Optically active antifungal azoles. IV. Synthesis and antifungal activity of (2R,3R)-3-azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanols.
(2R,3R)-3-Azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanols (III) were prepared from (2R,3S)-3-methyl-2-(substituted phenyl)-2-(1H-1,2,4-triazol-1-yl)methyloxiranes (21a-f) by a ring-opening reaction with 1H-1,2,3-triazole and 1H-tetrazole and evaluated for antifungal activity against Candida albicans in vitro and in vivo. The optically active oxiranes (21a--f) which serve as the key synthetic intermediates, were synthesized from 1-[(2R)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxypropanoyl]morpholin e (24) and substituted phenylmagnesium bromide (23) via six steps in a stereocontrolled manner. The 3-(1H-1,2,3,-triazol-1-yl)-(IIIa) and 3-(2H-2-tetrazolyl)-2-butanol (IIId) derivatives showed strong protective effects against candidosis in mice.
Tasaka
A
A
Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan.
Tamura
N
N
Matsushita
Y
Y
Kitazaki
T
T
Hayashi
R
R
Okonogi
K
K
Itoh
K
K
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D000440:Butanols / Q000138:chemical synthesis* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001393:Azoles; D000440:Butanols