DESIGN AND SYNTHESIS OF ANTIPLATELET NIPECOTAMIDES WITH A DUAL MECHANISM OF ACTION

Based on the knowledge of the platelet aggregation process, the nitric ester moiety which could spontaneously release NO, was incorporated i nto the nipecotamide structure. These compounds exhibited increased ac tivity, possibly due to a dual function consisting of (i) the spontane ous release of nitric oxide, which by itself inhibits platelet adhesio n and aggregation, and (ii) the nipecotamide part, which is known to s tabilize the platelet membrane complexes and prevent shape change, Com pounds containing the benzamidino moiety are known to possess platelet glycoprotein (gp) IIb/IIIa receptor-antagonist potential. New nipecot amide structures with a benzamidino group were synthesized. Among such compounds, the compound with the p-benzamidino group had greater acti vity. It may bind to the platelet gpIIb/IIIa receptor, in addition to stabilizing the platelet membrane.