Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one.
A series of 2H-pyrano[3,2-g]quinolin-2-ones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR). The parent compound, 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one, displayed moderate interaction with hAR, but substituted analogues were potent hAR modulators in vitro as measured by an hAR cotransfection assay in CV-1 cells and bound to hAR with high affinity in a whole cell assay. Several analogues were able to activate hAR-mediated gene transcription more potently and efficaciously than dihydrotestosterone.
Edwards
J P
JP
Department of Medicinal Chemistry, Ligand Pharmaceuticals, San Diego, CA 92121, USA.
Higuchi
R I
RI
Winn
D T
DT
Pooley
C L
CL
Caferro
T R
TR
Hamann
L G
LG
Zhi
L
L
Marschke
K B
KB
Goldman
M E
ME
Jones
T K
TK
D000728:Androgens; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D019556:COS Cells; D002460:Cell Line; D006801:Humans; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000728:Androgens; D001578:Benzopyrans; D015363:Quinolones; D011944:Receptors, Androgen