咖啡酸衍生物的合成及其抑制HIV整合酶活性  

Synthesis and HIV integrase inhibitory activity of caffeic acid derivatives

作　　者：赵桂森[1] 臧恒昌[1] 王小兵[1] 徐玉文[1] 袁玉梅[1] 

机构地区：[1]山东大学药学院,山东济南250012

出　　处：《中国药物化学杂志》2005年第2期70-75,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金资助项目 (2 0 4 72 0 4 5 ) ;山东省自然科学基金资助项目 (Y2 0 0 3C19)

摘　　要：目的合成新型咖啡酸衍生物并测定其抑制HIV 1整合酶活性。方法化学合成一系列N 取代咖啡酰萘磺胺类化合物,采用3 2 P标记法体外测定化合物抑制HIV 1整合酶活性。结果合成了2 0个咖啡酸衍生物,其结构经红外光谱、核磁共振氢谱及质谱确定。其中化合物Ⅰ2 、Ⅰ3 、Ⅰ4抑制HIV 1整合酶活性高于L 巨菊酸(IC50 =11 8μg·mL-1) ,3个化合物的IC50 分别为(8 .6±4 . 8)、(4. 5±3 .4 )、(7 .9±4 . 9) μg·mL-1。结论N 取代咖啡酰萘磺胺类化合物对HIV 1整合酶有较高抑制活性,值得深入研究。Aim To synthesize a series of new caffeic acid derivatives and test their HIV-1 integrase inhibitory activities.Methods A series of N-substituted caffeoyl-naphthalenesulfonaminde derivatives were synthesized by six-step reactions.HIV-1 integrase inhibitory assay of these compounds was carried out by ()^(32)P-marked experiments in vitro.Resluts Twenty caffeic acid derivatives were synthesized and confirmed by IR,()~1H-NMR and MS.Among these compounds,the HIV-1 integrase inhibitory activities of compounds Ⅰ_2,Ⅰ_3 and Ⅰ_4 were more potent than that of L-chicoric acid(IC_(50)=11.8 μg ·mL^(-1)).Conclusion N-substituted caffeoyl-naphthalenesulfonaminde derivatives show remarkable HIV-1 integrase inhibitory activities,and further research is underway.

关 键 词：药物化学 构效关系 化学合成 HIV-1整合酶抑制剂 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]