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

Stroke is one of the three most common causes of adult disability and death,and has become the second most common cause of death worldwide,especially among middle-aged and elderly people.Globally,about 4.6 million people die for stroke each year,and about two-thirds of those deaths are ischemic.A large number of studies have shown that oxidative stress is involved in the pathogenesis of various neurodegenerative diseases,such as alzheimer’s disease,Parkinson’s disease and ischemic stroke caused by acute central nervous system injury.Excessive generation of free radicals is an important cause of oxidative stress injury.Although there are many drugs on the market that can act on ischemic stroke,the therapeutic effect is not satisfactory.Researching and developing new anti-stroke neuroprotectants is a farreaching significance.This study focused on free radical scavengers/antioxidant neuroprotectants.Previous literature research and retrieval found that melatonin had anti-apoptosis activity.As a kind of free radical scavenger that can penetrate the blood-brain barrier,melatonin has both very effective antioxidant activity and significant neuronal protection.We selected melatonin as lead compounds and introduced a selective antagonist drugs of NMDA receptor(NR2B),which had neuroprotective activity in previous research to the structure of melatonin analogue.28 target compounds were designed and synthesized.The vast majority of the compounds were confirmed by high resolution mass spectrometry,nuclear magnetic resonance hydrogen and nuclear magnetic resonance of carbon(six compounds still lack a carbon spectrum).Moreover,the preliminary pharmacodynamics in vivo evaluation of some target compounds examined the influence on acute cerebral ischemia mice survival time.Among them,the target compounds FTT-T5,FTT-T7,FTT-T11,FTT-T19 and FTT-T26 could significantly prolong the survival time of mice with acute cerebral ischemia in the 200mg/kg group and showed better anti-cerebral ischemia activity.The comprehensive activity evaluation,in vitro cytotoxicity test,mechanism of action,pharmacodynamic evaluation and structure-activity relationship study of the target compounds in mice with acute cerebral ischemia will be carried out in the following studies.