title: Substituted 6-(1-pyrrolidine)quinolin-2(1H)-ones as novel selective androgen receptor modulators.
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.
authors: Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, California 92121, USA.
authors: Esther
authors: E
authors: Martinborough
authors: Yixing
authors: Y
authors: Shen
authors: Arjan van
authors: Av
authors: Oeveren
authors: Yun Oliver
authors: YO
authors: Long
authors: Thomas L S
authors: TL
authors: Lau
authors: Keith B
authors: KB
authors: Marschke
authors: William Y
authors: WY
authors: Chang
authors: Francisco J
authors: FJ
authors: López
authors: Eric G
authors: EG
authors: Vajda
authors: Peter J
authors: PJ
authors: Rix
authors: O Humberto
authors: OH
authors: Viveros
authors: Andrés
authors: A
authors: Negro-Vilar
authors: Lin
authors: L
authors: Zhi
mesh_terms: D000284:Administration, Oral; D045930:Anabolic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D011467:Prostate / Q000187:drug effects; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C524268:6-(2-methyl-5-(2,2,2-trifluoro-1-hydroxyethyl)pyrrolidin-1-yl)-4-trifluoromethylquinolin-2(1H)-one; D045930:Anabolic Agents; D059002:Androgen Receptor Antagonists; D000728:Androgens; D050071:Bone Density Conservation Agents; D011759:Pyrrolidines; D011804:Quinolines; D015363:Quinolones