alkyl, and wherein each alkyl, mercaptoamine or heteroaryl is optionally substituted with from 1 to 5 groups independently selected from halogen, hydroxy, -N(Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R30 Is selected from hydrogen, halogen, -NR33 R34 , C2-4 - mercaptoamine, -O(C1-4 -alkyl) and C1-4 -alkyl, where R33 And R34 The lines are independently selected from H, C1-4 An alkyl group and a heteroaryl group, and wherein each alkyl group, mercaptoamino group or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R30 Lined from NH2 , NH (CH3 ), NHCH2 CH2 OH, as needed1-4 -Alkyl-substituted NH-pyrazolyl, optionally via C1-4 -Alkyl-substituted NH-isoxazolyl, optionally via C1-4 An alkyl-substituted NH-triazolyl group and a methyl group (which is optionally substituted with 1 to 3 halogens). In other embodiments, R30 Lined from NH2 , NH (CH3 And methyl (which is substituted by 1 to 3 halogens as needed). In an embodiment, R31 Is selected from hydrogen, halogen, nitrile, -C(O)NR33 R34 , -N(R33 R34 ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R33 And R34 Is independently selected from hydrogen, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl and heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R31 Is selected from hydrogen, halogen, -O (C1-4 -alkyl), C1-4 An alkyl group, an aryl group and a heteroaryl group, wherein each of the alkyl group, the aryl group or the heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(RsRt) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R31 Is selected from the group consisting of Cl, F, methyl, methoxy, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C1-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In other embodiments, R31 Hydrogen. In an embodiment, R32 Is selected from hydrogen, halogen, nitrile, -C(O)NR33 R34 , -N(R33 R34 ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R33 And R34 Is independently selected from hydrogen, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl and heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R32 Is selected from hydrogen, halogen, -O (C1-4 -alkyl), C1-4 An alkyl group, an aryl group and a heteroaryl group, wherein each of the alkyl, aryl or heteroaryl groups is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru It is selected from the group consisting of hydroxyl, amine and halogen). In other embodiments, R32 Is selected from the group consisting of Cl, F, methyl, methoxy, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C1-3 -alkyl and -O(C1-3 Substituted by a group of -alkyl). In other embodiments, R31 Hydrogen. In an embodiment, R31 And R32 Each is independently hydrogen (or hydrazine). In one embodiment, R30 NH2 , NH (CH3 ), NHCH2 CH2 OH, as needed1-4 -Alkyl-substituted NH-pyrazolyl, optionally via C1-4 -Alkyl substituted NH-isoxazolyl or optionally C1-4 -alkyl substituted NH-triazolyl; and R31 And R32 Each is independently hydrogen (or hydrazine). In one embodiment, R30 NH2 Or as needed1-4 -alkyl substituted NH-pyrazolyl; and R31 And R32 Each is independently hydrogen (or hydrazine). In one embodiment, R30 NH2 Or NH (CH3 ); and R31 And R32 each Independently hydrogen (or hydrazine). In another embodiment, R30 NH2 And R31 And R32 Each is independently hydrogen (or hydrazine). In another embodiment, R30 Department NH (CH3 ); and R31 And R32 Each is independently hydrogen (or hydrazine). In another embodiment, R30 Is NH-pyrazolyl, which is optionally C1-4 -alkyl substitution; and R31 And R32 Each is independently hydrogen (or hydrazine). In another embodiment, R30 NHCH2 CH2 OH; and R31 And R32 Each is independently hydrogen (or hydrazine). In another embodiment, R30 NH-triazolyl, which is optionally C1-4 -alkyl substitution; and R31 And R32 Each is independently hydrogen (or hydrazine). In another embodiment, R30 Is a NH-isoxazolyl group, which is optionally C1-4 -alkyl substitution; and R31 And R32 Each is independently hydrogen (or hydrazine). In an embodiment: L-system - (CR6 R7 )p - where p is 1 and R6 And R7 One of them is hydrogen and the other is a C that needs to be replaced by a hydroxyl group.1-4 -alkyl; and R3 Is selected from a cycloalkyl or heteroaryl group, optionally containing 1 to 3 C, independently selected from a hydroxyl group, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl), NH2 NHSO2 CH3 , SO2 CH3 And CONH2 Replaced by the group. In other embodiments: L represents a direct key; and R3 Is selected from cycloalkyl or heteroaryl, optionally substituted by 1 to 4 C, optionally substituted by halogen or hydroxy, optionally with a hydroxyl group1-3 -alkyl, F, Cl, -O (C1-4 -alkyl), NH2 NHSO2 CH3 , SO2 CH3 And CONH2 Replaced by the group. In one embodiment: L represents a direct bond; and R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In another embodiment: L represents a direct key; and R3 Substituted by a hydroxy group and further optionally 1 to 3 C, optionally substituted by a hydroxy group, as desired1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In one embodiment: L represents a direct bond; and R3 (2-hydroxy)cyclohexyl. In one embodiment: L represents a direct bond; and R3 Is a dihydroindenyl group which is optionally substituted with 1 to 4 C, optionally substituted by halogen or hydroxy, if desired1-3 -alkyl, F, Cl, -O (C1-4 -alkyl) and CONH2 Replaced by the group. In another embodiment: L represents a direct key; and R3 Substituted by a hydroxy group and further optionally 1 to 3 C, optionally substituted by a hydroxy group, as desired1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted with a dihydroindenyl group. In one embodiment: L represents a direct bond; and R3 It is a (1-hydroxy) dihydroindenyl group or a (2-hydroxy) indanyl group. In one embodiment, the compound is characterized by formula (XIII),Or a pharmaceutically acceptable salt or prodrug thereof, wherein X1 , L, R3 , R4 , R5 , R16 , R17 And R30 Is as defined herein. In an embodiment: R30 Is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R33 R34 ), -N(R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R16 -O(C) substituted with 1 to 3 groups independently selected from halogen1-3 -alkyl) and R17 Hydrogen or halogen; X1 Is selected from NH, O or S; L represents a direct bond; R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In an embodiment: R30 Is selected from halogen, nitrile, -N (R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 -醯基,C2-4 - mercaptoamine, hydroxyl, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl, C1-8 -alkyl, C2-8 -alkenyl, C2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35 The lines are independently selected from H, C1-4 -alkyl, C1-4 -alkenyl, C2-4 - mercapto, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, alkenyl group, alkynyl group A cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N ( Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R16 -O(C) substituted with 1 to 3 groups independently selected from halogen1-3 -alkyl) and R17 Hydrogen or halogen; X1 Is selected from NH, O or S; L represents a direct bond; R3 Depending on the need, 1 to 4 C independently selected from a hydroxyl group, optionally substituted with a hydroxyl group1-3 -alkyl, Cl, -O(C1-4 -alkyl) and CONH2 The group is substituted for the cyclohexyl group. In another embodiment, R16 Methoxy and R17 Hydrogen. In another embodiment, R16 Methoxy and R17 Line Cl. In another embodiment, R16 Methoxy and R17 Is a methyl group. In one embodiment, the compound is characterized by formula (XIV),Or a pharmaceutically acceptable salt or prodrug thereof, wherein s is 0, 1, 2 or 3;36 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl, aryl and heteroaryl; and m, X1 , R2 , R4 , R5 And R30 Is as defined herein. In an embodiment, s is 0, 1 or 2. In other embodiments, the s is 1, 2 or 3. In other embodiments, s is 1 or 2. In other embodiments, s is zero. In other embodiments, s is 1. In other embodiments, s is 2. In an embodiment, each R36 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Is independently selected from hydrogen and optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-4 -alkyl or where Rv And Rw Forming 4 to 7 membered heterocyclic groups together with the intervening nitrogen atom), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment, R36 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, R36 It is bonded to a carbon atom of a cyclohexane ring which is bonded to an oxygen atom of a hydroxyl group. In one embodiment, the carbon atom bonded to the cyclohexane ring (which is bonded to the oxygen atom of the hydroxyl group)36 The group is selected from C1-3 - an alkyl group (for example, a methyl group). In an embodiment, s is 1 and R36 Is selected from halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In the embodiment, s system 2 and each R36 Is independently selected from the group consisting of halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In an embodiment, s is 2, the first R36 Hydroxyl group and second R36 Is selected from halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), sulfonyl, aminosulfonyl, sulfonylamino and optionally substituted by an amine or hydroxyl group or with 1 to 3 halogens1-4 -alkyl. In one embodiment, the compound is of formula (XIV)a Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, s, X1 , R2 , R4 , R5 , R30 And R36 Is as defined herein. In one embodiment, the compound is of formula (XIV)b Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, s, X1 , R2 , R4 , R5 , R30 And R36 Is as defined herein. In one embodiment, the compound is of formula (XIV)c Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, s, X1 , R2 , R4 , R5 , R30 And R36 Is as defined herein. In one embodiment, the compound is of formula (XIV)d Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, s, X1 , R2 , R4 , R5 , R30 And R36 Is as defined herein. In an embodiment: R30 Is selected from hydrogen, halogen, -C(O)N(R33 R34 ), -N(R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-4 -alkyl, where R33 To R35 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 Alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Lines are independently selected from H and C1-3 -alkyl; m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Is S, O or NH. In other embodiments: R30 Is selected from hydrogen, halogen, -N (R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-4 -alkyl, where R33 To R35 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 Alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen); m is 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Is S, O or NH. In other embodiments: R30 Is selected from hydrogen, halogen, -C(O)N(R33 R34 ), -N(R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-4 -alkyl, where R33 To R35 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 Alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Department S. In other embodiments: R30 Is selected from hydrogen, halogen, -N (R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-4 -alkyl, where R33 To R35 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 Alkenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and wherein each of the mercaptoamine, sulfonyl, aminosulfonyl, alkyl, cycloalkyl, heterocycloalkyl The aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).s Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Each independent line H; m series 0 or 1; R2 Is selected from halogen, hydroxyl, nitrile, C1-4 -alkyl and -O(C1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from halogen; and X1 Department S. In one embodiment, the compound is characterized by formula (XV),Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R4 , R5 , R16 , R17 , R30 And R36 Is as defined herein. In an embodiment, R30 Is selected from hydrogen, halogen, -N (R33 R34 ), -NHC(O)NR33 R34 ,-NHC(O)OR35 , -NHC(O)R35b , -C(O)R35b , C2-4 - mercaptoamine, -O(C1-8 -alkyl), -C(O)OR35 , sulfonyl, aminosulfonyl and C1-8 -alkyl, where R33 To R35 The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R35b The lines are independently selected from H, C1-4 -alkyl, C1-4 An alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkenyl group, a cycloalkane The base, heterocycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Independently H; R16 -O(C) substituted with 1 to 3 groups independently selected from halogen1-4 -alkyl);R17 Is selected from H, F, Cl and CH3 ;s system 0 or 1; R36 Is selected from halogen, hydroxyl, nitrile, -N (Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rv Rw ) (where Rv And Rw Are independently selected from hydrogen and C1-3 -alkyl), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment, R30 Department-N(R33 R34 ), where R33 And R34 The lines are independently selected from H, C1-4 -alkyl, C2-4 a fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group, and wherein each of the fluorenyl, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally subjected to 1 Substituted to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rs Rt ) (where Rs And Rt Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Ru (where Ru Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Independently H; R16 Methoxy; R17 H; and s is 0. In one embodiment, the compound is characterized by the formula (XVa),Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R4 , R5 , R16 , R17 , R30 And R36 Is as defined herein. In one embodiment, the compound is characterized by the formula (XVb),Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R4 , R5 , R16 , R17 , R30 And R36 Is as defined herein. In one embodiment, the compound is characterized by the formula (XVc),Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R4 , R5 , R16 , R17 , R30 And R36 Is as defined herein. In one embodiment, the compound is characterized by the formula (XVd),Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R4 , R5 , R16 , R17 , R30 And R36 Is as defined herein. In one embodiment, the compound is characterized by formula (XVI),Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R4 , R5 , R16 To R18 , R20 And R25 Is as defined herein. In an embodiment: R18 Is selected from hydrogen, halogen, -C(O)N(Rtwenty two Rtwenty three ), -N(Rtwenty two Rtwenty three ), -NHC(O)NRtwenty two Rtwenty three ,-NHC(O)ORtwenty four , -NHC(O)R24b , -C(O)R24b , C2-4 - mercaptoamine, -O(C1-4 -alkyl), -C(O)ORtwenty four , sulfonyl, aminosulfonyl and C1-4 -alkyl, where Rtwenty two To Rtwenty four The lines are independently selected from H, C1-4 -alkyl, C2-4 - anthracenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein R24b The lines are independently selected from H, C1-4 An alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, fluorenylamino group, sulfonyl group, aminosulfonyl group, alkyl group, cycloalkyl group, hetero The cycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen, halogen, nitrile, -N (Rtwenty two Rtwenty three ), C2-4 - mercaptoamine, -O(C1-4 -alkyl), sulfonyl, aminosulfonyl, C1-4 -alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein Rtwenty two And Rtwenty three Is independently selected from hydrogen, C1-4 -alkyl, C2-4 a mercapto group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the mercapto group, mercaptoamine group, sulfonyl group, aminosulfonyl group, alkyl group, alkynyl group, cycloalkyl group A heterocycloalkyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R).k Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R4 And R5 Independently H; R16 -O(C) substituted with 1 to 3 groups independently selected from halogen1-4 -alkyl);R17 Is selected from H, F, Cl and CH3 ;q is 0 or 1; and R25 Is selected from halogen, hydroxyl, nitrile, -N (Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), optionally substituted with a hydroxyl group or with 1 to 3 halogens -O(C1-4 -alkyl), C3-8 -cycloalkyl, C2-4 - mercaptoamine, -C(O)N(Rn Ro ) (where Rn And Ro Are independently selected from hydrogen and C1-3 -alkyl), C3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens.1-4 - alkyl, aryl and heteroaryl. In an embodiment: R18 Is selected from -N(Rtwenty two Rtwenty three ) and -NHC(O)NRtwenty two Rtwenty three , where Rtwenty two And Rtwenty three The lines are independently selected from H, C1-4 -alkyl, C2-4 a fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl group, and wherein each of the fluorenyl, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally subjected to 1 Substituted to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(Rk Rl ) (where Rk And Rl Are independently selected from hydrogen and C1-3 -alkyl), -O(C1-3 -alkyl), nitrile, C3-8 -cycloalkyl, C1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C1-4 -alkyl)-Rm (where Rm Is selected from the group consisting of hydroxyl, amine and halogen; R20 Is selected from hydrogen and halogen; R4 And R5 Independently H; R16 Methoxy; R17 H; and q is 0. In one embodiment, the compound is of formula (XVI)a Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R4 , R5 , R16 To R18 , R20 And R25 Is as defined herein. In another embodiment, the compound is of the formula (XVI)b Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R4 , R5 , R16 To R18 , R20 And R25 Is as defined herein. In another embodiment, the compound is of the formula (XVI)c Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R4 , R5 , R16 To R18 , R20 And R25 Is as defined herein. In another embodiment, the compound is of the formula (XVI)d Characterization,Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R4 , R5 , R16 To R18 , R20 And R25 Is as defined herein. In one aspect, the compound is selected from the group consisting of Compounds 1 through 86: Or a pharmaceutically acceptable salt or prodrug thereof. In one embodiment, the compound is selected from the group consisting of Compounds 1 to 49 or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 7, 12, 13, 15, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 and 46; or in medicine An acceptable salt or prodrug. In another embodiment, the compound is selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 15, 17, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 44, 45 and 46; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compounds 1, 2, 3, 4, 5, 20, 23, 24, 25, 26, 27, 28, 29, 30, 31, 35, 36, 37, 38, 39, 41, 44, 45 and 46; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compounds 1, 3, 5, 25, 26, 27, 30, 36, 37, 38, 39, and 41; or a pharmaceutically acceptable salt thereof Or a prodrug. In another embodiment, the compound is selected from the group consisting of compounds 1, 3, 5, 25, 26, 27, 30, 36, 37, 38, 39, 41, 50, 51, 53, 54, 55, 56, 58, 59, 60, 61, 62, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85 and 86; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 1, 5, 37, 38, 41, 55, 58, 59, 64, 65, 69, 74, 75, 76, 77, 78, 79, 81, 82, 83, 84, 85 and 86; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of compounds 1, 2, 3, 4, 5, 6, 20, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 and 45; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compounds 1, 2, 3, 4, 5, 24, 25, 26, 27, 28, 29, 30, 31, 35, 36, 37, 38, 39, 44 and 45; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 1, 5, 27, 30, and 41; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compound 1, 5, 27, 30, 38, 41, 54, 55, 56, 58, 59, 60, 61, 62, 64, 65, 66, 68, 69, 71, 72, 73, 74, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85 and 86; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of compounds 5, 55, 58, 59, 60, 64, 65, 69, 74, 76, 77, 78, 79, 80, 81, 82, 83 and 84; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compounds 59, 55, 76, 79, 64, 82, 71, 72, 60, 56, 69, 73, 58, 80, and 77; A pharmaceutically acceptable salt or prodrug. In another embodiment, the compound is selected from the group consisting of: Compounds 1, 2, 3, 4, 15, 20, 24, 25, 26, 30, 35, 36, and 38; or pharmaceutically acceptable Salt or prodrug. In another embodiment, the compound is selected from the group consisting of Compounds 1, 2, 3, 4, 15, 20, 24, 25, 35, and 36; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 1, 2, 3, 4, 24, 25, and 36; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: 1, 2, 3, 4, 20, 24, 25, 26, 27, 30, 35, 36, and 38; or pharmaceutically acceptable Salt or prodrug. In another embodiment, the compound is selected from the group consisting of Compounds 3, 4, 24, 25, 35, 36, and 38; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 4, 24, 25, 35, and 36; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 1, 2, 4, 20, 24, 25, 30, 35, 36, and 38; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 2, 4, 24, 25, 30, 36, and 38; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 2, 4, 25, 36, and 38; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compounds 1, 2, 3, 4, 20, 24, 25, 30, 35, 36, and 38; or a pharmaceutically acceptable salt thereof or medicine. In another embodiment, the compound is selected from the group consisting of Compounds 1, 2, 4, 24, 25, 36, and 38; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 2, 24, 25, and 36; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of compounds 2, 4, 24, 25, 36, 50, 54, 55, 56, 66, 69, 70, 72, 73, and 84; A pharmaceutically acceptable salt or prodrug. In another embodiment, the compound is selected from the group consisting of compounds 3, 4, 24, 25, 35, 36, 38, 50, 51, 54, 55, 56, 66, 69, 70, 72, 73 and 84; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 36, 54, 55, 66, 69, 70, 72, and 73; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of Compounds 2, 36, 50, 54, 55, 56, 66, 69, 70, 72, 73, and 84; or a pharmaceutically acceptable salt thereof Or a prodrug. In another embodiment, the compound is selected from the group consisting of Compounds 36, 54, 55, 66, 69, 70, 72, and 73; or a pharmaceutically acceptable salt or prodrug thereof. In another embodiment, the compound is selected from the group consisting of: Compounds 50, 51, 54, 55, 56, 66, 69, 70, 72, 73, and 84; or a pharmaceutically acceptable salt or pharmaceutically acceptable salt thereof medicine. The compounds of the invention are useful as kinase inhibitors. In particular, the compounds of the invention are useful as inhibitors of CSF-1R. Assays for determining the inhibitory activity of a compound against CSF-1R (e.g., anti-mouse or human CSF-1R or a fragment thereof having protein kinase activity) are known in the art and are also listed in the following examples. The activity values listed below can be determined, for example, according to the assays listed in the examples below. In an embodiment, the compound of the invention has the following IC50 Value (eg, anti-CSF-1R inhibitory activity in cell-free assays): less than 1.5 μM, less than 750 nM, less than 500 nM, less than 400 nM, less than 300 nM, less than 200 nM, less than 150 nM, less than 100 nM, Less than 75 nM, less than 50 nM, less than 40 nM, less than 30 nM, less than 25 nM, less than 20 nM, less than 15 nM, less than 10 nM, or less than 5 nM. In other embodiments, the compounds of the invention have the following ICs50 Value (eg, inhibitory activity against CSF-1R in cell-free assays): less than 4 nM, less than 3 nM, less than 2 nM, or less than 1 nM. In an embodiment, the compound of the invention has the following IC50 Value (eg, anti-CSF-1R inhibitory activity in cell-based assays): less than 10 μM, less than 5 μM, less than 2 μM, less than 1 μM, less than 750 nM, less than 500 nM, less than 400 nM, less than 300 nM Less than 200 nM, less than 150 nM, less than 100 nM or less than 75 nM. In other embodiments, the compounds of the invention have the following ICs50 Value (eg, inhibitory activity against CSF-1R in cell-based assays): less than 65 nM, less than 40 nM, less than 30 nM, or less than 20 nM. The compounds of the invention may be more selective for CSF-1R than for other kinases (e.g., c-KIT, PDGFRα, PDGFRβ, and/or FLT3). In particular, the compounds of the invention selectively inhibit the activity of CSF-1R but not the activity of other kinases (eg, c-KIT, PDGFRα, PDGFRβ, and/or FLT3). Assays for determining the selectivity of phase compounds to CSF-1R, but not to other kinases, are known in the art. Examples of assays for determining the selectivity of a compound for CSF-1R but not for other kinases are also listed in the following examples. The selectivity values listed below can be determined, for example, according to the assays listed in the examples below. In an embodiment, the selectivity of the compound of the invention for CSF-1R is at least a multiple of the selectivity to the other kinase: at least 10 fold, at least 11 fold, at least 12 fold, at least 13 fold, at least 14 fold, At least 15 times, at least 16 times, at least 17 times, at least 18 times, at least 19 times, at least 20 times, at least 25 times, at least 30 times, at least 35 times, at least 40 times, at least 45 times, at least 50 times, at least 55 Times, at least 60 times, at least 65 times, at least 70 times, at least 75 times, at least 80 times, at least 85 times, at least 90 times, at least 95 times, at least 100 times, at least 150 times, at least 200 times, at least 250 times, At least 300 times, at least 350 times, at least 400 times, at least 450 times, at least 500 times, at least 1000 times, at least 1500 