3-取代三唑醇类化合物的合成及抗真菌活性

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.结论含烷氧苯基哌嗪侧链的三唑醇类化合物具有较强的抗真菌活性.

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

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.