Arylamide derivatives as allosteric inhibitors of the integrin α2β1/type I collagen interaction

We herein report a group of allosteric inhibitors of integrin α2β1 based on an arylamide scaffold. Compound 4 showed an IC50 of 4.80 μM in disrupting integrin I-domain/collagen binding in an ELISA. These arylamide compounds are able to block collagen binding to integrin α2β1 on the platelet surface. Further we find that compound 4 recognizes a hydrophobic cleft on the side of the α2 I-domain, suggesting an alternative targeting site for drug development.