Design,Synthesis And Biological Activities Of A Novel Neuroprotectant Against Ischemic Stroke

Stroke is the second leading cause of long-term disability and death worldwide,According to the survey,the incidence of first stroke increase by an average of 8.3 percent per year.Because of the high disability rate of cerebral apoplexy,it not only brings pain to patients,but also brings heavy economic burden to patients’ families.Therefore,it is of great significance to continuously seek for the treatment of stroke.With these efforts,clinical treatment of cerebral ischemia has achieved certain results,such as mechanical thrombectomy.However,drug therapy such as glutamate receptor antagonists,sodium ions,calcium channel blockers,antioxidants/free radical scavengers,anti-inflammatory drugs,and serotonin agonists has not achieved satisfactory results in clinical practice.Therefore,finding suitable neuroprotectant has become an urgent problem.In this paper,active compounds 3# and 34# obtained from previous studies are used as lead s,compounds.Combined with structural analysis of reported Caspase-3 inhibitorThe structure of benzothiazoline-3-ketone was introduced by the combination principle.Thirty target compounds were designed and synthesized.They all have been verified by high resolution mass spectrometry,nuclear magnetic resonance spectroscopy and nuclear magnetic resonance carbon spectrum.and no literature has been reported.All the target compounds were tested in vivo biological activities,and the results showed that HJP-G7,HJP-G8 and HJP-G9 could significantly prolong the survival time of acute cerebral ischemia mice in the three measured dose groups,with better neuroprotective activity.Further studies on pharmacodynamic evaluation,mechanism of action and structure-activity relationship are in progress.