Bioorganic & Medicinal Chemistry Letters 1999-04-05

Switching androgen receptor antagonists to agonists by modifying C-ring substituents on piperidino[3,2-g]quinolinone.

L Zhi, C M Tegley, K B Marschke, T K Jones

Index: Bioorg. Med. Chem. Lett. 9(7) , 1009-12, (1999)

Full Text: HTML

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.