Diazepines. IV. Synthesis and Biological Action of 6-Phenyl-4H-imidazo [1,2-α] [1,5] benzodiazepin-5 (6H)-ones

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A series of 6-phenyl-4H-imidazo [1,2-α] [1,5] benzodiazepin-5 (6H)-ones (1) was synthesized starting from 2-nitrodiphenylamines (9) and was evaluated for CNS activity. Bromoacetylation of 9 to N-bromoacetyl-2-nitrodiphenylamines (10) and subsequent treatment of 10 with sodium cyanide gave N-cyanoacetyl-2-nitrodiphenylamines (11) which were also prepared directly from 9 by cyanoacetylation. The reduction of the nitro group of 11 to give 2-amino-N-cyanoacetyldiphenylamines (12) followed by cyclization of 12 with HCl afforded 4-amino-1-phenyl-2H-1,3-dihydro-1,5-benzodiazepin-2-ones (13). Treatment of 13 with propargylamine in the presence of p-toluenesulfonic acid or with α-bromoketone gave 1. Some of 1 were also synthesized by treatment of 13 with α-aminoaldehyde acetal to the amidine derivatives 14 followed by their cyclization in formic acid. Although the ED_<50> for the antipentetrazole activity of 8-chloro-2-ethyl-6-phenyl-4H-imidazo [1,2-α] [1,5] benzodiazepin-5 (6H)-one (1h) was 5.5 mg/kg, the ratio of antipentetrazole to muscle relaxant activity and that of taming to muscle relaxant activity of 1h were fairly large compared with those of diazepam.
社団法人日本薬学会の論文
1977-10-25