Peptidoaminobenzophenones, a novel class of ring-opened derivatives of 1,4-benzodiazepines

Abstract

A series of novel peptidoaminobenzophenones was prepared via several routes and was evaluated for CNS activity. The structure-activity relationships in the series are discussed. In general, dipeptido-N-methylaminobenzophenones showed higher activities than the corresponding NH derivatives. Some compounds had very high activities in antiphenylenetetrazole and antifighting tests in mice when orally administered. Very weak toxicity was found in these compounds. Water solubility of the peptidoaminobenzophenones and their salts was tested. Possible in vivo conversion of peptidoaminobenzophenone by enzymatic cleavage of the terminal amino acid, followed by chemical cyclization to 1,4-benzodiazepine, is discussed. Such novel open-ring derivatives of 1,4-benzodiazepine may serve as useful CNS agents.