Synthesis and activity of a new class of pathway-selective estrogen receptor ligands: hydroxybenzoyl-3,4-dihydroquinoxalin-2(1H)-ones.
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.
Mahaney
Paige E
PE
Chemical and Screening Sciences, Wyeth Research, Discovery Medicinal Chemistry, 500 Arcola Road, Collegeville, PA 19465, USA. mahanep@wyeth.com
Webb
Michael B
MB
Ye
Fei
F
Sabatucci
Joseph P
JP
Steffan
Robert J
RJ
Chadwick
Christopher C
CC
Harnish
Douglas C
DC
Trybulski
Eugene J
EJ
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
D008024:Ligands; D016328:NF-kappa B; D011810:Quinoxalines; D011960:Receptors, Estrogen