Synthesis and antifungal activities of (2R,3R)-2-aryl-1-azolyl-3-(substituted amino)-2-butanol derivatives as topical antifungal agents.

2-Aryl-1-azolyl-3-(substituted amino)-2-butanol derivatives I were prepared by ring-opening reaction of epoxides II with excess amine, and their antifungal activities were evaluated as topical agents. Azolyl-cyclic amine derivatives with a methylene group showed extremely strong activity with a broad spectrum in vitro. In general, anti-Trichophyton mentagrophytes activities of most of the topical antifungal agents are substantially reduced by addition of keratin (a major constituent of the keratinized tissue). However, the triazole derivative (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidino)-1-(1H-1,2 ,4- triazol-1-yl)-2-butanol ((-)-40, KP-103) showed very little deactivation by addition of keratin. This biological characteristic of triazole derivative (-)-40 resulted in excellent therapeutic efficacy on dermatophytosis superior to that of the corresponding imidazole derivative ((-)-41).