Carbon analogs of antifungal dioxane-triazole derivatives: Synthesis and in vitro activities

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 24; pp. 6538 - 6541
• Main Authors: Uchida, Takuya, Somada, Atsushi, Kagoshima, Yoshiko, Konosu, Toshiyuki, Oida, Sadao
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.12.2008; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Aspergillus; Biological and medical sciences; Candida; Carbon - chemistry; Chemistry, Pharmaceutical - methods; Cryptococcus; Dioxanes - chemistry; Drug Design; Epoxy Compounds - chemistry; Fluconazole - chemical synthesis; Fluconazole - pharmacology; Grignard reaction; Humans; In Vitro Techniques; Itraconazole - chemical synthesis; Itraconazole - pharmacology; Medical sciences; Microbial Sensitivity Tests; Models, Chemical; Pharmacology. Drug treatments; Stereoisomerism; Triazole; Triazoles - chemistry; Triazole; Grignard reaction; Antifungal; Dioxane derivatives; Fluconazole; Alcohol; In vitro; Biological activity; Fungi; Aspergillus; Antifungal agent; Butanol derivatives; Candida; Triazole derivatives; Fungi Imperfecti; Fluorine Organic compounds; Chemical synthesis; Ethylenic compound; Itraconazole
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.10.055

Stereoselective synthesis and in vitro antifungal activities of a novel series of triazole antifungal agents wherein the sulfur atom was replaced by a carbon atom are described. A new series of triazole compounds possessing a carbon atom in place of a sulfur atom were efficiently synthesized and their in vitro antifungal activities were investigated. The carbon analogs showed excellent in vitro activity against Candida, Cryptococcus, and Aspergillus species. The MICs of compound 1c against C. albicans ATCC24433, C. neoformans TIMM1855, and A. fumigatus ATCC26430 were 0.016, 0.016, and 0.125 μg/mL, respectively (MICs of fluconazole: 0.5, >4, and >4 μg/mL; MICs of itraconazole: 0.125, 0.25, and 0.25 μg/mL).