Novel selective androgen receptor modulators: SAR studies on 6-bisalkylamino-2-quinolinones.
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.
van Oeveren
Arjan
A
Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA.
Motamedi
Mehrnoush
M
Martinborough
Esther
E
Zhao
Shuo
S
Shen
Yixing
Y
West
Sarah
S
Chang
William
W
Kallel
Adam
A
Marschke
Keith B
KB
López
Francisco J
FJ
Negro-Vilar
Andrés
A
Zhi
Lin
L
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
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D007202:Indicators and Reagents; D011804:Quinolines; D011944:Receptors, Androgen; D013196:Dihydrotestosterone