Discovery of a potent and selective agonist of the prostaglandin EP4 receptor

Xavier Billot; Anne Chateauneuf; Nathalie Chauret; Danielle Denis; Gillian Greig; Marie Claude Mathieu; Kathleen M Metters; Deborah M Slipetz; Robert N Young

doi:10.1016/s0960-894x(03)00042-8

Discovery of a potent and selective agonist of the prostaglandin EP4 receptor

Bioorg Med Chem Lett. 2003 Mar 24;13(6):1129-32. doi: 10.1016/s0960-894x(03)00042-8.

Authors

Xavier Billot¹, Anne Chateauneuf, Nathalie Chauret, Danielle Denis, Gillian Greig, Marie Claude Mathieu, Kathleen M Metters, Deborah M Slipetz, Robert N Young

Affiliation

¹ Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, Canada H9R 4P8.

PMID: 12643927
DOI: 10.1016/s0960-894x(03)00042-8

Abstract

Analogues of PGE(2) wherein the hydroxycyclopentanone ring has been replaced by a lactam have been prepared and evaluated as ligands for the EP(4) receptor. An optimized compound (19a) shows high potency and agonist efficacy at the EP(4) receptor and is highly selective over the other seven known prostaglandin receptors.

MeSH terms

Cell Line
Cell Membrane / drug effects
Cell Membrane / metabolism
Dinoprostone / analogs & derivatives*
Dinoprostone / chemical synthesis
Dinoprostone / pharmacology*
Drug Design
Half-Life
Humans
Indicators and Reagents
Pyrrolidinones / chemical synthesis
Pyrrolidinones / pharmacology*
Receptors, Prostaglandin E / agonists*
Receptors, Prostaglandin E, EP4 Subtype
Tetrazoles / chemical synthesis
Tetrazoles / pharmacology*

Substances

CAY10598
Indicators and Reagents
PTGER4 protein, human
Pyrrolidinones
Receptors, Prostaglandin E
Receptors, Prostaglandin E, EP4 Subtype
Tetrazoles
Dinoprostone