times, at least 2000 times or at least 5000 times. "Selective" means the 50% maximal inhibition of the other kinase (IC)50 The concentration of the compound is at least a greater than the concentration of the compound which causes 50% of the maximum inhibition of CSF-1R. Therefore, there is an IC of 10 nM for CSF-1R50 Value and IC of 200 nM for another kinase50 The selectivity of the compound for CSF-1R is 20 times the selectivity for the other kinase. In an embodiment, the selectivity of the compound of the invention for CSF-1R is a multiple of the selectivity to PDGFRβ: at least 2 fold, at least 2.5 fold, at least 5 fold, at least 10 fold, at least 15 fold, at least 20 Multiple, at least 25 times, at least 30 times or at least 40 times. In an embodiment, the compound of the invention is at least 5, at least 10, at least 15 times, at least 20 times, at least 30 times, at least 40 times, at least 50 times more selective for CSF-1R than for PDGFRα At least 60 times, at least 70 times, at least 80 times, at least 90 times, at least 100 times, at least 150 times, at least 200 times or at least 250 times the value. In an embodiment, the compound of the invention has at least 15 fold, at least 20 fold, at least 30 fold, at least 40 fold, at least 50 fold, at least 100 fold, at least a selectivity to CSF-1R for c-KIT. 200 times, at least 300 times, at least 400 times, at least 500 times, at least 1000 times, at least 2000 times, at least 3000 times, at least 4000 times or at least 5000 times the value. In an embodiment, the compound of the invention is at least 50 times, at least 100 times, at least 200 times, at least 500 times, at least 1000 times, at least 1500 times, at least 2000 times more selective for CSF-1R than for FLT3. At least 3000 times, at least 4000 times or at least 5000 times the value.salt The present invention discloses that a compound which is substantially alkaline can generally form a variety of different salts with various inorganic and/or organic acids. While such salts are generally pharmaceutically acceptable for administration to animals and humans, it is generally practiced to first separate the compound from the reaction mixture of the pharmaceutically unacceptable salt and then treat it with an alkaline agent. The latter is simply converted back to the free base compound, and the free base is then converted to a pharmaceutically acceptable acid addition salt. The acid addition salts of basic compounds can be readily prepared using conventional techniques, for example, by using substantially equivalent amounts of the selected mineral or organic acid in an aqueous solvent medium or a suitable organic solvent such as, for example, methanol or ethanol. Treatment of alkali compounds. Once the solvent is carefully evaporated, the desired solid salt is obtained. The positively charged compounds of the present invention (e.g., containing quaternary ammonium) can also form salts with the anionic components of various inorganic and/or organic acids. The acid which can be used to prepare a pharmaceutically acceptable salt of the compound can form a non-toxic acid addition salt, for example, a salt containing a pharmacologically acceptable anion such as chloride, bromide, iodide, nitrate, Sulfate or hydrogen sulphate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or hydrogen tartrate, succinate, malate, maleate , fumarate, gluconate, sucrose, benzoate, methanesulfonate and pamoate [ie, 1,1'-methylene-bis-(2-hydroxy-3-) Naphthoate)] salt. The present invention discloses that a compound which is acidic in nature (e.g., a compound containing a carboxylic acid or tetrazole moiety) can generally form a variety of different salts with various inorganic and/or organic bases. Although such salts are generally pharmaceutically acceptable for administration to animals and humans, it is generally practiced to first separate the compound from the reaction mixture of the pharmaceutically unacceptable salt and then treat it with an acidic reagent. The latter is simply converted back to the free acid compound and the free acid is then converted to a pharmaceutically acceptable base addition salt. Such base addition salts can be readily prepared using conventional techniques, for example, by treating the corresponding acidic compound with an aqueous solution containing the desired pharmaceutically acceptable cation, and then evaporating the resulting solution to dryness, for example, Under reduced pressure. Alternatively, the base addition salt can also be prepared by mixing together the lower carbon number alkanol solution of the acidic compound and the desired alkali metal alkoxide, and then evaporating the resulting solution to dryness in the same manner as before. In either case, the stoichiometric amount of the reagent can be used to ensure the integrity of the reaction and the maximum product yield of the desired solid salt. The bases which may be used to prepare the pharmaceutically acceptable base addition salts of the compounds may form non-toxic base addition salts, for example, salts containing a pharmaceutically acceptable cation such as an alkali metal cation (e.g., potassium and sodium). ), alkaline earth metal cations (eg, calcium and magnesium), ammonium or other water-soluble amine addition salts (such as N-methylglucamine (meglumine), low carbon number alkanolammonium, and other organic amines) Etc. alkali).Prodrug Derivatives of pharmaceutically acceptable prodrugs of CSF-1R inhibitors for use according to the invention, for example, compounds characterized by formula (I), which can be converted in vivo to the compounds described herein. Prodrugs (which may themselves have some activity) may become fully pharmaceutically active in vivo when they are, for example, subjected to solvolysis under physiological conditions or by enzymatic degradation. Methods for preparing prodrugs of the compounds as described herein will be apparent to those skilled in the art from this disclosure.Stereochemistry Stereoisomers (e.g., cis and trans isomers) of the present invention and all optical isomers (e.g., R- and S-enantiomers) and racemic races thereof Diastereomeric and other mixtures are within the scope of the invention. For example, in the group R3 In the case of one or more pendant palm atoms, the compounds of the invention may exist predominantly as a single enantiomer (or diastereomer) or as a mixture of isomers (eg, enantiomers or non-pairs)映) exists. In the examples, the compounds of the invention are present as a racemic mixture, for example, the R- and S-isomers (or all enantiomers or diastereomers) are present in approximately equal amounts. In other embodiments, the compounds of the invention are present as a mixture of isomers wherein one enantiomer (or diastereomer) is at least about 5%, 10%, 25%, 40 in enantiomeric excess. %, 70%, 80%, 90%, 95%, 97%, 98% or 99% (eg, about 100%) are present. Methods for preparing enantiomerically enriched and/or enantiomerically pure compounds will be apparent to those skilled in the art from this disclosure. Examples of such methods include chemical resolution (eg, crystallization) and paired palm chromatography. The compounds disclosed herein may exist in several tautomeric forms, including the enol and imine forms, and the keto and enamine forms as well as the geometric isomers and mixtures thereof. Tautomers are present as a mixture of tautomers dissolved in a solution. In solid form, usually one tautomer is dominant. Although one tautomer can be described, all tautomeric systems are within the scope of the invention. Where the compound is characterized by a structural formula indicative of stereochemical information, the invention extends to a mixture of one or more of the compounds characterized by the structural formula. Thus, in an embodiment, the invention provides a formula (VII)a ) and (VIIb And a mixture of a pharmaceutically acceptable salt or prodrug of the compound or one or more thereof. In other embodiments, the invention provides a formula (VIII)a ) and (VIIIb And a mixture of a pharmaceutically acceptable salt or prodrug of the compound or one or more thereof.Other forms Pharmaceutically acceptable hydrates, solvates, polymorphs and the like of the compounds described herein are also within the scope of the invention. The compounds as described herein may be in amorphous form and/or in one or more crystalline forms. Isotope-labeled compounds are also within the scope of the invention. As used herein, "isotopically labeled compound" refers to a compound disclosed herein, including each of the pharmaceutical salts and prodrugs thereof, wherein one or more of the atomic systems are different from the atomic mass typically found in nature or Atomic displacement of atomic mass or mass of mass. Examples of isotopes that may be incorporated into the compounds disclosed herein include isotopes including hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine (such as, respectively,2 H,3 H,13 C,14 C,15 N,18 O,17 O,31 P,32 P,35 S,18 F and36 Cl). Deuterated compounds (e.g., compounds of the invention having one or more hydrogen atoms replaced by deuterium) are preferred.Pharmaceutical composition The invention provides a pharmaceutical composition comprising at least one compound of the invention (e.g., a compound characterized by Formula (I)) and at least one pharmaceutically acceptable excipient (e.g., for use in accordance with the methods disclosed herein) ). Pharmaceutically acceptable excipients can be any such excipients known in the art, including those described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro ed., 1985). Pharmaceutical compositions of the compounds disclosed herein can be prepared by conventional means known in the art, including, for example, mixing at least one compound of the present invention with a pharmaceutically acceptable excipient. The pharmaceutical composition or dosage form of the invention may comprise a pharmaceutical agent and another carrier, for example, a compound or composition, inert or active, such as a detectable agent, a marker, an adjuvant, a diluent, a binder, a stabilizer, Buffers, salts, lipophilic solvents, preservatives, adjuvants or the like. Carriers also include pharmaceutical excipients and additives, for example, proteins, peptides, amino acids, lipids, and carbohydrates (eg, sugars, including monosaccharides, di-, tri-, tetra-, and oligosaccharides; derived sugars (such as alditols) , aldonic acid, esterified sugars and the like); and polysaccharides or sugar polymers), which may be present alone or in combination, comprising a combination of from 1 to 99.99%, by weight or by volume. Exemplary protein excipients include serum albumin such as human serum albumin (HSA), recombinant human albumin (rHA), gelatin, casein, and the like. Typical amino acid/antibody components (which may also function as buffering agents) include alanine, glycine, arginine, betaine, histidine, glutamic acid, aspartic acid, cysteine, Amino acid, leucine, isoleucine, valine, methionine, phenylalanine, aspartame and the like. Carbohydrate excipients are also intended to be within the scope of the invention, and examples thereof include, but are not limited to, monosaccharides (such as sugar, maltose, galactose, glucose, D-mannose, sorbose, and the like); Sugars (such as lactose, sucrose, trehalose, cellobiose, and the like); polysaccharides (such as raffinose, melezitose, maltodextrin, polydextrose, starch, and the like); and alditols (such as nectar) Alcohol, xylitol, maltitol, lactitol, xylitol sorbitol (sorbitol) and inositol). Carriers which may be employed include buffers or pH adjusting agents; typically, the buffering agents are prepared from salts of organic acids or bases. Typical buffers include organic acid salts (such as citric acid, ascorbic acid, gluconic acid, carbonic acid, tartaric acid, succinic acid, acetic acid or citric acid); Tris, tromethamine hydrochloride or phosphate buffers. Additional carriers include polymeric excipients/additives such as polyvinylpyrrolidone, polysucrose (polymeric sugar), dextran (eg, cyclodextrin (such as 2-hydroxypropyl-beta-cyclodextrin) ), polyethylene glycol, flavoring agents, antibacterial agents, sweeteners, antioxidants, antistatic agents, surfactants (eg, polysorbates (such as "TWEEN 20" and "TWEEN 80")), lipids (eg , phospholipids, fatty acids), steroids (eg, cholesterol), and chelating agents (eg, EDTA). The invention also provides pharmaceutical compositions and kits comprising such compositions comprising at least one compound as described herein (e.g., a compound characterized by Formula (I)) and at least one additional pharmaceutically active agent. These pharmaceutical compositions and kits can be adapted to allow simultaneous, sequential and/or separate administration of the compound and another active agent. For example, the compound and the other active agent may be formulated in different dosage forms, for example, formulated in different tablets, capsules, lyophilizates or liquids, or the like, or may be formulated in the same dosage form, for example, formulated in the same lozenge, In capsules, lyophilizates or liquids. Where the compound and the other active agent are formulated in the same dosage form, the compound and the other active agent may be present substantially in the mixture, for example, in the core of the tablet, or the like, or substantially The separate zones of the dosage form, for example, are present in different layers of the same tablet. Another aspect of the invention provides a pharmaceutical composition comprising: (i) a compound as described herein, for example, a compound characterized by formula (I); (ii) another active agent; and (iii) pharmaceutically acceptable Accepted excipients. Another aspect of the invention provides a kit comprising: (i) a compound as described herein, for example, a compound characterized by formula (I); (ii) instructions for use of the compound in therapy, for example, Used in a method as described herein; and (iii) as needed another active agent. In an embodiment, the additional active agent is an anti-proliferative, anti-inflammatory, anti-angiogenic, chemotherapeutic or immunotherapeutic. The pharmaceutical compositions may be formulated so as to provide a slow, prolonged or controlled release of the active ingredient therein, using, for example, varying proportions of hydroxypropyl methylcellulose to provide the desired release profile, using other polymeric matrices, lipids Body and / or microspheres. The pharmaceutical compositions may also contain opacifying agents as needed and may, in a certain portion of the gastrointestinal tract, release (or preferentially) only (or preferentially) the active ingredient in a delayed manner (eg, by using an enteric coating). Composition. Examples of embedding compositions include polymeric materials and waxes. The active ingredient may also be in microencapsulated form, if desired, together with one or more pharmaceutically acceptable carriers, excipients or diluents well known in the art (see, for example, Remington&apos;s). The compounds disclosed herein can be formulated for sustained release according to methods well known to those of ordinary skill in the art. Examples of such formulations can be found in U.S. Patent Nos. 3,119,742, 3,492,397, 3,538,214, 4,060,598 and 4,173,626.Chemical synthesis An illustrative synthetic scheme (Scheme I) is shown below for the preparation of a compound characterized by Formula (I) wherein the group R4 And R5 Both are hydrogen:Scheme I In step (i) of Scheme I, Compound A (which is commercially available or prepared according to conventional synthetic methods known to those skilled in the art) is reacted with a substituted amine via a nucleophilic aromatic substitution to produce an intermediate Matter B. In step (ii), the methoxy group is deprotected (for example, using BBr)3 ) produces intermediate C. In step (iii), a cyclic group A carrying a carbon atom to which the leaving group "LG" is bonded (which may optionally be protected, for example, optionally substituted) is involved in the nucleophilic substitution or coupling reaction to produce Target compound D. Scheme I can be altered to obtain other compounds as disclosed herein. For example, in the ring group A, in the target compound D, an alkyl group, an alkenyl group, an alkynyl group or a (hetero)aryl group (ie, R)1 In the case of substitution, the target compound may be substituted with a substituted ring group R in step (iii) of Scheme I.1 -A-C(R4 R5 ) - LG gets. Alternatively, the target compound can be acyclic A-C (R)4 R5 - LG preparation, which is subjected to a halide on a ring via a halide or a pseudohalide (for example, a triflate or an alkoxy group)1 Replaced at the place of substitution. This produces a corresponding product D' which can then be (a) in the Suzuki reaction with an organoboron species (for example, R1 -B(OH)2 Coupling; (b) in the root-bank reaction with organic zinc species (for example, (R1 )2 Zn) coupling; or (for example) (c) coupling with an alkyne in a steamed head reaction. The coupled product can be further reacted (e.g., reduced) as needed to produce the desired end product. These steps are described in Schemes II and III below:Scheme II In Scheme II, the group "Y" is a halide or pseudohalide (e.g., triflate or alkoxy). Coupling under conditions suitable for Suzuki, root bank or steamed bread to produce product D, where R1 A group usually containing at least one carbon-carbon double or triple bond. R1 The unsaturated bond in the group can be reduced, for example, as illustrated in Scheme III, wherein Compound D is catalytically hydrogenated to produce the corresponding product.Scheme III By way of another example, an illustrative synthetic scheme (Scheme IV) is shown below for the preparation of a benzothiazole compound of formula (I), which includes R2 Group (such as -O(C1-4 -alkyl) or halogen), using -OMe as an exemplary R2 Group description:Scheme IV In Scheme IV, an alkoxynitrobenzene derivative E (which is obtainable from a commercial source or prepared, for example, from a corresponding halogenated precursor) is, for example, by using a reducing agent in step (iv) (such as Raney-Ni and ruthenium) treatment, followed by cyclization in step (v) (for example, using KSCN and CuSO4 Conversion to the corresponding alkoxyaminobenzothiazole derivative F. Compound F can then be used, for example, by using t-BuONO and CuBr2 The treatment is converted to the bromobenzothiazole intermediate G. G with group H2 N-L-R3 The reaction (e.g., as described in step (i) of Scheme I) yields Compound H, which can then be deprotected to yield the corresponding aryl alcohol I (e.g., using TFA). The product J can be obtained by reacting I with a group containing "ring A", for example, as shown in step (iii) of Scheme I. It should be understood that the "ring A" addition can be added to the group NH2 -L-R3 Previously, in this case the reactions (viii) and (ix) can be carried out before the reaction (vii). It should also be understood that an intermediate such as G may have an additional R on the benzothiazole ring.2 The group is substituted to produce the corresponding substituted product. By way of example, treatment of G with sulphur in acetonitrile yields a 7-fluoro derivative which can then be passed through a reaction scheme to provide the 7-fluoro-4-methoxybenzothiazole product. By way of yet another example, an illustrative synthetic scheme (Scheme V) is shown below for the preparation of a benzothiazole compound of formula (I), which includes R2 Group (such as -O(C1-4 -alkyl) or halogen), using -OMe as an exemplary R2 Group description:Scheme V In Scheme V, the moiety containing "Ring A" is introduced prior to the formation of the benzothiazole ring. In the step (x), the compound K containing "ring A" is coupled with a substituted p-nitrophenol, for example, using Cs2 CO3 To form the intermediate L. This compound is then reduced to the corresponding aniline M (for example, using hydrogen in the presence of a Pt-C catalyst) and further reacted to form a substituted thiourea compound N (eg, by reacting with bis(1H-imidazole). 1-yl) methylthione reaction and then with NH2 -L-R3 reaction). Compound N is then cyclized to form the corresponding benzothiazole O (e.g., using BSTFA and benzyltrimethylammonium tribromide). It should be understood that the product O can be further processed, for example, in R1 Substituted or deprotected to produce other compounds of formula (I). Usually in these reactions, R4 And R5 One or both of them are hydrogen. It is also understood that a halogenated derivative of K other than a bromomethyl derivative, for example, a chloromethyl derivative, can be used. By way of yet another example, an illustrative synthetic scheme (Scheme VI) is shown below for the preparation of a benzothiazole compound of formula (I), which includes R2 a group such as -O(C1-4 -alkyl) or halogen, illustrated as an exemplary R using -OMe2 Group:Scheme VI In Scheme VI, the ortho-methoxyaniline precursor P, optionally substituted, is brominated (for example, Br in solution)2 To produce compound Q, which is then converted to the corresponding benzothiazole compound R and then S (for example, as described in steps (v) and (vi) of Scheme IV). This intermediate can then be with NH2 -L-R3 The reaction produces a compound T (e.g., as described in step (i) of Scheme I). Corresponding formation of borate U (for example, using bis(pinacol) diboron and PCy3 And Pd2 (dba)3 And subsequent hydrolysis (for example, using hydrogen peroxide) to produce the hydroxybenzothiazole compound V. Product O can be obtained by reacting V with a group containing "Ring A" (for example, as shown in Step (iii) of Scheme I). Other methods for preparing the compounds according to the present invention will be apparent to those skilled in the art from the common general knowledge and content of the present application (specifically, examples below).Medical indications The compounds described herein and pharmaceutical compositions containing the same are suitable for use in therapy, particularly in the therapeutic treatment of CSF-1R-mediated disorders in an individual. Individuals to be treated according to the methods described herein include vertebrates (such as mammals). In a preferred embodiment, the mammal is a human patient. The invention provides a method for treating a CSF-1R mediated disease in a subject, the method comprising administering to the individual an effective amount of a compound as defined herein, for example, a compound characterized by Formula (I). The invention also provides a compound as defined herein, for example, a compound characterized by Formula (I) for use in a method of treating a CSF-1R mediated disease in a subject. The invention further provides the use of a compound as defined herein (e.g., a compound characterized by Formula (I)) for the manufacture of a medicament for the treatment of a CSF-1R mediated disease in a subject. CSF-1R and its ligands have been implicated in a number of disease states, including cancer; bone disorders such as osteolysis; inflammatory disorders such as rheumatoid arthritis, atherosclerosis and inflammatory bowel disease; And neurological disorders (such as Alzheimer's disease, ALS and brain damage). In an embodiment, the CSF-1R mediated disease is selected from the group consisting of cancer, bone disorders, inflammatory disorders, and neurological disorders. CSF-1R can mediate the development and/or progression of disease in a number of ways, including: abnormal communication, CSF-1R overexpression,CSF-1R Gene mutations, overexpression of their ligands CSF-1 and IL-34 and/or their role in the development and progression of macrophages, microglia and osteoclasts. In the examples, the CSF-1R mediated disease is characterized by the overexpression of CSF-1R. In an embodiment, the CSF-1R mediated disease is characterized by aberrant CSF-1R signaling. In an embodiment, the CSF-1R mediated disease is characterized by overexpression of CSF-1 and/or IL-34. In an embodiment, the CSF-1R mediated disease is caused byCSF-1R Mutational characterization in genes. Cancer Overexpression of CSF-1R and its ligand CSF-1 occurs in a significant number of cancer types, such as in giant cell tumors of the tendon sheath, breast cancer, ovarian cancer, prostate cancer, and endometrial cancer. Concentrations of CSF-1R and CSF-1 are associated with tumor progression, cell invasion, and poor prognosis. In non-metastatic breast cancer, CSF-1R performance is associated with decreased overall survival in patients (Kluger et al, Clin. Cancer Res. (2004) 10 (1, Pt. 1): 173-7). The high degree of performance of CSF-1R in tumor stromal cells, but not in cancer cells itself, may be a sign of lower survival in Jerg's lymphoma (Koh et al., Am. J. Clin. Pathol. (2014) 141 (4) ): 573-83). The high degree of performance of CSF-1 has also been reported to be associated with higher histological tumor grade, metastasis, and poor prognosis in various cancer types including breast, ovarian, and prostate cancer (Lin et al., supra). In particular, the high systemic