Discovery of substituted-2,4-dimethyl-(naphthalene-4-carbonyl)amino-benzoic acid as potent and selective EP4 antagonists.

A novel series of EP4 antagonists, based on a quinoline scaffold, has been discovered. Medicinal chemistry efforts to optimize the potency of the initial hit are described. A highly potent compound in a clinically relevant human whole blood assay was identified. Selectivity and pharmacokinetic profiles of this compound are discussed.