N-4-OXO-2,3-DIHYDRO-1,5-BENZOXAZEPIN-3-YL-5,6-DIHYDRO-4H-PYRROLO1,2-BPYRAZOL E-2-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS RIP1 KINASE INHIBITORS FOR TREATING E.G. IRRITABLE BOWEL SYNDROME (IBS)

摘要

The invention provides compounds having the general formula (I): or pharmaceutically acceptable salts thereof, wherein X, Y, R¹, R², R^7a, R^7b, X, R^B1, R^B2, n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and the compounds for use as receptor-interacting protein-1 (RIP1) kinase inhibitors in methods of treating e.g. Parkinson's or Alzheimer's disease, irritable bowel disorders (IBD), Crohn's disease, respiratory distress syndrome (ARDS) or chronic obstructive pulmonary disease (COPD). An exemplary compound is e.g. (4S,6S)-4-fluoro-6-phenyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-l,5- benzoxazepin-3-yl]-5,6-dihydro-4H-pyrrolo[l,2-b]pyrazole-2- carboxamide (example 11) with a Ki (uM) in a RIP1 assay of 0.0044 uM..