The discovery of a potent orally efficacious indole androgen receptor antagonist through in vivo screening.
A series of novel 2-(1H-indol-2-yl)-propan-2-ols have been designed, synthesized, and screened for their ability to inhibit testosterone-induced prostate weight increases in immature rats. Through the use of this paradigm, we were able to identify compounds that exhibited in vivo potency equal to that of the marketed antiandrogen Casodex when orally administered.
Lanter
James C
JC
Johnson & Johnson Pharmaceutical Research and Development L.L.C., 666 Stockton Drive, Exton, PA 19341, USA. jlanter@prdus.jnj.com
Fiordeliso
James J
JJ
Jiang
Weiqin
W
Allan
George F
GF
Lai
Muh-Tsann
MT
Linton
Olivia
O
Hahn
Do Won
do W
Lundeen
Scott G
SG
Sui
Zhihua
Z
D000284:Administration, Oral; D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000494:pharmacology
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000813:Anilides; D007211:Indoles; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide