| 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, 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 method for treating or ameliorating in a mammal a disorder or disease selected from the group consisting of: colon cancer, colorectal cancer, leukemia, breast cancer, skin cancer, prostate cancer, lung cancer, liver cancer, bone or cartilage disease, and osteoarthritis, the method comprising administering to the mammal a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof: wherein: R1 is -heteroarylR3R4; R2 is selected from the group consisting of H, -heteroarylR5, -heterocyclylR6 and -arylR7; R3 is selected from the group consisting of H, -heterocyclylR8, —NHC(═O)R9, —NHSO2R10, —NR11R12 and —(C1-6 alkyl)NR11R12; wherein R2 and R3 are not both H; R4 is 1-3 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13 and amino; each R5 is independently 1-4 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13, —C(═O)R11, amino and —(C1-6 alkyl)NR11R12; each R6 is independently 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13 and amino; each R7 is independently 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13, amino, —(C1-6 alkyl)NHSO2R11, —NR12(C1-6 alkyl)NR11R12 and —(C1-6 alkyl)NR11R12; R8 is 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13 and amino; R9 is selected from the group consisting of C1-9 alkyl, -heteroarylR5, -heterocyclylR6, -arylR7 and —CH2carbocyclyl; R10 is selected from the group consisting of C1-9 alkyl, -heteroarylR5, -heterocyclylR6, -arylR7, and -carbocyclylR14; each R11 is independently selected from C1-6 alkyl; each R12 is independently selected from the group consisting of H and C1-6 alkyl; each R11 and R12 are optionally linked to form a five or six membered heterocyclyl ring; each R13 is independently selected from the group consisting of H and C1-6 alkyl; and R14 is 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13 and amino; with the proviso that the compound of Formula I is not a compound selected from the group consisting of: |
