Discovery of G Protein-Biased EP2 Receptor Agonists.
Basic Information
ID: ALA3804774
Journal: ACS Med Chem Lett
Title: Discovery of G Protein-Biased EP2 Receptor Agonists.
Authors: Ogawa S, Watanabe T, Sugimoto I, Moriyuki K, Goto Y, Yamane S, Watanabe A, Tsuboi K, Kinoshita A, Kigoshi H, Tani K, Maruyama T.
Abstract: To identify G protein-biased and highly subtype-selective EP2 receptor agonists, a series of bicyclic prostaglandin analogues were designed and synthesized. Structural hybridization of EP2/4 dual agonist 5 and prostacyclin analogue 6, followed by simplification of the ω chain enabled us to discover novel EP2 agonists with a unique prostacyclin-like scaffold. Further optimization of the ω chain was performed to improve EP2 agonist activity and subtype selectivity. Phenoxy derivative 18a showed potent agonist activity and excellent subtype selectivity. Furthermore, a series of compounds were identified as G protein-biased EP2 receptor agonists. These are the first examples of biased ligands of prostanoid receptors.
CiteXplore: 26985320
DOI: 10.1021/acsmedchemlett.5b00455
Patent ID: ┄