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

J Med Chem. 1988 Apr;31(4):885-7. doi: 10.1021/jm00399a034.

Abstract

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.

MeSH terms

  • Androgen Antagonists* / pharmacology
  • Anilides* / pharmacology
  • Animals
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Isomerism
  • Male
  • Nitriles
  • Rats
  • Seminal Vesicles / drug effects
  • Tosyl Compounds

Substances

  • Androgen Antagonists
  • Anilides
  • Nitriles
  • Tosyl Compounds
  • bicalutamide