氟康唑衍生物的设计合成及体外抗真菌活性研究  

Design, Synthesis and in vitro Antifungal Activities of Fluconazole Derivatives

作　　者：王楠[1] 李文娟[1] 张雷[1] 高一军[1] 冀春梅[2] 陈营[1] 柴晓云[3] 孙海军[1] 毕毅[1] 吴秋业[3] 孟庆国[1] 

机构地区：[1]烟台大学药学院,烟台264005 [2]潍坊市人民医院,潍坊261041 [3]第二军医大学药学院,上海200433

出　　处：《有机化学》2012年第5期922-929,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.81072534)资助项目~~

摘　　要：为了寻找活性更好的抗真菌化合物,基于已有的计算机辅助药物设计结果,保留氟康唑母体结构必需药效团,设计、合成了22个含对甲酚和胸腺嘧啶的氟康唑新衍生物.目标化合物的结构经1H NMR、元素分析和ESI-MS确证,初步体外抗真菌活性试验结果表明,化合物5l对7种真菌都表现出了较好的抗真菌活性(烟曲霉菌除外),化合物5a～5e,5g,5h,7a和7b对不同真菌表现出了一定的抗真菌活性.炔丙基取代氨基侧链结构的引入有利于提高该类目标化合物体外抗真菌活性,值得进一步深入研究.In search of more effective antifungal agents, twenty-two new fluconazole derivatives containing 4-methyl phenol and thymine have been designed and synthesized based on the previous results of computer-aided drug design. All the derivatives retain the essential pharmacophore of fluconazole. Their structures are elucidated by 1H NMR, elemental analysis and ESI-MS. Preliminary in vitro antifungal activities bioassay showed that compound 51 exhibits better in vitro antifungal activities against eight fungi except Aspergillus fumigatus （7544） than fluconazole, compounds 5a-5e, 5g, 5h, 7a and 7b show only moderate in vitro antifungal activities against different fungus. The introduction of propargyl group to nitrogen atom can enhance in vitro antifungal activities of this type derivative and it is worth of further research.

关 键 词：氟康唑 衍生物 合成 设计 体外抗真菌活性 

分 类 号：TQ465[化学工程—制药化工]