Synthesis and antifungal activity of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-substituted acyl piperazin-1-yl)-2-propanols

Objective: To study the effect of fluconzole derivatives from a side chain containing 4-substituted acyl piperazin-1-yl on antifungal activity. Methods: Fourteen title compounds were synthesized and confirmed by the elementary analysis, 1HNMR and IR spectra. Five deep fungal strains and 3 shallow fungal strains were chosen as the experimental strains.Minimum inhibitory concentrations(MICs) of all title compounds were determined by the method recommended by the National Committee for Clinical Laboratory Standards (NCCLS) using RPMI 1640 test medium. Results: Among the 14 title compounds, 12 were first reported. The results of preliminary antifungal test showed that all the title compounds exhibited potent antifungal activities to a certain extent. The activity of 4 compounds were more than 4 times as high as that of fluconazole and equal to that of ketoconazole against Candida albicans in vitro(MIC 80 value≤0.125 μg/ml). Conclusion: Introduction of a side chain containing 4-substituted acyl piperazin-1-yl into the main part of fluconazole has important influence on antifungal activities of title compounds.