Indazole inhibitors of the Wnt signal pathway and therapeutic uses thereof
AssigneeBioSplice Therapeutics, Inc.
InventorsJohn Hood, David Mark Wallace, Sunil Kumar KC
Life of this patent
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Abstract
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.
Claims31
A method of treating a neurological disorder in a subject, wherein the neurological disorder is selected from:
- Alzheimer's disease, autism, schizophrenia, Williams Syndrome, bipolar disorder, Parkinson's disease, multiple sclerosis, and neural tube defects, the method comprising administering to the subject a therapeutically effective amount of a compound or pharmaceutically acceptable salt thereof having the structure of Formula I:
- 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;
- with the proviso that R2 and R3 are not both H;
- R4 is 1-3 substituents each selected from the group consisting of H, 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;
- R14 is 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, —CF3, —CN, OR13 and amino;
- and
- with the proviso that Formula I is not a structure selected from the group consisting of:
Dependencies are inferred from the claim text.