Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one

A series of 2H-pyrano[3,2-g]quinolin-2-ones was prepared and tested for the ability to modulate the transcriptional activity of the human androgen receptor (hAR). The parent compound, 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one, displayed moderate interaction with hAR, but substituted analogues were potent hAR modulators in vitro as mesaured by an hAR cotransfection assay in CV-I cells and bound to hAR with high affinity in a whole cell assay. Several analogues were able to activate hAR-mediated gene transcription more potently and efficaciously than dihydrotestosterone. (C) 1999 Elsevier Science Ltd. All rights reserved.