concentration of CSF-1 is associated with advanced metastatic cancer, such as men with prostate cancer metastasis to bone and women with progressive metastatic breast cancer. Macrophage differentiation and proliferation depend on the CSF-1R signaling pathway, and recruitment to the tumor environment is driven by the chemoattractin including CSF-1. Once recruited into the tumor microenvironment, tumor-associated macrophage (TAM) releases pro-angiogenic factors, important proteases for invasion, and other growth factors involved in the growth and movement of tumor cells. TAM is associated with many cancers, and high levels of TAM are associated with angiogenesis and malignant progression. In particular, a large number of TAMs have been identified as poor prognostic factors in several cancer types including breast cancer, prostate cancer, ovarian cancer, cervical cancer, pancreatic cancer, and Hodgkin's lymphoma (Bingle et al., 2002, supra). ; Pollard et al, Nat. Rev. Cancer. (2004) 4(1): 71-78). The reduction in the number of TAMs in various preclinical models has been shown to correlate with prolonged survival. Inhibition of CSF-1R signaling has been reported to reduce angiogenesis, reduce malignant cell growth, improve prognosis, prevent or reduce in various cancer models such as gastrointestinal stromal tumors, breast cancer, osteosarcoma, lung cancer, and prostate cancer models. Tumor progression and reduction in the number of TAM (Pyonteck et al, Nat. Med. (2013) 19(10): 1264-1272; Strachan et al, 2013, supra; Laoui et al, Front. Immunol. (2014) 5: A.489). Thus, in one embodiment, the CSF-1R mediated disease is cancer. In an embodiment, the cancer line is associated with a high amount of tumor associated macrophages (TAM). In an embodiment, the cancer line is associated with overexpression of CSF-1R and/or CSF-1. In an embodiment, the cancer line is associated with a CSF-1R mutation. Used to evaluate TAM, CSF-1R, CSF-1 andCSF-1R Methods of mutating are as described herein and/or are known to those skilled in the art. In one embodiment, the cancer is selected from the group consisting of breast cancer, cervical cancer, glioblastoma multiforme (GBM), hepatocellular carcinoma, Hodgkin's lymphoma, melanoma, pancreatic cancer, pigmentation Villonodular synovitis (PVNS), prostate cancer, ovarian cancer, giant cell tumor of the tendon sheath (TGCT), endometrial cancer, multiple myeloma, granulocytic leukemia, bone cancer, kidney cancer, brain cancer and myeloproliferative Disorder (MPD). In embodiments, administration of a compound as disclosed herein can treat an individual diagnosed with or at risk of developing cancer. In embodiments, administration of a compound as disclosed herein can improve prognosis, reduce angiogenesis, reduce the number of tumor-associated macrophages (TAM), reduce the growth of malignant cells, and/or prevent or reduce tumor progression. The inflammatory disease CSF-1R has been associated with many inflammatory disorders, such as rheumatoid arthritis, atherosclerosis, Crohn's disease, inflammatory bowel disease, sarcoma, glomerular Nephritis, allograft rejection, and atherosclerosis. Macrophages play a key role in chronic inflammation, and the increased number of such cells is associated with disease severity. These macrophage cell lines are important sources of pro-inflammatory interleukins such as TNF[alpha] and IL-Ib, which can induce CSF-1 expression in different cell types. This contributes to monocyte recruitment, differentiation and proliferation and further TNFα and IL-1b expression, which leads to a positive feedback loop that can help drive chronic inflammation. Rheumatoid arthritis is an inflammatory autoimmune disease caused by the accumulation of macrophages in connective tissue and synovial fluid. CSF-1R/CSF-1 mediated signaling has been shown to contribute to macrophage proliferation and penetration into synovial tissue. Inhibition of CSF-1R reduces disease progression, reduces damage to bone and cartilage, and reduces the number of macrophages present in the joints of patients with collagen-induced arthritis. Increased numbers of renal macrophages and high concentrations of CSF-1 are associated with several forms of immune-mediated nephritis, such as lupus nephritis. Reduced creatinine clearance is associated with high renal CSF-1 concentration. In a mouse model of lupus nephritis, CSF-1R antibodies are reduced in macrophage recruitment and proliferation at the site of nephritis. Microglia play an important role in the immune response in the central nervous system and are thought to play a role in regulating the neuroinflammatory response associated with brain diseases. CSF-1R signaling is important for the proliferation and survival of microglia in adult brain, and CSF-1R knockout mice lack microglia. The proliferation and activation coefficient of microglial cells are characterized by neuroinflammatory diseases, including experimental autoimmune encephalomyelitis (EAE), HIV encephalitis, neurodegenerative disorders (such as Alzheimer's disease and ALS). ), stroke and brain damage. Increased microglial cell proliferation is associated with increased CSF-1R up-regulation and in some cases with disease severity. CSF-1 has been reported to promote inflammation in Alzheimer's disease and ALS. In a mouse model of Alzheimer's disease, treatment with CSF-1R inhibitors has been reported to block microglial cell proliferation, deplete microglial cell populations, and promote anti-inflammatory patterns (Luo et al. J. Exp. Med. (2013) 210(1): 157-72; Dagher et al., J. Neuroinflammation (2015) 12: 139; Olmos-Alonso et al., Brain (2016) 139 (Pt. 3): 891 -907). Thus, in one embodiment, the CSF-1R mediated disease is an inflammatory disorder. In an embodiment, the inflammatory disorder is associated with high amounts of macrophages or microglia. In an embodiment, the inflammatory disorder is associated with high performance CSF-1R and/or CSF-1. In an embodiment, the inflammatory disorder is selected from the group consisting of psoriatic arthritis, arthritis, asthma, thyroiditis, glomerulonephritis, atherosclerosis, psoriasis, Hugh's syndrome, rheumatoid arthritis, Systemic lupus erythematosus (SLE), cutaneous lupus erythematosus, inflammatory bowel disease (including Crohn's disease and ulcerative colitis (UC)), type 1 diabetes, multiple sclerosis, and neuroinflammatory conditions (such as HIV) Encephalitis, Alzheimer's disease and ALS). Bone Diseases Osteoclasts can resorb bone-derived multinucleated cells and play a key role in several bone diseases including osteoporosis, inflammatory osteolysis and bone erosion. An increase in the number of osteoclasts and an imbalance in the number of osteoclast-osteoblasts results in an abnormally high rate of bone resorption. CSF-1 and CSF-1R play important roles in osteoclast survival and differentiation. It has been reported that mice with a single point mutation in CSF-1 have a reduced number of osteoclasts and developed osteosclerosis; simultaneous removal of CSF-1 from osteoclast culture leads to osteoclasts Apoptosis. Osteoporosis is a bone disease caused by osteoblast degeneration and increased osteoclast-dependent bone resorption. It has been reported that treatment of osteoporosis mouse models with anti-CSF-1 antibodies protects bone density and inhibits bone resorption (Sauter et al, J. Leukoc. Biol. (2014) 96(2): 265-274). Paget's disease is a metabolic disorder associated with increased bone turnover. Mutations have been made in many genes (includingCSF-1 It is recognized that these mutations are associated with the regulation of osteoclast function that makes individuals susceptible to Paget's disease. CSF-1 also plays a potential role in the pathogenesis of root-enveitis (a dental inflammatory disease associated with bone resorption) (Rabello et al, Biochem. Biophys. Comm. (2006) 3(1):791 -796). Studies have also shown that inhibition of CSF-1R contributes to bone protection. For example, treatment with inhibitors of CSF-1R has been reported to inhibit bone degeneration in osteoclast cultures, rat cranial crests, and rat fetal bones (Conway et al, Proc. Natl. Acad. Sci. USA (2005) 102 (44): 16078-16083). Thus, in one embodiment, the CSF-1R mediated disease is selected from the group consisting of osteoporosis, osteoarthritis, root periosteum, periprosthetic osteolysis, and bone disorders of Paget's disease. Combination Therapy In the Examples, treatment of a CSF-1R mediated disease as disclosed herein is achieved by administering a combination of a compound of the invention and another therapeutic intervention for the CSF-1R mediated disease. . Other therapeutic interventions can be carried out before, during and/or after administration of the compounds of the invention. In embodiments, other therapeutic interventions include administration of a pharmaceutical agent as disclosed herein, particularly an anti-proliferative, anti-inflammatory, anti-angiogenic, chemotherapeutic or immunotherapeutic. In the examples, other therapeutic interventions are adoptive t cell metastases. In other embodiments, the other therapeutic intervention is radiation therapy.Administration and dosage The compounds disclosed herein may be formulated for oral, buccal, parenteral (eg, intravenous, intraperitoneal, intramuscular or subcutaneous), topical, rectal or intranasal administration or for inhalation or A pharmaceutical composition is blown into the form of administration. In one embodiment, the compound or pharmaceutical composition is formulated for systemic administration, for example, via a parenteral route. In another embodiment, the compound or pharmaceutical composition is formulated for oral administration, for example, in solid form. Such modes of administration and methods for preparing suitable pharmaceutical compositions are described, for example, in Gibaldi&apos;s Drug Delivery Systems in Pharmaceutical Care (1st Edition, American Society of 15 Health-System Pharmacists 2007). In solid dosage forms for oral administration (eg, capsules, lozenges, pills, dragees, powders, granules, and the like), the active ingredient is combined with one or more pharmaceutically acceptable carriers, excipients or Diluent (such as sodium citrate or dicalcium phosphate) and / or any of the following: (1) filler or filler, such as starch, lactose, sucrose, glucose, mannitol, microcrystalline cellulose, calcium phosphate And/or citric acid; (2) binders such as, for example, carboxymethylcellulose, alginates, gelatin, pregelatinized corn starch, polyvinylpyrrolidone, hydroxypropylmethylcellulose, sucrose and / or gum arabic; (3) humectants, such as glycerin; (4) disintegrants, such as agar-agar, calcium carbonate, sodium starch glycolate, potato or tapioca starch, alginic acid, certain citrates and sodium carbonate (5) a solution retarder such as paraffin; (6) an absorption enhancer such as a quaternary ammonium compound; (7) a wetting agent such as, for example, sodium lauryl sulfate, ethyl citrate, and glyceryl monostearate; (8) absorbents such as kaolin and bentonite; (9) lubricants such as talc, two Of silicon, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and (10) coloring agents. In the case of capsules, lozenges and pills, the pharmaceutical compositions may also contain buffering agents. Solid compositions of a similar type may also be prepared in soft and hard-filled gelatin capsules using fillers and excipients such as lactose or milk sugar, and high molecular weight polyethylene glycols and the like. Tablets may be compressed or molded, optionally with one or more accessory ingredients. The compressed tablet may be a binder (for example, gelatin or hydroxypropyl methylcellulose), a lubricant, an inert diluent, a preservative, a disintegrant (for example, sodium starch glycolate or croscarmellose). Prepared by sodium, surfactants and/or dispersants. Molded lozenges can be prepared by molding in a suitable machine a mixture of the powdery active ingredient moistened with an inert liquid diluent. Tablets and other solid dosage forms, such as dragees, capsules, pills, and granules, may be prepared by scoring or by coating and shell, such as enteric coatings and other coatings well known in the art. In an embodiment, the pharmaceutical composition can be administered orally in solid form. Liquid dosage forms for active administration of active ingredients include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. Liquid preparations for oral administration can be presented as a dry product in water or other suitable vehicle before use. In addition to the active ingredient, the liquid dosage form may contain inert diluents conventional in the art such as, for example, water or other solvents, solubilizers and emulsifiers such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl Alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, oil (for example, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerin, tetrahydrofuranol, polyethylene glycol And fatty acid esters of sorbitol and mixtures thereof. In addition to the inert diluent, the liquid pharmaceutical compositions may include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening agents, flavoring agents, coloring agents, perfuming agents and preservatives, and the like. In addition to the active ingredient, the suspension may contain suspending agents such as, but not limited to, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, Bentonite, agar-agar and tragacanth and mixtures thereof. Suitable liquid preparations may employ pharmaceutically acceptable additives such as suspending agents (for example, sorbitol syrup, methylcellulose or hydrogenated edible fats); emulsifiers (for example, lecithin or gum arabic); non-aqueous carriers ( For example, almond oil, oily esters or ethanol) and/or preservatives (for example, methyl or propyl paraben or sorbic acid) are prepared by conventional means. The active ingredient can also be administered as a bolus, elixirs or paste. For buccal administration, the compositions may take the form of lozenges or lozenges formulated in a conventional manner. In an embodiment, the pharmaceutical composition is administered parenterally, such as by topical administration, transdermal administration, injection, and the like. In related embodiments, the pharmaceutical compositions are administered parenterally by injection, infusion or transplantation (eg, intravenous, intramuscular, intraarterial, subcutaneous, and the like). The compounds disclosed herein can be formulated for parenteral administration by injection, including the use of conventional catheterization or infusion. Formulations for injection may be presented in unit dosage form, for example, in ampoules or in multi-dose containers with the addition of a preservative. The compositions may take such forms as suspensions, solutions or emulsions in oils or aqueous vehicles, and may contain formulating agents such such such such such such such such such such such such, Alternatively, the active ingredient may be in the form of a powder reconstituted with a suitable carrier (for example, sterile pyrogen free water) before use. The pharmaceutical composition can be in the form of a sterile injectable preparation. The pharmaceutical compositions can be incorporated into the sterilizing agent by, for example, filtering a filter that retains the bacteria or by dissolving the sterilizing agent in a sterile solid composition that can be dissolved in sterile water or some other sterile injectable medium immediately prior to use. Sterilization. To prepare the compositions, the active ingredient is dissolved or suspended in a liquid carrier such as a parenterally acceptable carrier. Exemplary carriers and solvents include, but are not limited to, water; water adjusted to a suitable pH by the addition of an appropriate amount of hydrochloric acid, sodium hydroxide or a suitable buffer; 1,3-butanediol; Ringer's solution and the like Sodium chloride solution. The pharmaceutical composition may also contain one or more preservatives (for example, methylparaben, ethylparaben or n-propyl p-hydroxybenzoate). To improve solubility, a dissolution enhancer or solubilizer or solvent may be added to contain 10 to 60% w/w of propylene glycol or the like. The pharmaceutical compositions may contain one or more pharmaceutically acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions or emulsions or sterile powders which may be reconstituted into sterile injectable solutions or dispersions before use. liquid. Such pharmaceutical compositions may contain an antioxidant; a buffer; a bacteriostatic agent; a solute (which renders the formulation isotonic with the blood of the intended recipient); a suspending agent; a thickening agent; a preservative and the like. Examples of suitable aqueous and non-aqueous vehicles, which may be used in the pharmaceutical compositions of the invention, include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, Vegetable oils such as olive oil and injectable organic esters such as ethyl oleate. Suitable fluidity can be maintained, for example, by the use of a coating material such as lecithin; by the maintenance of the required particle size in the case of dispersion; and by the use of surfactants. In some embodiments, to prolong the effect of the active ingredient, it is desirable to slow the absorption of the compound from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of a crystalline or amorphous material having a poor water solubility. The rate of absorption of the active ingredient will depend on its rate of decomposition, which may further depend on the size of the crystal and the crystalline form. Alternatively, delayed absorption of the parenterally administered active ingredient is accomplished by dissolving or suspending the compound in an oil vehicle. In addition, extended absorption of the injectable pharmaceutical form can be brought about by the inclusion of agents which delay absorption, such as aluminum monostearate and gelatin. The controlled release parenteral composition can be in the form of an aqueous suspension, microspheres, microcapsules, magnetic microspheres, oil solution, oil suspension, emulsion, or the active ingredient can be incorporated into a biocompatible carrier, liposome, nai Rice granules, grafts or infusion devices. Materials for preparing microspheres and/or microcapsules include, but are not limited to, biodegradable/bioerodible polymers such as polylactic acid, poly(isobutyl cyanoacrylate), poly(2-hydroxyethyl) -L-glutamic acid) and poly(lactic acid). Biocompatible carriers that can be used in formulating controlled release parenteral formulations include carbohydrates (such as polydextrose), proteins (such as albumin, lipoproteins, or antibodies). The material for the graft may be non-biodegradable (eg, polydimethylmethoxane) or biodegradable (such as, for example, poly(caprolactone), poly(lactic acid), poly(glycolic acid) or poly (orthoester)). For topical administration, the compounds disclosed herein can be formulated as an ointment or cream. The compounds disclosed herein may also be formulated in rectal compositions such as suppositories or retention enemas, for example, containing conventional suppository bases such as cocoa butter or other glycerides. For intranasal administration or administration by inhalation, the compounds disclosed herein may be in the form of a solution or suspension that is squeezed or pumped by a patient from a pump spray container or from a pressurized container or nebulizer. The aerosol spray is presented and conveniently delivered using a suitable propellant (eg, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas). In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. The pressurized container or nebulizer can contain a solution or suspension of the compounds disclosed herein. Capsules and medicated cartridges (e.g., made from gelatin) for use in an inhaler or insufflator can be formulated to contain a powder mixture of a compound of the present invention and a suitable powder base such as lactose or starch. Generally, the agents and compositions described herein are administered in an amount or amount effective to inhibit CSF-1R in an individual receiving the agent or composition. Generally, the dosage can be adjusted based on, for example, age, physical condition, weight, sex, diet, time of administration, and other clinical factors. The effective amount may also vary depending on the mode of administration (eg, intravenous injection as compared to oral administration) and the nature of the composition (eg, rapid decomposition compared to sustained release compositions). The determination of the effective amount is within the capabilities of those skilled in the art. Generally, an effective amount for administration to an individual is in the range of from about 0.1 to 1000 mg/kg. In other aspects, the invention provides a dosage form or pharmaceutical composition for use in therapy (e.g., for use in a method as defined herein) as described herein. The following general description is provided to provide the following non-limiting examples to further illustrate the invention. InstanceInstance 1 to 49 : Chemical synthesis Example 1: (1R,2R)-2-((6-((2-Amino-3-chloropyridin-4-yl)methoxy)benzo[d]thiazol-2-yl)amino)cyclo) Hex-1-olThe title compound was synthesized according to the following synthetic scheme:Step 1: 2,3-Dichloroisonicotinic acid (960 mg, 5.00 mmol) and BH at 60 ° C3 • A mixture of THF (1.0 M, 25 mL, 25 eq.) was heated for 4 hours. After cooling to room temperature, MeOH (5 mL) was added and the volatiles were evaporated. The reaction mixture was diluted with water (50 mL) and EtOAc (EtOAc) The combined organic phase is washed with brine (100 mL) over Na2 SO4 Drying, filtration and concentration gave (2,3-dichloropyridin-4-yl)methanol (400 mg, 45%). MS (ES+) C6 H5 Cl2 NO required value: 178, measured value: 179 [M+H]+ .1 H NMR (500 MHz, d6 - DMSO) δ 8.38 (d, J = 5 Hz, 1H), 7.58 (d, J = 5 Hz, 1H), 5.85-5.75 (br s, 1 H), 4.61 (s, 2H). Step 2: (2,3-Dichloropyridin-4-yl)methanol (200 mg, 1.12 mmol) and (4-methoxyphenyl)methanamine (1.0 mL, 7.65 mmol, 6.8 eq. The mixture was heated for 4 hours. The reaction mixture was concentrated. Residues were preparative HPLC by mass triggering (mobile phase: A = 0.1% TFA/H2 O, B = 0.1% TFA/MeCN; gradient: B = 10 - 90%; 12 min; column: C18) purified to give (3-chloro-2-(4-methoxybenzylamine) as a white solid Base pyridin-4-yl)methanol (200 mg, 64%). MS (ES+) C14 H15 ClN2 O2 Required value: 278, measured value: 279 [M+H]+ .1 H NMR (500 MHz, d6 -DMSO) δ 7.93 (d, J = 5.5 Hz, 1H), 7.23 (d, J = 9 Hz, 2H), 6.85 (d, J = 9 Hz, 2H), 6.78 (d, J = 5.5 Hz, 1H ), 4.53 (s, 2H), 4.50 (s, 2H), 3.70 (s, 3H). Step 3: 3-Chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methanol (50 mg, 0.18 mmol) and SOCI at rt2 (2.0 mL, 27 mmol) mixture in DCM (2 mL) The volatiles were removed under reduced pressure to give 3-chloro-4-(chloromethyl)-N-(4-methoxybenzyl)pyridin-2-amine (50 mg, 94%). MS (ES+) C14 H14 Cl2 N2 O required value: 297, measured value: 298 [M+H]+ .1 H NMR (500 MHz, d6 -DMSO) δ 7.96 (d, J = 5.5 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 5.5 Hz, 1H ), 4.76 (s, 2H), 4.60 (s, 2H), 3.71 (s, 3H). Step 4: 2-Bromo-6-methoxybenzo[d]thiazole (3.00 g, 12.3 mmol) and (1R,2R)-2-aminocyclohexanol (4.25 g, 36.9 mmol) at 110 °C The mixture was heated for 6 hours. The reaction was cooled to room temperature, diluted with H~~~~ The combined organic extract is tied to Na2 SO4 Drying and concentrating to give (1R,2R)-2-((6-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol as a brown solid (3.5 g, 88 %). MS (ES+) C14 H18 N2 O2 S required value: 278, measured value: 279 [M+H]+ .1 H NMR (500 MHz, CDCl3 ) δ 7.37 (d, J = 11 Hz, 1H), 7.03 (d, J = 3.5 Hz, 1H), 6.84 (dd, J = 11, 3.5 Hz, 1H), 6.27 (bs, 1H), 3.78 (s , 3H), 3.4-3.35 (m, 2H), 2.12-2.01 (m, 2H), 1.70-1.65 (m, 2H), 1.38-1.16 (m, 4H). Step 5: Slowly at 0 ° C to a solution of 2-(6-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (3.00 g, 10.8 mmol) in DCM (30 mL) Boron tribromide (5.4 g, 21 mmol) was added. The resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was then treated with ice water (20 mL) followed by saturated NaHCO3 (10 mL) slowly diluted. The resulting precipitate was filtered and collected to give 2-((((((()))))))). . MS (ES+) C13 H16 N2 O2 S required value: 264, measured value: 265 [M+H]+ .1 H NMR (500 MHz, d4 -MeOD) δ 7.12 (d, J = 9 Hz, 1H), 6.89 (d, J = 2 Hz, 1H), 6.62 (dd, J = 9, 2 Hz, 1H), 3.50-3.41 (m, 1H) , 3.31-3.36 (m, 1H), 2.10-2.03 (m, 1H), 1.98-1.93 (m, 1H), 1.70-1.59 (m, 2H), 1.36-1.17 (m, 4H). Step 6: 3-Chloro-4-(chloromethyl)-N-(4-methoxybenzyl)pyridin-2-amine (50 mg, 0.17 mmol), 2-((1R,) at 80 °C. 2R)-2-hydroxycyclohexylamino)benzo[d]thiazole-6-ol (45 mg, 0.17 mmol) and Cs2 CO3 The mixture (110 mg, 0.34 mmol) in DMF (2 mL The volatiles were removed under reduced pressure. The residue was prepared by preparative HPLC (mobile phase: A = 0.1% TFA/H)2 O,B = 0.1% TFA/MeCN; Gradient: B = 5 - 95%; 12 min; Column: C18) Purified to give (1R,2R)-2-(6-(3-chloro) as a white solid 