Design, Synthesis And Activity Assay Of Podocarpamide And The Derivatives

Cardiovascular Diseases (CVDs) are common diseases that seriously threaten people’s health in the world,which are mainly caused by coronary thrombosis. As we all know, platelets play a key role in hemostasis and thrombosis. P2Y12receptor can amplify the signal during the process of platelet activation. In addition, P2Y12receptor is over expressed on the platelet membrane. These make it become the ideal anti-thrombotic target.In our previous research, we choose the active constituent podocarpamide from Chinese traditional herbs, which can inhibit ADP-induced platelet aggregation. Catechol was chosen as the raw material, podocarpamide was synthesized via six steps. At the same time, The analogues were synthesized in the same way.Then the podocarpamide derivative was designed by the pharmacophore model. From the raw material of ligustrazine, the derivative was synthesized.All the compounds were characterized by MS and NMR.Podocarpamide and its analogues were evaluated for their antithrombotic activity in vitro using the platelet from healthy rabbits with ADP as inducers. The results showed9compounds possessed higher platelet aggregation inhibition than podocarpamide. Specifically, compound6a,6b and6e showed inhibition rates of45.8%,60.8%and53.3%at200μmol/L.