Abstract
An investigation into the structure–activity relationship of a lead compound, prolyl-5-aminopentanoic acid 4, led to the identification of a novel series of 4-piperidinylacetic acid, 1-piperazinylacetic acid, and 4-aminobenzoic acid derivatives as potent VLA-4 antagonists with low nanomolar IC 50 values. A representative compound morpholinyl-4-piperidinylacetic acid derivative ( 13d: IC 50 = 4.4 nM) showed efficacy in the Ascaris-antigen sensitized murine airway inflammation model by oral administration.
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