Constraining the amide bond in N-Sulfonylated dipeptide VLA-4 antagonists

The integrin VLA-4 is implicated in several inflammatory disease states. In search of non-peptidic antagonists of VLA-4, rotational constraints were imposed on the amide bond of prototypical N-sulfonylated dipeptide VLA-4 antagonists. By judicious structural modi. cation of the side chains, trisubstituted imidazoles with moderate binding potencies were obtained, for example, 19, VLA-4 IC50 = 237 nM. (C) 2008 Elsevier Ltd. All rights reserved.