1-(1H-1,2,4-三唑-1-基)-2-(2,4-二氟苯基)-3-[(4-取代)-哌嗪-1-基]-2-丙醇的合成及其抗真菌活性

目的研究不同取代哌嗪侧链的引入对三唑醇类化合物抗真菌活性的影响.方法设计合成了13个三唑醇类新化合物;选择8种真菌为实验菌株,进行体外抑菌活性测试.结果目标化合物对8种真菌特别是深部真菌均有一定的抑制活性,其中有8个化合物对白色念珠菌的MIC80值小于或等于0.125μg/mL,是氟康唑活性的4倍以上,与酮康唑活性相当.结论脂水分配系数和立体化学因素的改变对该类化合物体外抑菌活性有较大影响.

Synthesis and the antifungal activity of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted)-piperazine-1-yl]-2-propanols

Aim To study the effect of the fluconzole derivatives from introducing the side chain containing(4-substituted)-piperazine-1-yl on the antifungal activity of fluconzole compounds.Methods Thirteen title compounds were synthesized and confirmed by the elementary analysis, 1H-NMR and IR spectra.The MICs 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 All of the title compounds were firstly reported.The results of the preliminary antifungal test showed that all the title compounds exhibited potent antifungal activities to a certain extent.The activity of the eight compounds were more than 4 times as high as that of fluconazole and equal to that of ketoconazole against Candida albicans in vitro.Conclusion The lipid/water distribution coefficient and stereochemistry have important influence on the antifungal activities of the title compounds.