The Synthesis And Preminary Pharmacology Study On The Coumarins And Hexhydrobenzo"a"quinolizin-4-one Derivatives

Cardiovascular(CV) system diseases are common diseases,Many drugs that possessed potential effect have been explored.But they possessed toxicities.So it is important to find potential effect and low toxicity cardiovascular drugs. Coumarins were discovered originally in plants. It has many kinds of pharmaceutical activities,such as anticoagulant,antibacterial,vasodilatation,driving worm and relieving pain et al. Alkaloids exist widely among the plants. It can cure multi-disease. It is universally effective on sedation,analgesia,expanding the blood vessel,checking diarrhea and Ca24 antagonizing activities et al. They are usually synthesized because of very trivial and complicated extract and separation.lt is a important way current to explore new drugs applying active components in Chinese drugs as lead compounds.Some natural active Coumarins and Alkaloids as lead compound have been modificated to find new drugs.In this paper,three series of Coumarin(Ax B and C series) and a series of Hexhydrobenzo[a]quinolizin-4-one(D series) derivatives,total 23 target compounds and 40 intermediate have been designed andsynthesized. Their structures were confirmed with IR13CNMR et al. The 23 target compounds and 9 mid-product have neverbeen reported before.The reactive conditions and the synthetic technology of target compounds and intermediates were explored in the experiment.The compounds of Series B have been synthesized succucessfully by methods of Microwave.Cyclization and the reactive conditions of phenyl-ethylamine in series D have both been explored.Some of target compounds have been determined on their effect on initial pharmacology test.Eight compounds (Ai A -. A4,B DI DI Dsand Dg) appeared strongly inhibitive effect on potentital-dependent.Ca24 channel(PDC) by applying Ca2+ transmembrane influx technique. Compouns B DI Di D3and Dg posses Ca2+ antagonizing activity .Four compounds (2 3- 5 and Ce ) have been determined on anticoagulant activity by applying Coagulant Time(CT) technique. Preliminary results show that Ci and Ce posses notable anticoagulant activity.It may be a foundation for the further research of pharmacoligy,structure-activity relationship and new drug design on these compounds.