title: Switching androgen receptor antagonists to agonists by modifying C-ring substituents on piperidino[3,2-g]quinolinone.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Ligand Pharmaceuticals, Inc., San Diego, CA 92121, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhi
authors.forename: C M
authors.initials: CM
authors.lastname: Tegley
authors.forename: K B
authors.initials: KB
authors.lastname: Marschke
authors.forename: T K
authors.initials: TK
authors.lastname: Jones
mesh_terms: 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
chemical_list: C119489:7,8-diethyl-4-trifluoromethyl-2(1H)-piperidino(3,2-g)quinolinone; D000726:Androgen Antagonists; D000728:Androgens; D010880:Piperidines; D015363:Quinolones