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.
Yun Oliver Long  1 ,  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
Affiliations
  • 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.