氟康唑衍生物的设计与合成  

Design and synthesis of fluconazole derivatives

作　　者：高一军[1] 王楠[1] 李文娟[1] 张雷[1] 柴晓云[2] 王文艳[1] 孙海军[1] 毕毅[1] 吴秋业[2] 孟庆国[1] 

机构地区：[1]烟台大学药学院,烟台264005 [2]第二军医大学药学院,上海200433

出　　处：《中国新药杂志》2012年第6期681-685,700,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81072534)

摘　　要：目的:设计并合成氟康唑衍生物。方法:基于前期计算机辅助药物设计结果,以氟康唑为先导化合物,保留2,4-二氟苯基、叔醇羟基和一个三氮唑,在3位C上引入不同的取代氨基,设计经取代,酯化,溴代,缩合,皂化,缩合6步反应合成目标化合物。结果:合成了13个新化合物,结构经1H-NMR,MS确证。结论:合成路线设计合理,目标化合物结构正确,可供下一步的药理研究。Objective： To design and synthesize fluconazole derivatives. Methods： Based on the previous result of computer-aided drug design, we systematically altered the structure of fluconazole according to the structure-activity relationships of the azoles in antifungal compounds and synthesized target compounds in six steps. Results： Thirteen new compounds were synthesized. The structures were confirmed by ^1H-NMR and MS. Conclusion： The design of synthetic route is reasonable. Target compounds are correct and can be used for further study of pharmacological activities.

关 键 词：氟康唑 衍生物 设计 合成 

分 类 号：R914.5[医药卫生—药物化学]