Interactions between the integrin, alpha2beta1, and extracellular matrix (ECM), particularly collagen, play a pivotal role in platelet adhesion and thrombus formation. Platelets interact with collagen in the subendothelial matrix that is exposed by vascular damage. To evaluate the potential of alpha2beta1 inhibitors for anticancer and antithrombotic applications, we have developed a series of small molecule inhibitors of this integrin based on a prolyl-2,3-diaminopropionic acid (DAP) scaffold using solid-phase parallel synthesis. A benzenesulfonamide substituent at the N-terminus of the dipepetide and a benzyl urea at the DAP side chain resulted in tight and highly selective inhibition of alpha2beta1-mediated adhesion of human platelets and other cells to collagen.