Resolution of the nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'- (trifluoromethyl)-propionanilide and the determination of the absolute configuration of the active enantiomer.
The nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2- hydroxy-2-methyl-3'-(trifluoromethyl)-propionanilide (1) (ICI 176334) has been resolved by chromatographic separation of the diastereomeric (R)-camphanyl esters of the precursor thioether 2 followed by hydrolysis and oxidation of the isolated enantiomers. In addition, an asymmetric synthesis of (S)-3-bromo-2-hydroxy-2-methylpropanoic acid (11) and subsequent conversion into the (S)-sulfone 6a has established that the more potent enantiomer of 1 has the R absolute configuration.
Tucker
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Imperial Chemical Industries PLC, Pharmaceuticals Division, Macclesfield, Cheshire.
Chesterson
G J
GJ
D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D008297:Male; D009570:Nitriles; D051381:Rats; D012669:Seminal Vesicles / Q000187:drug effects; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide