title: Novel selective androgen receptor modulators: SAR studies on 6-bisalkylamino-2-quinolinones.
abstract: A series of selective androgen receptor modulators (SARMs) with a wide spectrum of receptor modulating activities was developed based on optimization of the 4-substituted 6-bisalkylamino-2-quinolinones (3). Significance of the trifluoromethyl group on the side chains and its interactions with amino acid residues within the androgen receptor (AR) ligand binding domain are discussed. A representative analog (9) was tested orally in a rodent model of hypogonadism and demonstrated desirable tissue selectivity.
authors.affiliation: Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Arjan
authors.initials: A
authors.lastname: van Oeveren
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Motamedi
authors.forename: Esther
authors.initials: E
authors.lastname: Martinborough
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhao
authors.forename: Yixing
authors.initials: Y
authors.lastname: Shen
authors.forename: Sarah
authors.initials: S
authors.lastname: West
authors.forename: William
authors.initials: W
authors.lastname: Chang
authors.forename: Adam
authors.initials: A
authors.lastname: Kallel
authors.forename: Keith B
authors.initials: KB
authors.lastname: Marschke
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López
authors.forename: Andrés
authors.initials: A
authors.lastname: Negro-Vilar
authors.forename: Lin
authors.initials: L
authors.lastname: Zhi
mesh_terms: D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005837:Genitalia, Male / Q000187:drug effects; D007006:Hypogonadism / Q000188:drug therapy; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D011467:Prostate / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry*; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D007202:Indicators and Reagents; D011804:Quinolines; D011944:Receptors, Androgen; D013196:Dihydrotestosterone