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A novel series of β-lactam derivatives that was designed and synthesized to target RGD-binding and leukocyte integrins is reported. The compound library was evaluated by investigating the effects on integrin-mediated cell adhesion and cell signaling in cell lines expressing α v β 3 , α v β 5 , α v β 6 , α 5 β 1 , α IIb β 3 , α 4 β 1 , and α L β 2 integrins. SAR analysis of the new series of azetidinones enabled the recognition of structural elements associated with integrin selectivity. We obtained selective and potent agonists that could induce cell adhesion and promote cell signaling mediated by α v β 3 , α v β 5 , α 5 β 1 , or α 4 β 1 integrin, and antagonists for the integrins α v β 3 and α 5 β 1, as well as α 4 β 1 and α L β 2 , preventing the effects elicited by the respective endogenous agonists.

New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins