Design, synthesis, computational and biological evaluation of new benzodiazepines as CNS agents

Abstract

Two series of new benzodiazepines were synthesized and the target compounds (E1-10 and G1- 10) were evaluated for antianxiety and skeletal muscle relaxant activity as CNS agents in albino mice. The chemical structures of the compounds were confirmed on the basis of their TLC, IR, H-1 NMR and C-13 NMR analysis. In computational studies, the physicochemical similarity of the target compounds was assessed by calculating from a set of physicochemical properties using software programs and test compounds demonstrated moderate physiochemical similarity with respect to diazepam. Log P values of the target compounds indicates good penetration to CNS. Molecular docking studies revealed that the target compounds correctly dock into the binding pocket of the GABAA receptor, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. The test compounds (E1-10 and G1-10) were screened for antianxiety and skeletal muscle relaxant activity using Elevated plus maze and Rotarod method respectively. Among them, the compounds E10 and G7 showed maximum potency as CNS agents. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.