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

Stroke is the leading cause of human disability and the second largest cause of death in the world.It has characteristics of high prevalence,high recurrence rate,high disability rate and high mortality.Its main disease population is middle-aged and elderly people.Fnding effective new anti-stroke drugs is imminent for people in the world.Chemic stroke accounts for about 70%～80% of all strokes.Therefore,the main research direction of this paper is the synthesis and biological activity of novel anti-ischemic stroke drugs.In recent years,it has been confirmed from morp Hology and molecular biology that apoptosis play a major role in cerebral ischemia-reperfusion injury.Since the Caspase family plays a role in regulating and acting in the signal transduction stage of apoptosis,it is considered that cerebral ischemia-reperfusion injury is related to the Caspase family.The expression of Caspase-3 in the ischemic brain region after reperfusion is also studied.Both the expression index and the activation level were abnormal.According to reports,the 3,4-dihydropyrimido（1,2-a）fluorene-10（2H）-one structure as the parent nucleus,designed and synthesized Caspase-3 inhibitor with anti-stroke,neuroprotection and other biological functions are good drug lead compounds for the treatment of various diseases or p Hysiological processes.Before this study,the high-content screening（HCS）and Western blot analysis confirmed that the aryloxyacetamide and cinnamamide derivatives 3# and 34# have a certain Caspase-3 inhibitory activity.Combined with the structural analysis of reported Caspase-3 inhibitors,we incorporated them into a 3,4-dihydropyrimido-（1,2-a）fluorene-10（2H）-one structure.After preliminary bioactivity tests,compound CXH-B8 showed good neuroprotective activity.The results showed that the target compound containing the cinnamamide structure has better neuroprotective activity and they may have better Caspase-3 inhibitory activity.Further bioassay and structural optimizing of these derivatives as neuroprotective agents are in progress.