2-(4-Methoxybenzylamino)pyridin-4-yl)methoxy)benzo[d]thiazol-2-ylamino)cyclohexanol (30 mg, 34%). MS (ES+) C27 H29 ClN4 O3 S required value: 524, measured value: 525 [M+H]+ . Step 7: (1R,2R)-2-(6-((3-Chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy)benzoate at room temperature A mixture of [d]thiazol-2-ylamino)cyclohexanol (30 mg, 0.06 mmol) in EtOAc (2 mL) The volatiles were removed under reduced pressure. The residue was prepared by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 5 - 95%; 12 min; Column: C18) Purified to give (1R,2R)-2-(6-(2-amino-3-) as a white solid Chloropyridin-4-yl)methoxy)benzo[d]thiazol-2-ylamino)cyclohexanol (5 mg, 21%). MS (ES+) C19 Htwenty one ClN4 O2 S required value: 404, measured value: 405 [M+H]+ .1 H NMR (500 MHz, d6 -DMSO) δ 7.90 (d, J = 5.0 Hz, 1H), 7.72 (d, J = 7.5 Hz, 1H), 7.36 (d, J = 2.5 Hz, 1H), 7.26 (d, J = 8.5 Hz, 1H ), 6.88 (dd, J = 8.5, 2.5 Hz, 1H), 6.72 (d, J = 5.0 Hz, 1H), 6.31 (s, 2H), 5.07 (s, 2H), 4.73 (d, J = 5.5 Hz) , 1H), 3.52~3.48 (m, 1H), 3.36~3.31 (m, 1H), 2.06~2.04 (m, 1H), 1.89~1.86 (m, 1H), 1.64 – 1.60 (m, 2H), 1.29 – 1.17 (m, 4H). The following examples in Table 1 were prepared similarly to Example 1. Table 1: Instance 50 to 86 : Chemical synthesis Example 50: (1R,2R)-2-({6-[(2-Amino-3-chloropyridin-4-yl)methoxy]-4-methoxy-1,3-benzothiazole- Synthesis of 2-yl}amino)cyclohexan-1-olThe title compound was synthesized according to the following synthetic scheme:Step 1: To a solution of phenylmethanol (41.0 g, 380 mmol) in EtOAc (EtOAc) The reaction mixture was stirred for 0.5 h then 4-fluoro-2-methoxy-1-nitrobenzene (50.0 g, 292 mmol). The mixture was stirred at room temperature for 1 hour. The reaction was quenched with EtOAc (EtOAc)EtOAc. LC-MS (ES+) C14 H13 NO4 Required value: 259, measured value: 260 (M+H)+ . Step 2: Add Raney Nickel (3.0 g) to a solution of 4-(benzyloxy)-2-methoxy-1-nitrobenzene (75.0 g, 290 mmol) in MeOH (800 mL). ), then drop N2 H4 .H2 O (44.0 g, 870 mmol). The mixture was stirred overnight at room temperature. The reaction mixture is saturated NH4 OH (200 ml) was quenched and extracted with EtOAc (100 mL EtOAc). The organic layer was dried, filtered and concentrated under reduced vacuum to afford 4-(benzyloxy)-2-methoxyaniline (56 g, 84%). LC-MS (ES+) C14 H15 NO2 Required value: 229, measured value: 230 (M+H)+ . Step 3: Add KSCN (59.3 g, 0.611 mol) to a solution of 4-(benzyloxy)-2-methoxyaniline (28.0 g, 0.122 mol) in methanol (600 mL).4 (195g, 1.22 mol). The mixture was stirred at 90 ° C overnight and concentrated under reduced pressure. The residue was dissolved in DCM (500 mL). The combined organic layer is saturated NH4 Wash with OH (500 mL). The aqueous layer was extracted with dichloromethane. The combined organic layers were concentrated under reduced pressure. The residue was purified by oxime gel chromatography (50% to 100% EtOAc in petroleum ether) to yield 6-(benzyloxy)-4-methoxybenzo[d]thiazole-2 as a black solid. -Amine (13 g, 37%). LC-MS (ES+) C15 H14 N2 O2 S required value: 286, measured value: 287 (M+H)+ . Step 4: Add to a suspension of 6-(benzyloxy)-4-methoxybenzo[d]thiazol-2-amine (22.0 g, 0.077 mol) in acetonitrile (100 mL) at 0 °C -BuONO (11.8 g, 0.110 mol). The mixture was stirred for 30 minutes and then CuBr was added.2 (10.3 g, 0.046 mol). The reaction was stirred for a further 2 hours at room temperature. Water was added, the precipitate was filtered and the filtrate was extracted with EtOAc. The combined organic layer is water, dilute saturated NH4 Wash with OH, brine and concentrate under reduced pressure. The residue was purified by silica gel chromatography (10%EtOAcEtOAcEtOAc) elute g, 30%). LC-MS (ES+) C15 H12 BrNO2 S required value: 349, measured value: 350 (M+H)+ . Step 5: 6-(Benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (3.50 g, 10.0 mmol), (1R, 2R)-2-amino ring at 110 °C A mixture of hexanol (3.45 g, 30.0 mmol) and DIPEA (5.16 g, 40.0 mmol) in DMF (10 mmol The reaction was cooled to room temperature, diluted with EtOAc EtOAc m. The combined organic extracts are washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying and concentrating to give (1R,2R)-2-(6-(benzyloxy)-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol as a brown solid ( 3.8 g, 100%, coarse). MS (ES+) Ctwenty one Htwenty four N2 O3 S required value: 384, measured value: 385 [M+H]+ . Step 6: (1R,2R)-2-(6-(Benzyloxy)-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (1152 mg, at 65 ° C, 3.0 mmol) of the solution in TFA (10 mL) was heated for 48 hours. The solvent was removed and the reaction mixture was saturated NaHCO3 It was slowly diluted and extracted with EtOAc (3×50 mL). The combined organic extracts are washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying and concentrating to give 2-((1R,2R)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol (882 mg, 100%, Crude). MS (ES+) C14 H18 N2 O3 S required value: 294, measured value: 295 [M+H]+ . Step 7: 3-Chloro-4-(chloromethyl)-N-(4-methoxybenzyl)pyridin-2-amine (Example 1, Step 3; 202 mg, 0.68 mmol) at 80 °C 2-((1R,2R)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol (200 mg, 0.68 mmol) and Cs2 CO3 The mixture (443 mg, 1.36 mmol) in DMF (2 mL The mixture was diluted with water (30 mL) and EtOAc (3 &lt The combined organic phase is washed with water (100 ml) and brine (100 ml) over Na2 SO4 Drying and concentrating to give (1R,2R)-2-(6-((3-chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy) as a brown solid. 4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (300 mg, 79%, crude). MS (ES+) C28 H31 ClN4 O4 S required value: 554, measured value: 555 [M+H]+ . Step 8: (1R,2R)-2-(6-((3-Chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy)-4 at room temperature A mixture of methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (300 mg, 0.54 mmol) in TFA (2 mL) The volatiles were removed under reduced pressure. The residue was prepared by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 5 - 95%; 12 min; Column: C18) Purified to give (1R,2R)-2-(6-(2-amino-3-) as a white solid Chloropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (19 mg, 8%). MS (ES+) C20 Htwenty three ClN4 O3 S required value: 434, measured value: 435 [M+H]+ .1 H NMR (500 MHz, DMSO) δ 8.50 (s, 1H), 7.95 (d, J = 5.4 Hz, 1H), 7.04 (s, 1H), 6.85 (d, J = 5.5 Hz, 1H), 6.69 (s , 1H), 5.14 (s, 2H), 3.88 (s, 3H), 3.60 (d, J = 11.0 Hz, 1H), 3.32 (dd, J = 17.5, 11.8 Hz, 1H), 2.01 (d, J = 13.0 Hz, 1H), 1.89 (d, J = 8.9 Hz, 1H), 1.70 – 1.56 (m, 2H), 1.42 – 0.92 (m, 4H). The following examples in Table 2 were prepared analogously to Example 50. Table 2: Example 54: (1S,2S)-2-((6-((2-Amino-3-fluoropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazole-2- Amino)cyclohexan-1-olThe title compound was synthesized according to the following synthetic scheme:Step 1: a solution of 2-chloro-3-fluoroisonicotinic acid (5.0 g, 28 mmol) and 4-methylmorpholine (3.8 mL, 7.0 mmol) in anhydrous THF (150 mL) Isobutyl chloroformate (4.5 mL, 34 mmol) was added dropwise and stirred for 1 hour. The reaction mixture was diluted with THF (50 mL) and filtered over Celite. Cool the filtrate to 0 ° C and add NaBH4 (1.0 g, 28 mmol), and the mixture was stirred for 30 min. The reaction mixture is made up of 10% KHSO4 (5 mL) was discontinued. The volatiles were removed under reduced pressure and the mixture was diluted with EtOAc EtOAc. Separate the layers and the organic layer with water (50 mL) followed by saturated NaHCO3 (2 x 50 mL) cleaning in MgSO4 Dry over, filter and concentrate under reduced pressure. The residue was triturated with 5:1 hexane-ether (50 mL). The resulting solid was filtered and collected to give (2-chloro-3-fluoropyridin-4-yl)methanol (3.7 g, 80%). MS (ES+) C6 H5 ClFNO required value: 161, measured value: 162 [M+H]+ . Step 2: To a solution of (2-chloro-3-fluoropyridin-4-yl)methanol (1.0 g, 6.2 mmol) in DCM (25 mL) The resulting mixture was stirred at 0 ° C for 2 hours and then stirred at room temperature overnight. The reaction mixture was diluted with DCM (20 mL) and 10% NaHCO3 (5 mL) for cleaning. The layers were separated and the organic layer was washed with brine (5 mL)4 It was dried, filtered and concentrated under reduced pressure to give 4-(bromomethyl)-2-chloro-3-fluoropyridine (1.1 g, 79%). MS (ES+) C6 H4 BrClFN required value: 223, measured value: 224, 226 [M+H]+ . Step 3: To 3-methoxy-4-nitrophenol (0.750 g, 4.46 mmol) and 4-(bromomethyl)-2-chloro-3-fluoropyridine (1.0 g, 4.4 mmol) Add Cs to the solution in DMF/THF (10 mL)2 CO3 (2.2 g, 6.7 mmol) and the mixture was stirred at room temperature for 20 hours. Ice cold water (20 mL) was added to the reaction mixture, stirred for 10 min and filtered over a Buchner funnel. The solid was washed with cold water (10 mL) and dried in vacuo for 2 hr to afford 2-chloro-3-fluoro-4-((3-methoxy-4-nitrophenoxy)methyl as a white solid. Pyridine (1.34 g, 96%). MS (ES+) C13 H10 ClFN2 O4 Required value: 312, measured value: 313 [M+H]+ . Step 4: The reaction vessel was charged with 2-chloro-3-fluoro-4-((3-methoxy-4-nitrophenoxy)methyl)pyridine (1.3 g, 15 mmol), 10% Pt. -C (130 mg) and 5:1 THF/MeOH (24 mL). Suspension by N2 Degas for 1 minute and use H2 Purify for 1 minute. In H2 The reaction mixture was stirred at 20 PSI for 1 hour under an atmosphere. The reaction mixture is N2 Purification, filtration through celite, and concentration under reduced pressure to give 4-((2-chloro-3-fluoropyridin-4-yl)methoxy)-2-methoxyaniline as a pale yellow powder. g, 94%). MS (ES+) C13 H12 ClFN2 O2 Required value: 282, measured value: 283 [M+H]+ . Step 5: To a solution of 4-((2-chloro-3-fluoropyridin-4-yl)methoxy)-2-methoxyaniline (1.1 g, 3.9 mmol) in DCM (60 mL) (1H-Imidazol-1-yl)methylthione (0.97 g, 5.5 mmol) and the mixture was stirred at room temperature for 3 hr. To this solution was added (1S,2S)-2-aminocyclohexanol (0.9 g, 7.8 mmol) and the mixture was stirred at room temperature for 3 hr. The volatiles were removed under reduced pressure. The residue was purified by silica gel chromatography (20 to 80% EtOAc in hexanes) to yield of 1-(4-((2-chloro-3-fluoropyridin-4-yl)methoxy) 2-Methoxyphenyl)-3-((1S,2S)-2-hydroxycyclohexyl)thiourea (1.59 g, 93%). MS (ES+) C20 Htwenty three ClFN3 O3 S required value: 439, measured value: 440 [M+H]+ . Step 6: To 1-(4-((2-chloro-3-fluoropyridin-4-yl)methoxy)-2-methoxyphenyl)-3-((1S,2S)-2-hydroxyl To a solution of cyclohexyl)thiourea (0.90 g, 2.1 mmol) in DCM (EtOAc) (EtOAc) Solid benzyltrimethylammonium tribromide (0.80 g, 2.1 mmol) was then added. After 10 minutes, the saturated NaHCO will be3 (30 mL) was added to the reaction mixture and stirred for 5 minutes. The reaction mixture was diluted with DCM (20 mL) and the layers were separated. Organic layer with saturated NaHCO3 (30 mL) followed by 10% Na2 S2 O3 Wash in aqueous solution (20 mL) in MgSO4 Dry over, filter and concentrate under reduced pressure. The residue was triturated with EtOAc / EtOAc (EtOAc)EtOAc. (1S,2S)-2-((6-((2-Chloro-3-fluoropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amine The cyclohexanol was isolated as an off-white powder (810 mg, 90%). MS (ES+) C19 Htwenty one ClN4 O3 S required value: 437, measured value: 438 [M+H]+ . Step 7: Acetamide (0.221 g, 3.73 mmol), (1S, 2S)-2-((6-((2-chloro-3-fluoropyridin-4-yl)methoxy)-4-methoxy Benzo[d]thiazol-2-yl)amino)cyclohexanol (1.09 g, 2.49 mmol) and Cs2 CO3 (1.62 g, 4.98 mmol) in a suspension of dioxane (12 mL) with N2 Degas for 2 minutes. Add Pd2 (dba)3 (0.057 g, 0.062 mmol) and Xantphos (0.072 g, 0.12 mmol) and the mixture was re-used with N2 Degas for 2 minutes. The reaction mixture was heated to 100 ° C and stirred for 5 hours. The reaction mixture was diluted with DCM (20 mL) and EtOAc. The layers were separated and the aqueous layer was extracted with DCM (2 x 10 mL)4 Dry over, filter and concentrate under reduced pressure. The residue was purified by silica gel chromatography (0 to 100%EtOAc in hexanes w/ 10% MeOH) to yield N-(3-fluoro-4-(((2-((( 1S,2S)-2-hydroxycyclohexyl)amino)-4-methoxybenzo[d]thiazole-6-yl)oxy)methyl)pyridin-2-yl)acetamidamine (320 mg, 28%). MS (ES+) Ctwenty two H25 FN4 O4 S required value: 460, measured value: 461 [M+H]+ . Step 8: To N-(3-fluoro-4-(((2-(((1(2))))-2-hydroxycyclohexyl)amino)-4-methoxybenzo[d]thiazole-6- Add HCl (185 μl, 0.738 mmol, 4M) to dioxane as a solution of EtOAc (methanol) EtOAc (EtOAc) The resulting mixture was stirred at 60 ° C for 2 hours. The reaction mixture was concentrated. Residues with Et2 O (2 x 2 mL) was triturated, the filtrate was carefully removed, and the solid was dried in vacuo to give (1S,2S)-2-((6-((2-amino)-3-fluoropyridine) as a pale white fluffy solid. 4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol (65 mg, 97%, HCl salt). MS (ES+) C20 Htwenty three FN4 O3 S required value: 418, measured value: 419 [M+H]+ ;1 H NMR (600 MHz, DMSO-d6 ) δ 9.36 (br s, 1H), 8.00 (br s, 2H), 7.84 (d, J = 6.2 Hz, 1H), 7.13 (d, J = 2.3 Hz, 1H), 6.91 (t, J = 5.7 Hz) , 1H), 6.79 (s, 1H), 5.26 (s, 2H), 3.92 (s, 3H), 3.76 – 3.67 (m, 1H), 3.37 – 3.31 (m, 1H), 2.02 – 1.95 (m, 1H) ), 1.95 – 1.86 (m, 1H), 1.68 – 1.64 (m, 2H), 1.33 – 1.20 (m, 4H). Example 55: (1S,2S)-2-(4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy) Benzo[d]thiazol-2-ylamino)cyclohexanolThe title compound was synthesized according to the following synthetic scheme:(1S,2S)-2-((6-((2-Chloropyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexane Alcohol (Example 66, Step 5) (4.0 g, 9.5 mmol), 1-methyl-1H-pyrazol-4-amine (1.84 g, 19 mmol), DIPEA (2.45 g, 19 mmol) in DMA (30 mL) The mixture was heated to 120 ° C for 10 hours. Water (100 ml) was added to the mixture and the mixture was extracted with EtOAc (100 mL×3). The combined EtOAc phase is washed with brine in Na2 SO4 Dry over, filter and concentrate. The residue was purified by EtOAc (EtOAc) (EtOAc) The crude product was then subjected to reverse phase HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 0 - 100%; 20 min; Column: C18) Purified to give (1S,2S)-2-(4-methoxy-6-(2) as a brown solid -(1-Methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[d]thiazol-2-ylamino)cyclohexanol (1.4 mg, 31% ). MS (ES+) Ctwenty three H27 N7 O3 S required value: 481, measured value: 482 [M+H]+ .1 H NMR (500 MHz, MeOD) δ 8.37 (d, J = 5 Hz, 1H), 7.94 (s, 1H), 7.56 (s, 1 H), 6.86-6.91 (m, 2 H), 6.64 (d, J = 2 Hz, 1H), 5.08 (s, 2H), 3.93 (s, 3H), 3.85 (s, 3H), 3.57-3.62 (m, 1H), 3.39-3.43 (m, 1H), 2.14-2.16 (m, 1H), 2.03-2.05 (m, 1H), 1.72-1.79 (m, 2H), 1.24-1.43 (m, 4H). The following examples in Table 3 were prepared analogously to Example 55. table 3: Examples 61 and 62: 6-((2-Aminopyrimidin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2 -amineThe title compound was synthesized according to the following synthetic scheme:Step 1: 6-(Benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (Example 50, Step 4) (700 mg, 1.80 mmol) in TFA (10 mL) at 65 °C The mixture was stirred for 16 hours. The reaction mixture is concentrated by saturating NaHCO3 (50 ml) was diluted and extracted with EtOAc (50 mL×3). The combined organic layer is washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying, filtration and concentration gave 2-bromo-4-methoxybenzo[d]thiazole-6-ol (520 mg, 100%). MS (ES+) C8 H6 BrNO2 S required value: 259, 261, found: 262 [M+H]+. Step 2: To 2-bromo-4-methoxybenzo[d]thiazole-6-ol (520 mg, 2.00 mmol) and (2-aminopyrimidin-4-yl)methyl methanesulfonate (406 mg) , 2.00 mmol) solution added to Cs in DMF (10 mL)2 CO3 (1.9 g, 6.0 mmol). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (50 ml) andEtOAcEtOAc The combined organic layer is washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying, filtration and concentration to give 4-((2-bromo-4-methoxybenzo[d]thiazol-6-yloxy)methyl)pyrimidin-2-amine (400 mg, 54%). MS (ES+) C13 H11 BrN4 O2 S required value: 366, measured value: 367 [M + H]+ . Step 3: To 4-((2-bromo-4-methoxybenzo[d]thiazol-6-yloxy)methyl)pyrimidin-2-amine (367 mg, 1.00 mmol) and 3,3- A solution of difluorocyclohexylamine hydrochloride (516 mg, 3.00 mmol) was added to DIPEA (774 mg, 6.00 mmol) in DMF (5 mL). The reaction mixture was stirred at 140 ° C for 16 hours. The reaction mixture was prepared by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O, B = MeCN; gradient: B = 5 - 95%; 12 min; column: C18) purified to give 6-((2-aminopyrimidin-4-yl)methoxy)-N as a white solid. -(3,3-Difluorocyclohexyl)-4-methoxybenzo[d]thiazol-2-amine (48 mg, 11%). MS (ES+) C19 Htwenty one F2 N5 O2 S required value: 421, measured value: 422 [M + H]+ . The final product was isolated by palm chromatography (mobile phase: EtOH (1% methanolic ammonia) column: cellulose-SC 4.6 x 100 mm 5 μm] to produce two isomers. Isomer 1 (Compound 60) (5.9 mg) as a white solid. MS (ES+) C19 Htwenty one F2 N5 O2 S required value: 421, measured value: 422 [M + H] +;1 H NMR (500 MHz, MeOD) δ 8.25 (d, J = 5.1 Hz, 1H), 6.83 (dd, J = 6.2, 3.7 Hz, 2H), 6.62 (d, J = 2.2 Hz, 1H), 4.96 (s , 2,,,,, (ddd, J = 37.7, 24.5, 11.3 Hz, 3H), 1.38 - 1.24 (m, 2H); isomer 2 (Compound 61) (6.8 mg) as a white solid. MS (ES+) C19 Htwenty one F2 N5 O2 S required value: 421, measured value: 422 [M + H] +;1 H NMR (500 MHz, MeOD) δ 8.25 (d, J = 5.1 Hz, 1H), 6.83 (dd, J = 6.2, 3.7 Hz, 2H), 6.62 (d, J = 2.3 Hz, 1H), 4.96 (s , 2H), 4.09 – 3.97 (m, 1H), 3.95 – 3.89 (m, 3H), 2.46 (dd, J = 19.1, 10.9 Hz, 1H), 2.15 (dd, J = 10.9, 7.5 Hz, 1H), 2.05 (dd, J = 21.9, 11.1 Hz, 1H), 1.85. The following examples in Table 4 were prepared analogously to Examples 61 and 62. Table 4: Example 64: N-(3,3-Difluorocyclohexyl)-4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl Methoxy)benzo[d]thiazol-2-amineThe title compound was synthesized according to the following synthetic scheme:Step 1: 6-(Benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (Example 50, Step 4) (300 mg, 0.86 mmol), 3,3-difluorocyclohexane A mixture of the amine hydrochloride (296 mg, 1.72 mmol) and DIPEA (222 mg, 1.72 mmol) in NMP (1 ml) was warmed to 180 ° C for 4 hours. Add saturated NH4 Cl solution (100 ml), and the mixture was extracted with EtOAc (50 mL×3). The combined organic phase is washed with brine in Na2 SO4 Dry over, filter and concentrate. The residue was purified by silica gel chromatography (50% EtOAcEtOAcEtOAc) elute Benzo[d]thiazol-2-amine (130 mg, 37%). MS (ESI+) Ctwenty one Htwenty two F2 N2 O2 S required value: 404, measured value: 405 [M + H]+ . Step 2: 6-(Benzyloxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazol-2-amine (130 mg, 0.32 mmol) at 55 °C The mixture in TFA (3 ml) was stirred for 2 hours. The TFA was evaporated <RTI ID=0.0> Organic layer with saturated NaHCO3 Cleaning, in Na2 SO4 Drying, filtration and concentration gave 2-(3,3-difluorocyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol (90 mg, 89%). MS (ESI+) C14 H16 F2 N2 O2 S required value: 314, measured value: 315 [M+H]+ . Step 3: 2-(3,3-Difluorocyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol (90 mg, 0.29 mmol), 2-chloro- at 80 °C 4-(Chloromethyl)pyrimidine (57 mg, 0.35 mmol) and Cs2 CO3 The mixture (189 mg, 0.58 mmol) in DMF (5 mL The volatiles were removed under reduced pressure. The residue was purified by silica gel chromatography (10%EtOAcEtOAcEtOAc) elut Difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine (60 mg, 43%). MS (ESI+) C19 H19 ClF2 N4 O2 S required value: 440, measured value: 441 [M+H]+ . Step 4: 6-((2-Chloropyrimidin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole at 110 °C 2-Amine (60 mg, 0.14 mmol), 1-methyl-1H-pyrazole-4-amine (23 mg, 0.17 mmol) and TsOH.H2 A mixture of O (12 mg, 0.07 mmol) in dioxane (2 ml) was stirred for 16 h. This mixture was diluted with EtOAc using saturated NaHCO3 Cleaning, and Na2 SO4 Dry on top. The combined organic layer and residue are concentrated by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 5 - 95%; 12 min; column: C18) purified to give N-(3,3-difluorocyclohexyl)-4-methoxy-6 as a white solid. -((2-(1-Methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[d]thiazol-2-amine (3 mg, 5%). MS (ES+) Ctwenty two H25 N7 O3 S required value: 501, measured value: 502 [M+H]+ .1 H NMR (500 MHz, d6-DMSO) δ 9.51 (s, 1H), 8.40 (d, J = 5 Hz, 1H), 7.78 - 7.88 (m, 2H), 7.46 (s, 1 H), 6.98 (s , 1 H), 6.81 (d, J = 5 Hz, 1H), 6.61 (d, J = 2 Hz, 1H), 5.04 (s, 2H), 3.89 (s, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 3.26 (s, 1H), 1.97 - 2.01 (m, 2H), 1.72 - 1.84 (m, 3H), 1.43 - 1.50 (m, 1H), 1.21 - 1.33 (m, 1H). Example 65: (1S,2S)-2-(6-((2-Amino-3-chloropyridin-4-yl)methoxy)-4-fluorobenzo[d]thiazol-2-ylamino CyclohexanolThe title compound was synthesized according to the following synthetic scheme:Step 1: To a solution of 2-fluoro-4-methoxyaniline (3.0 g, 21 mmol) in EtOAc (EtOAc) Cool the reaction mixture to 0 ° C and add Br2 (4.6 g, 25 mmol). The reaction mixture was stirred at room temperature for 4 hours. Saturated NH4 The pH of the reaction mixture was adjusted to pH = 7 by OH. The mixture was extracted with EtOAc (3 x 80 mL).2 SO4 Dry over and concentrate under reduced pressure. The residue was purified by silica gel chromatography (30% EtOAc in EtOAc) to afford 4-fluoro-6-methoxybenzo[d] thiazol-2-amine (2.1 g, 50%). MS (ES+) C8 H7 FN2 OS required value: 198, measured value: 199 [M+H]+ . Step 2: A solution of 4-fluoro-6-methoxybenzo[d]thiazol-2-amine (1.3 g, 5.8 mmol) in MeCN (40 mL) was cooled to -5. Slowly add CuBr2 (1.3 g, 5.8 mmol) andt BuONO (0.67 mg, 5.80 mmol). The reaction was stirred at 0 to 5 °C for 30 minutes. The reaction mixture was heated to 40 ° C and stirred for 6 hours. The reaction mixture was filtered. The filtrate was washed with 1 N HCl solution at Na2 SO4 It was dried, filtered and concentrated under reduced pressure to give 2-bromo-4-fluoro-6-methoxybenzo[d]thiazole (1.2 g, 70%). MS (ESI+) C8 H5 BrFNOS required value: 261, measured value: 262 [M+H]+ . Step 3: 2-Bromo-4-fluoro-6-methoxybenzo[d]thiazole (300 mg, 1.15 mmol), (1S,2S)-2-aminocyclohexanol (297 mg, 2.30 mmol) The mixture of DIPEA (397 mg, 3.45 mmol) in DMA (10 ml) was heated to 100 ° C overnight. Add saturated NH4 Cl solution (80 ml) was extracted with EtOAc (3×10 mL). The combined organic layer is tied to Na2 SO4 Dry over, filter and concentrate under reduced pressure. The residue was purified by silica gel chromatography (30% EtOAc in EtOAc) to yield (1S,2S)-2-(4-fluoro-6-methoxybenzo[d]thiazole-2 as a brown solid. -ylamino)cyclohexanol (236 mg, 43%). MS (ESI+) C14 H17 FN2 O2 S required value: 296, measured value: 297 [M+H]+ . Step 4: (1S,2S)-2-(4-Fluoro-6-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (490 mg, 1.64 mmol) in DCM (10 ml Cooling solution to 0 ° C and adding BBr3 (4 ml, 17%), the resulting solution was stirred overnight at room temperature. Add saturated NH4 Cl solution, filter the suspension, and collect the solid to provide 4-fluoro-2-((1S,2S)-2-hydroxycyclohexylamino)benzo[d]thiazole-6-ol (360 mg, 77%) . MS (ESI+) C13 H15 FN2 O2 S required value: 282, measured value: 283 [M+H]+ . Step 5: 4-Fluoro-2-((1S,2S)-2-hydroxycyclohexylamino)benzo[d]thiazole-6-ol (80 mg, 0.28 mmol), 3-chloro at 80 °C 4-(Chloromethyl)-N-(4-methoxybenzyl)pyridin-2-amine (Example 1, Step 3; 116 mg, 0.34 mmol) and Cs2 CO3 The mixture (183 mg, 0.56 mmol) in DMF (5 mL) was stirred overnight. The volatiles were removed under reduced pressure and purified by EtOAc (EtOAc:EtOAc) -2-(4-Methoxybenzylamino)pyridin-4-yl)methoxy)-4-fluorobenzo[d]thiazol-2-ylamino)cyclohexanol (82 mg, 54% ). MS (ESI+) C27 H28 ClFN4 O3 S required value: 542, measured value: 543 [M+H]+ . Step 6: (1S,2S)-2-(6-((3-Chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy)-4 at room temperature A mixture of fluorobenzo[d]thiazol-2-ylamino)cyclohexanol (82 mg, 0.15 mmol) in TFA (3 mL) was stirred overnight. The volatiles were removed under reduced pressure. The residue was prepared by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 5 - 95%; 12 min; Column: C18) Purified to give (1S,2S)-2-(6-(2-amino-3-) as a white solid Chloropyridin-4-yl)methoxy)-4-fluorobenzo[d]thiazol-2-ylamino)cyclohexanol (19.4 mg, 31%). MS (ES+) C19 H20 ClFN4 O2 S required value: 422, measured value: 423 [M+H]+ .1 H NMR (500 MHz, d6-DMSO) δ 7.9-7.95 (m, 2H), 7.24 (d, J = 2.5 Hz, 1H), 6.84-6.87 (m, 1H), 6.71 (d, J = 5 Hz, 1H), 6.34 (s, 2H), 5.08(s, 2H), 4.75 (d, J = 5 Hz, 1H), 3.49-3.52 (m, 1H), 2.03-2.07 (m, 1H), 1.86-1.89 (m, 1H), 1.61-1.65 (m, 2H), 1.17-1.30 (m, 4H). Example 66: (1S,2S)-2-((6-((2-Aminopyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amine Cyclohexan-1-olThe title compound was synthesized according to the following synthetic scheme:Step 1: To 2-chloro-4-methylpyrimidine (5.0 g, 39 mmol) in CCl4 NCS (7.8 g, 58 mmol) and AIBN (0.64 g, 3.9 mmol) were added to a solution (100 ml) and the mixture was heated under reflux for 18 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was filtered through a pad of Celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (10 to 40%EtOAcEtOAcEtOAc) MS (ES+) C5 H4 Cl2 N2 Required value: 162, measured value: 163 [M+H]+ . Step 2: To 3-methoxy-4-nitrophenol (2.83 g, 16.7 mmol) and 2-chloro-4-(chloromethyl)pyrimidine (3.0 g, 18 mmol) in DMF (16 ml) Solution addition K2 CO3 (2.8 g, 20 mmol) and the mixture was stirred at room temperature for 