3-取代三唑类抗真菌化合物的设计、合成及体外抗真菌活性  

Design,synthesis,and antifungal activity of 3-substituted triazole derivatives

作　　者：王保刚[1] 邹敏辉[1] 李文哲[1] 柴晓云[2] 俞世冲[2] 吴秋业[2] 

机构地区：[1]第二军医大学研究生管理大队学员13队,上海200433 [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》2010年第10期1114-1119,共6页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(20772153);上海市科委基金(09dZ1976700);上海市重点学科资助项目(B906)~~

摘　　要：目的合成1,2,3-三唑侧链取代三唑醇类化合物并考察其体外抗真菌活性。方法设计合成了21个三唑醇类新化合物,所得化合物结构都经过1HNMR、MS确证;选择8种真菌为实验菌株,进行体外抗真菌活性测试。结果所合成的化合物均具有一定的体外抗真菌活性,其中化合物7{1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-[N,N-(4-亚甲基-1-取代苄基-1H-1,2,3三唑)]-2-丙醇}对白色念珠菌的MIC80值为0.25μg/ml,是氟康唑活性的4倍,化合物Ⅵ{1-(1H-1,2,4-三唑-1-基)-2-(2,4二氟苯基)-3-(N,N-二炔丙基)-2-丙醇}对白色念珠菌的MIC80值为0.0156μg/ml,是氟康唑活性的64倍,是伊曲康唑的4倍。结论利用13偶极加成反应可以方便地在化合物中引入1,2,3-三唑基;较大的侧链结构可能不利于目标化合物活性的提高。Objective To study the in vitro antifungal activity of triazole alcohols by introduction of 1,2,3-triazole as the side chain.Methods Twenty-one novel triazole alcohol compounds were designed,synthesized,and characterized by 1 HNMR and MS spectra.The in vitro antifungal activities of the compounds were evaluated using eight kinds of pathogenic fungi.Results All the synthesized compounds exhibited certain antifungal activities.The MIC80value of compound7 1-（1 H-1,2,4-triazole-1-yl）-2-（2,4-difluorophenyl）-3-[N,N-（1-substituted-benzyl-4-methylene-1 H-1,2,3-triazole）]against Candida albicans was 0.25μg/ml,with its activity being 4times that of fluconazole.The MIC80value of compoundⅥ1-（1 H-1,2,4-triazole-1-yl）-2-（2,4-difluorophenyl）-3-（N,N-dipropargyl）-2-propanols against Candida albicans was 0.015 6μg/ml,with its activity being 64times that of fluconazole and 4times that of itraconazole.Conclusion The 1,2,3-triazole can be efficiently introduced by intermolecular 1,3-dipolar cycloaddition.Large side chains may be a disadvantage for improving the antifungal activity of the title compounds.

关 键 词：合成 三唑类 抗真菌药 1 3偶极加成反应 

分 类 号：R978.5[医药卫生—药品]