Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonists

Document Type

Article

Publication Date

2013

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.

Publication Title

ACS Medicinal Chemistry Letters

Volume

4

Issue

7

First Page

616

Last Page

621

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.

This document is currently not available here.

COinS