20 hours. Ice-cold water (30 ml) was added and the mixture was stirred for 10 min then filtered over a Buchner funnel. The solid was washed with cold water (10 mL) and dried in vacuo for 2 s to yield of <RTIgt; 4.6 g, 93%). MS (ES+) C12 H10 ClN3 O4 Required value: 295, measured value: 296 [M+H]+ . Step 3: The reaction vessel was charged with 2-chloro-4-((3-methoxy-4-nitrophenoxy)methyl)pyrimidine (4.6 g, 15.6 mmol), 10% Pt-C (460 Mg, 0.12 mmol) and THF-MeOH (5:1, 60 ml). Suspension by N2 Degas for 3 minutes and pass H2 Purify for 3 minutes. In H2 The reaction mixture was stirred at 1 atm for 2 hours under an atmosphere. The reaction mixture is N2 Purified, filtered through Celite, and concentrated under reduced pressure to give 4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxyaniline as a pale yellow powder (4.0 g, 97% ). MS (ES+) C12 H12 ClN3 O2 Required value: 265, measured value: 266 [M+H]+ . Step 4: To a solution of 4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxyaniline (4.0 g, 15 mmol) in DCM (200 mL) 1-yl)methylthione (3.2 g, 18 mmol) and the resulting mixture was stirred at room temperature for 4 hours. (1S,2S)-2-Aminocyclohexanol (3.5 g, 30 mmol) was added and the mixture was stirred at room temperature for 3 hr. The volatiles were removed under reduced pressure. The residue was purified by silica gel chromatography (25 to 100% EtOAc in hexane) to yield white 1-(4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxy Phenyl))-3-((1S,2S)-2-hydroxycyclohexyl)thiourea (6.1 g, 96%). MS (ES+) C19 Htwenty three ClN4 O3 S required value: 422, measured value: 423 [M+H]+ . Step 5: To 1-(4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxyphenyl)-3-((1S,2S)-2-hydroxycyclohexyl)sulfide BSTFA (1.3 ml, 4.7 mmol) was added to a solution of urea (1.0 g, 2.3 mmol) in DCM (100 ml) and the mixture was stirred for 5 min. Solid benzyltrimethylammonium tribromide (0.92 g, 2.3 mmol) was added to the previous reaction mixture. After 20 minutes, add saturated NaHCO3 (30 ml) and the reaction mixture was stirred for 5 minutes. The biphasic mixture was transferred to a separatory funnel with an additional 20 ml of DCM and separate layers. Organic layer with saturated NaHCO3 Aqueous solution (30 ml) followed by 10% Na2 S2 O3 Wash in aqueous solution (1 x 20 ml) in MgSO4 Dry over, filter, and concentrate under reduced pressure. The residue was triturated with 1:2 ether / hexanes (30 ml). After washing with 1:1 ether/hexane (10 ml), (1S,2S)-2-((6-((2-chloropyrimidin-4-yl)) was obtained as a white powder (945 mg, 95%). Methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol (0.945 g, 95%). MS (ES+) C19 Htwenty one ClN4 O3 S required value: 420, measured value: 421 [M+H]+ . Step 6: Charge the (1S,2S)-2-((6-((2-chloropyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazole-2 in a microwave vial -Amino)cyclohexanol (300 mg, 0.71 mmol) and ammonia (7 M in MeOH, 2.0 mL). The vial was sealed and the reaction mixture was heated to 120 ° C in a microwave reactor for 4 hours. The volatiles were removed under reduced pressure. The residue was prepared by reverse phase preparative HPLC (mobile phase: A = 0.1% TFA/H)2 O, B = 0.1% TFA/MeCN; Gradient: B = 10 - 90%; 20 min; Column: C18) Purified to give an off-white powder as the TFA salt (182 mg, 64%) (1S, 2S) 2-((6-((2-Aminopyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol. MS (ES+) C19 Htwenty three N5 O3 S required value: 401, measured value: 402 [M+H]+ ;1 H NMR (600 MHz, DMSO-d6 ) δ 8.23 (d, J = 5.0 Hz, 1H), 7.60 (d, J = 7.5 Hz, 1H), 6.90 (d, J = 2.4 Hz, 1H), 6.70 – 6.58 (m, 3H), 6.55 (d , J = 2.4 Hz, 1H), 4.90 (s, 2H), 4.75 (d, J = 4.9 Hz, 1H), 3.82 (s, 3H), 3.54 – 3.45 (m, 1H), 3.37 – 3.32 (m, 1H), 2.10 – 1.98 (m, 1H), 1.91 – 1.83 (m, 1H), 1.69 – 1.51 (m, 2H), 1.35 – 1.10 (m, 4H). Example 67: 6-((2-Amino-3-chloropyridin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole 2-amineThe title compound was synthesized according to the following synthetic scheme:Step 1: To a solution of 6-(benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (Example 50, Step 4) (3.0 g, 8.5 mmol) in DMF (20 mL) Add NaSMe (1.2 g, 17 mmol). The reaction was stirred at room temperature for 16 hours. The reaction mixture was diluted with water (100 ml) and used with Et2 O (100 ml × 3) extraction. The combined organic layer is washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying, filtration and concentration gave 6-(benzyloxy)-4-methoxy-2-(methylthio)benzo[d]thiazole (2.7 g, 100%). MS (ES+) C16 H15 NO2 S2 Required value: 317, found: 318 [M+H]+. Step 2: 6-(Benzyloxy)-4-methoxy-2-(methylthio)benzo[d]thiazole (2.7 g, 8.5 mmol) in TFA (20 ml) at 65 °C The mixture was stirred for 16 hours. The solvent was removed under reduced pressure. Add saturated NaHCO3 (50 ml) and the mixture was extracted with EtOAc (50 ml. The combined organic layer is washed with brine (100 mL) in Na2 SO4 Drying, filtration and concentration gave 4-methoxy-2-(methylthio)benzo[d]thiazole-6-ol (1.9 g, 100%) as a brown oil. MS (ES+) C9 H9 NO2 S2 Required value: 227, found: 228 [M+H]+. Step 3: 4-Methoxy-2-(methylthio)benzo[d]thiazole-6-ol (1.8 g, 8.0 mmol), 3-chloro-4-(chloromethyl) at 80 °C -N-(4-methoxybenzyl)pyridin-2-amine (2.4 g, 8.0 mmol) and Cs2 CO3 The mixture (7.8 g, 24 mmol) in DMF (20 mL The reaction mixture was diluted with water (100 ml) with Et2 Extract with O (100 ml) and EtOAc (50 ml x 3). The combined organic phase is washed with water (100 ml) and brine (100 ml) over Na2 SO4 Drying, filtration and concentration to give 3-chloro-4-((4-methoxy-2-(methylthio)benzo[d]thiazole-6-yloxy)methyl) as a white solid. N-(4-Methoxybenzyl)pyridin-2-amine (2.1 g, 53%). MS (ES+) Ctwenty three Htwenty two ClN3 O3 S2 Required value: 487, found: 488 [M+H]+. Step 4: 3-Chloro-4-((4-methoxy-2-(methylthio)benzo[d]thiazol-6-yloxy)methyl)-N-(4) at 0 °C m-CPBA (834 mg, 4.1 mmol) was added to a solution of methoxybenzyl)pyridin-2-amine (2.0 g, 4.1 mmol) in DCM (100 mL). The reaction mixture was stirred at room temperature for 2 hours. The mixture is saturated with Na2 S2 O3 (100 ml), saturated NaHCO3 (100 ml) and brine (100 ml) for cleaning at Na2 SO4 Drying, filtration and concentration to give 3-chloro-4-((4-methoxy-2-(methylsulfinyl)benzo[d]thiazol-6-yloxy) A as a white solid -N-(4-Methoxybenzyl)pyridin-2-amine (2.1 g, 97%). MS (ES+) Ctwenty three Htwenty two ClN3 O4 S2 Required value: 503, found: 504 [M+H]+. Step 5: 3-Chloro-4-((4-methoxy-2-(methylsulfinyl)benzo[d]thiazole-6-yloxy)methyl)-N at 140 °C A mixture of -(4-methoxybenzyl)pyridin-2-amine (50 mg, 0.1 mmol) and 3,3-difluorocyclohexylamine (135 mg, 1 mmol) was stirred for 6 hr. The reaction mixture was diluted with water (50 ml) andEtOAcEtOAc The combined organic layer is washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying, filtration and concentration to give 6-((3-chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy)-N- (3,3) as a yellow solid. -Difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine (50 mg, 87%). MS (ES+) C28 H29 ClF2 N4 O3 S required value: 574, found: 575 [M+H]+. Step 6: 6-((3-Chloro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy)-N-(3,3-difluorocyclohexane) at room temperature A mixture of hexyl)-4-methoxybenzo[d]thiazol-2-amine (50 mg, 0.09 mmol) in EtOAc (5 mL) The reaction mixture was prepared by preparative HPLC (mobile phase: A = 10 mM ammonium bicarbonate / H)2 O, B = acetonitrile; gradient: B = 60% - 95% in 18 min; column: Welch Xtimate® C18, 10 μm, 21.2 mm x 250 mm) purified to give a white solid 6-((2- Amino-3-chloropyridin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine (5.0 mg, 12 %). MS (ES+) C20 Htwenty one ClF2 N4 O2 S required value: 454, measured value: 455 [M + H] +;1 H NMR (500 MHz, DMSO) δ 8.01 – 7.86 (m, 3H), 6.98 (d, J = 2.3 Hz, 1H), 6.75 (d, J = 5.0 Hz, 1H), 6.58 (d, J = 2.3 Hz , 1H), 6.33 (s, 2H), 5.07 (s, 2H), 3.94 (d, J = 5.7 Hz, 2H), 3.83 (s, 3H), 2.61 (d, J = 4.6 Hz, 3H). Example 69: (1S,2S)-2-((6-((2-Aminopyrimidin-4-yl)methoxy)-7-chloro-4-methoxybenzo[d]thiazole-2- Amino)cyclohexan-1-olThe title compound was synthesized according to the following synthetic scheme:Step 1: Add N-succinimide chloride (0.868 g, 6.50 mmol) to a solution of 3-methoxy-4-nitrophenol (1.0 g, 5.9 mmol) at 0 ° C and at 50 ° C The resulting mixture was stirred for 2 hours. The reaction mixture was diluted with EtOAc (20 mL) and washed with water. The layers were separated and the organic layer was washed with saturated NaCI (10 mL)4 Drying, filtration and concentration under reduced pressure afforded 2-chloro-5-methoxy-4-nitrophenol (1.2 g, ~100%) as a yellow solid. MS (ES+) C7 H6 ClNO4 Required value: 203, measured value: 204 [M+H]+ . Step 2: To K2 CO3 Addition of 2-chloro-4-(chloroform) to a suspension of (0.758 g, 5.48 mmol) and 2-chloro-5-methoxy-4-nitrophenol (0.93 g, 4.5 mmol) in DMF (4.57 ml) The pyrimidine (0.89 g, 5.4 mmol) was stirred at 50 ° C for 15 hours. The reaction was diluted with water (15 mL), stirred for 5 min and filtered on a Buchner funnel. The solid was washed with water (2 x 10 mL). After drying, 2-chloro-4-((2-chloro-5-methoxy-4-nitrophenoxy)methyl)pyrimidine (1.31 g, 83%) was isolated as a brown solid. MS (ES+) C12 H9 Cl2 N3 O4 Required value: 329, measured value: 330 [M+H]+. Step 3: At N2 The reaction vessel was charged with 10% Pt-C (0.80 g, 0.20 mmol), 2-chloro-4-((2-chloro-5-methoxy-4-nitrophenoxy)methyl Pyrimidine (1.3 g, 4.1 mmol) and THF (41 ml). Suspension by N2 Degas for 2 minutes and pass H2 Purify for 2 minutes. In H2 The reaction mixture was stirred at 1 atm for 2 hours under an atmosphere. The reaction mixture is N2 Purified, filtered through diatomaceous earth, and concentrated under reduced pressure to provide 5-chloro-4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxy as an orange-brown amorphous material. Aniline (1.2 g, 99%). MS (ES+) C12 H11 Cl2 N3 O2 Required value: 299, measured value: 300 [M+H]+. Step 4: To a solution of 5-chloro-4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxyaniline (1.2 g, 4.0 mmol) in DCM (20 mL) (1H-Imidazol-1-yl)methylthione (0.78 g, 4.4 mmol) and the mixture was stirred at room temperature for one hour. (1S,2S)-2-Aminocyclohexanol (0.92 g, 8.0 mmol) was added and the yellow brown mixture was stirred at room temperature for an additional hour. The volatiles were removed under reduced pressure. The reaction mixture was diluted with EtOAc (30 mL) and washed with water. Separate the layers and the organic layer with saturated NaHCO3 (10 mL) washed in MgSO4 Drying, filtration and concentration under reduced pressure to give 1-(5-chloro-4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxyphenyl as a light brown solid. )-3-((1S,2S)-2-hydroxycyclohexyl)thiourea (1.8 g, 90%). MS (ES+) C19 Htwenty two Cl2 N4 O3 S required value: 456, measured value: 457 [M+H]+ . Step 5: To 1-(5-chloro-4-((2-chloropyrimidin-4-yl)methoxy)-2-methoxyphenyl)-3-((1S,2S)-2-hydroxyl Add (Z)-2,2,2-trifluoro-N-(trimethylformamidinyl)acetamidite to a solution of cyclohexyl)thiourea (1.8 g, 3.5 mmol) in DCM (30 ml) Trimethylformamidine (1.88 ml, 7.08 mmol) and the resulting mixture was stirred at room temperature for 5 minutes. Then benzyltrimethylammonium tribromide (1.38 g, 3.54 mmol) was added as a solution in DCM (15 mL). After 15 minutes, the reaction mixture was saturated NaHCO3 (10 mL), water (20 mL) and saturated Na2 S2 O4 (5 mL) diluted. The resulting mixture was stirred for 5 minutes, the layers were separated and the organic layer was applied4 Dry over, filter and concentrate under reduced pressure. The residue is 1:1 Et2 O/hexane (20 mL) was triturated. The resulting solid was filtered through a Buchner funnel using 1:1 Et2 O/hexane (10 mL) was washed, and (1S,2S)-2-((7-chloro-6-((2-chloropyrimidin-4-yl)methoxy)) was isolated as a light brown solid. 4-Methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol (1.60 g, 94%). MS (ES+) C19 H20 Cl2 N4 O3 S required value: 454, measured value: 455 [M+H]+ . Step 6: In a microwave vial (1S,2S)-2-((7-chloro-6-((2-chloropyrimidin-4-yl)) in MeOH (7.0 ml, 49 mmol, 7M) Oxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexanol (0.90 g, 2.0 mmol) and NH3 . The vial was sealed and the reaction mixture was heated to 120 ° C in a microwave reactor for 3 hours. The volatiles were removed under reduced pressure. The residue was diluted with water (15 mL), stirred at 50 &lt;0&gt;C for 10 min and collected on a Buchner funnel. After drying, the residue was subjected to reverse phase HPLC (mobile phase: A = 0.1% NH)4 OH/H2 O, B = 0.1% NH4 OH/MeCN; Gradient: B = 0 - 100%; 20 min; Column: C18) Purified to provide (1S,2S)-2-((6-((2-aminopyrimidine-4)) as a light brown solid -yl)methoxy)-7-chloro-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol (620 mg, 72%). MS (ES+) C19 Htwenty two ClN5 O3 S required value: 435, measured value: 436 [M+H]+ ;1 H NMR (600 MHz, DMSO-d6 ) δ 8.27 (d, J = 5.0 Hz, 1H), 7.89 (d, J = 7.7 Hz, 1H), 6.79 (s, 1H), 6.74 (d, J = 4.9 Hz, 1H), 6.67 (s, 2H) ), 5.04 (s, 2H), 4.75 (d, J = 5.1 Hz, 1H), 3.85 (s, 3H), 3.53 – 3.46 (m, 1H), 3.36 – 3.32 (m, 1H), 2.09 – 1.99 ( m, 1H), 1.92 – 1.84 (m, 1H), 1.69 – 1.56 (m, 2H), 1.31 – 1.16 (m, 4H). Example 70: (1S,2S)-2-(6-((2-Aminopyrimidin-4-yl)methoxy)-7-fluoro-4-methoxybenzo[d]thiazol-2-yl Amino)cyclohexanolThe title compound was synthesized according to the following synthetic scheme:Step 1: 6-(Benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (Example 50, Step 4) (750 mg, 2.15 mmol), Selectfluor (835 mg) at 80 °C , 2.36 mmol) in CH3 The mixture in CN (50 ml) was stirred overnight. Saturated NaCl (100 mL) was added. The reaction mixture was extracted with EtOAc (3×50 mL).2 SO4 Dry over, filter and concentrate under reduced pressure. The residue was purified by silica gel chromatography (10%EtOAcEtOAcEtOAc) toield Thiazole (300 mg, 38%). MS (ESI+) C15 H11 BrFNO2 S required value: 367, measured value: 368 [M+H]+ . Step 2: Mix the mixture 6-(benzyloxy)-2-bromo-7-fluoro-4-methoxybenzo[d]thiazole (300 mg, 0.810 mmol) and (1S, 2S) at 120 °C. 2-Aminocyclohexanol (234 mg, 2.03 mmol) was stirred for 6 hours. The mixture was partitioned between EtOAc and water. The organic layer was dried and concentrated. The residue was purified by silica gel chromatography (0 to 50% EtOAc in EtOAc) to afford (1S,2S)-2-(6-(benzyloxy)- 7-Fluoro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol. MS (ES+) Ctwenty one Htwenty three ClN2 O3 S required value: 402, found: 403 [M+H]+. Step 3: (1S,2S)-2-(6-(Benzyloxy)-7-fluoro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol at 55 °C The mixture (90 mg, 0.22 mmol) in 5 mL of TFA was stirred for 2 h. The solvent was removed and the reaction mixture was saturated NaHCO3 (50 ml) was diluted and extracted with EtOAc (50 mLEtOAc). The combined organic layer is washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying, filtration and concentration to give 7-fluoro-2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol as a black solid ( 70 mg, 100%). MS (ES+) C14 H17 FN2 O3 S required value: 312, measured value: 313 [M + H]+ . Step 4: 7-Fluoro-2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol (70 mg, 0.22) at 80 °C Methyl), 2-chloro-4-(chloromethyl)pyrimidine (37 mg, 0.22 mmol) and Cs2 CO3 The mixture (216 mg, 0.66 mmol) in DMF (2 mL The reaction mixture was diluted with water (50 mL) andEtOAcEtOAc. The combined organic layer is washed with water (100 ml) and brine (100 ml) in Na2 SO4 Drying, filtration and concentration to give (1S,2S)-2-(6-((2-chloropyrimidin-4-yl)methoxy)-7-fluoro-4-methoxybenzene as a yellow solid. [d]thiazol-2-ylamino)cyclohexanol (96 mg, 100%). MS (ES+) C19 H20 ClFN4 O3 S required value: 438, measured value: 439 [M + H]+ . Step 5: Will be NH at 100 ° C4 (1S,2S)-2-(6-((2-chloropyrimidin-4-yl)methoxy)-7-fluoro-4-methoxybenzo[d]thiazole in OH (2 ml) 2-Aminoamino)cyclohexanol (60 mg, 0.14 mmol) was stirred for 1 hour. The reaction mixture was prepared by preparative HPLC (mobile phase: A = 10 mM ammonium bicarbonate / H)2 O, B = acetonitrile; gradient: B = 60% - 95% in 18 min; column: Welch Xtimate® C18, 10 μm, 21.2 mm x 250 mm) purified to give a white solid (1S, 2S)- 2-(6-((2-Aminopyrimidin-4-yl)methoxy)-7-fluoro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (5.0 mg , 8%). MS (ES+) C19 Htwenty two FN5 O3 S required value: 419, measured value: 420 [M+H]+;1 H NMR (500 MHz, MeOD) δ 8.35 (d, J = 5.9 Hz, 1H), 7.14 (d, J = 5.9 Hz, 1H), 6.87 (d, J = 6.8 Hz, 1H), 5.20 (s, 2H) ), 3.96 (s, 3H), 3.69 (dt, J = 11.7, 4.2 Hz, 1H), 3.46 (dt, J = 13.0, 4.8 Hz, 1H), 2.11 (dd, J = 47.6, 15.4 Hz, 2H) , 1.84 – 1.73 (m, 2H), 1.41 (dt, J = 24.5, 15.1 Hz, 4H). Example 71: N-(4-((2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazol-6-yloxy)methyl)pyridine -2-yl) acetamidineThe title compound was synthesized according to the following synthetic scheme:2-((1S,2S)-2-Hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol was prepared at 80 ° C as described for Example 50, steps 1 to 6 (20 mg, 0.068 mmol), N-(4-(chloromethyl)pyridin-2-yl)acetamide (15 mg, 0.082 mmol) and Cs2 CO3 The mixture (44 mg, 0.136 mmol) in DMF (3 mL) was stirred overnight. The volatiles and residues were removed under reduced pressure by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 5 - 95%; 12 min; Column: C18) Purified to give N-(4-((1S,2S)-2-hydroxy) ring as a white solid Hexylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-yl)acetamide (9 mg, 30%). MS (ES+) Ctwenty two H26 N4 O4 S required value: 442, measured value: 443 [M+H]+ .1 H NMR (500 MHz, d6-DMSO) δ 10.51 (s, 1H), 8.29 (d, J = 5 Hz, 1H), 8.16 (s, 1H), 7.61 (d, J = 7.5 Hz, 1H), 7.13 (d, J = 4 Hz, 1H), 6.93 (s, 1H), 6.55 (s, 1H), 5.12 (s, 2H), 4.76 (d, J = 5.5 Hz, 1H), 3.81 (s, 3H) , 3.43 - 3.49 (m, 1H), 2.08 (s, 3H), 2.02 - 2.05 (m, 1H), 1.86 - 1.90 (m, 1H), 1.60 - 1.64 (m, 2H), 1.18 - 1.30 (m, 4H). The following examples in Table 5 were prepared analogously to Example 71. table 5: Example 73: (1S,2S)-2-(6-((2-Aminopyrimidin-4-yl)methoxy)-4-methoxy-7-methylbenzo[d]thiazole-2- CyclohexanolThe title compound was synthesized according to the following synthetic scheme:Step 1: Add Br to the solution of 4-bromo-2-methoxy-5-methylaniline (10 g, 73.0 mmol) in DCM (200 mL)2 (11.7 g, 73.0 mmol) for 10 minutes. The reaction mixture was stirred overnight at room temperature. The reaction was carried out at 0 ° C with NaHCO3 The aqueous solution (200 mL) was quenched and EtOAc (EtOAc &EtOAc) The mixture is tied to Na2 SO4 Dry over, filter and concentrate. The residue was purified by EtOAc (EtOAc:EtOAcEtOAcEtOAcEtOAc ). MS (ES+) C8 H10 BrNO, required: 215, found: 216 [M+H]+. Step 2: Add KSCN (3.6 g, 37 mmol) and CuSO to a solution of 4-bromo-2-methoxy-5-methylaniline (4.0 g, 18 mmol) in MeOH (200 mL)4 (14.9 g, 93 mmol). The reaction mixture was stirred at 80 ° C overnight. The reaction mixture is NH3 The aqueous solution (7M, 200 mL) was quenched eluted with EtOAc (EtOAc) The reaction mixture is tied to Na2 SO4 Dry over, filter and concentrate. The residue was purified by silica gel chromatography (0% to 10% MeOH in DCM) to yield 6-bromo-4-methoxy-7-methylbenzo[d]thiazole-2- Amine (2.0 g, 39.5%). MS (ES+) C9 H9 BrN2 OS, required value: 272, measured value: 274 [M+H]+ . Step 3: Add butyl nitrite (754 mg, 7.32 mmol) to CuBr at 0 °C2 (3.2 g, 14 mmol) and 6-bromo-4-methoxy-7-methylbenzo[d]thiazol-2-amine (2.0 g, 7.32 mmol) in CH3 Mixture of CN (20 mL). The mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried and concentrated to give 2,6-dibromo-4-methoxy-7-methylbenzo[d]thiazole (2.1 g, 89.3%) as a beige solid. MS (ES+) C9 H7 Br2 NOS required value: 335, measured value: 336, 338 [M+H]+ . Step 4: 2,6-Dibromo-4-methoxy-7-methylbenzo[d]thiazole (1.5 g, 4.45 mmol) and (1S,2S)-2-amino ring at 130 °C A mixture of hexanol (768 mg, 6.67 mmol) was stirred for 1 hour. The mixture was partitioned between EtOAc and water. The organic layer was dried and concentrated. The crude residue was purified by silica gel chromatography (10% to 50%EtOAcEtOAcEtOAcEtOAc) 4-methoxy-7-methylbenzo[d]thiazol-2-ylamino)cyclohexanol. MS (ES+) C15 H19 BrN2 O2 S required value: 370, measured value: 370, 372 [M+H]+ . Step 5: (1S,2S)-2-(6-Bromo-4-methoxy-7-methylbenzo[d]thiazol-2-ylamino)cyclohexanol (500 mg) at 100 °C , 1.35 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis 1,3,2-dioxaborane) (513 mg , 2.02 mmol), KOAc (265 mg, 2.70 mmol), PCy3 (37 mg, 0.13 mmol) and Pd2 (dba)3 A mixture of (137 mg, 0.135 mmol) in 5 mL 1,4-dioxane was stirred for 16 h. The reaction mixture was filtered and purified by silica gel chromatography (10% to 50% EtOAc in pet ether) to afford (1S,2S)-2-(4-methoxy-7- Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-ylamino)cyclohexanol (500 mg, 88.6%). MS (ES+) Ctwenty one H31 BN2 O4 S required value: 418, measured value: 419 [M+H]+ . Step 6: H at 0 °C2 O2 (30 drops) was added dropwise to (1S,2S)-2-(4-methoxy-7-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxo A solution of the heteroborane-2-yl)benzo[d]thiazol-2-ylamino)cyclohexanol (500 mg, 1.20 mmol) in MeOH (12 mL). The reaction mixture was stirred at EtOAc (EtOAc)EtOAc. The residue was purified by silica gel chromatography (0% to 10% MeOH in EtOAc) -7-Methylbenzo[d]thiazole-6-ol (250 mg, 67%). MS (ES+) C15 H20 N2 O3 S, required value: 308, measured value: 309 [M+H]+ . Step 7: To 2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxy-7-methylbenzo[d]thiazole-6-ol (100 mg, at room temperature Add Cs to a solution of 0.325 mmol) and 2-chloro-4-(chloromethyl)pyrimidine (52 mg, 0.32 mmol) in DMF (1 mL)2 CO3 (211 mg, 0.650 mmol). The reaction was then stirred at 80 ° C for 2 hours. The reaction was quenched with EtOAc (3 mL)EtOAc2 SO4 Dry over, filter and concentrate. The residue was purified by silica gel chromatography (0 to 20%EtOAcEtOAcEtOAc) elute Oxy)-4-methoxy-7-methylbenzo[d]thiazol-2-ylamino)cyclohexanol (20 mg, 14.3%). MS (ES+) C20 Htwenty three ClN4 O3 S required value: 434, measured value: 434, 436 [M+H]+ . Step 8: (1S,2S)-2-(6-((2-Chloropyrimidin-4-yl)methoxy)-4-methoxy-7-methylbenzo[d] at 100 °C Thiazol-2-ylamino)cyclohexanol (20 mg, 0.046 mmol) in NH4 The solution in OH (0.5 mL) was stirred overnight. The reaction mixture was prepared by preparative HPLC (mobile phase: A = 10 mM ammonium bicarbonate / H)2 O, B = acetonitrile; gradient: B = 60% - 95% in 18 min; column: Welch Xtimate® C18, 10 μm, 21.2 mm x 250 mm) purified to provide a white solid ((1S, 2S) -2-(6-((2-Aminopyrimidin-4-yl)methoxy)-4-methoxy-7-methylbenzo[d]thiazol-2-ylamino)cyclohexanol ( 5 mg, 26%). MS (ES+) Ctwenty one H26 N4 O3 S required value: 415, found: 416 [M+H]+.1 H NMR (500 MHz, MeOD) δ 8.42 – 8.16 (m, 1H), 7.02 – 6.80 (m, 1H), 6.62 (s, 1H), 5.00 (s, 2H), 3.90 (s, 3H), 3.70 – 3.54 (m, 1H), 3.51 – 3.39 (m, 1H), 2.30 (s, 3H), 2.20 – 2.12 (m, 1H), 2.09 – 1.95 (m, 1H), 1.89 – 1.61 (m, 2H), 1.49 – 1.21 (m, 5H). Example 74: (1S,2S)-2-(6-((2-Amino-3-fluoropyridin-4-yl)methoxy)-7-chloro-4-methoxybenzo[d]thiazole -2-ylamino)cyclohexanolThe title compound was synthesized according to the following synthetic scheme:Step 1: 6-(Benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (Example 50, Step 4) (0.5 g, 1.4 mmol) in NMP (5 mL) NCS (0.17 g, 2.8 mmol) was added to the solution. The mixture was stirred at 50 ° C for 2 hours. The resulting mixture was diluted with water (10 mL) andEtOAcEtOAc. The combined organic layer was washed with brine (10 mL) over Na2 SO4 Dry over, filter and concentrate under reduced pressure. The residue was purified by EtOAc (EtOAcEtOAcEtOAcEtOAcEtOAcEtOAc 4-methoxybenzo[d]thiazole. MS (ES+) C15 H11 BrClNO2 S required value: 383, measured value: 384 [M + H]+ . Step 2: 6-(Benzyloxy)-2-bromo-7-chloro-4-methoxybenzo[d]thiazole (0.2 g, 0.5 mmol) in DMA (5 mL) (1S,2S)-2-Aminocyclohexanol (0.12 g, 1 mmol) and DIPA (0.65 g, 5.0 mmol) were added as a solution. The mixture was stirred at 90 ° C overnight. The resulting mixture is H2 O (10 mL) was diluted and extracted with EtOAc (3×10 mL). The combined organic layer was washed with brine (10 mL) over Na2 SO4 Dry over, filter and concentrate under reduced pressure. The residue was purified by silica gel chromatography (30-50%EtOAcEtOAcEtOAc) elute 7-Chloro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol. MS (ES+) Ctwenty one Htwenty three ClN2 O3 S required value: 418, measured value: 419 [M + H]+ . Step 3: (1S,2S)-2-(6-(Benzyloxy)-7-chloro-4-methoxybenzo[d]thiazol-2-ylamino)-cyclohexane at 50 °C A solution of the alcohol (0.20 g, 0.48 mmol) in TFA (2 mL) After cooling to room temperature, the mixture was saturated with NaHCO3 Neutralize and extract with EtOAc (3 x 10 mL). The combined organic layer was washed with brine (10 mL) over Na2 SO4 Drying, filtration and concentration under reduced pressure to give 7-chloro-2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxy as a yellow solid (90 mg, 60%) Benzo[d]thiazole-6-ol. MS (ES+) C14 H17 ClN2 O3 S required value: 328, measured value: 329 [M+H]+ . Step 4: 7-Chloro-2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol (90 mg, 0.27 at room temperature) Addition of 4-(chloromethyl)-3-fluoro-N-(4-methoxybenzyl)pyridin-2-amine (92 mg, 0.33 mmol) and Cs in EtOAc (3 mL)2 CO3 (0.18 g, 0.54 mmol). The mixture was