Neuroprotective compounds and pharmaceutical compositions comprising them

摘要

Benzoxazine or quinazoline derivatives (I) are used to prepare neuroprotective medicaments for preventing or treating neuronal deterioration. Benzoxazine or quinazoline derivatives of formula (I) are used to prepare neuroprotective medicaments for preventing or treating neurodegenerative diseases. a, d : 0 or 1; b, c : single or double bonds; X : O or N, provided that d = 0 when X is O and d = 1 when X is N; R 1-R 4H, halo, OH or 1-2C alkoxy; R 5, R 6H, 1-6C (cyclo)alkyl, or phenyl optionally substituted with halo, OH, 1-2C alkoxy, CF 3 or NO 2; R 7H, OH or 1-3C alkyl or hydroxyalkyl; R 8O or NR 9R 10, provided that b is a single bond and c is a double bond when R 8 is O and that b is a double bond and c is a single bond when T 8 is NR 9R 10; R 9, R 10H, OH or 1-3C alkyl or hydroxyalkyl. Independent claims are also included for: (1) pharmaceutical composition comprising a compound (I) and a compound (II) intended for preventing or treating epilepsy, cerebral, ischemic or hemorrhagic vascular accidents, neurodegenerative diseases, phacomatoses, neuropathies, neuritis, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia, depression, brain tumors, Parkinson's disease and dementia; (2) product comprising compounds (I) and (II) as a combination product for separate, simultaneous or sequential use for preventing or treating neuronal deterioration associated with the above diseases. [Image] ACTIVITY : Neuroprotective. Oral administration of desethyl-etifoxine in doses of 30, 100, 200 and 300 mg/kg to mice subjected to hypobaric hypoxia increased their survival time from 55.5 seconds to 81.5, 95.3, 99.5 and 115.5 seconds respectively. MECHANISM OF ACTION : Glutamate antagonist.