Synthesis and Antifungal Activity of Novel Thiazole-Containing Triazole Antifungals

Abstract

A new series of thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. Among these compounds, (±)-1-(2, 4-difluorophenyl)-1-[4-(2, 4-difluorophenyl)thiazol-2-yl]-2-(1H-1, 2, 4-triazol-1-yl)ethanol (ER-24161) showed the most potent and well-balanced in vitro activities and excellent in vivo efficacy. We also achieved an enantioselective synthesis of the more potent enantiomer of ER-24161.