CONFORMATIONALLY FLEXIBLE PLATELET-AGGREGATION INHIBITORS BASED ON THE TETRAPEPTIDE ARG-GLY-ASP-ARG

A series of nonpeptide fibrinogen receptor antagonists based upon the tetrapeptide Arg-Gly-Asp-Arg were prepared. These relatively simple de rivatives incorporate a high degree of conformational flexibility that was anticipated to allow them to attain the requisite conformation fo r binding to the platelet fibrinogen receptor. Optimization of the dis tances between the required acidic and basic functional groups led eve ntually to compound 7, which is a one hundred-fold more potent inhibit or of platelet aggregation than the peptide it is based upon.