Diazepines. 5. Synthesis and biological action of 6-phenyl-4H-pyrrolo[1,2-a][1,4]benzodiazepines.
A series of 6-phenyl-4H-pyrrolo[1,2-a][1,4]benzodiazepines (2) has been prepared with 2-phthalimidomethylfurans (12) and 1-phthalimidoalkane-2,5-diones (15) or 2,5-dimethoxy-2-phthalimidomethyltetrahydrofurans (16) as the key intermediates and subsequently evaluated for CNS activity. The structure-activity data generated indicate that, in general, introduction of the methyl and/or ethyl group(s) in the pyrrole ring and a chlorine atom at the ortho position of the 6-phenyl group increases the activity and that substitution of the above chlorine atom for a fluorine atom decreases the activity. 8-Chloro-6-(2-chlorophenyl)-1,3-dimethyl-4H-pyrrolo[,2-a][1,4]benzodiazepine (2p), the most potent among the compounds synthesized, was equipotent in taming and sedative activities to diazepam. The acute LD50 of 2p in mice was larger than 3000 mg/kg po.
D000818:Animals; D000927:Anticonvulsants; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D006993:Hypnotics and Sedatives; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009125:Muscle Relaxants, Central; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D009125:Muscle Relaxants, Central; D011758:Pyrroles; D001569:Benzodiazepines