title: Optically active antifungal azoles. VIII. Synthesis and antifungal activity of 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]- 3-(4-substituted phenyl)-2(1H,3H)-imidazolones and 2-imidazolidinones.
abstract: New optically active antifungal azoles, 1-[(1R,2R)-2-(2,4-difluoro- and 2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl ]-3-(4- substituted phenyl)-2(1H,3H)-imidazolones (1,2) and 2-imidazolidinones (3,4), were prepared in a stereocontrolled manner from (1S)-1-[(2R)-2-(2,4- difluoro- and 2-fluorophenyl)-2-oxiranyl]ethanols (15, 16). Compounds 1-4 showed potent antifungal activity against Candida albicans in vitro and in vivo, as well as a broad antifungal spectrum for various fungi in vitro. Furthermore, the imidazolidinones, 3b--e and 4d, e, were found to exert extremely strong growth-inhibitory activity against Aspergillus fumigatus.
authors.affiliation: Medicinal Chemistry Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kitazaki
authors.forename: A
authors.initials: A
authors.lastname: Tasaka
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
authors.forename: H
authors.initials: H
authors.lastname: Hosono
authors.forename: R
authors.initials: R
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Okonogi
authors.forename: K
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D003455:Cryptococcus neoformans / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D014230:Triazoles