哌啶并[2,3-b]哌嗪类衍生物的设计、合成及其抗血小板聚集活性研究

Design, Synthesis and Anti-Platelet Aggregation Activity of Piperido[2,3-b]piperazine Derivatives

以2,3-二氨基吡啶和2,3-丁二酮为起始原料,经环化、催化氢化和亲核取代反应合成了10个新型哌啶并[2,3-b]哌嗪类衍生物(3a~3j),其结构经^(1)H NMR、^(13)C NMR和HR-MS确证。体外抗血小板聚集活性研究表明,化合物3d、3e、3g、3h和3j具有一定的抗血小板聚集作用,其中化合物3h(IC_(50)=1.24mmol/L)的活性显著优于母体化合物川芎嗪(IC_(50)=3.96mmol/L)和阳性药物阿司匹林(IC_(50)=2.41mmol/L)。

Using 2,3-diaminopyridine and 2,3-butanedione as the starting material, ten new piperido [2,3-b]piperazine derivatives(3 a~3 j) were synthesized by cyclization, catalytic hydrogenation and nucleophilic substitution reaction. Their structures were confirmed by ^(1)H NMR, ^(13)C NMR and HRMS. The in vitro antiplatelet aggregation activity study showed that compounds 3 d, 3 e, 3 g, 3 h and 3 j had a certain antiplatelet aggregation effect, and the activity of compound 3 h(IC_(50)=1.24 mmol/L) was significantly better than that of the lead compound ligustrazine(IC_(50)=3.96 mmol/L) and the positive drug aspirin(IC_(50)=2.41 mmol/L).