Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives

Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11-13 under acidi c conditions afforded a series of diorane-triazole compounds 14-6. The anti fungal activities of the compounds 14-16 were evaluated in vivo in mice inf ection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ri ng substituted with an electron-withdrawing group in the side chain, Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) sh owed excellent in vivo activities against Canndida, Aspergillus and Cryptoc occus species. It also showed high tolerance in a preliminary toxicity stud y in rats.