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(1H)-piperidino-[3,2-g]quinolinone 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.