Oxorhenium-Mediated Assembly of Noncyclic Selective Integrin Antagonists: A Combinatorial Approach

The parallel oxorhenium-mediated assembly of 288 noncyclic RGD analogues is reported. All complexes contain a NS2+S chelating motif that enables the unambiguous coordination of the oxorhenium and oxotechnetium cores. In this study, modules S contain a variety of pending guanidinium groups whereas the NS2 modules are made of a series of N-acylated amino acids. Combination of sets of NS2 and S modules together with tetrabutylammonium tetrachlorooxorhenate gave the corresponding oxorhenium complexes in good yields and satisfactory purities. Evaluation of these metalloconstructs towards integrins alpha(V)beta(3), alpha(IIb)beta(3), and alpha(V)beta(5) led to the identification of micromolar and submicromolar antagonists of theses integrins. These compounds exhibit interesting selectivities and promise attractive applications for the molecular imaging of integrin-dependent pathologies.