普拉格雷类似物的合成及抗血小板聚集活性

Synthesis and antiplatelet aggregation activities of prasugrel derivatives

采用前药设计原理,以普拉格雷代谢物为先导化合物,设计并合成了一系列2-羟基四氢噻吩并吡啶烷氧羰基酯类衍生物(1～8),结构均经IR、1H NMR、13C NMR、MS和HRMS确证。对目标化合物进行了抗血小板聚集的药理活性评价,活性测试结果显示除化合物5外,其余大部分化合物都显示出较好的抗血小板聚集活性,部分化合物显示了与普拉格雷相当的抗血小板聚集活性。

With the metabolite of prasugrel as a lead compound,a series of 2-hydroxytetrahydrothienopyridine derivatives were designed and synthesized based on prodrug theory.Their structures were confirmed by IR,1 H NMR,13 C NMR,MS,and HRMS.The target compounds 1-8 were biologically evaluated for their antiplatelet aggregation activity.Except for compound 5,most of the test compounds exhibited potent antiplatelet aggregation activity,some exhibiting similar potent activity to prasugrel.The compounds are worthy of further study to search for novel antithrombotic agents with improved potency,safety profile and chemical stability.