Synthesis and biological evaluation of amino-pyridines as androgen receptor antagonists for stimulating hair growth and reducing sebum production

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5693-7. doi: 10.1016/j.bmcl.2007.07.059. Epub 2007 Aug 19.

Abstract

A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, (R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.

MeSH terms

  • Aminopyridines / chemical synthesis
  • Aminopyridines / chemistry*
  • Aminopyridines / pharmacology*
  • Androgen Receptor Antagonists*
  • Animals
  • Dose-Response Relationship, Drug
  • Hair / drug effects*
  • Hair / growth & development*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Models, Molecular
  • Molecular Structure
  • Receptors, Androgen / metabolism
  • Sebum / drug effects*
  • Sebum / metabolism*
  • Structure-Activity Relationship

Substances

  • Aminopyridines
  • Androgen Receptor Antagonists
  • Receptors, Androgen