Structure-activity relationship studies on ortho-substituted cinnamic acids, a new class of selective EP3 antagonists

Abstract

A series of novel ortho-substituted cinnamic acids have been synthesized, and their binding activity and selectivity on the four prostaglandin E 2 receptors evaluated. Many of them are very potent and selective EP3 antagonists (Ki 3-10 nM), while compound 9 is a very good and selective EP2 agonist (Ki 8 nM). The biological profile of the EP2 agonist 9 in vivo and the metabolic profile of selected EP3 antagonists are also reported. © 2004 Elsevier Ltd. All rights reserved.