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 rec eptor (hAR). The parent compound, 4-(trifluoromethyl)-2H-pyrano[3,2-g]quino lin-2-one, displayed moderate interaction with hAR, but substituted analogu es 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 as say. Several analogues were able to activate hAR-mediated gene transcriptio n more potently and efficaciously than dihydrotestosterone. (C) 1999 Elsevi er Science Ltd. All rights reserved.