2,3-Diarylthiophenes as selective EP1 receptor antagonists

Abstract The synthesis and the EP 1 receptor binding affinity of 2,3-diarylthiophene derivatives are described. The evaluation of the structure–activity relationship (SAR) in this series led to the identification of compounds 4 , 7 , and 12a , which exhibit high affinity for the human EP 1 receptor and a selectivity greater than 100-fold against the EP 2 , EP 3 , EP 4 , DP, FP, and IP receptors and greater than 25-fold versus the TP receptor. These three antagonists present good pharmacokinetics in rats and significant differences in the way they are distributed in the brain.