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Substituted 6-(1-Pyrrolidine)quinolin-2(1H)-ones as Novel Selective Androgen Receptor Modulators

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journal contribution
posted on 18.10.2007, 00:00 by Esther Martinborough, 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
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.