3,6-substituted 5-arylamino-1h-pyridine-2-one derivatives and related compounds as poly (adp-ribose) polymerase (parp) inhibitors in the treatment of tissue damage or disease caused by necrosis or apoptosis

摘要

5-SUBSTITUTED 5-ARYLAMINO-1H-PYRIDINE-2-ONA DERIVATIVES AND COMPOUNDS RELATED TO POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS IN TREATMENT OF DAMAGE OR DISEASE CAUSED BY NECROSIS OR APOPTOSIS. The invention relates to compounds of formula 1 wherein: R1 and R3 independently of each other represent fluorine, methoxy, -OCF-3 ~, C-2-C-3-alkenyl or C-1-C ~ 4-alkyl which is optionally substituted by chlorine, methoxy or one, two or three fluorine atoms; R 2 represents hydrogen, fluorine, methoxy, -OCF-3 ~, C-2-C-3-alkenyl or C-1-C-4-alkyl which is optionally substituted by chlorine, methoxy or one, two or three fluorine atoms; X represents O, S, NH or N (C 1 -C 1 -C 3 alkyl); Ar represents unsubstituted or at least monosubstituted aryl or heteroaryl. Said compounds are poly (ADP-ribose) polymerase (PARP) inhibitors and are used in medicaments for the treatment of a disease which is selected from the following: tissue damage resulting from cell damage or cell death due to necrosis or apoptosis, neuronal mediated tissue damage or disorders, cerebral ischemia, head injury, stroke, reperfusion damage, neurological disorders, and neurodegenerative diseases, stroke, cardiovascular disorders, myocardial infarction, experimental allergic encephalomyelitis (experimental allergic encephalomyelitis ( (EAE)), multiple sclerosis (MS)), cardiac surgery-related ischemia, age-related macular degeneration, arthritis, atherosclerosis, cancer, degenerative skeletal muscle disorders resulting in replicative senescence, diabetes, and diabetes-related myocardial disorders .