Apoptosis signal-regulating kinase inhibitors
AssigneeGilead Sciences, Inc.
InventorGregory Notte
Life of this patent
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Abstract
The present invention relates to compounds of Formula (I): Wherein variables are as defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases, diabetes, diabetic nephropathy, cardio-renal diseases, including kidney disease, fibrotic diseases, respiratory diseases, COPD, idiopathic pulmonary fibrosis, acute lung injury, acute and chronic liver diseases, and neurodegenerative diseases.
Claims13
A compound of Formula (I):
- wherein:
- R1 is C1-C3 alkyl or C3-C6 cycloalkyl, wherein the alkyl or cycloalkyl is optionally substituted with one to three halogen atoms;
- R2 is hydrogen or C1-C6 alkyl wherein the alkyl is optionally substituted with halo.
- R3 is hydrogen or C1-C3 alkyl;
- R4 is hydrogen or C1-C3 alkyl;
- R5 is hydrogen, C1-C3 alkyl, ORa or —NHRa;
- R6 is hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, or C3-C6 cycloalkyl wherein the cycloalkyl is optionally substituted with C1-C3 alkyl, C1-C3 haloalkyl, or 1 or 2 halogen atoms;
- Ra and Rb are independently hydrogen, C1-C3 alkyl or Ra and Rb combine with the nitrogen atom to which they are attached to form a four to six member heterocyclic ring optionally containing an oxygen or a nitrogen atom in the ring;
- or a pharmaceutically acceptable salt or enantiomer thereof.
A compound selected from the group consisting of:
- namely 4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiazol-4-yl)-5-morpholinopicolinamide;
- namely 4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiazol-4-yl)-5-(3-hydroxy-3-methylazetidin-1-yl)picolinamide;
- namely (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-5-morpholino-N-(2-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)thiazol-4-yl)picolinamide;
- namely (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-5-(3-hydroxy-3-methylazetidin-1-yl)-N-(2-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)thiazol-4-yl)picolinamide;
- and
- namely (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-5-(dimethylamino)-N-(2-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)thiazol-4-yl)picolinamide;
- or a pharmaceutically acceptable salt or enantiomer thereof.
The compound,
- namely (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-5-(dimethylamino)-N-(2-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)thiazol-4-yl)picolinamide or a pharmaceutically acceptable salt or enantiomer thereof.
The compound
- namely (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-5-(3-hydroxy-3-methylazetidin-1-yl)-N-(2-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)thiazol-4-yl)picolinamide or a pharmaceutically acceptable salt or enantiomer thereof.
The compound
- namely 4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)thiazol-4-yl)-5-(3-hydroxy-3-methylazetidin-1-yl)picolinamide or a pharmaceutically acceptable salt or enantiomer thereof.
Dependencies are inferred from the claim text.