title: Synthesis and activity of a new class of pathway-selective estrogen receptor ligands: hydroxybenzoyl-3,4-dihydroquinoxalin-2(1H)-ones.
abstract: The anti-inflammatory activity of non-selective estrogens has been attributed to their ability to antagonize the activity of nuclear factor kappaB (NF-kappaB), a known mediator of inflammatory responses. Here we report the identification of a potent new class of pathway-selective ER ligands that selectively antagonize NF-kappaB functional activity, while exhibiting a lack of classical estrogenic effect.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, Discovery Medicinal Chemistry, 500 Arcola Road, Collegeville, PA 19465, USA. mahanep@wyeth.com
authors.forename: Paige E
authors.initials: PE
authors.lastname: Mahaney
authors.forename: Michael B
authors.initials: MB
authors.lastname: Webb
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Sabatucci
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Steffan
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Chadwick
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Harnish
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Trybulski
mesh_terms: D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008024:Ligands; D016328:NF-kappa B; D011810:Quinoxalines; D011960:Receptors, Estrogen