title: Optically active antifungal azoles. VI. Synthesis and antifungal activity of N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazo l-1- yl)propyl]-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones and 5(1H,4H)-tetrazolones.
abstract: A new series of optically active antifungal azoles, N-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-tria zol-1- yl)propyl]-N'-(4-substituted phenyl)-3(2H,4H)-1,2,4-triazolones (1,2) and 5(1H,4H)-tetrazolones (3), were prepared from the triflate derivative of (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol (13) by an SN2 displacement reaction with the anion of an azolone (17-19) and subsequent ring-opening reaction with 1H-1,2,4-triazole. The optically active oxiranylethanol 13 was synthesized from methyl (R)-lactate in a stereo-controlled manner. The azolones 1-3 prepared showed potent antifungal activities in vitro and in vivo.
authors.affiliation: Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kitazaki
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.forename: A
authors.initials: A
authors.lastname: Tasaka
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
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: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013237:Stereoisomerism; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D013777:Tetrazoles; D014230:Triazoles