Author/Authors :
Yves Ducharme، نويسنده , , Marc Blouin، نويسنده , , Marie-Claude Carrière، نويسنده , , Anne Chateauneuf، نويسنده , , Bernard Côté، نويسنده , , Danielle Denis، نويسنده , , Richard Frenette، نويسنده , , Gillian Greig، نويسنده , , Stacia Kargman، نويسنده , , Sonia Lamontagne، نويسنده , , Evelyn Martins، نويسنده , , François Nantel، نويسنده , , Gary O’Neill، نويسنده , , Nicole Sawyer، نويسنده , , Kathleen M. Metters، نويسنده , , Richard W. Friesen، نويسنده ,
Abstract :
The synthesis and the EP1 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 EP1 receptor and a selectivity greater than 100-fold against the EP2, EP3, EP4, 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.
