Synthesis and antifungal activity of novel thiazole-containing triazole antifungals.
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 (ER24161) 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.
Tsuruoka
A
A
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Kaku
Y
Y
Kakinuma
H
H
Tsukada
I
I
Yanagisawa
M
M
Naito
T
T
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects; D002175:Candida / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
D000935:Antifungal Agents; D013844:Thiazoles; D014230:Triazoles