2. Academic Validation
  3. 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

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.
Thomas J Caggiano 1,  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 C Harnish
Affiliations

Affiliation

  • 1 Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, New Jersey 08540-8000, USA. caggiat@wyeth.com
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.

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