title: Synthesis and antifungal activities of R-102557 and related dioxane-triazole derivatives.
abstract: Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11-13 under acidic conditions afforded a series of dioxane-triazole compounds 14-16. The antifungal activities of the compounds 14-16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Oida
authors.forename: Y
authors.initials: Y
authors.lastname: Tajima
authors.forename: T
authors.initials: T
authors.lastname: Konosu
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Somada
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Habuki
authors.forename: T
authors.initials: T
authors.lastname: Harasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kamai
authors.forename: T
authors.initials: T
authors.lastname: Fukuoka
authors.forename: S
authors.initials: S
authors.lastname: Ohya
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001231:Aspergillus flavus; D001232:Aspergillus fumigatus; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans; D004146:Dioxanes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013058:Mass Spectrometry; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D011916:Rats, Inbred F344; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D004146:Dioxanes; C413251:R 102557; D014230:Triazoles