The design and synthesis of benzylpiperazine-based edaravone derivatives and their neuroprotective activities

New edaravone derivatives containing a benzylpiperazine moiety are designed and synthesized. The structures characterized by 1 H NMR, 13 C high-resolution mass spectrometry. potential neuroprotective activities of the target compounds evaluated in differentiated rat pheochromocytoma cells (PC12 cells) mice subjected to acute cerebral ischemia. Most showed both vivo vitro, especially 1-(4-(4-fluorobenzyl) piperazin-1-yl)-2-(4-(5-hydroxy-3-methyl-1 H-pyrazol-1-yl)phenoxy)ethanone 1-(4-(4-nitrobenzyl)piperazin-1-yl)-2-(4-(5-hydroxy-3-methyl-1 H-pyrazol-1-yl)phenoxy)ethanone, which displayed significant protective effects on cell viability against damage caused 2 O , remarkably prolonged survival time ischemia decreased mortality rate at all doses. These represent lead for further discovery agents treating ischemic stroke. Molecular docking studies basic structure–activity relationships also presented.