1. Novel peptidoaminobenzophenones, terminal N-substituted peptidoaminobenzophenones, and N-(acylglycyl)aminobenzophenones as open-ring derivatives of benzodiazepines
- Author
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Kentaro Hirai, Y. Tsukinoki, Hirohiko Sugimoto, Toshio Fujishita, Teruyuki Ishiba, and Katsumi Hirose
- Subjects
Male ,Chemical Phenomena ,Muscle Relaxants, Central ,Chemistry ,Halide ,Ring (chemistry) ,Chloroacetyl chloride ,Medicinal chemistry ,Lethal Dose 50 ,Benzodiazepines ,Benzophenones ,Mice ,chemistry.chemical_compound ,Anti-Anxiety Agents ,Chloracetamide ,Hexamethylphosphoramide ,Drug Discovery ,Animals ,Molecular Medicine ,Dimethylformamide ,Anticonvulsants ,Cns activity ,Postural Balance - Abstract
Peptidoaminobenzophenones (1), terminal N-substituted peptidoaminobenzophenones (14), and acylglycylaminobenzophenones (16) were prepared as a novel series of ring-opened derivatives of 1,4-benzodiazepine. Z-Gly- and Z-Ala-N-methylaminobenzophenones (4) were treated with HBr-HOAc to give Gly- and Ala-N-methylaminobenzophenone hydrobromides (8). Reaction of 8 with chloroacetyl chloride in dimethylformamide (DMF) or hexamethylphosphoramide (HMPA) gave chloracetamide (13), which was allowed to react with various amines to afford a number of terminal N-substituted derivatives (14). Reaction of 8 with various acyl halides in HMPA or DMF gave a number of acylglycyl-N-methylaminobenzophenones (16). Peptidoaminobenzophenones (1) were also prepared by several convenient methods. Many of these compounds exhibited high CNS activity in animals when given orally. In antianxiety activity the potency of some compounds is equal to or higher than that of diazepam.
- Published
- 1981
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