Optically active antifungal azoles. X. Synthesis and antifungal activity of N.
New optically active antifungal azoles, N-14-(azolyl)phenyl]- and N-14-(azolylmethyl)phenyl]-N'-[(IR,2R)-2(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(IH-1,2,4-triazol-1-yl)propyllazolones (1, 2, 3), were prepared in a stereocontrolled manner. Compounds 1-3 showed strong antifungal activity against Candida albicans in vitro. Among them, the imidazolidinones 3 showed a broad antifungal spectrum in vitro as well as potent in vivo activity against candidiasis and aspergillosis in mice. The imidazolidinones (3i, j, k) having 1H-1,2,3-triazol-1-yl, 2H-2-tetrazolyl and IH-1-tetrazolyl moieties were found to exert strong protective effect against aspergillosis.
Kitazaki
T
T
Discovery Research Laboratories V, Pharmaceutical Discovery Research Division Takeda Chemical Industries, Ltd, Osaka, Japan.
Ichikawa
T
T
Tasaka
A
A
Hosono
H
H
Matsushita
Y
Y
Hayashi
R
R
Okonogi
K
K
Itoh
K
K
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001393:Azoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation
D000935:Antifungal Agents; D001393:Azoles