N-[2-(2,4-二氟苯基)-2-羟基-3-(1H-1,2,4-三唑-1-基)丙基]-N-′(4-取代苯基)-3(2H,4H)-1,2,4-三唑酮的合成和抗真菌活性  

Synthesis and Antifungal Activity of N-[2-(2,4-Diflurophenyl)-2-Hydroxy-3-(1H-1,2,4-Triazol-1-yl) Propyl]-N′-(4-Substituted Phenyl)-3-(2H,4H)-1,2,4-Triazolones

作　　者：盛春泉[1] 朱杰[1] 张万年[1] 曹永兵[1] 宋云龙[1] 张珉[1] 季海涛[1] 姚建忠[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《中国药学杂志》2006年第6期469-471,共3页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目(30430750);军队"十五"指令性课题(011057)

摘　　要：目的寻找广谱、高效、低毒的新一代三唑类抗真菌药物。方法根据靶酶活性位点的空间特征、各种力场和关键残基分布,设计并合成了N-[2-(2,4-二氟苯基)-2-羟基-3-(1H-1,2,4-三唑-1-基)丙基]-N-′(4-取代苯基)-3(2H,4H)-1,2,4-三唑酮类化合物,并测定了体外抗真菌活性。结果体外抑菌测试结果表明,目标化合物对8种致病真菌均有一定程度的抗真菌活性,对深部真菌的活性明显优于浅部真菌。结论目标化合物对白色念珠菌均显示有较强的体外抗真菌活性,化合物1具有广谱、高活性的优点,值得进一步结构优化。OBJECTIVE To synthesize a series of triazole antifungals and to search for novel triazole antiftmgals with more potent activity, less toxicity and broader spectrum. METHODS N-[2-（2,4-Diflurophenyl）-2-hydroxy-3-（ 1H-1,2,4-Triazol-1-yl）propyl]-N＇-（4-substituted phenyl） -3-（2H,4H）-1,2,4-triazolones were designed and synthesized, on the basis of the three dimensional structure of P450 cytochrome 14α-sterol demethylase（ CYP51 ）.Their antifungal activities were also evaluated. RESULTS The results of preliminary biological tests showed that all compounds exhibited activity against the eight common pathogenic fungi and the activities against deep fungi were higher than that against shallow fungi. CONCLUSION All the title compounds show high antifungal activity against Candida Albicans. Compound 1 show optimum antifungal activity with broad antifungal spectrum and are chosen for further structural optimization.

关 键 词：三唑类 合成 抗真菌活性 

分 类 号：R914.5[医药卫生—药物化学]