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, 1 H NMR and 13 C 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 GABA A 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.