4-甲基-(3'S,4'S)-凯林硫代内酯衍生物的合成及其体外抗血小板聚集活性研究  

Synthesis of 4-methyl-(3′S, 4′S)-khelthiolactone derivatives and their anti-platelet aggregation activities in vitro

作　　者：胡梦楠[1] 闫超群[1] 何素海 梁泰刚[1] 李青山[1] 

机构地区：[1]山西医科大学药学院,山西太原030001

出　　处：《现代药物与临床》2015年第9期1051-1056,共6页Drugs & Clinic

基　　金：国家自然科学基金资助项目(81101687)

摘　　要：目的设计并合成凯林硫代内酯衍生物,并测定其体外血小板聚集抑制活性。方法以7-羟基-4-甲基香豆素为原料,经亲核取代、克莱森重排、硫化反应、sharpless不对称羟基化、酯化反应制备目标化合物5a^5h;采用微量反应板酶标仪比浊法评价目标化合物的抗血小板聚集活性。结果合成了8个新化合物,其结构经1H-NMR、13C-NMR及MS确证。活性测试结果表明,化合物5h、5b的活性强于阳性对照药奥扎格雷钠,具有抗血小板聚集活性。结论 4-甲基-(3'S,4'S)-凯林硫代内酯衍生物具有良好的抗血小板聚集活性,值得进一步研究。Objective To design and synthesize khelthiolactone derivatives, and to evaluate their anti-platelet aggregation activities in virto. Methods 7-Hydroxy-4-methyl coumarin was used as starting material to synthesize the target compounds by nucleophilic substitution reaction, claisen rearrangement, sulfuration reaction, sharpless asymmetrical dihydroxylation, and esterification reactions. The anti-platelet aggregation activities of the synthesized compounds were evaluated by microplate reader method.Results Eight novel khelthiolactone derivatives were synthesized and characterized by1H-NMR,13C-NMR, and MS data. Thein vitro assay indicated that compounds 5h and5b exhibited remarkable anti-platelet aggregation activities, and they were better than control drug ozagrel sodium.Conclusion4-Methyl-（3′S, 4′S）-khelthiolactone derivatives have good anti-platelet aggregation activities, which could be a valuable candidate for further development.

关 键 词：凯林硫代内酯 7-羟基-4-甲基香豆素 奥扎格雷钠 合成 抗血小板聚集活性 

分 类 号：R914[医药卫生—药物化学]