3-取代三唑醇类化合物的合成及抗真菌活性  

Synthesis and the antifungal activities of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted group-2-propanols

作　　者：刘超美[1] 徐帆[1] 梁爽[1] 孙青龑[1] 姜元英[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《中国药物化学杂志》2004年第3期129-133,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金资助项目 (30 2 715 4 2 ) ;全军医药卫生科研基金资助项目 (0 1MA15 6 )

摘　　要：目的设计合成 1 (1H 1,2 ,4 三唑 1 基 ) 2 (2 ,4 二氟苯基 ) 3 烷氧基苯基哌嗪 2 丙醇和 1 (1H 1,2 ,4 三唑 1 基 ) 2 (2 ,4 二氟苯基 ) 3 取代硫醚 2 丙醇化合物 ,并进行体外抗真菌活性测试。方法以间二氟苯为起始原料 ,经多步反应 ,得到中间体环氧化物甲烷磺酸盐 ,再与各种烷氧基苯基哌嗪和取代硫醇开环得到目标化合物 ,按国际标准抗真菌敏感性实验方法测定其体外抗真菌活性。结果共合成 12个 (其中 11个为新化合物 )目标化合物 ,经元素分析 ,1H NMR和IR确证结构 ,其中 4个化合物的抗真菌活性强于对照品氟康唑和酮康唑。Aim To design and synthesize 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-alkyloxyphenylpiperazin-1-yl)-2-propanols and 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted sulfur ether-2-propanols and investigate their antifungal activities in vitro.Methods The desired compounds were synthesized through the reaction of the intermediate epoxide and 4-alkyloxyphenylpiperazines or substituted sulfur alcohols and confirmed by the elementary analysis,~1H-NMR and IR spectra.MIC_(80) of all the title compounds were determined by the method recommended by the National Committee for Clinical Laboratory Standards(NCCLS)using the RPMI1640 test medium.Results Twelve compounds were synthesized.The results of the preliminary antifungal test showed that all the title compounds exhibited potent antifungal activities to a certain extent.The antifungal activity of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-alkyloxyphenylpiperazin-1-yl)-2-propanols was more potent than that of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted sulfur ether-2-propanols in vitro.Conclusion The antifungal activities of the four compounds in 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-alkyloxyphenylpiperazin-1-yl)-2-propanols are more potent than that of fluconazole or equal to that of ketoconazole in vitro.

关 键 词：药物化学 制备 化学合成 哌嗪 三唑醇 抗真菌活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]