Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11-13 under acidic conditions afforded a series of dioxane-triazole compounds 14-16. The antifungal activities of the compounds 14-16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.

New triazole compounds were designed and synthesized as potential inhibitors of the fungal cytochrome P-450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (2R,3R)-3-acylamino-2-aryl-2-butanol derivatives III exhibited remarkably high efficacy after oral or parenteral administration. The structure-activity relationships of these amidoalcohols were evaluated.

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