Optically active antifungal azoles. X. Synthesis and antifungal activity of N-[4-(azolyl)phenyl]- and N-[4-(azolylmethyl)phenyl]-N′-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy -1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-azolones

Abstract

New optically active antifungal azoles, N-[4-(azolyl)phenyl]- and N-[4-(azolylmethyl)phenyl]-N′-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy -1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]azolones (1, 2, 3), were prepared in a stereocontrolled manner. Compounds 1-3 showed strong antifungal activity against Candida albicans in vitro. Among them, the imidazolidinones 3 showed a broad antifungal spectrum in vitro as well as potent in vivo activity against candidiasis and aspergillosis in mice. The imidazolidinones (3i, j, k) having 1H-1,2,3-triazol-1-yl, 2H-2-tetrazolyl and 1H-1-tetrazolyl moieties were found to exert strong protective effect against aspergillosis.