Synthesis and in Vitro Antifungal Activities of Novel Triazole Antifungal Agent CS-758

• Published in: Chemical & pharmaceutical bulletin Vol. 49; no. 12; pp. 1647 - 1650
• Main Authors: KONOSU, Toshiyuki, OIDA, Sadao, NAKAMURA, Yoshie, SEKI, Shinobu, UCHIDA, Takuya, SOMADA, Atsushi, MORI, Makoto, HARADA, Yoshiko, KAMAI, Yasuki, HARASAKI, Tamako, FUKUOKA, Takashi, OHYA, Satoshi, YASUDA, Hiroshi, SHIBAYAMA, Takahiro, INOUE, Shin-ichi, NAKAGAWA, Akihiko, SETA, Yasuo
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.12.2001; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; antifungal; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Biological and medical sciences; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; CS-758; Fluconazole - pharmacology; Fungi - drug effects; Horner-Wadsworth-Emmons reaction; Indicators and Reagents; Itraconazole - pharmacology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; Microbial Sensitivity Tests; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; R-120758; Science & Technology; triazole; Triazoles - chemical synthesis; Triazoles - pharmacology; Homer-Wadsworth-Emmons reaction; antifungal; R-120758; CS-758; triazole; Candida albicans; Wittig reaction; Organic hydroxysulfide; Aspergillus flavus; Nitrile; Cryptococcus neoformans; Nitrogen heterocycle; Benzene derivatives; Oxygen heterocycle; In vitro; Fungi; Stereoselectivity; Antifungal agent; Structure activity relation; Trans stereoisomer; Conjugated dienic compound; Triazole derivatives; Fluorine Organic compounds; Fungi Imperfecti; Secondary alcohol; Aspergillus fumigatus; Chemical synthesis; Thallophyta
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.49.1647

Synthesis and in vitro antifungal activities of a novel triazole antifungal agent CS-758 (former name, R-120758) are described. The minimum inhibitory concentrations (MICs) of a series of dioxane-triazole compounds related to R-102557 were examined. Variation of the length of the chain between the dioxane ring and the phenyl ring revealed that the linkage with two double bonds is the most preferable. When a cyano group was introduced to the C4 position on the benzene ring, MICs improved further. A fluorine atom was introduced to obtain CS-758. The MICs of CS-758 surpassed those of fluconazole and itraconazole against Candida, Aspergillus and Cryptococcus species. The precursor (E,E)-aldehyde was synthesized stereoselectively from 3-fluoro-4-methylbenzonitrile using the Horner-Wadsworth-Emmons reaction.