Estrogen Receptor Dependent Inhibitors of NF-B Transcriptional Activation-1 Synthesis and Biological Evaluation of Substituted 2-Cyanopropanoic Acid Derivatives: Pathway Selective Inhibitors of NF-B,
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- 作者：Thomas J. Caggiano ; Antony Brazzale ; Douglas M. Ho ; Christina M. Kraml ; Eugene Trybulski ; Christopher C. Chadwick ; Sue Chippari ; Lisa Borges-Marcucci ; Amy Eckert ; James C. Keith ; Thomas Kenney ; Douglas
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：November 1, 2007
- 年：2007
- 卷：50
- 期：22
- 页码：5245 - 5248
- 全文大小：61K
- 年卷期：v.50,no.22(November 1, 2007)
- ISSN：1520-4804
文摘
Pathway selective ligands of the estrogen receptor inhibittranscriptional activation of proinflammatory genes mediated by NF-B. Substituted 2-cyanopropanoic acid derivatives were developedleading to the discovery of WAY-204688, an orally active, pathwayselective, estrogen receptor dependent anti-inflammatory agent. Thispropanamide was shown to be orally active in preclinical models ofinflammatory diseases, such as rheumatoid arthritis, without theproliferative effect associated with traditional estrogens.