Design, Synthesis Of Novel Series Derivatives Of TMP Aromatic Acid And Activity Of Anti-platelet Aggregation

With the development of economy and society, cardiovascular diseases become the most serious disease to human body. According to the report of The World Health Organization, more than 1/3 of the deaths were caused by cardiovascular disease in the world every year. It is well known that most of the cardiovascular diseases were associated with thrombogenesis and thromboembolism. Therefore, a great deal of efforts are focused on antithrombotics for treatment of cardiovascular diseasesIn order to discover new antiplatelet aggregation drugs, ferulic acid and tetramethyl pyrazine were chosen as lead structures due to their important role in promoting blood circulation in traditional chinese medicine. In addition, we introduced the fragment to the lead structure and designed 6 new pyrazine-benzamide deriatives based on the bioisosterism principle and the hybrid principle in medicinal chemistry.Tetramethyl pyrazine were used as starting material and then do the reaction followed by bromidation, Gabriel reaction, acyltion, Williams reaction and finally hydrolyzed with alkali solution to yield target compounds. All the target compounds were identified with1H-NM,13C-NMR, ESI-MS and IR.The preliminary biological evaluation was carried out using Ozagrel as positive control. Inhibitory activity against adenosine diphosphate (ADP) induced platelet aggregation were assessed and screened by Born method. The results showed that most of the target compounds possess inhibition in some extent.