stirred overnight at 100 °C. The resulting mixture was diluted with water (10 mL) andEtOAcEtOAc. The combined organic layer was washed with brine (10 mL) over Na2 SO4 Drying, filtration and concentration under reduced pressure to give (1,,,,,,,,,,,,,,,,,, Oxybenzylamino)pyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol. MS (ES+) C28 H30 ClFN4 O4 S required value: 572, measured value: 573 [M+H]+ . Step 5: (1S,2S)-2-(7-chloro-6-((3-fluoro-2-(4-methoxybenzylamino)pyridin-4-yl)methoxy) at room temperature A solution of 4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (50 mg, 0.09 mmol) in TFA (2 mL) was stirred overnight. The mixture is NaHCO3 The mixture was neutralized with EtOAc (3×10 mL). The combined organic layer was washed with brine (10 mL) over Na2 SO4 It was dried, filtered and concentrated under reduced pressure to give crude material from preparative HPLC (mobile phase: A = 0.01% TFA/H2 O,B = MeCN; Gradient: B = 5% - 95% in 8 min; Column: XBridge C18, 5 μm, 30 mm × 150 mm) Purified to give a white solid (17.3 mg, 44%) 1S,2S)-2-(6-((2-Amino-3-fluoropyridin-4-yl)methoxy)-7-chloro-4-methoxybenzo[d]thiazol-2-yl Amino) cyclohexanol. MS (ES+) C20 Htwenty two ClFN4 O3 S required value: 452, measured value: 453 [M+H]+;1 H NMR (400 MHz, DMSO) δ 7.90 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 4.0 Hz, 1H), 6.85 (s, 1H), 6.69 (t, J = 4.0 Hz, 1H ), 6.24 (s, 2H), 5.21 (s, 2H), 4.75 (d, J = 4.0 Hz, 1H), 3.87 (s, 3H), 2.03 (d, J = 4.0 Hz, 1H), 1.87 (d , J = 4.0 Hz, 1H), 1.63 (t, J = 12.0 Hz, 2H), 1.24 (m, 6H). The following examples in Table 6 were prepared analogously to Example 74. Table 6: Example 76: (1S,2S)-2-(7-Chloro-4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl) Methoxy)benzo[d]thiazol-2-ylamino)cyclohexanolThe title compound was synthesized according to the following synthetic scheme:(1S,2S)-2-(7-chloro-6-((2-chloropyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazole-2- at 110 °C Cyclohexanol (Example 74, Step 5) (60 mg, 0.13 mmol), 1-methyl-1H-pyrazol-4-amine (21 mg, 0.15 mmol) and TsOH.H2 A mixture of O (11 mg, 0.065 mmol) in dioxane (2 ml) was stirred overnight. The mixture was diluted with EtOAc (5 mL) using saturated NaHCO3 Cleaning, and Na2 SO4 Dry on top. The combined organic layers were concentrated. The residue was prepared by preparative HPLC (mobile phase: A = 0.1% NH)4 HCO3 /H2 O,B = MeCN; Gradient: B = 5 - 95%; 12 min; Column: C18) Purified to provide (1S,2S)-2-(7-chloro-4-methoxy-6 as a white solid. -((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[d]thiazol-2-ylamino)cyclohexanol (3.5 Mg, 5%). MS (ES+) Ctwenty three H26 ClN7 O3 S required value: 515, measured value: 516 [M+H]+ .1 H NMR (500 MHz, d6-DMSO) δ 9.51 (s, 1H), 8.44 (d, J = 4.5 Hz, 1H), 7.89 (d, J = 9.5 Hz, 2H), 7.48 (s, 1 H), 6.83 - 6.89 (m, 2H), 5.17 (s, 2H), 4.17 (d, J = 5.5 Hz, 1H), 3.77 (s, 3H), 3.49 (s, 3H), 2.02 - 2.08 (m, 1H) , 1.86 - 1.89 (m, 1H), 1.60 - 1.65 (m, 2H), 1.19 - 1.30 (m, 4H). The following examples in Table 7 were prepared analogously to Example 76. Table 7: Example 79: 4-((2-((1S,2S)-2-Hydroxycyclohexylamino)-4-methoxybenzo[d]thiazol-6-yloxy)methyl)pyridine-2- Methyl carbamideThe title compound was synthesized according to the following synthetic scheme:Step 1: Stir a solution of 4-(chloromethyl)pyridin-2-ylaminecarboxylic acid tert-butyl ester (700 mg, 2.88 mmol) in HCl-dioxane (4M, 5 mL) at 55 °C hour. The reaction mixture was concentrated under reduced pressure to give 4-(chloromethyl)pyridin-2-amine, which was used in the next step without further purification. MS (ES+) C6 H7 ClN2 Required value: 142, measured value: 143 [M+H]+ . Step 2: Add Et to a solution of 4-(chloromethyl)pyridin-2-amine (300 mg, 2.1 mmol) in DCM (8 mL)3 N (637 mg, 6.3 mmol) and methyl chloroformate (199 mg, 2.1 mmol). The resulting mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with water (10 mL) andEtOAc. The combined organic layer is tied to Na2 SO4 Dry over, filter and concentrate. The residue was purified by EtOAc (EtOAc) (EtOAc) MS (ES+) C8 H9 ClN2 O2 Required value: 200, measured value: 201 [M+H]+ . Step 3: To methyl 4-(chloromethyl)pyridin-2-ylcarbamate (100 mg, 0.5 mmol) and 2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxy Addition of a solution of the benzo[d]thiazole-6-ol (prepared as described in Example 50, steps 1 to 6) (138 mg, 0.47 mmol) in DMF (3 mL)2 CO3 (130 mg, 0.94 mmol). The reaction mixture was stirred at 90 ° C for 3 hours. The mixture is mass-triggered preparative HPLC (mobile phase: A = 10 M NH4 HCO3 /H2 O,B = MeCN; Gradient: B = 40-70%; 8.5 min; Column: C18) Filtration and purification to give 4-((2-((1S,2S)-2-hydroxycyclohexyl) as a white solid. Methylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-ylcarbamate (18 mg, 9%). MS (ES+) Ctwenty two H26 N4 O5 S required value: 458, measured value: 459 [M+H]+ .1 H NMR (500MHz, DMSO) δ 10.23 (s, 1H), 8.25 (d, J = 5.0 Hz, 1H), 7.94 (s, 1H), 7.63 (d, J = 7.5 Hz, 1H), 7.10 (d, J = 5.1 Hz, 1H), 6.94 (d, J = 2.3 Hz, 1H), 6.56 (d, J = 2.3 Hz, 1H), 5.13 (s, 2H), 4.78 (d, J = 5.0 Hz, 1H) , 3.83 (s, 3H), 3.67 (s, 3H), 3.50 (s, 1H), 2.03 (d, J = 13.1 Hz, 1H), 1.86 (s, 1H), 1.63 (s, 2H), 1.31 - 1.16 (m, 5H). Example 80: 1-(4-((2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazol-6-yloxy)methyl)pyridine -2-yl)-3-methylureaThe title compound was synthesized according to the following synthetic scheme:Step 1: Stir a solution of 4-(chloromethyl)pyridin-2-ylaminecarboxylic acid tert-butyl ester (400 mg, 1.65 mmol) in HCl-dioxane (4M, 3 mL) at 55 °C hour. The reaction mixture was concentrated to give 4-(chloromethyl)pyridin-2-amine. The residue was used in the next step without further purification. MS (ES+) C6 H7 ClN2 Required value: 142, measured value: 143 [M+H]+ . Step 2: Add Et to a solution of 4-(chloromethyl)pyridin-2-amine (300 mg, 2.1 mmol) in DCM (8 mL)3 N (4 mL) and methylaminoformamidine chloride (589 mg, 6.3 mmol). The resulting mixture was stirred overnight at room temperature. The reaction mixture was washed with water (10 mL) andEtOAc. Organic layer attached to Na2 SO4 Dry over, filter and concentrate. The residue was purified by silica gel chromatography (0-95%EtOAcEtOAcEtOAcEtOAc) Mg, 13%). MS (ES+) C8 H10 ClN3 O required value: 199, measured value: 200 [M + H]+ . Step 3: To 1-(4-(chloromethyl)pyridin-2-yl)-3-methylurea (50 mg, 0.25 mmol) and 2-((1S,2S)-2-hydroxycyclohexylamino) -4-Methoxybenzo[d]thiazole-6-ol (prepared as described in Example 50, steps 1 to 6) (74 mg, 0.25 mmol) in DMF (1 mL)2 CO3 (69 mg, 0.5 mmol). The reaction mixture was stirred at 90 ° C for 3 hours. The mixture is mass-triggered preparative HPLC (mobile phase: A = 10 M NH4 HCO3 /H2 O,B = MeCN; Gradient: B = 30-60%; 9.5 min; Column: C18) Filtration and purification to give 1-(4-((1S,2S)-2-) as a white solid Hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-yl)-3-methylurea (27 mg, 24%). MS (ES+) Ctwenty two H27 N5 O4 S required value: 457, measured value: 458 [M+H]+ .1 H NMR (500MHz, DMSO) δ 9.29 (s, 1H), 8.27 - 8.01 (m, 2H), 7.62 (d, J = 7.5 Hz, 1H), 7.39 (s, 1H), 6.95 (dd, J = 21.8 , 3.5 Hz, 2H), 6.55 (d, J = 1.9 Hz, 1H), 5.07 (s, 2H), 4.77 (d, J = 4.9 Hz, 1H), 3.83 (s, 3H), 3.51 (s, 1H) ), 2.73 (d, J = 4.5 Hz, 3H), 2.02 (s, 1H), 1.86 (s, 1H), 1.63 (s, 2H), 1.32 - 1.12 (m, 5H). The following examples in Table 8 were prepared analogously to Example 80. Table 8: Example 81: (1S,2S)-2-(4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyridin-4-yl)methoxy) Benzo[d]thiazol-2-ylamino)cyclohexanolThe title compound was synthesized according to the following synthetic scheme:Step 1: To a solution of (2-bromopyridin-4-yl)methanol (1.0 g, 5.3 mmol) and DIPEA (2.06 g, 15.9 mmol) in DCM (20 mL) 5.6 mmol). The resulting mixture was warmed to room temperature and stirred for 2 hours. The mixture was diluted with DCM (10 mL) and sat.4 Cl (20 mL), saturated aqueous Na2 CO3 (20 mL) and brine (10 mL) for cleaning. The mixture is tied to Na2 SO4 Dry over, filter and concentrate. The residue was purified by silica gel chromatography (0 to 50%EtOAcEtOAcEtOAc) MS (ES+) C7 H8 BrNO3 S required value: 265, measured value: 266 [M+H]+ . Step 2: To (2-bromopyridin-4-yl)methyl methanesulfonate (300 mg, 1.13 mmol) and 2-((1S,2S)-2-hydroxycyclohexylamino)-4-methoxy Addition of benzo[d]thiazole-6-ol (as prepared for Example 50, as described in steps 1 to 6) (332 mg, 1.13 mmol) in DMF (4 mL)2 CO3 (736 mg, 2.26 mmol). The resulting mixture was stirred at 80 ° C for 20 minutes. The reaction mixture was mass-triggered preparative HPLC (mobile phase: A = 10 M NH4 HCO3 /H2 O,B = MeCN; Gradient: B = 40-70%; 10.85 min; Column: C18) Filtration and purification to give (1S,2S)-2-(6-((2-bromopyridine) as a white solid. 4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (185 mg, 35%). MS (ES+) C20 Htwenty two BrN3 O3 S required value: 463, measured value: 464 [M + H]+ . Step 3: In a pressure tube, 1-methylpyrazol-4-amine HCl (21 mg, 0.16 mmol), (1S, 2S)-2-(6-((2-bromopyridin-4-yl)) Methoxy)-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol (60 mg, 0.13 mmol), RuPhos Pd G4 (11 mg, 0.013 mmol), RuPhos (6 mg, 0.013 mmol) and Cs2 CO3 (127 mg, 0.39 mmol) was dissolved in 1,4-dioxane (2 mL). Seal the tube and use N2 Purification. The reaction mixture was stirred at 85 ° C for 3 hours. The reaction was monitored by LCMS. The mixture is mass-triggered preparative HPLC (mobile phase: A = 10 M NH4 HCO3 /H2 O,B = MeCN; Gradient: B = 30-60%; 10.0 min; Column: C18) Filtration and purification to give (1S,2S)-2-(4-methoxy-6-( (2-(1-Methyl-1H-pyrazol-4-ylamino)pyridin-4-yl)methoxy)benzo[d]thiazol-2-ylamino)cyclohexanol (5 mg, 9%). MS (ES+) Ctwenty four H28 N6 O3 S required value: 480, measured value: 481 [M + H]+ .1 H NMR (500MHz, DMSO) δ 8.81 (s, 1H), 8.07 (d, J = 5.3 Hz, 1H), 7.91 (s, 1H), 7.61 (d, J = 7.5 Hz, 1H), 7.37 (s, 1H), 6.91 (d, J = 2.3 Hz, 1H), 6.70 (s, 1H), 6.65 (d, J = 5.3 Hz, 1H), 6.54 (d, J = 2.2 Hz, 1H), 5.02 (s, 2H), 4.77 (d, J = 5.0 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 3.51 (s, 1H), 2.02 (s, 1H), 1.87 (d, J = 11.2 Hz, 1H), 1.63 (t, J = 10.8 Hz, 2H), 1.23 (s, 5H). The following examples in Table 9 were prepared analogously to Example 81. Table 9: Example 84: 6-((2-Aminopyrimidin-4-yl)methoxy)-7-chloro-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole 2-amineThe title compound was synthesized according to the following synthetic scheme:Step 1: 6-(Benzyloxy)-2-bromo-4-methoxybenzo[d]thiazole (Example 50, Step 4) (750 mg, 2.14 mmol) and NCS under argon at 50 °C The mixture (570 mg, 4.29 mmol) in NMP (10 mL) was stirred for 3 h. Water was added and the mixture was extracted with EtOAc (3 x 5 mL). The organic layer was washed with brine, dried and evaporated tolulululululululululululululululululululululu MS (ES+) C15 H11 BrClNO2 S required value: 383, measured value: 384, 386 [M+H]+ . Step 2: 6-(Benzyloxy)-2-bromo-7-chloro-4-methoxybenzo[d]thiazole (160 mg, 0.41 mmol) and 3,3-difluoro ring at 180 °C A mixture of hexylamine hydrochloride (140 mg, 0.82 mmol) in DIPEA (20 drops) and NMP (20 drops) was stirred for 4 hours. The reaction mixture was diluted with water and extracted with EtOAc EtOAc. The combined organic layer is tied to Na2 SO4 Dry and concentrate. The residue was purified by silica gel chromatography (0% to 10%EtOAcEtOAcEtOAc) toield ) 4-methoxybenzo[d]thiazol-2-amine (100 mg, 54.9%). MS (ES+) Ctwenty one Htwenty one ClF2 N2 O2 S, required value: 438, measured value: 439 [M + H]+ . Step 3: 6-(Benzyloxy)-7-chloro-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine (100) at 65 °C The solution in mg of TFA (3 mL) was stirred for 16 h. The TFA was evaporated <RTI ID=0.0> The combined organic layer is saturated with NaHCO3 Solution cleaning, in Na2 SO4 Drying and concentrating to provide 7-chloro-2-(3,3-difluorocyclohexylamino)-4-methoxybenzo[d]thiazole-6-ol as a brown oil (100 mg, crude) . MS (ES+) C14 H15 ClF2 N2 O2 S required value: 348, measured value: 349 [M + H]+ . Step 4: (2-Aminopyrimidin-4-yl)methyl methanesulfonate (52 mg, 0.26 mmol), 7-chloro-2-(3,3-difluorocyclohexylamino) at room temperature 4-methoxybenzo[d]thiazole-6-ol (90 mg, 0.26 mmol) and Cs2 CO3 The mixture (2168 mg, 0.52 mmol) in DMF (1 mL The reaction mixture was prepared by preparative HPLC (mobile phase: A = 0.01% TFA/H)2 O, B = MeCN; Gradient: B = 60% - 95% in 18 min; Column: Venusil CBP C18 (L) C18, 10 μm, 21.2 mm x 250 mm, Cat. NO. : VX902520-L) To give 6-((2-aminopyrimidin-4-yl)methoxy)-7-chloro-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[ d] thiazol-2-amine (20 mg, 15%). MS (ES+) C19 H20 ClF2 N5 O2 S, required value: 455, measured value: 456 [M + H] +;1 H NMR (500 MHz, DMSO) δ 8.32 (d, J = 5.2 Hz, 1H), 8.08 (d, J = 7.5 Hz, 1H), 7.08 (s, 2H), 6.83 (s, 2H), 5.10 (s , 2H), 3.95 – 3.90 (m, 1H), 3.87 (s, 3H), 2.46 – 2.42 (m, 1H), 2.05 – 1.96 (m, 2H), 1.87 – 1.72 (m, 3H), 1.52 – 1.45 (m, 1H), 1.39 – 1.29 (m, 1H). Examples 85 and 86: The following examples in Table 10 were prepared similarly to Example 1: Table 10: Instance 87 : CSF-1R Competitive combination analysis Compounds that bind to CSF-1R are measured by FRET-based competitive binding assay (LanthaScreen® Eu Kinase Binding Assay; Invitrogen). The binding of Alexa Fluor® conjugate tracer No. 236 (cat no. PV5592) to His-tagged hCSF1R (aa538-910) was detected by the addition of an Eu-labeled anti-His antibody. The binding of the tracer and antibody to CSF1R results in a high degree of FRET, while the replacement of the tracer with a kinase inhibitor results in a loss of FRET. His-CSF1R (5 μl) is spiked with 5 μl of compound concentration in reaction buffer (50 mM HEPES [pH 7.5], 10 mM MgCl)2 , 1 mM EGTA, 0.003% Tween 20) was incubated for 20 minutes, then mixed with 5 μl of antibody and incubated at room temperature for 90 minutes. The final concentrations of CSF1R, tracer and anti-His antibodies were 3 nM, 10 nM and 2 nM, respectively. The FRET signal is followed in a plate reader (excitation: 320 nm; emission: 615 nm). Dose-response curve using IC50 Regression curve fitting (GeneData Screener) analysis. Table 11 below summarizes the results of the CSF-1R competitive binding assay, in which the IC of each compound50 Values are indicated as follows: (A) less than 50 nM; (B) 50 nM to 200 nM; (C) 200 nM to 500 nM; (D) 500 nM to 1.5 μM; and (E) > 1.5 μM. Table 11: Competitive binding analysis of CSF-1R Instance 88 : mCSF Dependent cell proliferation assay M-NFS-60 cells (ATCC – CRL-1838) were resuspended in medium containing 10 ng/mL recombinant mouse m-CSF (R&D Systems – 416-ML-010) (RPMI-1640, GlutaMax Supplement, HEPES – Gibco 72400-047). The cells were then plated in 384-well plates (5000 cells/well, 35 μL/well) and at 37 ° C, 5% CO2 Cultivate overnight. Dilute DMSO (control) or increasing concentrations of the compound in the medium, add to a 384-well plate (5 μL/well, final DMSO concentration 0.5%), and use the compound at 37 ° C, 5% CO2 The culture was carried out for 72 hours. Cell viability was then measured by adding 35 μL of CellTiter-Glo 2.0 (Promega, G9243) using the manufacturer's recommendations. Cell lines were incubated with CellTiter-Glo 2.0 for 10 minutes at room temperature and then luminescence was read by Envision plate reader. Dose-response curve using IC50 Regression curve fitting (GeneData Screener) analysis. The curves were normalized to high control without inhibitor and low control with 1 μM staurosporine. Table 12 below summarizes the results of mCSF-dependent cell proliferation assays in which ICs of each compound50 Values are indicated as follows: (A) less than 1 μM; (B) 1 μM to 2 μM; (C) 2 μM to 5 μM; (D) 5 μM to 10 μM; (E) greater than 10 μM. Table 12: mCSF-dependent cell proliferation assay Instance 89 : Kinase selectivity The compounds of the invention were evaluated for their selectivity for CSF-1R over the kinases c-Kit, FLT3, PDGFRα and PDGFRβ. For CSF-1R, FLT3, c-KIT, PDGFRα and PDGFRβ kinase assays, kinase-tagged T7 phage strains were prepared in E. coli hosts derived from the BL21 strain. E. coli was grown to log phase, infected with T7 phage and cultured at 32 °C until the cells were lysed. The lysate was centrifuged and filtered to remove cell debris. The magnetic beads coated with streptavidin were treated with biotinylated small molecule ligands for 30 minutes at room temperature to produce an affinity resin for kinase analysis. The ligand-treated beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligands and reduce non- Specific binding. The binding reaction was assembled by combining kinases, ligand-treated affinity beads, and test compounds in 1x binding buffer (20% SeaBlock, 0.17x PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 111X stock solutions in 100% DMSO. Kd values were determined using a 11-point, 3-fold dilution series of compounds with three DMSO control points. All compounds used for Kd measurement were dispensed by acoustic transfer (non-contact dispensing) in 100% DMSO. The compound was then directly diluted into the assay such that the final concentration of DMSO was 0.9%. All reactions were carried out in polypropylene 384 well plates. The final volume of each line is 0.02 ml. The assay plates were incubated at room temperature for 1 hour with shaking and the affinity beads were washed with wash buffer (1 x PBS, 0.05% Tween 20). The beads were then resuspended in dissolution buffer (1 x PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated for 30 minutes at room temperature with shaking. The concentration of the kinase in the eluate was measured by qPCR. Compound Treatment 11-point 3-fold serial dilutions of each test compound were prepared in 100% DMSO at 100x final test concentration and then diluted to 1x in the assay (final DMSO concentration = 1%). Most Kd values were determined using the highest concentration of compound = 30,000 nM. If the initial Kd of the assay is < 0.5 nM (the lowest concentration tested), repeat measurements are taken starting from successive dilutions of the lower highest concentration. A Kd value recorded as 40,000 nM indicates that the Kd was determined to be > 30,000 nM. The binding constant (Kd) binding constant is calculated using the standard equation for the standard dose-response curve: Reaction = Background + Signal - Background 1 + (KdHill Slope / Dose Hill Slope) Set the Hill slope to -1. The curves were fitted using the Lemberg-Marquardt algorithm using a nonlinear least squares fit. Table 13 below summarizes the results of the selectivity analysis in which the Kd values for c-Kit, FLT3, PDGFRα, and PDGFRβ measurements are relative to the Kd values for CSF-1R. The selectivity of each compound for CSF-1R relative to c-Kit is given as follows: (A) > 50 times; (B) 10 to 50 times; (C) 5 to 10 times; and (D) less than 5 times more Selective. The selectivity of each compound for CSF-1R relative to FLT3 is given as follows: (A) > 500 times; (B) 200 to 500 times; (C) 100 to 200 times; and (D) less than 100 times more selective Sex. The selectivity of each compound for CSF-1R relative to PDGFRα is given as follows: (A) > 15 times; (B) 10 to 15 times; (C) 5 to 10 times; and (D) less than 5 times more selective Sex. The selectivity of each compound for CSF-1R relative to PDGFRβ is given as follows: (A) > 10 fold; (B) 2.5 to 10 fold; (C) 1.5 to 2.5 fold; and (D) less than 1.5 fold more selective Sex. Table 13: Kinase selectivity of compounds Instance 90 : CSF-1R Cell target junction analysis THP-1 cells were resuspended in RPMI medium (no phenol red) containing 10% HI FBS and 0.1% β-Me, and then plated in 96-well TC plates (125 μl, 250K cells/well). These cell lines are at 37 ° C, 5% CO2 The cells were incubated for 20 hours, followed by the addition of 0.1% DMSO (control) or varying concentrations of CSF-1R inhibitor. After incubation for 30 minutes at 37 ° C, the cell lines were treated with 50 ng/mL human MCSF (Sigma M6518) for 5 minutes and then added to 125 μl of cell lysis buffer (R&D Systems SAMPLE diluent CONC 2). After incubation for 45 minutes at room temperature, tyrosine phosphorylated CSF-1R was assessed by sandwich ELISA (R&D Systems DYC 3268) following the manufacturer's protocol. Briefly, Nunc-Immuno MaxiSorp plates (Sigma 9410) were coated with anti-human CSF-1R, blocked, and bound to 100 μL of THP-1 cell lysate at room temperature for 2 hours. After washing, HRP-labeled anti-phosphophosphoryl tyrosine was added to the plate and incubated for an additional 2 hours at room temperature. After washing, the ELISA signal was induced and stopped by a 1-step Ultra TMB-ELISA substrate (Life Technologies 34028) and 2 N sulfuric acid, respectively. The absorbance at 450 nm and 540 nm was measured on a BioTek Neo plate reader and the ELISA signal was calculated as Ab450nm -Ab540nm . The standard dose response curve is fitted by the Genedata Screener software using a variable slope model: Signal = SignalNegative control + (signalDMSO Control -signalNegative control )/(1+(IC50 /Dose)^Hill slope) Only the signal and dose are treated as known values in the equation. Table 14 below summarizes the results of the cell target junction analysis, in which the IC of each compound50 Values are indicated as follows: (A) less than 250 nM; (B) 250 nM to 500 nM; (C) 500 nM to 1 μM; (D) 1 μM to 2 μM; (E) greater than 2 μM. Table 14: Cell target junction analysis The teachings of all patents, published applications and references cited herein are hereby incorporated by reference in their entirety. Although the present invention has been particularly shown and described with reference to the embodiments of the present invention, it will be understood that Spirit and scope.

Claims (61)

