Development of novel N-3-bromoisoxazolin-5-yl substituted 2,3-benzodiazepines as noncompetitive AMPAR antagonists

Abstract

In this work, we designed and synthesized novel N-3-bromoisoxazolin-5-yl substituted 2,3-benzodiazepines as noncompetitive AMPAR antagonists, with the aim that this heterocycle could establish favourable interactions with a putative binding pocket of the receptor, like the thiadiazole nucleus of GYKI 47409 does. Within this investigation, we identified some active molecules and, among these 2,3-benzodiazepines, 4c showed a much improved inhibitory potency as compared with unsubstituted 2,3-benzodiazepines.

Keywords: 2,3-Benzodiazepine; 3-Bromoisoxazolines; AMPA receptors; Noncompetitive antagonists; Whole-cell recording.