Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents

A series of azolylmethyloxolane derivatives with modified sterol side-chain structures, designed as potential dual functional inhibitors of cytochrome P450 14 alpha-demethylase (14DM) and Delta(24)-sterol methyltransferase (2 4-SMT) based on the common characteristic features of 24-aminosterols and a zole antifungal agents, were synthesized and evaluated for their antifungal activities and inhibitory activities of 14DM and 24-SMT. Among these compo unds, imidazolylmethyloxolane derivatives 28a and 28b showed potent in vitr o antifungal activities comparable to those of itraconazole. However, the i n vitro bioactivities have not been linearly translated into in vivo protec tion data for some unknown reasons. (C) 2000 Elsevier Science Ltd. All righ ts reserved.