Novel synthetic RGD analogs incorporating salicylic acid derivatives show antiplatelet activity in vitro

Continuing our investigational efforts for more active GpIIb/IIIa inhibitors we have synthesized four novel RGD (Arg-Gly-Asp) analogs incorporating salicylic acid derivatives at their N-terminal amino group using the solid phase synthesis. The synthesized compounds 5-Cl-2-HO-C₆H₃-CO-Arg-Gly-Asp(OBzl)-NH₂ and 5-Br-2-HO-C₆H₃-CO-Arg-Gly-Asp(OBzl)-NH₂ were tested for their inhibitory activity on human platelet aggregation in vitro and found to be potent inhibitors of the platelet aggregation with 75 and 67% inhibitory activity respectively. In order to confirm our results flow cytometry with monoclonal antibodies against GpIb, GpIIb/IIIa, GpIIIa and GMP140 receptors was used.