title: Potent, nonsteroidal selective androgen receptor modulators (SARMs) based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones.
abstract: A series of androgen receptor modulators based on 8H-[1,4]oxazino[2,3-f]quinolin-8-ones was synthesized and evaluated in an androgen receptor transcriptional activation assay. The most potent analogues from the series exhibited single-digit nanomolar potency in vitro. Compound 18h demonstrated full efficacy in the maintenance of muscle weight, at 10 mg/kg, with reduced activity in prostate weight in an in vivo model of androgen action.
authors: Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA. rhiguchi@ligand.com
authors: Robert I
authors: RI
authors: Higuchi
authors: Anthony W
authors: AW
authors: Thompson
authors: Jyun-Hung
authors: JH
authors: Chen
authors: Thomas R
authors: TR
authors: Caferro
authors: Marquis L
authors: ML
authors: Cummings
authors: Charlotte P
authors: CP
authors: Deckhut
authors: Mark E
authors: ME
authors: Adams
authors: Christopher M
authors: CM
authors: Tegley
authors: James P
authors: JP
authors: Edwards
authors: Francisco J
authors: FJ
authors: López
authors: E Adam
authors: EA
authors: Kallel
authors: Donald S
authors: DS
authors: Karanewsky
authors: William T
authors: WT
authors: Schrader
authors: Keith B
authors: KB
authors: Marschke
authors: Lin
authors: L
authors: Zhi
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008958:Models, Molecular; D009919:Orchiectomy; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D011944:Receptors, Androgen / Q000737:chemistry / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000737:chemistry / Q000187:drug effects; D011986:Receptors, Somatotropin / Q000737:chemistry / Q000187:drug effects; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000097:blood
chemical_list: D007202:Indicators and Reagents; D010078:Oxazines; D015363:Quinolones; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D011986:Receptors, Somatotropin; D013739:Testosterone
references: J Clin Endocrinol Metab. 2005 Feb;90(2):678-88
references: 15562020
references: N Engl J Med. 1996 Mar 14;334(11):707-14
references: 8594431
references: J Med Chem. 2006 Oct 19;49(21):6143-6
references: 17034117
references: Bioorg Med Chem Lett. 2006 Nov 15;16(22):5763-6
references: 16959487
references: Proc Soc Exp Biol Med. 1953 May;83(1):175-80
references: 13064212
references: J Med Chem. 1995 Dec 8;38(25):4855-74
references: 8523397
references: J Clin Endocrinol Metab. 1997 Feb;82(2):407-13
references: 9024227
references: J Med Chem. 2006 Dec 28;49(26):7596-9
references: 17181141
references: J Med Chem. 1998 Feb 12;41(4):623-39
references: 9484511
references: J Clin Endocrinol Metab. 1999 Oct;84(10):3459-62
references: 10522980
references: J Med Chem. 2007 May 17;50(10):2486-96
references: 17439112
references: J Med Chem. 2004 Feb 12;47(4):993-8
references: 14761201
references: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Nov 1;62(Pt 11):1067-71
references: 17077481
references: Biol Pharm Bull. 2003 Nov;26(11):1563-9
references: 14600402
references: Clin Endocrinol (Oxf). 2003 Jun;58(6):691-5
references: 12780744