Methods of using indazole-3-carboxamides and their use as Wnt/β-catenin signaling pathway inhibitors
AssigneeBioSplice Therapeutics, Inc.
InventorsVishal Deshmukh, Eric Anthony Murphy, John Hood
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Abstract
This disclosure features the use of one or more indazole-3-carboxamide compounds or salts or analogs thereof, in the treatment of one or more diseases or conditions independently selected from the group consisting of a tendinopathy, dermatitis, psoriasis, morphea, ichthyosis, Raynaud's syndrome, and Darier's disease; and/or for promoting wound healing. The methods include administering to a subject (e.g., a subject in need thereof) a therapeutically effective amount of one or more indazole-3-carboxamide compounds or salts or analogs thereof as described anywhere herein.
Claims31
A method of treating tendinosis the method comprising administering to a subject a compound or pharmaceutically acceptable salt thereof having the structure of Formula I:
- wherein:
- R1, R2 and R4 are independently selected from the group consisting of H, C1-9 alkyl, halide, —N(R10)2, —XR10, CN, —OCF3 and —CF3;
- R3 is selected from the group consisting of carbocyclylR6, heterocyclylR6, arylR6 and heteroarylR6;
- R5 is selected from the group consisting of —(C1-9 alkyl)ncarbocyclylR7, —(C1-9 alkyl)nheterocyclylR7, —(C1-9 alkyl)narylR7 and —(C1-9 alkyl)nheteroarylR7;
- each R6 is 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, amino, —OCF3, —CF3, —CN, —XR10, —(C1-9 alkyl)ncarbocyclylR8, —(C1-9 alkyl)nheterocyclylR8, —(C1-9 alkyl)narylR8, —(C1-9 alkyl)nheteroarylR8, —C(═O)R11, —N(R10)C(═O)R11, —(C1-9)alkyl)nN(R10)2, —(C1-9alkyl)nN(R10)SO2R11 and —SO2R11;
- each R7 is 1-5 substituents each selected from the group consisting of H, C1-9 alkyl, halide, amino, —OCF3, —CF3, —CN, —XR10, —(C1-9 alkyl)ncarbocyclylR9, —(C1-9 alkyl)nheterocyclylR9, —(C1-9 alkyl)narylR9, —(C1-9 alkyl)nheteroarylR9, —C(═O)R11, —N(R10)C(═O)R11, —(C1-9)alkyl)nN(R10)2, —(C1-9)alkyl)nN(R10)SO2R11 and —SO2R11;
- each R8 is 1-5 substituents each selected from the group consisting of H, C1-3 alkyl, halide, amino, OCF3, —CF3—CN, —XR12, —C(═O)R13, —N(R12)C(═O)R13, —(C1-9 alkyl)nN(R12)2, —(C1-9 alkyl)nN(R12)SO2R13 and —SO2R13;
- each R9 is 1-5 substituents each selected from the group consisting of H, C1-3 alkyl, halide, amino, —OCF3, —CF3—CN, —XR12, —C(═O)R13, —N(R12)C(═O)R13, —(C1-9 alkyl)nN(R12)2, —(C1-9 alkyl)nN(R12)SO2R13 and —SO2R13;
- each R10 is independently selected from the group consisting of H, C1-9 alkyl, —(C1-9 alkyl)nN(R14)2, —(C1-9 alkyl)ncarbocyclylR8, —(C1-9 alkyl)nheterocyclylR8, —(C1-9 alkyl)narylR8 and —(C1-9 alkyl)nheteroarylR8;
- each R11 is independently selected from the group consisting of C1-9 alkyl, —N(R14)2, —(C1-9 alkyl)ncarbocyclylR8, —(C1-9 alkyl)nheterocyclylR8, —(C1-9 alkyl)narylR8 and —(C1-9 alkyl)nheteroarylR8;
- each R12 is independently selected from the group consisting of H, C1-9 alkyl, —(C1-9 alkyl)nN(R14)2, —(C1-9 alkyl)ncarbocyclyl, —(C1-9 alkyl)nheterocyclyl, —(C1-9 alkyl)naryl and —(C1-9 alkyl)nheteroaryl;
- each R13 is independently selected from the group consisting of C1-9 alkyl, —N(R14)2, —(C1-9 alkyl)ncarbocyclyl, —(C1-9 alkyl)nheterocyclyl, —(C1-9 alkyl)naryl and —(C1-9 alkyl)nheteroaryl;
- each R14 is independently selected from the group consisting of H, C1-3 alkyl, carbocyclyl and aryl;
- each X is selected from the group consisting of a bond, —O— and —S—;
- and
- each n is 0 or 1.
A method of treating tendinosis the method comprising administering to a subject a compound or pharmaceutically acceptable salt thereof having the structure of Formula Ia:
- wherein:
- R3 is 3-pyridylR6;
- R5 is selected from the group consisting of pyridylR7, -pyrimidinylR7, and -pyridazinylR7;
- R6 is —CH2heterocyclylR8;
- R7 is 1-2 substituents each independently selected from the group consisting of H, F, methyl, —NH2, —CF3, —CN, —OMe, —SO2Me,
- and
- R8 is 1-2 substituents each independently selected from the group consisting of H and halide.
Dependencies are inferred from the claim text.