Girisopam

Benzodiazepines have been widely used therapeutically for their ability to act as tranquilizers, sedative-hypnotics, antiepileptics and frequently prescribed to women during pregnancy for managing preeclampsia or eclampsia.The present report deals with quant. structure-toxicity relationship (QSTR) modeling of a series of benzodiazepines, in the context of the 3R concept, to provide an insight into the main structural fragments that impart toxicity to these mols.Three different in silico techniques, namely descriptor-based QSTR, group-based QSTR and 3D-toxicophore mapping, were employed to obtain statistically significant models.Multiple in silico models made it possible to reach a unified conclusion regarding the structural fragments and features responsible for the toxicity and provide consensus predictions which can be effectively utilized to design and predict less toxic new benzodiazepines.

Novel one-pot synthesis of 2,3-benzodiazepines from aryne precursors was accomplished. Tofisopam, well-known anxiolytics, could be synthesized via C–C bond insertion of 4,5-dimethoxybenzyne with 2-ethyl-1-(3,4-dimethoxyphenyl)butane-1,3-dione, followed by the reaction with hydrazine hydrate in a one-pot operation. This protocol is applicable to the synthesis of other biologically active 2,3-benzodiazepines, such as Girisopam and Nerisopam.