非核苷类逆转录酶抑制剂的研究XVⅢ：4-烯丙基和4-叠氮基取代的三嗪类化合物的合成及抗HIV活性(英文)  

Non-nucleoside reverse transcriptase inhibitors (Part 18):Synthesis and anti-HIV activity of 4-allylamino or 4-azido substituted diaryltriazines

作　　者：熊远珍[1] 胡海荣[2] 陈芬儿[1,3] Jan Balzarini Christophe Pannecouque Erik De Clercq 

机构地区：[1]复旦大学药学院,上海200031 [2]复旦大学生命科学院,上海200433 [3]复旦大学化学系,上海200031 [4]Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven Belgium B-3000

出　　处：《药学学报》2009年第2期145-149,共5页Acta Pharmaceutica Sinica

基　　金：supported by the National Science Foundation of China (No.30672536)

摘　　要：在已有工作基础上,基于分子对接设计合成了8个新的4-烯丙基取代和4-叠氮基取代的二芳基三嗪类衍生物。抗HIV-1活性的测试结果表明所有新化合物均具有抗HIV-1活性。其中化合物7c不仅抑制HIV-1野生株的复制(IC50=0.034μmol·L-1,SI=6475),且对Y181C和K103C双突变酶显示出较强的抑制活性,其IC50值为9.39μmol·L-1,高于奈韦拉平。Eight new diaryltriazine derivatives containing 4-allylamino and 4-azido substitutes guided by molecular docking have been designed and synthesized based on our previous work. The evaluation of HIV inhibitory activity demonstrated that all compounds were potent against HIV-1 replication. The most active compound 7c exhibited activity against HIV-1 （IC50 = 0.034 μmol·L^-1, SI = 6 475） and the double mutant strain （IC50 = 9.39 μmol·L^-1） in the micromolar range, which was more ootent than neviranine.

关 键 词：非核苷类逆转录酶抑制剂 抗HIV活性 4-烯丙基取代二芳基三嗪 4-叠氮基取代二芳基三嗪 

分 类 号：R916.2[医药卫生—药学]