Synthesis and Antifungal Activity of Novel Thiazole-Containing Triazole Antifungals. II. Optically Active ER-30346 and Its Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 46; no. 4; pp. 623 - 630
• Main Authors: TSURUOKA, Akihiko, KAKU, Yumiko, KAKINUMA, Hiroyuki, TSUKADA, Itaru, YANAGISAWA, Manabu, NARA, Kazumasa, NAITO, Toshihiko
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.04.1998; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Biological and medical sciences; Candida; Candidiasis - drug therapy; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Culture Media; ER-30346; Fungi - drug effects; Life Sciences & Biomedicine; Medical sciences; Mice; Microbial Sensitivity Tests; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Science & Technology; Stereoisomerism; Structure-Activity Relationship; thiazole-containing triazole antifungal; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; AZOLES; thiazole-containing triazole antifungal; ORAL TRIAZOLE; CANDIDA-ALBICANS; ER-30346; RESISTANCE; AGENTS; antifungal activity; FLUCONAZOLE; Candida albicans; Candidiasis; Nitrile; Mycosis; Cryptococcus neoformans; Nitrogen heterocycle; Thiazole derivatives; Fungi; Antifungal agent; Structure activity relation; Fungi Imperfecti; Chemical synthesis; Thallophyta; Sulfur nitrogen heterocycle; Haloalcohol; Rodentia; Candida glabrata; In vitro; Infection; In vivo; Vertebrata; Mammalia; Mouse; Animal; Triazole derivatives; Fluorine Organic compounds; Aspergillus fumigatus
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.46.623

A series of novel 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. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R, 3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2, 4-difluorophenyl)-1-(1H-1, 2, 4-triazol-1-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.