川芎嗪-丁苯酞衍生物的设计、合成及抗血小板聚集活性研究  

Synthesis and Anti-platelet Aggregation Activity Evaluation of Ligustrazine and 3-n-Butylphthalide Derivatives

作　　者：朱桃[1] 李毅[1] 樊玲玲[1] 陈文章[1] 汤磊[1] 

机构地区：[1]贵州医科大学药学院,贵州贵阳550004

出　　处：《化学试剂》2017年第4期353-356,共4页Chemical Reagents

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);贵州省卫生计生委科学技术基金项目(gzwjkj2016-1-050)

摘　　要：以邻苯二甲酸酐和川芎嗪为原料,经自由基取代、正丁基锂亲核加成、对甲基苯磺酸催化脱水、Pd/C加氢还原、水解、酯化等反应合成了3个川芎嗪与丁苯酞拼合衍生物,其结构经~1HNMR、^(13)CNMR和HR-MS确证。其中(3,5,6-三甲基吡嗪-2-基)甲基-2-戊酰基苯甲酸酯对由腺苷二磷酸(ADP)诱导的血小板聚集活性抑制率IC_(50)为0.26 mmol/L,优于母体化合物川芎嗪和丁苯酞,是具有良好开发前景的候选化合物。Using phthalic anhydride and ligustrazine as the ingredients,three conjugated derivatives of ligustrazine and 3-n-butylphthalide were synthesized via free-radical substitution,n-Bu Li nucleophilic addition,p-tolunenesulfonic acid dehydration,Pd/C catalysis-hydrogenation,hydrolysis,esterification.The structures were confirmed by ~1HNMR,^（13）CNMR and HR-MS.The inhibitory activity of the target compound（3,5,6-trimethylpyrazin-2-yl） methyl-2-pentanoylbenzoate against adenosine diphosphate（ADP）induced platelet aggregation was 0.26 mmol/L.In comparison with ligustrazine and 3-n-butylphthalide（NBP）,the compound possessed better antiplatelet aggregation activity.Therefore,it may be utilized as lead compound for further investigation.

关 键 词：川芎嗪 丁苯酞 合成 抗血小板聚集活性 

分 类 号：R914.5[医药卫生—药物化学]