New nonsteroidal androgen receptor modulators based on 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g] quinolinone.
A series of 2(1H)-pyrrolidino[3,2-g]quinolinones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR). The parent compound, 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g]quinolinone, displayed moderate interaction with hAR, but more substituted analogues, particularly 6,7-disubstituted compounds, were potent hAR agonists in vitro.
Edwards
J P
JP
Department of Medicinal Chemistry, Ligand Pharmaceuticals, San Diego, CA 92121, USA.
West
S J
SJ
Pooley
C L
CL
Marschke
K B
KB
Farmer
L J
LJ
Jones
T K
TK
D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000813:Anilides / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D015195:Drug Design; D005485:Flutamide / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009570:Nitriles; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D011759:Pyrrolidines; D011804:Quinolines; D015363:Quinolones; D011944:Receptors, Androgen; D011994:Recombinant Proteins; D014105:Tosyl Compounds; D005485:Flutamide; C053541:bicalutamide