一種以式(I)表徵之化合物，或其醫藥上可接受之鹽或前藥，其中： A係5至10員雜芳基，其環原子係由C、至少一個N及視需要O或S組成； n係0、1、2、3或4； m係0、1或2； X1 係選自NH、O、S、-CH=N-及-N=CH-； L表示直接鍵或其係基團-(CR6 R7 )p -，其中： p係1、2或3，及 各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素及羥基、視需要經1至3個鹵素取代之C1-4 -烷基、視需要經1至3個鹵素取代之-O(C1-4 -烷基)、胺醯基、醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-N(R’R” )之基團取代，其中R’ 及R” 係獨立地選自氫及C1-3 -烷基； R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代； R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經取代； R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該醯基、烷基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代；及 R4 及R5 係獨立地選自H及C1-3 -烷基， 或R4 及R5 與居間的碳原子一起形成3至6員環烷基或雜環烷基，其視需要經一或多個鹵素原子取代。a compound characterized by the formula (I), Or a pharmaceutically acceptable salt or prodrug thereof, wherein: A is a 5 to 10 membered heteroaryl group having a ring atomic system consisting of C, at least one N, and optionally O or S; n is 0, 1, 2 3 or 4; m system 0, 1 or 2; X 1 is selected from NH, O, S, -CH=N- and -N=CH-; L represents a direct bond or a group thereof - (CR 6 R 7 And p- , wherein: p is 1, 2 or 3, and each R 6 and each R 7 are independently selected from the group consisting of hydrogen and C 1-4 -alkyl, wherein each alkyl group is optionally and independently Up to 3 -O(C 1-4 -alkyl) independently selected from halogen and hydroxy, optionally substituted with 1 to 3 halogens, C 1-4 -alkyl, optionally substituted with 1 to 3 halogens a group substituted with an amine sulfhydryl group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, and a -N(R'R " ), wherein R ' and R " are independently selected from Hydrogen and C 1-3 -alkyl; R 1 is in each case independently selected from the group consisting of halogen, nitrile, -C(O)N(R 8 R 9 ), -N(R 8 R 9 ), -NHC ( O) NR 8 R 9 , -NHC(O)OR 10 , -NHC(O)R 10b , -C(O)R 10b , C 2-4 -fluorenyl, C 2-4 -decylamino, hydroxy , -O (C 1-8 - alkyl), - C (O) OR 10, sulfonylurea group, a sulfo group acyl, C 1-8 - alkyl, C 2-8 - Group, C 2-8 - alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl, wherein R 8 and R 9 are independently selected H, C 1 -4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 10 is independently selected from H, C 1-4 -alkyl, C 1- 4 -alkenyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R 10b are independently selected from H, C 1- 4 -alkyl, C 1-4 -alkenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, and wherein each of the fluorenyl, decylamino, Sulfosyl, aminosulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl groups optionally substituted; R 2 in each case independently selected from the group consisting of halogen, hydroxy, nitrile, C 1-4 -alkyl and -O(C 1-4 -alkyl), wherein each alkyl group is optionally substituted; R 3 is Selected from a C 1-8 -alkyl group, a C 2-4 -fluorenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, wherein each of the fluorenyl group and the alkane Base, cycloalkyl, heterocycle An alkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted; and R 4 and R 5 are independently selected from H and C 1-3 -alkyl, or R 4 and R 5 together with the intervening carbon atom form a 3 to 6 membered cycloalkyl or heterocycloalkyl group which is optionally substituted with one or more halogen atoms. 如請求項1之化合物，其中： R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 及R9 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 及 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)；及/或 R2 在各情況下係獨立地選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)， 其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及/或 R3 係選自C1-8 -烷基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中各該烷基、醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。The compound of claim 1, wherein: R 1 is independently selected from the group consisting of halogen, nitrile, -C(O)N(R 8 R 9 ), -N(R 8 R 9 ), -NHC(O) )NR 8 R 9 , -NHC(O)OR 10 , -NHC(O)R 10b , -C(O)R 10b , C 2-4 -mercapto, C 2-4 -mercaptoamine, hydroxyl group, -O(C 1-8 -alkyl), -C(O)OR 10 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 Alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 8 and R 9 are independently selected from H, C 1-4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 10 is independently selected from H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 - mercapto, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, R 10b is independently selected from H, C 1-4 -alkyl, C a 1-4 -alkenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, and each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amine group Sulfhydryl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl To with 1 to 5 substituents independently selected from the group: halogen, hydroxy, -N (R a R b) ( wherein R a and R b are independently selected hydrogen and C 1-3 - alkyl) , -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 - Alkyl)-R c (wherein R c is selected from the group consisting of hydroxyl, amine and halogen); and/or R 2 is in each case independently selected from the group consisting of halogen, hydroxy, nitrile, C 1-4 -alkyl and O(C 1-4 -alkyl), wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and/or R 3 is selected from C 1-8 An alkyl group, a C 2-4 -fluorenyl group, a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group and a heteroaryl group, wherein each of the alkyl group, the fluorenyl group, the cycloalkyl group, A heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R d R e ) (wherein R d and R e are independently selected from hydrogen and, if desired, an amine or a hydroxyl group or a C 1-4 -alkyl group substituted with 1 to 3 halogens), optionally via a hydroxyl group or via 1 to 3 Halogen substituted -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 -decylamino, -C(O)N(R f R g ) (wherein R f and R g are independently selected from hydrogen and C 1-4 -alkyl or wherein R f and R g together with the intervening nitrogen atom form a 4 to 7 membered heterocyclic group), C 3-8 -cycloalkenyl, sulfonyl, aminosulfonyl, sulfonate A mercaptoamine group, optionally a C 1-4 -alkyl group, an aryl group and a heteroaryl group substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 如請求項1或請求項2之化合物，其中A係6員單環雜芳基。The compound of claim 1 or claim 2, wherein the A is a 6 membered monocyclic heteroaryl group. 如前述請求項中任一項之化合物，其中n係1或2。A compound according to any one of the preceding claims, wherein n is 1 or 2. 如前述請求項中任一項之化合物，其中R1 在各情況下係獨立地選自鹵素、腈、-C(O)N(R8 R9 )、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-C(O)R10b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR10 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R8 、R9 及R10 係各獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R10b 係獨立地選自H、C1-4 -烷基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。A compound according to any one of the preceding claims, wherein R 1 is in each case independently selected from the group consisting of halogen, nitrile, -C(O)N(R 8 R 9 ), -N(R 8 R 9 ), - NHC(O)NR 8 R 9 , -NHC(O)OR 10 , -NHC(O)R 10b , -C(O)R 10b , C 2-4 -fluorenyl, C 2-4 -decylamino , hydroxy, -O(C 1-8 -alkyl), -C(O)OR 10 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 8 , R 9 and R 10 are each independently selected from H, C 1-4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 10b is independently selected from H, C 1-4 -alkyl, naphthenic a base, a heterocycloalkyl group, an aryl group and a heteroaryl group, and wherein each of the fluorenyl group, a fluorenylamino group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a hetero The cycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R a R b ) ( Wherein R a and R b are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R c (wherein R c is selected from a hydroxyl group, an amine Base and halogen). 如前述請求項中任一項之化合物，其中R1 在各情況下係獨立地選自鹵素、-N(R8 R9 )、-NHC(O)NR8 R9 、-NHC(O)OR10 、-NHC(O)R10b 、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中R8 及R9 係獨立地選自H、C1-4 -烷基及雜芳基， R10 及R10b 係獨立地選自H及C1-4 -烷基，及 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Ra Rb )(其中Ra 及Rb 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C1-4 -烷基及(C1-4 -烷基)-Rc (其中Rc 係選自羥基、胺基及鹵素)。A compound according to any of the preceding claims, wherein R 1 is in each case independently selected from halogen, -N(R 8 R 9 ), -NHC(O)NR 8 R 9 , -NHC(O)OR 10 , -NHC(O)R 10b , -O(C 1-4 -alkyl), C 1-4 -alkyl, aryl and heteroaryl, wherein R 8 and R 9 are independently selected from H, C 1-4 -alkyl and heteroaryl, R 10 and R 10b are independently selected from H and C 1-4 -alkyl, and each of the alkyl, aryl or heteroaryl groups is optionally subjected to 1 Substituted to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R a R b ) (wherein R a and R b are independently selected from hydrogen and C 1-3 -alkyl), -O (C 1-3 -alkyl), nitrile, C 1-4 -alkyl and (C 1-4 -alkyl)-R c (wherein R c is selected from the group consisting of a hydroxyl group, an amine group and a halogen). 如前述請求項中任一項之化合物，其中R1 在各情況下係獨立地選自Cl、Br及胺基或選自甲基胺基、-NHC(O)OCH3 、 -NHC(O)CH3 、-NHC(O)NHCH3 、甲基、甲氧基、-NH-吡唑基、苯基及吡唑基，其各視需要經1至3個獨立地選自鹵素、C1-3 -烷基及-O(C1-3 -烷基)之基團取代。A compound according to any one of the preceding claims, wherein R 1 is in each case independently selected from the group consisting of Cl, Br and an amine group or selected from the group consisting of methylamino, -NHC(O)OCH 3 , -NHC(O) CH 3 , -NHC(O)NHCH 3 , methyl, methoxy, -NH-pyrazolyl, phenyl and pyrazolyl, each optionally 1 to 3 independently selected from halogen, C 1- Substituents of 3 -alkyl and -O(C 1-3 -alkyl) groups. 如前述請求項中任一項之化合物，其中m係1或2，及R2 係選自鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。A compound according to any one of the preceding claims, wherein m is 1 or 2, and R 2 is selected from the group consisting of halogen, hydroxy, nitrile, C 1-4 -alkyl and -O(C 1-4 -alkyl), Each of the alkyl groups is optionally substituted with 1 to 3 groups independently selected from halogen. 如前述請求項中任一項之化合物，其中R3 係C1-8 -烷基，其視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、胺基磺醯基、磺醯基胺基及視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)。A compound according to any of the preceding claims, wherein R 3 is C 1-8 -alkyl, which is optionally substituted with from 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N ( R d R e ) (wherein R d and R e are independently selected from hydrogen and, if desired, an amino group or a hydroxyl group or a C 1-4 -alkyl group substituted by 1 to 3 halogens), an aminosulfonyl group, A sulfonylamino group and optionally a -O(C 1-4 -alkyl) group substituted by a hydroxyl group or with 1 to 3 halogens. 如請求項1至8中任一項之化合物，其中R3 係選自環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中各該環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-4 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基。The compound of any one of claims 1 to 8, wherein R 3 is selected from the group consisting of a cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, a heterocycloalkenyl group, an aryl group, and a heteroaryl group, wherein each of the cycloalkyl groups A heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R d R e) (wherein R d and R e are independently selected hydrogen and an optionally hydroxy or amino group or with 1 to 3 substituents of halogen, C 1-4 - alkyl), hydroxy or optionally substituted with 1 to 3 halogen substituted -O(C 1-4 -alkyl), C 3-8 -cycloalkyl, C 2-4 -decylamino, -C(O)N(R f R g ) (wherein R f and R g are independently selected from hydrogen and C 1-4 -alkyl or wherein R f and R g together with the intervening nitrogen atom form a 4 to 7 membered heterocyclic group), C 3-8 -cycloalkenyl A sulfonyl group, an aminosulfonyl group, a sulfonylamino group, a C 1-4 -alkyl group, an aryl group and a heteroaryl group optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. 如請求項10之化合物，其中R3 係經羥基取代及進一步視需要經1至3個獨立地選自以下之基團取代之環己基：鹵素、羥基、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基、-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基或其中Rf 及Rg 與居間的氮原子一起形成4至7員雜環基)及視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基。The compound of claim 10, wherein R 3 is substituted with a hydroxy group and further optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R d R e ) (wherein R d and R e are independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with hydroxy or substituted with 1 to 3 halogens, -O(C 1-4 -alkyl), C 2 a 4 -mercaptoamine group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, -C(O)N(R f R g ) (wherein R f and R g are independently selected from hydrogen and C 1-3 - alkyl, or wherein R f and R g together with the nitrogen atom intervening 4-7 heterocyclyl), and optionally substituted with hydroxy or amino group or with 1 to 3 halogen C 1-4 of -alkyl. 如請求項10之化合物，其中R3 係二氫茚基(2,3-二氫-1H-茚基)，其視需要經1至4個獨立地選自以下之基團取代：羥基、視需要經羥基取代之C1-3 -烷基、F、Cl、腈、-N(Rd Re )(其中Rd 及Re 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C2-4 -醯基胺基、磺醯基、胺基磺醯基、磺醯基胺基及-C(O)N(Rf Rg )(其中Rf 及Rg 係獨立地選自氫及C1-3 -烷基)。The compound of the requested item 10, wherein R 3 based indanyl (2,3-dihydro -1H- indenyl), which is optionally substituted with 1 to 4 substituents independently selected from the group of substituents: hydroxy, depending C 1-3 -alkyl, F, Cl, nitrile, -N(R d R e ) substituted with a hydroxy group (wherein R d and R e are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-4 -alkyl), C 2-4 -mercaptoamine, sulfonyl, aminosulfonyl, sulfonylamino group substituted by hydroxyl group or with 1 to 3 halogens as needed And -C(O)N(R f R g ) (wherein R f and R g are independently selected from hydrogen and C 1-3 -alkyl). 如前述請求項中任一項之化合物，其中R4 及R5 皆係氫。A compound according to any one of the preceding claims, wherein R 4 and R 5 are both hydrogen. 如前述請求項中任一項之化合物，其中L係-(CR6 R7 )p -，其中p係1或2且其中各R6 及各R7 係獨立地選自氫及C1-4 -烷基，其中各該烷基係視需要且獨立地經1至3個獨立地選自鹵素及羥基之基團取代。A compound according to any one of the preceding claims, wherein L is -(CR 6 R 7 ) p -, wherein p is 1 or 2 and wherein each R 6 and each R 7 is independently selected from hydrogen and C 1-4 An alkyl group, wherein each of the alkyl groups is optionally and independently substituted with 1 to 3 groups independently selected from a halogen and a hydroxyl group. 如前述請求項中任一項之化合物，其中存在之所有R6 及R7 基團係氫。A compound according to any one of the preceding claims, wherein all of the R 6 and R 7 groups present are hydrogen. 如請求項1至13中任一項之化合物，其中L表示直接鍵。The compound of any one of claims 1 to 13, wherein L represents a direct bond. 如前述請求項中任一項之化合物，其中X1 係選自NH、O及S。A compound according to any one of the preceding claims, wherein X 1 is selected from the group consisting of NH, O and S. 如請求項25之化合物，其中X1 係S。The compound of claim 25, wherein X 1 is S. 如請求項1之化合物，其係以式(II)表徵，或其醫藥上可接受之鹽或前藥，其中 Q1 、Q2 、Q3 及Q4 係獨立地選自N、CH及C(R1 )，其中該Q1 、Q2 、Q3 及Q4 中不少於一者且不多於兩者可表示N；及 n、m、X1 、L及R1 至R5 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by formula (II), Or a pharmaceutically acceptable salt or prodrug thereof, wherein Q 1 , Q 2 , Q 3 and Q 4 are independently selected from N, CH and C(R 1 ), wherein the Q 1 , Q 2 , Q 3 and Not less than one of Q 4 and no more than two may represent N; and n, m, X 1 , L and R 1 to R 5 are as defined in any of the preceding claims. 如請求項1之化合物，其係以式(III)表徵，或其醫藥上可接受之鹽或前藥，其中 X2 係選自N、CH或C(R1 )； R11 及R12 係獨立地選自氫、鹵素、腈、-C(O)N(R13 R14 )、-N(R13 R14 )、-NHC(O)NR13 R14 、-NHC(O)OR15 、-NHC(O)R15b 、-C(O)R15b 、C2-4 -醯基、C2-4 -醯基胺基-羥基、-O(C1-8 -烷基)、-C(O)OR15 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， 其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R15 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基， R15b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經取代；及 m、X1 、L及R2 至R5 係如請求項1至18中任一項中定義。The compound of claim 1, which is characterized by formula (III), Or a pharmaceutically acceptable salt or prodrug thereof, wherein X 2 is selected from N, CH or C(R 1 ); R 11 and R 12 are independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N (R 13 R 14 ), -N(R 13 R 14 ), -NHC(O)NR 13 R 14 , -NHC(O)OR 15 , -NHC(O)R 15b , -C(O)R 15b , C 2-4 - acyl, C 2-4 - acyl amino - hydroxy, -O (C 1-8 - alkyl), - C (O) OR 15, acyl sulfo, sulfo acyl group, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 13 and R 14 are independently selected from the group consisting of H, C 1-4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and R 15 is independently selected. From H, C 1-4 -alkyl, C 1-4 -alkenyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl And R 15b are independently selected from the group consisting of H, C 1-4 -alkyl, C 1-4 -alkenyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl And wherein each of the fluorenyl, fluorenylamino, sulfonyl, aminosulfonyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, ring Group, heterocycloalkenyl, aryl or heteroaryl group optionally substituted lines; and m, X 1, L, and R 2 to R 5 as defined in any one of lines requested items 1 to 18. 如請求項20之化合物，其中R11 係選自氫、鹵素、腈、-C(O)N(R12 R13 )、C1-3 -烷基、羥基及-O(C1-3 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素之基團取代。The compound of claim 20, wherein R 11 is selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R 12 R 13 ), C 1-3 -alkyl, hydroxy, and -O(C 1-3 - Alkyl), wherein each of the alkyl groups is optionally substituted with from 1 to 3 groups independently selected from halogen. 如請求項20或21之化合物，其中R12 係選自鹵素、C(O)N(R13 R14 )、磺醯基、C1-4 -烷基、C2-4 -炔基、環烷基、雜環烷基、芳基及雜芳基，其中R13 及R14 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且其中各該磺醯基、烷基、炔基、環烷基、雜環烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rh Ri )(其中Rh 及Ri 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rj (其中Rj 係選自羥基及胺基及鹵素)。The compound of claim 20 or 21, wherein R 12 is selected from the group consisting of halogen, C(O)N(R 13 R 14 ), sulfonyl, C 1-4 -alkyl, C 2-4 -alkynyl, ring An alkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein R 13 and R 14 are independently selected from H, C 1-4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocyclic An alkyl group, an aryl group, and a heteroaryl group, and wherein each of the sulfonyl, alkyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups is optionally selected from 1 to 5 Substituted from the following groups: halogen, hydroxy, -N(R h R i ) (wherein R h and R i are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 - Alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R j (where R j is selected from the group consisting of a hydroxyl group and an amine group and a halogen). 如請求項20至22中任一項之化合物，其中X2 係N。The compound of any one of claims 20 to 22, wherein X 2 is N. 如請求項1之化合物，其係以式(IV)表徵，或其醫藥上可接受之鹽或前藥，其中 X3 係選自N、CH及CR1 ； n係0、1、2或3；及 m、X1 、L及R1 至R5 係如請求項1至26中任一項中定義。The compound of claim 1, which is characterized by formula (IV), Or a pharmaceutically acceptable salt or prodrug thereof, wherein X 3 is selected from N, CH and CR 1 ; n is 0, 1 , 2 or 3; and m, X 1 , L and R 1 to R 5 are as It is defined in any one of claims 1 to 26. 如請求項1之化合物，其係以式(V)表徵，或其醫藥上可接受之鹽或前藥，其中 R16 及R17 係獨立地選自氫、鹵素、羥基、腈、C1-4 -烷基及-O(C1-4 -烷基)，其中各該烷基係視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代；及 其中n、X1 、X3 、L、R1 及R3 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (V), Or a pharmaceutically acceptable salt or prodrug thereof, wherein R 16 and R 17 are independently selected from the group consisting of hydrogen, halogen, hydroxy, nitrile, C 1-4 -alkyl and -O(C 1-4 -alkyl) Wherein each alkyl group is optionally substituted with 1 to 3 groups independently selected from the group consisting of halogen, hydroxy and nitrile; and wherein n, X 1 , X 3 , L, R 1 and R 3 are as claimed above Defined in any of the items. 如請求項25之化合物，其中R16 及R17 係獨立地選自氫、鹵素、羥基、腈及視需要經1至3個獨立地選自鹵素、羥基及腈之基團取代之-O(C1-4 -烷基)。The compound of claim 25, wherein R 16 and R 17 are independently selected from the group consisting of hydrogen, halogen, hydroxy, nitrile, and optionally -O substituted by 1 to 3 groups independently selected from the group consisting of halogen, hydroxy, and nitrile ( C 1-4 -alkyl). 如請求項1之化合物，其係以式(VI)表徵，或其醫藥上可接受之鹽或前藥，其中 R18 、R19 、R20 及R21 係獨立地選自氫、鹵素、腈、-C(O)N(R22 R23 )、-N(R22 R23 )、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、-C(O)R24b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR24 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R22 及R23 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R24 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基，且 R24b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基， 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)；及 其中m、X1 、L及R2 至R5 係如請求項1至18中任一項中定義。The compound of claim 1, which is characterized by the formula (VI), Or a pharmaceutically acceptable salt or prodrug thereof, wherein R 18 , R 19 , R 20 and R 21 are independently selected from the group consisting of hydrogen, halogen, nitrile, -C(O)N(R 22 R 23 ), -N (R 22 R 23 ), -NHC(O)NR 22 R 23 , -NHC(O)OR 24 , -NHC(O)R 24b , -C(O)R 24b , C 2-4 -fluorenyl, C 2-4 - mercaptoamine, hydroxy, -O(C 1-8 -alkyl), -C(O)OR 24 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 -alkenyl, C 2-8 -alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 22 and R 23 are independently selected From H, C 1-4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 24 is independently selected from H, C 1-4 -alkane a group, C 1-4 -alkenyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, and R 24b is independently selected from H, C 1-4 -alkane a C 1-4 alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group, wherein each of the fluorenyl group, the fluorenylamino group, the sulfonyl group, the amino sulfonyl group, the alkyl group, Alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl groups are optionally 1 to 5 independent Substituted by a group selected from the group consisting of halogen, hydroxy, -N(R k R l ) (wherein R k and R l are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1- 3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R m ( Wherein R m is selected from the group consisting of a hydroxyl group, an amine group, and a halogen; and wherein m, X 1 , L, and R 2 to R 5 are as defined in any one of claims 1 to 18. 如請求項27之化合物，其中R18 係選自氫、鹵素、-NR22 R23 、-NHC(O)NR22 R23 、-NHC(O)OR24 、-NHC(O)R24b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R22 及R23 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R24 及R24b 係獨立地選自H及C1-4 -烷基，及 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。The compound of claim 27, wherein R 18 is selected from the group consisting of hydrogen, halogen, -NR 22 R 23 , -NHC(O)NR 22 R 23 , -NHC(O)OR 24 , -NHC(O)R 24b , C 2-4 - mercaptoamine, -O(C 1-4 -alkyl) and C 1-4 -alkyl, wherein R 22 and R 23 are independently selected from H, C 1-4 -alkyl and a heteroaryl group, wherein R 24 and R 24b are independently selected from H and C 1-4 -alkyl, and wherein each alkyl, decylamino or heteroaryl group is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxy, -N(R k R l ) (wherein R k and R l are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R m (wherein The R m is selected from the group consisting of a hydroxyl group, an amine group, and a halogen). 如請求項27或28之化合物，其中R20 係選自氫、鹵素、-O(C1-4 -烷基)、C1-4 -烷基、芳基及雜芳基， 其中各該烷基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rk Rl )(其中Rk 及Rl 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Rm (其中Rm 係選自羥基、胺基及鹵素)。The compound of claim 27 or 28, wherein R 20 is selected from the group consisting of hydrogen, halogen, -O(C 1-4 -alkyl), C 1-4 -alkyl, aryl and heteroaryl, wherein each of the alkyl groups The aryl, aryl or heteroaryl group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, hydroxy, -N(R k R l ) (wherein R k and R l are independently selected from Hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, Heteroaryl and (C 1-4 -alkyl)-R m (wherein R m is selected from the group consisting of a hydroxyl group, an amine group, and a halogen). 如請求項27至29中任一項之化合物，其中R19 及R21 各獨立地係氫。The compound of any one of claims 27 to 29, wherein R 19 and R 21 are each independently hydrogen. 如請求項1之化合物，其係以式(VII)表徵，或其醫藥上可接受之鹽或前藥，其中 q係0、1、2或3； R25 係獨立地選自鹵素、羥基、腈、-N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rn Ro )(其中Rn 及Ro 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 、R18 及R20 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by formula (VII), Or a pharmaceutically acceptable salt or prodrug thereof, wherein q is 0, 1, 2 or 3; R 25 is independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R n R o ) (wherein R n and R o is independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with hydroxy or substituted with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl , C 2-4 -mercaptoamine, -C(O)N(R n R o ) (wherein R n and R o are independently selected from hydrogen and C 1-3 -alkyl), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, a C 1-4 -alkyl group, an aryl group and a heteroaryl group optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. And m, X 1 , R 2 , R 4 , R 5 , R 18 and R 20 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(VIIa )或(VIIb )表徵， 或其醫藥上可接受之鹽或前藥，其中 m、q、X1 、R2 、R4 、R5 、R18 、R20 及R25 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (VII a ) or (VII b ), Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, q, X 1 , R 2 , R 4 , R 5 , R 18 , R 20 and R 25 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(VIII)表徵，或其醫藥上可接受之鹽或前藥，其中 r係0、1、2或3； R26 係獨立地選自鹵素、羥基、腈、-N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rq Rr )(其中Rq 及Rr 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 、R18 及R20 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by formula (VIII), Or a pharmaceutically acceptable salt or prodrug thereof, wherein r is 0, 1, 2 or 3; R 26 is independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R q R r ) (wherein R q and R r is independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with hydroxy or substituted with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl , C 2-4 -decylamino, -C(O)N(R q R r ) (wherein R q and R r are independently selected from hydrogen and C 1-3 -alkyl), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, a C 1-4 -alkyl group, an aryl group and a heteroaryl group optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. And m, X 1 , R 2 , R 4 , R 5 , R 18 and R 20 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(VIIIa )或(VIIIb )表徵， 或其醫藥上可接受之鹽或前藥，其中m、r、X1 、R2 、R4 、R5 、R18 、R20 及R26 係如前述請求項中任一項中定義。The compound of the requested item 1, which is based in formula (VIII a) or (VIII b) characterized Or a pharmaceutically acceptable salt or prodrug thereof, wherein m, r, X 1 , R 2 , R 4 , R 5 , R 18 , R 20 and R 26 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(IX)表徵，或其醫藥上可接受之鹽或前藥，其中 n係0、1或2； X4 係NH、O或S；及 m、X1 、L及R1 至R5 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by formula (IX), Or a pharmaceutically acceptable salt or prodrug thereof, wherein n is 0, 1 or 2; X 4 is NH, O or S; and m, X 1 , L and R 1 to R 5 are as defined in the preceding claims A definition in one. 如請求項1之化合物，其係以式(X)表徵，或其醫藥上可接受之鹽或前藥，其中 n係0、1或2； X5 係NH、O或S；及 m、X1 、L及R1 至R5 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by formula (X), Or a pharmaceutically acceptable salt or prodrug thereof, wherein n is 0, 1 or 2; X 5 is NH, O or S; and m, X 1 , L and R 1 to R 5 are as claimed in the preceding claims A definition in one. 如請求項1之化合物，其係以式(XI)表徵，或其醫藥上可接受之鹽或前藥，其中n、m、X1 、L及R1 至R5 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (XI), Or a pharmaceutically acceptable salt or prodrug thereof, wherein n, m, X 1 , L and R 1 to R 5 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(XII)表徵，或其醫藥上可接受之鹽或前藥，其中 R30 、R31 及R32 係獨立地選自氫、鹵素、腈、-C(O)N(R33 R34 )、-N(R33 R34 )、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、-C(O)R35b 、C2-4 -醯基、C2-4 -醯基胺基、羥基、-O(C1-8 -烷基)、-C(O)OR35 、磺醯基、胺基磺醯基、C1-8 -烷基、C2-8 -烯基、C2-8 -炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基及雜芳基，其中 R33 及R34 係獨立地選自H、C1-4 -烷基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、C2-4 -醯基、環烷基、雜環烷基、芳基及雜芳基， R35b 係獨立地選自H、C1-4 -烷基、C1-4 -烯基、環烷基、雜環烷基、芳基及雜芳基，且 其中各該醯基、醯基胺基、磺醯基、胺基磺醯基、烷基、烯基、炔基、環烷基、雜環烷基、環烯基、雜環烯基、芳基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)；及 其中m、X1 、L及R2 至R5 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (XII), Or a pharmaceutically acceptable salt or prodrug thereof, wherein R 30 , R 31 and R 32 are independently selected from the group consisting of hydrogen, halogen, nitrile, —C(O)N(R 33 R 34 ), —N (R 33 R 34 ), -NHC(O)NR 33 R 34 , -NHC(O)OR 35 , -NHC(O)R 35b , -C(O)R 35b , C 2-4 -mercapto, C 2-4 - mercaptoamine, hydroxy, -O(C 1-8 -alkyl), -C(O)OR 35 , sulfonyl, aminosulfonyl, C 1-8 -alkyl, C 2-8 Alkenyl, C 2-8 -alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl and heteroaryl, wherein R 33 and R 34 are independently selected from H, C 1-4 -alkyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 35 is independently selected from H, C 1-4 -alkyl, C 1-4 - alkenyl, C 2-4 -fluorenyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, R 35b are independently selected from H, C 1-4 -alkyl, C 1 a 4 -alkenyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, and a heteroaryl group, and each of the fluorenyl group, a mercaptoamine group, a sulfonyl group, an aminosulfonyl group, an alkyl group, an alkenyl group, Alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl groups are optionally selected from 1 to 5 Of the following radicals: halogen, hydroxy, -N (R s R t) ( wherein R s and R t are independently selected hydrogen and C 1-3 - alkyl), - O (C 1-3 - alkyl , nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R u (where R u Is selected from the group consisting of a hydroxyl group, an amine group, and a halogen; and wherein m, X 1 , L, and R 2 to R 5 are as defined in any one of the preceding claims. 