title: Nonsteroidal androgen receptor agonists based on 4-(trifluoromethyl)-2H-pyrano[3,2-g]quinolin-2-one.
abstract: 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 measured by an hAR cotransfection assay in CV-1 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.
authors.affiliation: Department of Medicinal Chemistry, Ligand Pharmaceuticals, San Diego, CA 92121, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Edwards
authors.forename: R I
authors.initials: RI
authors.lastname: Higuchi
authors.forename: D T
authors.initials: DT
authors.lastname: Winn
authors.forename: C L
authors.initials: CL
authors.lastname: Pooley
authors.forename: T R
authors.initials: TR
authors.lastname: Caferro
authors.forename: L G
authors.initials: LG
authors.lastname: Hamann
authors.forename: L
authors.initials: L
authors.lastname: Zhi
authors.forename: K B
authors.initials: KB
authors.lastname: Marschke
authors.forename: M E
authors.initials: ME
authors.lastname: Goldman
authors.forename: T K
authors.initials: TK
authors.lastname: Jones
mesh_terms: D000728:Androgens; D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D019556:COS Cells; D002460:Cell Line; D006801:Humans; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D000728:Androgens; D001578:Benzopyrans; D015363:Quinolones; D011944:Receptors, Androgen