1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-(N-正丁基-N-取代苄基氨基)-2-丙醇的合成及其抗真菌活性  

Synthesis and antifungal activity of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N-butyl-N-substituted benzylamino)-2-propanol

作　　者：魏宁[1] 赵小忠[1] 柴晓云[2] 管忠俊[2] 但志刚[2] 俞世冲[2] 吴秋业[2] 

机构地区：[1]解放军空军总医院门诊部,北京100036 [2]第二军医大学药学院有机化学教研室,上海200433

出　　处：《第二军医大学学报》2009年第9期1052-1057,共6页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(20772153);上海市重点学科资助项目(B906)~~

摘　　要：目的:研究具有正丁基和取代苄基侧链结构的三唑醇类化合物的抗真菌活性。方法:设计并合成了14个1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-(N-正丁基-N-取代苄基氨基)-2-丙醇化合物,其结构都经过1HNMR、IR和LC-MS确证。选择8种临床常见的真菌为实验菌株,进行体外抑菌活性测试。结果:体外抑菌测试结果表明,所有化合物对除熏烟曲霉菌外的所有菌株均有一定程度的抑制活性,对深部真菌的抑制活性明显优于浅部真菌。其中化合物6a、6d和6j对石膏样小孢子菌的抑制活性(MIC800.0156μg/ml)是氟康唑的16倍;化合物6m和6n对白念珠菌的抑制活性(MIC800.0039μg/ml)是氟康唑的128倍,比其他对照药活性都高。结论:引入正丁基和取代苄基侧链的目标化合物都具有一定的抗真菌活性。Objective：To study the antifungal activity of triazole alcohols by introducing N-butyl and substituted benzyl as side chain.Methods：Fourteen title compounds were synthesized and characterized by 1H NMR,IR,and LC-MS.The MICs of the compounds were determined by in vitro test using 8 clinical pathogenic fungi.Results：The title compounds exhibited potent antifungal activities against nearly all fungi tested（except for Aspergillus fumigatus）,especially for the deep infection ones.Compounds 6a,6d,and 6j showed a 16-fold activity（with a MIC80 value of 0. 015 6 μg/ml） as that of fluconazole against Microsporum gypseum. Compounds 6m and 6n showed a 128-fold activity（with a MIC,0 value of 0. 003 9 μg/ml） as that of fluconazole against Candida albicans ,and their activities were higher than those of other positive controls. Conclusion： The title compounds with N-butyl and substituted benzyl all have antifungal activities.

关 键 词：合成 正丁基 取代苄基 抗真菌药 构效关系 

分 类 号：R978.5[医药卫生—药品]