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Abstract: A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure–activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS and 1H NMR. Results of preliminary antifungal tests against eight human pathogenic fungi (Candida albicans, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans, Aspergillus fumigatus, Trichophyton rubrum, Fonsecaea compacta, and Microsporum gypseum) in vitro showed that all title compounds exhibited activity against fungi tested to some extent. Among the compounds tested, all compounds showed higher activity against C. albicans than fluconazole in vitro. Compounds 3, 6–8, 28, 29, and 32 exhibited the same activities against C. albicans as voriconazole (with the MIC value of 0.0152μg/mL). Compounds 3, 6, and 7 showed higher activity against C. parapsilosis than all five positive controls. [Copyright &y& Elsevier]

Abstract: A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and synthesized on the basis of the structure–activity relationships and antimycotic mechanism of azole antifungal agents. Their structures were confirmed by elemental analysis, IR, MS, 1H NMR and 13C NMR. Results of preliminary antifungal tests against six human pathogenic fungi (Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Candida tropicalis, inherently fluconazole-resistant Candida krusei, Candida glabrata) in vitro showed that all title compounds exhibited activity against fungi tested to some extent except against C. tropicalis. Compound 5b showed higher activity against C. albicans, C. parapsilosis and C. krusei than fluconazole, and its MIC values were determined to be 0.5μg/mL, 1μg/mL and 4μg/mL, respectively. Compound 5k showed higher activities against Torulopsis glabrata than fluconazole (with the MIC value of 2μg/mL). Compounds 5a, 5c, 5f, 5g, 5i exhibited higher activities against C. parapsilosis than fluconazole (with the MIC values of 2μg/mL, 2μg/mL, 2μg/mL, 1μg/mL and 2μg/mL, respectively). [Copyright &y& Elsevier]