Design,synthesis And Biological Activities Of Novel Neuroprotective Agents For Acute Stroke

It is of great significance to find a new type of neuroprotective agent for stroke.Stroke has become the first cause of death in China.The economic burden caused by stroke is up to 40 billion RMB a year,and the incidence of stroke in China is rising at 8.7%annually.In addition to Edaravone,most of the current neuroprotective drugs,such as glutamate receptor antagonists,calcium channel blockers,have shown good efficacy in animal experiments,but they have not been successful in improving clinical trials.It is difficult that the neuroprotective agent of single target to play the ideal neuroprotective effect.The study of Edaravone-NO donor co-drug has been reported that the co-drug had both NO donor and antioxidant activity,and the multi-target neuroprotective agent had good development prospects.In this paper,the co-drug was designed to combine the edaravone with the selective antagonist of NMDA receptor NR2B,and the 32 target compounds were synthesized.Compound LYL-O1 and LYL-O7 showed good neuroprotective activity by the preliminary pharmacological screening.The results showed that the target compounds containing 4-benzoyl piperidine structure had better neuroprotective activity,which could have better NR2B selectivity.Further bioassay and structural optimizing of these derivatives as neuroprotective agents are in progress.