Discovery and characterization of carbamothioylacrylamides as EP2 selective antagonistsACS Medicinal Chemistry Letters
AbstractProstanoid 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.
Citation InformationThota 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/