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

Article Details

Citation

Martinborough E, Shen Y, Oeveren Av, Long YO, Lau TL, Marschke KB, Chang WY, Lopez FJ, Vajda EG, Rix PJ, Viveros OH, Negro-Vilar A, Zhi L

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

J Med Chem. 2007 Oct 18;50(21):5049-52. Epub 2007 Sep 21.

PubMed ID
17887661 [ View in PubMed
]
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-trif luoromethylquinolin-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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
BicalutamideAndrogen receptorKi (nM)707.437Details
BicalutamideAndrogen receptorIC 50 (nM)1287.437Details
LGD-2226Androgen receptorKi (nM)4.67.437Details
LGD-2226Androgen receptorEC 50 (nM)0.27.437Details
LGD2941Androgen receptorKi (nM)1.57.437Details
LGD2941Androgen receptorEC 50 (nM)7.17.437Details
StanoloneAndrogen receptorKi (nM)0.27.437Details
StanoloneAndrogen receptorEC 50 (nM)5.17.437Details