1-(1H-1,2,4-三唑-1-基)-(2,4-二氟苯基)-3-取代-2-丙醇类化合物的合成及其抗真菌活性

目的研究不同取代哌啶和环仲胺侧链的引入对三唑醇类化合物抗真菌活性的影响。方法以氟康唑为先导化合物,设计合成了9个三唑醇类新化合物,化合物的结构均通过核磁、红外光谱确证;选择8种真菌为实验菌株,根据美国国家临床实验室标准委员会(NCCLS)推荐的标准化抗真菌敏感性实验方法,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作用,其中化合物4、5对白色念珠菌的MIC80值小于或等于0.125μg.mL-1,是氟康唑活性的4倍以上,与伊曲康唑活性相当。结论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 antifungal activities of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)- 3-[(4-substituted-piperazine)-1-yl]-2-propanols

Aim To study the effect of the triazole derivatives with the side chain containing(4-substituted-piperidine)-1-yl or second amine on the antifungal activity of triazole compounds.Methods Nine title compounds were synthesized and determined 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 RPMI 1640 test medium.Results All of the title compounds displayed potent antifungal activities to some extent.The activity of the two compounds 4,5 were more than 4 times as high as that of fluconazole and itraconazole against Candida albicans in vitro.Conclusion The stereochemistry has important influence on the antifungal activities of the title compounds.