Diazepines. 5. Synthesis and biological action of 6-phenyl-4H-pyrrolo[1,2-a][1,4]benzodiazepines

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Abstract
A series of 6-phenyl-4H-pyrrolo[1,2-a][1,4]benzodiazepines was prepared with 2-phthalimidomethylfurans and 1-phthalimidoalkane-2,5-diones or 2,5-dimethoxy-2-phthalimidomethyltetrahydrofurans as the key intermediates and subsequently evaluated for CNS activity. The structure-activity data generated indicated that introduction of the methyl and/or ethyl group(s) in the pyrrole ring and a Cl atom at the ortho position of the 6-phenyl group increases the activity and that substitution of the above Cl atom for a fluorine atom decreases the activity. 8-Chloro-6-(2-chlorophenyl)-1,3-dimethyl-4H-pyrrolo[1,2-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 p.o. [per os].