Substituted 6-(1-pyrrolidine)quinolin-2(1H)-ones as novel selective androgen receptor modulators

  • J Med Chem. 2007 Oct 18;50(21):5049-52. doi: 10.1021/jm070231h.
Esther Martinborough  1 ,  Yixing Shen ,  Arjan van Oeveren ,  Yun Oliver Long ,  Thomas L S Lau ,  Keith B Marschke ,  William Y Chang ,  Francisco J López ,  Eric G Vajda ,  Peter J Rix ,  O Humberto Viveros ,  Andrés Negro-Vilar ,  Lin Zhi
Affiliations
  • 1. Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, California 92121, USA.
PMID: 17887661 DOI: 10.1021/jm070231h
Abstract

The Androgen Receptor is a ligand inducible transcription factor that is involved in a broad range of physiological functions. Here we describe the discovery of a new class of orally available selective Androgen Receptor modulators. The lead compound, 6-[(2R,5R)-2-methyl-5-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl]-4-trifluoromethylquinolin-2(1H)-one (6a), showed excellent anabolic activity in muscle with reduced effect on the prostate in a rat model of hypogonadism. The compound also improved bone strength in a rat model of post-menopausal Osteoporosis.

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