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 EP 3 antagonists ( K i 3–10 nM), while compound 9 is a very good and selective EP 2 agonist ( K i 8 nM). The biological profile of the EP 2 agonist 9 in vivo and the metabolic profile of selected EP 3 antagonists are also reported.