Design and synthesis of an array of selective androgen receptor modulators

J Comb Chem. 2007 Jan-Feb;9(1):107-14. doi: 10.1021/cc060096e.

Abstract

We describe the design, using shape comparison and fast docking computer algorithms, and rapid parallel synthesis of a 1300 member array based on GSK7721, a 4-aminobenzonitrile androgen receptor (AR) antagonist identified by focused screening of the GSK compound collection. The array yielded 352 submicromolar and 17 subnanomolar AR agonists as measured by a cell-based reporter gene functional assay. The rapid synthesis of a large number of active compounds provided valuable information in the optimization of AR modulators, which may be useful in treating androgen deficiency in aging males.

MeSH terms

  • Algorithms
  • Androgen Receptor Antagonists*
  • Androgens
  • Animals
  • Cell Line
  • Combinatorial Chemistry Techniques / methods*
  • Drug Design
  • Haplorhini
  • Magnetic Resonance Spectroscopy
  • Nitriles / chemical synthesis*
  • Nitriles / chemistry
  • Nitriles / pharmacology*
  • Spectrometry, Mass, Fast Atom Bombardment
  • Structure-Activity Relationship

Substances

  • Androgen Receptor Antagonists
  • Androgens
  • Nitriles
  • 4-aminobenzonitrile