Selective androgen receptor modulators based on a series of 7H-[1,4]oxazino[3,2-g]quinolin-7-ones with improved in vivo activity.
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.
Long
Yun Oliver
YO
Discovery Research, Ligand Pharmaceuticals, 10275 Science Center Drive, San Diego, CA 92121, USA.
Higuchi
Robert I
RI
Caferro
Thomas R
TR
Lau
Thomas L S
TL
Wu
Min
M
Cummings
Marquis L
ML
Martinborough
Esther A
EA
Marschke
Keith B
KB
Chang
William Y
WY
López
Francisco J
FJ
Karanewsky
Donald S
DS
Zhi
Lin
L
D000284:Administration, Oral; D045930:Anabolic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D008297:Male; D008956:Models, Chemical; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010078:Oxazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011467:Prostate / Q000033:anatomy & histology / Q000187:drug effects*; D015363:Quinolones / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000494:pharmacology
D045930:Anabolic Agents; D059002:Androgen Receptor Antagonists; D000728:Androgens; D010078:Oxazines; D015363:Quinolones; D011944:Receptors, Androgen; D013739:Testosterone