| It is well recognized that antiplatelet therapy can effectively reduce the incidence of cardiovascular events in patients with atherothrombotic diathesis. Clopidogrel is a new thieno[3,2-c]pyridine derivative, which selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor (P2Y12) and the subsequent ADP-mediated activation of the glycoprotein GPâ…¡b/â…¢a complex, thereby inhibiting platelet aggregation.Aim: This study is to design and synthesize a series of thieno[3,2-c] pyridine derivatives, to test the pharmacological activity of anti-platelet aggregation and to evaluate the metabolism in vitro in Rat liver homogenate.Methods: 1. The thieno[3,2-c] pyridine derivatives were prepared from clopidogrel by Condensation, Acylation and Sulfonation. The thin layer chromatography (TLC) was used to control the reaction process. High Performance Liquid Chromatography (HPLC) and Nuclear Magnetic Resonance (NMR) were used as analytical methods for structure determination.2. The antiplatelet aggregation activity of the title compounds was measured by Born's method.3. The metabolism of the title compounds were studied in Homogenized Liver of Rats.The concentration of compound 22 will be determined at 0,30,60,90,120 and 240 min by HPLC.The Hydrolysis reaction of the title compounds were studied by HPLC.Results: The sythsesized compounds were not found in literature. The test data showed that the sythsesized thieno[3,2-clpyridine derivatives displayed better anti-platelet aggregation activities. The inhibition rates of compound 20 and 25 were 42.2% and 41.8% ,respectively. Therefore, they are regard as valuable compounds for futher study to develop new anti-platelet aggregation agents.Conclusion: In conclusion, many of the sythsesized thieno[3,2-c]pyridine compounds have definite anti-platelet aggregation activity, and some of them are promising for developing new anti-platelet agents.
|
PDF Full Text Request