Synthesis and activity of a new class of pathway-selective estrogen receptor ligands: Hydroxybenzoyl-3,4-dihydroquinoxalin-2(1 H)-ones

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 10; pp. 3455 - 3466
• Main Authors: Mahaney, Paige E., Webb, Michael B., Ye, Fei, Sabatucci, Joseph P., Steffan, Robert J., Chadwick, Christopher C., Harnish, Douglas C., Trybulski, Eugene J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-05-2006; Elsevier Science
• Subjects: Anti-inflammatory activity; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cells, Cultured; Drug Evaluation, Preclinical; Estrogen receptor ligands; Humans; Hydroxybenzoyl-3,4-dihydroquinoxalin-2(1 H)-ones; Ligands; Medical sciences; Molecular Structure; NF-kappa B - antagonists & inhibitors; NF-kappa B - drug effects; NF-κB; Pharmacology. Drug treatments; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; Receptors, Estrogen - drug effects; Receptors, Estrogen - metabolism; Signal Transduction - drug effects; Estrogen receptor ligands; NF-κB; Anti-inflammatory activity; Hydroxybenzoyl-3,4-dihydroquinoxalin-2(1 H)-ones; Quinoxaline derivatives; Estrogen receptor; Ligand; Antiinflammatory agent; NF-KB; Hydroxybenzoyl-3,4-dihydroquinoxalin-2( 1H)-ones; Selectivity; In vitro; Biological activity; Phenols; Transcription factor NFκB; Chemical synthesis; Hormonal receptor
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.01.001

The anti-inflammatory activity of non-selective estrogens has been attributed to their ability to antagonize the activity of nuclear factor κB (NF-κB), 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-κB functional activity, while exhibiting a lack of classical estrogenic effect.