Imidazopyridines as VLA-4 integrin antagonists

We describe a novel series of imidazopyridine substituted phenylalanines which are potent VLA-4 antagonists. A wide variety of substituents are tolerated as replacements for the pendant 3-pyridyl ring. A clear structure–activity relationship was identified around the substitution of the 3-amino-cyclobut-2-enone portion of the molecule.

Graphical abstractThe synthesis and SAR of a novel series of imidazopyridine VLA-4 antagonist is described. Compound 15c is a representative example of this series with a human whole blood IC50 of 3 nM.Figure optionsDownload full-size imageDownload as PowerPoint slide