Identified a morpholinyl-4-piperidinylacetic acid derivative as a potent oral active VLA-4 antagonist.

An investigation into the structure–activitiy relationship of a lead compound led to the identification of a novel series of piperidinylacetic acid, piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivatives (13d: IC50=4.4nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration.