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.
Lain-Yen Hu  1 ,  Huangshu John Lei ,  Daniel Du ,  Theodore R Johnson ,  Victor Fedij ,  Catherine Kostlan ,  Wen Song Yue ,  Mark Lovdahl ,  Jie Jack Li ,  Mathew Carroll ,  Danielle Dettling ,  Jeffrey Asbill ,  Conglin Fan ,  Kimberly Wade ,  David Pocalyko ,  Kimberly Lapham ,  Radhika Yalamanchili ,  Brian Samas ,  Derek Vrieze ,  Susan Ciotti ,  Teresa Krieger-Burke ,  Drago Sliskovic ,  Howard Welgus
Affiliations
  • 1. Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. [email protected]
PMID: 17766112 DOI: 10.1016/j.bmcl.2007.07.059
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.