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Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists
ACS Medicinal Chemistry Letters
  • Thota Ganesh
  • Jianxiong Jiang
  • Rangaiah Shashidharamurthy, Philadelphia College of Osteopathic Medicine
  • Ray Dingledine
Document Type
Article
Publication Date
1-1-2013
Disciplines
Abstract
Prostanoid receptor EP2 is emerging as a novel target for development of anti-inflammatory drugs for the treatment of chronic neurodegenerative and peripheral diseases; however, the availability of EP2 antagonist probes for exploration of peripheral disease models is very limited. We now report identification and characterization of a novel chemical class of compounds that show nanomolar potency and competitive antagonism of the EP2 receptor. A compound in this class, TG6-129, showed prolonged plasma half-life and did not cross the blood-brain barrier. This compound also suppressed the induction of inflammatory mRNA markers in a macrophage cell line upon activation of EP2. Thus, this compound could be useful as a probe for a variety of peripheral chronic inflammatory diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease, in which EP2 appears to play a pathogenic role.
Comments

This article was published in ACS Medicinal Chemistry Letters, Volume 4, Issue 7, Pages 616-621.

The published version is available at http://dx.doi.org/10.1021/ml400112h.

Copyright © 2013 ACS.

Citation Information
Thota Ganesh, Jianxiong Jiang, Rangaiah Shashidharamurthy and Ray Dingledine. "Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists" ACS Medicinal Chemistry Letters Vol. 4 Iss. 7 (2013) p. 616 - 621
Available at: http://works.bepress.com/rangaiah_shashidharamurthy/30/