N-aryl-oxazolidin-2-imine muscle selective androgen receptor modulators enhance potency through pharmacophore reorientation

J Med Chem. 2009 May 14;52(9):2794-8. doi: 10.1021/jm801583j.

Abstract

A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

MeSH terms

  • Androgens*
  • Animals
  • Crystallography, X-Ray
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Models, Molecular
  • Molecular Conformation
  • Muscles / drug effects*
  • Muscles / metabolism*
  • Oxazoles / chemistry*
  • Oxazoles / pharmacology*
  • Prostate / drug effects
  • Prostate / metabolism
  • Rats
  • Substrate Specificity

Substances

  • Androgens
  • Oxazoles
  • oxazolidine

Associated data

  • PDB/3G0W