Discovery of G Protein-Biased EP2 Receptor Agonists

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2016 Mar 18

PMID 26985320

Citations 4

Authors

Seiji Ogawa

Toshihide Watanabe

Isamu Sugimoto

Kazumi Moriyuki

Yoshikazu Goto

Shinsaku Yamane

Akio Watanabe

Kazuma Tsuboi

Atsushi Kinoshita

Hideo Kigoshi

Kousuke Tani

Toru Maruyama

Affiliations

Soon will be listed here.

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.

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