155432-64-7Relevant articles and documents
Optically active antifungal azoles. IX. An alternative synthetic route for 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol- 1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-3(2H,4H)1,2,4- triazolone and its analogs
Kitazaki, Tomoyuki,Tasaka, Akihiro,Hosono, Hiroshi,Matsushita, Yoshihiro,Itoh, Katsumi
, p. 360 - 368 (2007/10/03)
A new route for the synthesis of the optically active antifungal azole TAK-187, 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4- triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluoroptopoxy)phenyl]3(2H,4H)-1,2,4- triazolone, was established. The key synthetic intermediate, 2-[(1R)-2-(2,4- difluorophenyl)-2-oxo-1-methylethyl]-4-[4-(2,2,3,3- tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (8), was prepared starting from the esters (11a, b) of (S)-lactic acid in a stereocontrolled manner. This optically active propiophenone derivative 8 was converted to the one carbon-elongated (1R,2S)-diol 7, which was then reacted with 1H-1,2,4- triazole to yield TAK-187. This newly developed route was applied to the synthesis of the analogs (25a, b - 28a, b) containing an imidazolone or imidazolidinone nucleus.
Optically active antifungal azoles. VII. Synthesis and antifungal activity of stereoisomers of 2-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1- methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-[4-(2,2,3,3- tetrafluoropropoxy)phenyl]-3(2H,4H)-1,2,4-triazolone (TAK-187)
Tasaka, Akihiro,Kitazaki, Tomoyuki,Tsuchimori, Noboru,Matsushita, Yoshihiro,Hayashi, Ryogo,Okonogi, Kenji,Itoh, Katsumi
, p. 321 - 326 (2007/10/03)
2-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4- triazol-1-yl)propyl]-4-[4-(2,2,3,3-tetrafluopropoxy)phenyl]-3(2H,4H)-1,2,4- triazolone [(1R,2R)-1: TAK-187] is a new antifungal agent selected as a candidate for clinical trials. The three stereoisomers [(1S,2S)-, (1R,2S)- and (1S,2R)-1] of this compound were prepared to clarify the relationship between the stereochemistry and the biological activities. In vitro and in vivo assays of antifungal activity revealed TAK-187 [(1R,2R)-1] is the most potent among the four stereoisomers. Furthermore, TAK-187 was found to exert a strong and selective inhibitory effect on the sterol synthesis in Candida albicans as compared with that in rat liver.
Optically active azole derivatives, their production and use
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, (2008/06/13)
A process for preparing a compound of the formula (IV) or a salt thereof, , wherein R1 is an optionally substituted aliphatic or aromatic hydrocarbon residue or an optionally substituted aromatic heterocyclic group, one of Y and Z is a nitrogen atom and t