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

作　　者：李毅 罗碧兰 赵菊琴 李永 张毅 汤磊 樊玲玲 Li Yi;Luo Bilan;Zhao Juqin;Li Yong;Zhang Yi;Tang Lei;Fan Lingling(School of Pharmacy,Guizhou Medical University,Guiyang,550004;Guizhou Chemical Drug Research and Development Engineering Technical Center,Guizhou Medical University,Guiyang,550004)

机构地区：[1]贵州医科大学药学院,贵阳550004 [2]贵州医科大学贵州省化学合成药物研发利用工程技术研究中心,贵阳550004

出　　处：《化学通报》2021年第2期162-166,97,共6页Chemistry

基　　金：贵州省化学合成药物研发利用工程技术研究中心项目(黔科合[2016]平台人才5402);贵州省普通高等学校药物化学工程研究中心项目(黔教合KY字[2014]219号);贵州省科技支撑计划项目(黔科合支撑[2017]2835号,[2016]2848号,[2019]2785号);贵州省科技计划项目(黔科合基础[2019]1269号);贵州省大学生创新创业训练计划项目(20195200883)资助。

摘　　要：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).

关 键 词：哌啶并[2 3-b]哌嗪 合成 抗血小板聚集活性 

分 类 号：TQ460.1[化学工程—制药化工] O626[理学—有机化学]