如請求項38之化合物，其中R30 係選自氫、鹵素、-NR33 R34 、-NHC(O)NR33 R34 、-NHC(O)OR35 、-NHC(O)R35b 、C2-4 -醯基胺基、-O(C1-4 -烷基)及C1-4 -烷基，其中R33 及R34 係獨立地選自H、C1-4 -烷基及雜芳基，且其中R35 及R35b 係獨立地選自H及C1-4 -烷基，及 其中各烷基、醯基胺基或雜芳基係視需要經1至5個獨立地選自以下之基團取代：鹵素、羥基、-N(Rs Rt )(其中Rs 及Rt 係獨立地選自氫及C1-3 -烷基)、-O(C1-3 -烷基)、腈、C3-8 -環烷基、C1-4 -烷基、雜環烷基、芳基、雜芳基及(C1-4 -烷基)-Ru (其中Ru 係選自羥基、胺基及鹵素)。The compound of claim 38, wherein R 30 is selected from the group consisting of hydrogen, halogen, -NR 33 R 34 , -NHC(O)NR 33 R 34 , -NHC(O)OR 35 , -NHC(O)R 35b , C 2-4 -mercaptoamine, -O(C 1-4 -alkyl) and C 1-4 -alkyl, wherein R 33 and R 34 are independently selected from H, C 1-4 -alkyl and a heteroaryl group, and wherein R 35 and R 35b are independently selected from H and C 1-4 -alkyl, and wherein each alkyl, mercaptoamine or heteroaryl group is optionally 1 to 5 independently Substituted by a group selected from the group consisting of halogen, hydroxy, -N(R s R t ) (wherein R s and R t are independently selected from hydrogen and C 1-3 -alkyl), -O(C 1-3 -alkyl), nitrile, C 3-8 -cycloalkyl, C 1-4 -alkyl, heterocycloalkyl, aryl, heteroaryl and (C 1-4 -alkyl)-R u (wherein R u is selected from the group consisting of a hydroxyl group, an amine group, and a halogen). 如請求項38或39之化合物，其中R31 及R32 各獨立地係氫。The compound of claim 38 or 39, wherein R 31 and R 32 are each independently hydrogen. 如請求項1之化合物，其係以式(XIV)表徵，或其醫藥上可接受之鹽或前藥，其中 s係0、1、2或3； R36 係獨立地選自鹵素、羥基、腈、-N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、視需要經羥基或經1至3個鹵素取代之-O(C1-4 -烷基)、C3-8 -環烷基、C2-4 -醯基胺基、-C(O)N(Rv Rw )(其中Rv 及Rw 係獨立地選自氫及C1-3 -烷基)、C3-8 -環烯基、磺醯基、胺基磺醯基、磺醯基胺基、視需要經胺基或羥基或經1至3個鹵素取代之C1-4 -烷基、芳基及雜芳基；及 m、X1 、R2 、R4 、R5 及R30 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (XIV), Or a pharmaceutically acceptable salt or prodrug thereof, wherein s is 0, 1, 2 or 3; R 36 is independently selected from the group consisting of halogen, hydroxy, nitrile, -N(R v R w ) (wherein R v and R w is independently selected from hydrogen and C 1-3 -alkyl), optionally substituted with hydroxy or substituted with 1 to 3 halogens -O(C 1-4 -alkyl), C 3-8 -cycloalkyl , C 2-4 -decylamino, -C(O)N(R v R w ) (wherein R v and R w are independently selected from hydrogen and C 1-3 -alkyl), C 3-8 a cycloalkenyl group, a sulfonyl group, an aminosulfonyl group, a sulfonylamino group, a C 1-4 -alkyl group, an aryl group and a heteroaryl group optionally substituted with an amine group or a hydroxyl group or with 1 to 3 halogens. And m, X 1 , R 2 , R 4 , R 5 and R 30 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(XV)表徵，或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (XV), Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R 4 , R 5 , R 16 , R 17 , R 30 and R 36 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(XVa)或式(XVb)表徵， 或其醫藥上可接受之鹽或前藥，其中s、R4 、R5 、R16 、R17 、R30 及R36 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (XVa) or the formula (XVb), Or a pharmaceutically acceptable salt or prodrug thereof, wherein s, R 4 , R 5 , R 16 , R 17 , R 30 and R 36 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(XVI)表徵，或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by the formula (XVI), Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R 4 , R 5 , R 16 to R 18 , R 20 and R 25 are as defined in any one of the preceding claims. 如請求項1之化合物，其係以式(XIVa)或式(XIVb)表徵， 或其醫藥上可接受之鹽或前藥，其中q、R4 、R5 、R16 至R18 、R20 及R25 係如前述請求項中任一項中定義。The compound of claim 1, which is characterized by formula (XIVa) or formula (XIVb), Or a pharmaceutically acceptable salt or prodrug thereof, wherein q, R 4, R 5, R 16 to R 18, R 20 and R 25 requests a preceding line as defined in any of items. 一種化合物，其選自由以下組成之群： 化合物1： (1R,2R)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物2： (1S,2S)-2-({6-[(2-胺基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物3： (1R,2R)-2-[(6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物4： (1R,2R)-2-({6-[(3-溴吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物5： (1S,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物6： (1S,2S)-2-[(6-{[2-(甲基胺基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物7： N-環己基-6-(吡啶-4-基甲氧基)-1,3-苯并噻唑-2-胺 化合物8： N-環己基-6-(吡啶-3-基甲氧基)-1,3-苯并噻唑-2-胺 化合物9： N-環己基-6-(1,3-噻唑-4-基甲氧基)-1,3-苯并噻唑-2-胺 化合物10： N-環己基-6-(吡啶-2-基甲氧基)-1,3-苯并噻唑-2-胺 化合物11： N-環己基-6-(吡嗪-2-基甲氧基)-1,3-苯并噻唑-2-胺 化合物12： N-環己基-6-(嘧啶-4-基甲氧基)-1,3-苯并噻唑-2-胺 化合物13： N-環己基-6-(1,3-噻唑-2-基甲氧基)-1,3-苯并噻唑-2-胺 化合物14： N-環己基-6-(1,3-噻唑-5-基甲氧基)-1,3-苯并噻唑-2-胺 化合物15： 6-[(2-胺基吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物16： 6-[(6-氯吡嗪-2-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物17： 6-[(5-氯吡啶-3-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物18： N-環己基-6-[(2-甲基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-胺 化合物19： 4-({[2-(環己基胺基)-1,3-苯并噻唑-6-基]氧基}甲基)-N-甲基吡啶-2-甲醯胺 化合物20： N-環己基-6-[(3-甲基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-胺 化合物21： 5-({[2-(環己基胺基)-1,3-苯并噻唑-6-基]氧基}甲基)-N-甲基吡啶-2-甲醯胺 化合物22： (1R,2R)-2-({6-[(2-胺基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物23： 6-[(3-氯吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物24： (1R,2R)-2-({6-[(3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物25： (1S,2S)-2-({6-[(3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物26： N-環己基-6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-胺 化合物27： (1S,2S)-2-[(6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物28： (1R,2S)-1-({6-[(3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物29： (1R,2S)-1-({6-[(2-胺基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物30： (1S,2S)-2-({6-[(3-溴吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物31： 6-[(3-溴吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物32： N-環己基-6-{[3-(1-甲基-1H-吡唑-4-基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-胺 化合物33： N-環己基-6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-胺 化合物34： (1R,2R)-2-({6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物35： (1S,2S)-2-({6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物36： (1R,2S)-1-({6-[(3-溴吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物37： (1R,2R)-2-{[6-({3-氯-1H-吡咯并[2,3-b]吡啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物38： (1R,2S)-1-[(6-{1H-吡咯并[2,3-b]吡啶-4-基甲氧基}-1,3-苯并噻唑-2-基)胺基]-2,3-二氫-1H-茚-2-醇 化合物39： 6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-N-環己基-1,3-苯并噻唑-2-胺 化合物40： (1R,2S)-1-({6-[(3-苯基吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物41： (1R,2S)-1-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)-2,3-二氫-1H-茚-2-醇 化合物42： N-環己基-6-{[2-(甲基胺基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-胺 化合物43： (1R,2R)-2-[(6-{[2-(甲基胺基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物44： (1R,2R)-2-[(6-{[2-胺基-3-(三氟甲氧基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物45： (1S,2S)-2-[(6-{[2-胺基-3-(三氟甲氧基)吡啶-4-基]甲氧基}-1,3-苯并噻唑-2-基)胺基]環己-1-醇 化合物46： (1R,2R)-2-((6-((2-胺基-3-(三氟甲基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物47： (1S,2S)-2-((6-((2-胺基-3-(三氟甲基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物48： (1R,2R)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物49： (1S,2S)-2-((6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物50： (1R,2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物51： (1S,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物52： N-[(1S,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己基]甲磺醯胺 化合物53： (2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-4-甲氧基-1,3-苯并噻唑-2-基}胺基)-4-甲基戊-1-醇 化合物54： (1S,2S)-2-((6-((2-胺基-3-氟吡啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物55： (1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇 化合物56： (1S,2S)-2-{[4-甲氧基-6-({2-[(1-甲基-1H-吡唑-3-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物57： (1S,2S)-2-{[6-({2-[(2-羥乙基)胺基]嘧啶-4-基}甲氧基)-4-甲氧基-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物58： (1S,2S)-2-{[4-甲氧基-6-({2-[(1,2-噁唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物59： (1S,2S)-2-{[4-甲氧基-6-({2-[(1H-吡唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物60： (1S,2S)-2-{[4-甲氧基-6-({2-[(1-甲基-1H-1,2,3-三唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物61： 6-((2-胺基嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物62： 6-((2-胺基嘧啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物63： 6-((2-胺基嘧啶-4-基)甲氧基)-N-(4,4-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物64： N-(3,3-二氟環己基)-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-胺 化合物65： (1S,2S)-2-(6-((2-胺基-3-氯吡啶-4-基)甲氧基)-4-氟苯并[d]噻唑-2-基胺基)環己醇 化合物66： (1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物67： 6-((2-胺基-3-氯吡啶-4-基)甲氧基)-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物68： 1-{4-[({2-[(3,3-二氟環己基)胺基]-4-甲氧基-1,3-苯并噻唑-6-基}氧基)甲基]吡啶-2-基}-3-甲脲 化合物69： (1S,2S)-2-((6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基)胺基)環己-1-醇 化合物70： (1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-7-氟-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇 化合物71： N-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)乙醯胺 化合物72： N-(4-{[(2-{[(1R,2R)-2-羥基環己基]胺基}-4-甲氧基-1,3-苯并噻唑-6-基)氧基]甲基}吡啶-2-基)乙醯胺 化合物73： (1S,2S)-2-(6-((2-胺基嘧啶-4-基)甲氧基)-4-甲氧基-7-甲基苯并[d]噻唑-2-基胺基)環己醇 化合物74： (1S,2S)-2-(6-((2-胺基-3-氟吡啶-4-基)甲氧基)-7-氯-4-甲氧基苯并[d]噻唑-2-基胺基)環己醇 化合物75： (1S,2S)-2-({6-[(2-胺基吡啶-4-基)甲氧基]-7-氯-4-甲氧基-1,3-苯并噻唑-2-基}胺基)環己-1-醇 化合物76： (1S,2S)-2-(7-氯-4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)嘧啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇 化合物77： (1S,2S)-2-{[7-氯-4-甲氧基-6-({2-[(1-甲基-1H-1,2,3-三唑-4-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物78： (1S,2S)-2-{[7-氯-4-甲氧基-6-({2-[(1-甲基-1H-吡唑-3-基)胺基]嘧啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物79： 4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基胺甲酸甲酯 化合物80： 1-(4-((2-((1S,2S)-2-羥基環己基胺基)-4-甲氧基苯并[d]噻唑-6-基氧基)甲基)吡啶-2-基)-3-甲脲 化合物81： (1S,2S)-2-(4-甲氧基-6-((2-(1-甲基-1H-吡唑-4-基胺基)吡啶-4-基)甲氧基)苯并[d]噻唑-2-基胺基)環己醇 化合物82： (1S,2S)-2-{[4-甲氧基-6-({2-[(1-甲基-1H-吡唑-3-基)胺基]吡啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物83： (1S,2S)-2-{[4-甲氧基-6-({2-[(2-甲基嘧啶-4-基)胺基]吡啶-4-基}甲氧基)-1,3-苯并噻唑-2-基]胺基}環己-1-醇 化合物84： 6-((2-胺基嘧啶-4-基)甲氧基)-7-氯-N-(3,3-二氟環己基)-4-甲氧基苯并[d]噻唑-2-胺 化合物85： (1R,2S)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 及 化合物86： (1S,2R)-2-({6-[(2-胺基-3-氯吡啶-4-基)甲氧基]-1,3-苯并噻唑-2-基}胺基)環己-1-醇 及其醫藥上可接受之鹽及前藥。A compound selected from the group consisting of: Compound 1: (1R, 2R)-2-((6-((2-amino-3-chloropyridin-4-yl)methoxy)benzo[d] ]thiazol-2-yl)amino)cyclohexan-1-ol Compound 2: (1S,2S)-2-({6-[(2-aminopyridin-4-yl)methoxy]-1, 3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 3: (1R,2R)-2-[(6-{1H-pyrrolo[2,3-b]pyridine-4- Methyloxy}-1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 4: (1R, 2R)-2-({6-[(3-bromopyridine-4) -yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 5: (1S, 2S)-2-({6-[(2-amino) 3-chloropyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 6: (1S, 2S)-2-[(6 -{[2-(Methylamino)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 7: N-cyclohexyl -6-(pyridin-4-ylmethoxy)-1,3-benzothiazol-2-amine compound 8: N-cyclohexyl-6-(pyridin-3-ylmethoxy)-1,3- Benzothiazole-2-amine compound 9: N-cyclohexyl-6-(1,3-thiazol-4-ylmethoxy)-1,3-benzothiazol-2-amine compound 10: N-cyclohexyl -6-(pyridin-2-ylmethoxy)-1,3-benzo Azole-2-amine compound 11: N-cyclohexyl-6-(pyrazin-2-ylmethoxy)-1,3-benzothiazol-2-amine compound 12: N-cyclohexyl-6-(pyrimidine) -4-ylmethoxy)-1,3-benzothiazol-2-amine compound 13: N-cyclohexyl-6-(1,3-thiazol-2-ylmethoxy)-1,3-benzene And thiazol-2-amine compound 14: N-cyclohexyl-6-(1,3-thiazol-5-ylmethoxy)-1,3-benzothiazol-2-amine compound 15: 6-[(2 -aminopyridin-4-yl)methoxy]-N-cyclohexyl-1,3-benzothiazol-2-amine compound 16: 6-[(6-chloropyrazin-2-yl)methoxy ]-N-cyclohexyl-1,3-benzothiazol-2-amine compound 17: 6-[(5-chloropyridin-3-yl)methoxy]-N-cyclohexyl-1,3-benzo Thiazol-2-amine compound 18: N-cyclohexyl-6-[(2-methylpyridin-4-yl)methoxy]-1,3-benzothiazol-2-amine compound 19: 4-({ [2-(Cyclohexylamino)-1,3-benzothiazol-6-yl]oxy}methyl)-N-methylpyridine-2-carboxamide Compound 20: N-cyclohexyl-6- [(3-methylpyridin-4-yl)methoxy]-1,3-benzothiazol-2-amine compound 21: 5-({[2-(cyclohexylamino)-1,3-benzene) And thiazol-6-yl]oxy}methyl)-N-methylpyridine-2-carboxamide Compound 22: (1R, 2R)-2-({6-[(2-aminopyridinium) 4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol compound 23: 6-[(3-chloropyridin-4-yl)methoxy ]-N-cyclohexyl-1,3-benzothiazol-2-amine compound 24: (1R, 2R)-2-({6-[(3-chloropyridin-4-yl)methoxy]-1 , 3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 25: (1S,2S)-2-({6-[(3-chloropyridin-4-yl)methoxy] -1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 26: N-cyclohexyl-6-{1H-pyrrolo[2,3-b]pyridin-4-yl Oxy}-1,3-benzothiazol-2-amine Compound 27: (1S,2S)-2-[(6-{1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy }-1,3-Benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 28: (1R,2S)-1-({6-[(3-chloropyridin-4-yl)) Oxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 29: (1R, 2S)-1-({6-[ (2-Aminopyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 30: ( 1S,2S)-2-({6-[(3-bromopyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol compound 31 : 6-[(3-Bromopyridin-4-yl)methoxy]-N-cyclohexyl-1,3-benzothiazol-2-amine Compound 32: N- Hexyl-6-{[3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-amine Compound 33: N- Cyclohexyl-6-[(3-phenylpyridin-4-yl)methoxy]-1,3-benzothiazol-2-amine Compound 34: (1R, 2R)-2-({6-[( 3-phenylpyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 35: (1S, 2S)-2-({6 -[(3-Phenylpyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 36: (1R, 2S)-1- ({6-[(3-Bromopyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-inden-2-ol Compound 37: (1R,2R)-2-{[6-({3-Chloro-1H-pyrrolo[2,3-b]pyridin-4-yl}methoxy)-1,3-benzothiazole -2-yl]amino}cyclohexan-1-ol compound 38: (1R, 2S)-1-[(6-{1H-pyrrolo[2,3-b]pyridin-4-ylmethoxy} -1,3-benzothiazol-2-yl)amino]-2,3-dihydro-1H-indol-2-ol Compound 39: 6-[(2-Amino-3-chloropyridine-4- Methoxy]-N-cyclohexyl-1,3-benzothiazol-2-amine compound 40: (1R, 2S)-1-({6-[(3-phenylpyridin-4-yl)) Methoxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 41: (1R, 2S)-1-({6- [(2-Amino- 3-chloropyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)-2,3-dihydro-1H-indol-2-ol Compound 42: N-ring Hexyl-6-{[2-(methylamino)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-amine compound 43: (1R, 2R)-2-[(6 -{[2-(Methylamino)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 44: (1R, 2R -2-[(6-{[2-Amino-3-(trifluoromethoxy)pyridin-4-yl]methoxy}-1,3-benzothiazol-2-yl)amino] Cyclohexan-1-ol compound 45: (1S,2S)-2-[(6-{[2-amino-3-(trifluoromethoxy)pyridin-4-yl]methoxy}-1, 3-benzothiazol-2-yl)amino]cyclohexan-1-ol Compound 46: (1R,2R)-2-((6-((2-Amino-3-(trifluoromethyl))pyridine) 4-yl)methoxy)benzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 47: (1S,2S)-2-((6-((2-amino)) -3-(Trifluoromethyl)pyridin-4-yl)methoxy)benzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 48: (1R,2R)-2- ((6-((2-Amino-3-chloropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 49: (1S,2S)-2-((6-((2-Amino-3-chloropyridin-4-yl)methoxy)-4-methoxybenzo[d]thiatyl) Zyridin-2-yl)amino)cyclohexan-1-ol Compound 50: (1R, 2R)-2-({6-[(2-amino-3-chloropyridin-4-yl)methoxy] 4-methoxy-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol compound 51: (1S, 2S)-2-({6-[(2-amino)- 3-chloropyridin-4-yl)methoxy]-4-methoxy-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 52: N-[(1S, 2S)-2-({6-[(2-Amino-3-chloropyridin-4-yl)methoxy]-4-methoxy-1,3-benzothiazol-2-yl}amino) Cyclohexyl]methanesulfonamide compound 53: (2R)-2-({6-[(2-amino-3-chloropyridin-4-yl)methoxy]-4-methoxy-1, 3-benzothiazol-2-yl}amino)-4-methylpentan-1-ol Compound 54: (1S,2S)-2-((6-((2-Amino-3-fluoropyridine)- 4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 55: (1S,2S)-2-(4-methoxy -6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[d]thiazol-2-ylamino)cyclohexane Alcohol compound 56: (1S,2S)-2-{[4-methoxy-6-({2-[(1-methyl-1H-pyrazol-3-yl))amino]pyrimidin-4-yl }Methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 57: (1S,2S)-2-{[6-({2-[(2- Hydroxyethyl)amine Pyrimidin-4-yl}methoxy)-4-methoxy-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 58: (1S, 2S)-2- {[4-Methoxy-6-({2-[(1,2-oxazol-4-yl)amino]pyrimidin-4-yl}methoxy)-1,3-benzothiazole-2 -amino]amino}cyclohexan-1-ol compound 59: (1S,2S)-2-{[4-methoxy-6-({2-[(1H-pyrazol-4-yl))) Pyrimidin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 60: (1S, 2S)-2-{[4-methoxy -6-({2-[(1-methyl-1H-1,2,3-triazol-4-yl)amino]pyrimidin-4-yl}methoxy)-1,3-benzo Thiazol-2-yl]amino}cyclohexan-1-ol compound 61: 6-((2-aminopyrimidin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)- 4-methoxybenzo[d]thiazole-2-amine compound 62: 6-((2-aminopyrimidin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)- 4-methoxybenzo[d]thiazole-2-amine compound 63: 6-((2-aminopyrimidin-4-yl)methoxy)-N-(4,4-difluorocyclohexyl)- 4-methoxybenzo[d]thiazole-2-amine compound 64: N-(3,3-difluorocyclohexyl)-4-methoxy-6-((2-(1-methyl-1H) -pyrazol-4-ylamino)pyrimidin-4-yl)methoxy)benzo[d]thiazole-2-amine Compound 65: (1S,2S)-2-(6-((2-amine) 3-chloropyridin-4-yl)methoxy)-4-fluorobenzo[d]thiazol-2-ylamino)cyclohexanol compound 66: (1S,2S)-2-((6- ((2-Aminopyrimidin-4-yl)methoxy)-4-methoxybenzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 67: 6-((2 -amino-3-chloropyridin-4-yl)methoxy)-N-(3,3-difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine Compound 68: 1 -{4-[({2-[(3,3-Difluorocyclohexyl)amino]-4-methoxy-1,3-benzothiazol-6-yl}oxy)methyl]pyridine- 2-yl}-3-methylurea compound 69: (1S,2S)-2-((6-((2-aminopyrimidin-4-yl)methoxy)-7-chloro-4-methoxy Benzo[d]thiazol-2-yl)amino)cyclohexan-1-ol Compound 70: (1S,2S)-2-(6-((2-Aminopyrimidin-4-yl)methoxy) -7-fluoro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol compound 71: N-(4-((1S,2S)-2-hydroxycyclohexyl) Amino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-yl)acetamide Compound 72: N-(4-{[(2-{[( 1R,2R)-2-hydroxycyclohexyl]amino}-4-methoxy-1,3-benzothiazol-6-yl)oxy]methyl}pyridin-2-yl)acetamide Compound 73 : (1S,2S)-2-(6-((2-Aminopyrimidin-4-yl)methoxy)-4-A Benzyl-7-methylbenzo[d]thiazol-2-ylamino)cyclohexanol compound 74: (1S,2S)-2-(6-((2-amino-3-fluoropyridine-4-) Methoxy)-7-chloro-4-methoxybenzo[d]thiazol-2-ylamino)cyclohexanol Compound 75: (1S,2S)-2-({6-[(2) -Aminopyridin-4-yl)methoxy]-7-chloro-4-methoxy-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol Compound 76: (1S , 2S)-2-(7-chloro-4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyrimidin-4-yl)methoxy) Benzo[d]thiazol-2-ylamino)cyclohexanol Compound 77: (1S,2S)-2-{[7-Chloro-4-methoxy-6-({2-[(1-A) -1H-1,2,3-triazol-4-yl)amino]pyrimidin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1 -Alcohol compound 78: (1S,2S)-2-{[7-chloro-4-methoxy-6-({2-[(1-methyl-1H-pyrazol-3-yl)amino)] Pyrimidine-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 79: 4-((2-((1S,2S)-2-) Methyl hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-ylaminecarboxylate Compound 80: 1-(4-((2-) (1S,2S)-2-hydroxycyclohexylamino)-4-methoxybenzo[d]thiazole-6-yloxy)methyl)pyridin-2-yl)-3 -Methylurea compound 81: (1S,2S)-2-(4-methoxy-6-((2-(1-methyl-1H-pyrazol-4-ylamino)pyridin-4-yl) Methoxy)benzo[d]thiazol-2-ylamino)cyclohexanol Compound 82: (1S,2S)-2-{[4-methoxy-6-({2-[(1-A) -1H-pyrazol-3-yl)amino]pyridin-4-yl}methoxy)-1,3-benzothiazol-2-yl]amino}cyclohexan-1-ol Compound 83: ( 1S,2S)-2-{[4-methoxy-6-({2-[(2-methylpyrimidin-4-yl)amino]pyridin-4-yl}methoxy)-1,3 -benzothiazol-2-yl]amino}cyclohexan-1-ol compound 84: 6-((2-aminopyrimidin-4-yl)methoxy)-7-chloro-N-(3,3 -difluorocyclohexyl)-4-methoxybenzo[d]thiazole-2-amine Compound 85: (1R,2S)-2-({6-[(2-Amino-3-chloropyridine-4) -yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol and compound 86: (1S,2R)-2-({6-[(2-amine) Alkyl-3-chloropyridin-4-yl)methoxy]-1,3-benzothiazol-2-yl}amino)cyclohexan-1-ol and pharmaceutically acceptable salts and prodrugs thereof. 如前述請求項中任一項之化合物，其針對CSF-1R具有小於200 nM之抑制活性(以IC50 值量測呈現)。Requesting a compound as claimed in any one of the items, which have inhibitory activity of less than 200 nM (IC 50 value measured amount presented) for CSF-1R. 如前述請求項中任一項之化合物，其對CSF-1R之選擇性係對PDGFRβ之選擇性之至少5倍之值及/或對CSF-1R之選擇性係對PDGFRα之選擇性之至少10倍之值及/或對CSF-1R之選擇性係對c-KIT之選擇性之至少20倍之值及/或對CSF-1R之選擇性係對FLT3之選擇性之至少200倍之值。A compound according to any one of the preceding claims, wherein the selectivity to CSF-1R is at least 5 times greater than the selectivity to PDGFRβ and/or the selectivity to CSF-1R is at least 10 to the selectivity of PDGFRα. The value of the multiple and/or the selectivity to CSF-1R is at least 20 times the selectivity to c-KIT and/or the selectivity to CSF-1R is at least 200 times the selectivity to FLT3. 一種醫藥組合物，其包含如請求項1至48中任一項之化合物及至少一種醫藥上可接受之賦形劑。A pharmaceutical composition comprising a compound according to any one of claims 1 to 48 and at least one pharmaceutically acceptable excipient. 如請求項49之醫藥組合物，其包含選自由以下組成之群之另一活性劑：抗增殖劑、抗炎劑、抗血管生成劑、化學治療劑及免疫治療劑。The pharmaceutical composition according to claim 49, which comprises another active agent selected from the group consisting of an anti-proliferative agent, an anti-inflammatory agent, an anti-angiogenic agent, a chemotherapeutic agent, and an immunotherapeutic agent. 如請求項1至48中任一項之化合物或如請求項49或請求項50之醫藥組合物，其用於治療中。A compound according to any one of claims 1 to 48, or a pharmaceutical composition according to claim 49 or claim 50, for use in therapy. 一種用於治療個體中經CSF-1R介導之疾病之方法，該方法包括向該個體投與有效量之如請求項1至48中任一項之化合物。A method for treating a CSF-1R mediated disease in an individual, the method comprising administering to the individual an effective amount of a compound of any one of claims 1 to 48. 如請求項52之方法，其中該經CSF-1R介導之疾病係選自癌症、骨失調症、炎性失調症及神經失調症。The method of claim 52, wherein the CSF-1R-mediated disease is selected from the group consisting of cancer, bone disorders, inflammatory disorders, and neurological disorders. 如請求項52或請求項53之方法，其中該經CSF-1R介導之疾病係係具有以下表徵：CSF-1R之過表現、異常CSF-1R傳訊、CSF-1及/或IL-34之過表現及/或CSF-1R 基因中之突變。The method of claim 52 or claim 53, wherein the CSF-1R-mediated disease system has the following characteristics: CSF-1R overexpression, abnormal CSF-1R signaling, CSF-1 and/or IL-34 Overexpression and/or mutations in the CSF-1R gene. 如請求項53或請求項54之方法，其中該經CSF-1R介導之疾病係選自以下之癌症：乳癌、子宮頸癌、多形性神經膠質母細胞瘤(glioblastoma multiforme；GBM)、肝細胞癌、何傑金氏淋巴瘤(Hodgkin’s lymphoma)、黑色素瘤、胰臟癌、色素沈著絨毛結節性滑膜炎(pigmented villondular synovitis；PVNS)、前列腺癌、卵巢癌、腱鞘巨細胞腫瘤(Tenosynovial giant cell tumor；TGCT)、子宮內膜癌、多發性骨髓瘤、粒細胞白血病、骨癌、腎癌、腦癌及骨髓增生性失調症(myeloproliferative disorder；MPD)。The method of claim 53 or claim 54, wherein the CSF-1R-mediated disease is selected from the group consisting of breast cancer, cervical cancer, glioblastoma multiforme (GBM), liver Cell carcinoma, Hodgkin's lymphoma, melanoma, pancreatic cancer, pigmented villondular synovitis (PVNS), prostate cancer, ovarian cancer, tendon sheath giant cell tumor (Tenosynovial giant) Cell tumor; TGCT), endometrial cancer, multiple myeloma, granulocyte leukemia, bone cancer, kidney cancer, brain cancer, and myeloproliferative disorder (MPD). 如請求項53至55中任一項之方法，其係用於治療經診斷為患有癌症或處於發展癌症之風險下之個體。The method of any one of claims 53 to 55 for treating an individual diagnosed as having or at risk of developing cancer. 如請求項53或請求項54之方法，其中該經CSF-1R介導之疾病係選自以下之炎性失調症：牛皮癬性關節炎、關節炎、氣喘、甲狀腺炎、腎絲球腎炎、動脈粥樣硬化、牛皮癬、休格倫氏症候群(Sjogren’s syndrome)、類風濕性關節炎、全身性紅斑性狼瘡(systemic lupus erythematosis；SLE)、皮膚紅斑狼瘡、炎性腸疾病(包括克羅恩氏病(Crohn’s disease)及潰瘍性結腸炎(UC))、1型糖尿病、多發性硬化症及神經炎性病症(諸如HIV腦炎、阿茲海默症(Alzheimer’s disease)及ALS)。The method of claim 53 or claim 54, wherein the CSF-1R-mediated disease is selected from the group consisting of inflammatory disorders: psoriatic arthritis, arthritis, asthma, thyroiditis, glomerulonephritis, arteries Atherosclerosis, psoriasis, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosis (SLE), cutaneous lupus erythematosus, inflammatory bowel disease (including Crohn's disease) (Crohn's disease) and ulcerative colitis (UC)), type 1 diabetes, multiple sclerosis, and neuroinflammatory conditions (such as HIV encephalitis, Alzheimer's disease, and ALS). 如請求項53或請求項54之方法，其中該經CSF-1R介導之疾病係選自以下之骨失調症：骨質疏鬆症、骨關節炎、齒根骨膜炎、假體周圍骨質溶解及佩吉特氏病(Paget’s disease)。The method of claim 53 or claim 54, wherein the CSF-1R-mediated disease is selected from the group consisting of osteoporosis, osteoarthritis, root periosteum, periprosthetic osteolysis, and peritoneal Paget's disease. 如請求項52至58中任一項之方法，其包括針對該經CSF-1R介導之疾病投與該化合物與另一治療干預之組合。The method of any one of claims 52 to 58, which comprises administering a combination of the compound and another therapeutic intervention for the CSF-1R mediated disease. 如請求項1至48中任一項之化合物，其用於如請求項52至59中任一項定義之方法中。The compound of any one of claims 1 to 48, which is used in the method as defined in any one of claims 52 to 59. 一種如請求項1至48中任一項之化合物之用途，其用於製造用於如請求項52至59中任一項定義之方法中之藥劑。Use of a compound according to any one of claims 1 to 48 for the manufacture of a medicament for use in a method as defined in any one of claims 52 to 59.
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