Nonpeptide RGD antagonists: A novel class of mimetics, the 5,8-disubstituted 1-azabicyclo[5.2.0]nonan-2-one lactam

The 1-azabicyclo[5.2.0]nonan-2-one lactam 1 adequately substituted on both cycles A and B as scaffolds mimics the conformationally constrained β-turn of the tripeptide RGD signaling motif of fibronectin. Using an in vitro assay, we establish that trans diastereoisomer 1b dissociates a soluble fibronectin–integrin α5β1 complex at concentrations comparable to those of a linear RGDS peptide as a competitor.