Switching androgen receptor antagonists to agonists by modifying C-ring substituents on piperidino[3,2-g]quinolinone.
New nonsteroidal human androgen receptor (hAR) agonists were developed from an hAR antagonist pharmacophore, 2(1H)-piperidino[3,2-g]quinolinone. (+/-)-trans-7,8-Diethyl-4-trifluoromethyl-2(H)-piperidino-[3,2-g]quinoli none was synthesized and demonstrated potent hAR agonist activity (EC50=3 nM) in the cell-based cotransfection assay and high binding affinity (Ki=16 nM) in the competitive receptor binding assay.
Zhi
L
L
Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Tegley
C M
CM
Marschke
K B
KB
Jones
T K
TK
D000726:Androgen Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D000728:Androgens; D006801:Humans; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014162:Transfection
C119489:7,8-diethyl-4-trifluoromethyl-2(1H)-piperidino(3,2-g)quinolinone; D000726:Androgen Antagonists; D000728:Androgens; D010880:Piperidines; D015363:Quinolones