叔丁基三唑衍生物的合成及抗真菌活性研究

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

目的研究具有叔丁基结构的三唑醇类化合物的抗真菌活性以及各种4-(4-烷氧基苯基)哌嗪侧链的引入对抗真菌活性的影响。方法以一氯频那酮、三氮唑为原料,经多步反应合成目标化合物,化合物结构经IR1、H-NMR谱确证;选择8种真菌为实验菌株,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。结果设计合成了10个新化合物。10个目标化合物对8种真菌均具有一定的抑制活性,其中,有4个化合物对白色念珠菌的MIC80值小于或等于0.125 mg.L-1,是氟康唑的4倍以上,与伊曲康唑相当。结论可以通过引入更多的疏水基团设计三唑醇类化合物,立体化学因素对该类化合物的体外抑菌活性有较大影响。

Aim To study antifungal activity of the triazole derivatives bearing the side chain containing tertbutyl and 4-（4-alkyloxyphenyl）-piperazin-l-yl and to compare their antifungal activities with that of fluconazole and itraconazole. Methods According to the structure of fluconazole, ten target compounds were designed and synthesized. All of them were confirmed by ^1H-NMR and IR spectra respectively. The MIC80 of all the target compounds were determined by the method recommended by the national committee for clinical laboratory standards （NCCLS） using the RPMI-1640 test medium. Results All the target compounds were firstly reported. The results of the preliminary antifungal test show that all the target compounds exhibit potent antifungal activities to a certain extent. The activities of four target compounds are 4 times as high as that of fluconazole and equal to that of itraconazole against Candida albicans in vitro. Conclusion More hydrophobic groups can be introduced to design triazole compounds and stereochemistry have important influence on the antifungal activities of the target compounds.