3-(BENZOIMIDAZOL-2-YL)-INDAZOLE INHIBITORS OF THE WNT SIGNALING PATHWAY AND THERAPEUTIC USES THEREOF

摘要

Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure 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, Alzheimer's disease, lung disease 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 pharmaceutically acceptable salt thereof, of Formula I: wherein: R1 is -heteroarylR3R4; R2 is selected from the group consisting of H, halide, C1-3 alkyl, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10, -heteroarylR5, -heterocyclylR6 and -arylR7; R3 is 1 substituent attached to the heteroaryl ring and is selected from the group consisting of H, C1-3 alkyl, —CF3, —NR9R10, —NHC(═O)R8, —(C1-3 alkyl)heterocyclylR6 and —(C1-3 alkyl)NR9R10; R4 is 1 substituent attached to the heteroaryl ring and is selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3; R5 is 1-3 substituents attached to the heteroaryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3; R6 is 1-3 substituents attached to the heterocyclyl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3; R7 is 1-3 substituents attached to the aryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —OR8, —OH, —(C1-3 alkyl)OR8, —NR9R10, —(C1-3 alkyl)NR9R10 and —OCF3; each R8 is independently selected from the group consisting of C1-9 alkyl, -heteroarylR12, -heterocyclylR13, -arylR14, carbocyclylR11, —(C1-3 alkyl)heteroarylR12, —(C1-3 alkyl)heterocyclylR13, —(C1-3 alkyl)arylR14 and —(C1-3 alkyl)carbocyclylR11; each R9 is independently selected from the group consisting of H, C1-6 alkyl, -heteroarylR12, -heterocyclylR13, -arylR14, carbocyclylR11, —(C1-3 alkyl)heteroarylR12, —(C1-3 alkyl)heterocyclylR13, —(C1-3 alkyl)arylR14 and —(C1-3 alkyl)carbocyclylR11; each R10 is independently selected from the group consisting of H and C1-6 alkyl; R9 and R10 are optionally linked to form a five or six membered heterocyclyl ring; R11 is 1-3 substituents attached to the carbocyclyl ring and each independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3; R12 is 1-3 substituents attached to the heteroaryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3; R13 is 1-3 substituents attached to the heterocyclyl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3; R14 is 1-3 substituents attached to the aryl ring and each is independently selected from the group consisting of H, C1-3 alkyl, —CF3, halide, —CN, —O(R10), —(C1-3 alkyl)OR10, —N(R10)2, —(C1-3 alkyl)N(R10)2 and —OCF3; with the proviso that a compound of Formula I is not a compound selected from the group consisting of: