2-(1H-INDAZOL-3-YL)-1H-IMIDAZO[4,5-C]PYRIDINE AND THERAPEUTIC USES THEREOF

摘要

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

主权项

1. A compound, or a pharmaceutically acceptable salt thereof, of Formula I: wherein: R1, R2, and R4 are independently selected from the group consisting of H and halide; R3 is selected from the group consisting of -heteroaryl(R6)q and -heterocyclyl(R7)h; R5 is selected from the group consisting of -heteroaryl(R8)q, -heterocyclyl(R9)h, and -aryl(R10)k; each R6 is one substituent attached to the heteroaryl and is independently selected from the group consisting of halide, —(C1-6 alkyl), —(C1-4 alkylene)pheterocyclyl(R11)h, —(C1-4 alkylene)pcarbocyclyl(R12)j, —(C1-4 alkylene)paryl(R13)k, —NHC(═O)R14, —NR15R16, —(C1-6 alkylene)NR17R18, and —OR24; each R7 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; each R8 is one substituent attached to the heteroaryl and is independently selected from the group consisting of —(C1-6 alkyl), halide, —CF3, —OCH3, —CN, and —C(═O)R19; each R9 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of —(C1-6 alkyl), halide, —CF3, —CN, and —OCH3; each R10 is one substituent attached to the aryl and is independently selected from the group consisting of —(C1-6 alkyl), halide, —CF3, —CN, —OCH3, —(C1-6 alkylene)pNHSO2R19, —NR15(C1-6 alkylene)NR15R16, —(C1-6 alkylene)pNR15R16, and —OR27; each R11 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of amino, —(C1-4 alkyl), halide, —CF3, and —CN; each R12 is one substituent attached to the carbocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; each R13 is one substituent attached to the aryl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; each R14 is independently selected from the group consisting of —(C1-9 alkyl), -heteroaryl(R20)q, -aryl(R21)k, —CH2aryl(R21)k, -carbocyclyl(R22)j, —CH2carbocyclyl(R22)j, —(C1-4 alkylene)pNR25R26, -heterocyclyl(R23)h, and —CH2heterocyclyl(R23)h; each R15 is independently selected from the group consisting of H and —(C1-6 alkyl); each R16 is independently selected from the group consisting of H, —(C1-6 alkyl), —CH2aryl(R21)k, and —CH2carbocyclyl(R22)j; each R17 is independently selected from the group consisting of H and —(C1-6 alkyl); each R18 is independently selected from the group consisting of H, —(C1-6 alkyl), —CH2aryl(R21)k, and —CH2carbocyclyl(R22)j; each R19 is a —(C1-6 alkyl); each R20 is one substituent attached to the heteroaryl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; each R21 is one substituent attached to the aryl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; each R22 is one substituent attached to the carbocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; each R23 is one substituent attached to the heterocyclyl and is independently selected from the group consisting of —(C1-4 alkyl), halide, —CF3, and —CN; R24 is selected from the group consisting of H, —(C1-6 alkyl), —(C1-4 alkylene)pheterocyclyl(R23)h, —(C1-4 alkylene)pcarbocyclyl(R22)j, —(C1-4 alkylene)paryl(R21)k, and —(C1-6 alkylene)pNR25R26; each R25 is independently selected from the group consisting of H and —(C1-6 alkyl); each R26 is independently selected from the group consisting of H and —(C1-6 alkyl); R27 is selected from the group consisting of H, —(C1-6 alkyl), —(C1-4 alkylene)pheterocyclyl(R23)h, and —(C1-6 alkylene)pNR25R26; each p is independently 0 or 1; each q is independently 0 to 4; each h is independently 0 to 10; each k is independently 0 to 5; and each j is independently 0 to 12.