Naphthalene/quinoline amides and sulfonylureas as potent and selective antagonists of the EP4 receptor.

Abstract Two new series of EP 4 antagonists based on naphthalene/quinoline scaffolds have been identified as part of our on-going efforts to develop treatments for inflammatory pain. One series contains an acidic sulfonylurea pharmacophore, whereas the other is a neutral amide. Both series show subnanomolar intrinsic binding potency towards the EP 4 receptor, and excellent selectivity towards other prostanoid receptors. While the amide series generally displays poor pharmacokinetic parameters, the sulfonylureas exhibit greatly improved profile. MF - 592 , the optimal compound from the sulfonylurea series, has a desirable overall preclinical profile that suggests it is suitable for further development.