Estrogen receptor dependent inhibitors of NF-kappaB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives: pathway selective inhibitors of NF-kappaB, a potential treatment for rheumatoid arthritis
- J Med Chem. 2007 Nov 1;50(22):5245-8. doi: 10.1021/jm701013k.
Affiliations
- 1. Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, New Jersey 08540-8000, USA. [email protected]
PMID: 17902637
DOI: 10.1021/jm701013k
Abstract
Pathway selective ligands of the Estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF-kappaB. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, Estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional estrogens.
Products
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Cat. No.Product NameDescriptionTargetResearch Area
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target: NF-κBResearch Areas: Inflammation/Immunology