Selective androgen receptor modulators based on a series of 7H-[1,4]oxazino[3,2-g]quinolin-7-ones with improved in vivo activity

Yun Oliver Long; Robert I Higuchi; Thomas R Caferro; Thomas L S Lau; Min Wu; Marquis L Cummings; Esther A Martinborough; Keith B Marschke; William Y Chang; Francisco J López; Donald S Karanewsky; Lin Zhi

doi:10.1016/j.bmcl.2008.03.062

Selective androgen receptor modulators based on a series of 7H-[1,4]oxazino[3,2-g]quinolin-7-ones with improved in vivo activity

Bioorg Med Chem Lett. 2008 May 1;18(9):2967-71. doi: 10.1016/j.bmcl.2008.03.062. Epub 2008 Mar 23.

Authors

Yun Oliver Long¹, Robert I Higuchi, Thomas R Caferro, Thomas L S Lau, Min Wu, Marquis L Cummings, Esther A Martinborough, Keith B Marschke, William Y Chang, Francisco J López, Donald S Karanewsky, Lin Zhi

Affiliation

¹ Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA.

PMID: 18400499
DOI: 10.1016/j.bmcl.2008.03.062

Abstract

Modification on a lead series of [1,4]oxazino[3,2-g]quinolin-7-ones at the 2-position led to selective androgen receptor modulators with improved in vivo activity. The most potent analog (-)-33a exhibited full maintenance of levator ani muscle at 3mg/kg and reduced activity on ventral prostate weight in a 2-week orally-dosed and orchidectomized rat maintenance assay.

MeSH terms

Administration, Oral
Anabolic Agents / chemical synthesis
Anabolic Agents / pharmacology*
Androgen Receptor Antagonists
Androgens
Animals
Male
Models, Chemical
Orchiectomy
Organ Size / drug effects
Oxazines / chemical synthesis
Oxazines / pharmacology*
Prostate / anatomy & histology
Prostate / drug effects*
Quinolones / chemical synthesis
Quinolones / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Androgen*
Structure-Activity Relationship
Testosterone / pharmacology

Substances

Anabolic Agents
Androgen Receptor Antagonists
Androgens
Oxazines
Quinolones
Receptors, Androgen
Testosterone