丁苯酞杂合衍生物的合成及抗血小板凝集活性研究  

Synthesis and anti-platelet aagglutination activity of hybrid butylphthalide derivatives

作　　者：吴涛涛 贾镇 杨娅 樊玲玲 李永 WU Tao-tao;JIA Zheng;YANG Ya;FAN Ling-ling;LI Yong(School of Pharmacy,Guizhou Medical University,Guizhou Province Engineering Technology Research Center for Chemical Drug R&D,Guiyang 550025,China)

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

出　　处：《化学研究与应用》2025年第4期1005-1013,共9页Chemical Research and Application

基　　金：国家自然科学基金项目(32060627)资助;贵州省科技计划项目(黔科合基础[2020]1Y111号)资助;贵州省卫生健康委科学技术基金项目(gzwjkj2020-1-206)资助。

摘　　要：为了提高丁苯酞的抗血小板凝集活性,分别以6-羧基丁苯酞、6-胺基丁苯酞、阿司匹林和阿魏酸为起始原料,经还原、氯代、亲核取代、氧化、酰化、酯化、醚化、硝化、和环化等多步反应合成了10个丁苯酞衍生物,其结构经^(1)H-NMR、^(13)C-NMR和HRMS确证。体外抗血小板凝集活性测试结果表明化合物7(IC_(50)=1033μmol·L^(-1))和12a(IC_(50)=739.7μmml·L^(-1))对二磷酸腺苷(ADP)诱导的血小板凝集具有一定的抑制活性,优于阳性对照丁苯酞(IC_(50)=1252μmol·L^(-1))、阿司匹林(IC_(50)=1153μmol·L^(-1))和阿魏酸(IC_(50)=2016μmol·L^(-1))。化合物3(IC_(50)=37.1μmol·L^(-1))和4(IC_(50)=34.4μmol·L^(-1))对花生四烯酸(AA)诱导的血小板凝集的抑制活性高于阿司匹林(IC_(50)=42.9μmol·L^(-1))和丁苯酞(IC_(50)=262.5μmol·L^(-1)),可作为潜在的候选化合物进行深入研究。In order to improve the anti-platelet agglutination activity of butylphthalide,6-carboxylbutylphthalide,6-aminobutylphthalide,aspirin and ferulic acid were used as starting materials,10 butylphthalide derivatives were synthesized by reduction,chlorination,nucleophilic substitution,oxidation,acylation,esterification,etherification,nitrification and cyclization reactions.Their structures were confirmed by~1H-NMR,~(13)C-NMR and HRMS.The in vitro anti-platelet agglutination activity results showed that compounds 7(IC50=1033μmol·L^(-1))and 12a(IC_(50)=739.7μmol·L^(-1))exhibited moderate inhibitory activity against ADP-induced platelet aggregation,which were better than the lead compounds butylphthalide(IC_(50)=1252μmol·L^(-1)),aspirin(IC50=1153μmol·L^(-1)),and ferulic acid(IC_(50)=2016μmol·L^(-1)).Compounds 3(IC_(50)=37.1μmol·L^(-1))and 4(IC_(50)=34.4μmol·L^(-1))displayed superior inhibitory activity against AA-induced platelet aggregation to butylphthalide(IC_(50)=42.9μmol·L^(-1))and aspirin(IC_(50)=262.5μmol·L^(-1)),which could be considered as the potential candidates for further study.

关 键 词：丁苯酞 阿司匹林 阿魏酸 结构修饰 抗血小板凝集活性 

分 类 号：O626[理学—有机化学]