Inhibition of ADP-induced human platelet aggregation by a new class of soluble guanylate cyclase activators capable of nitric oxide generation.

Diazetidine-di-N-oxide derivatives have been found capable of the nonenzymatic generation of nitric oxide by a principally new mechanism of nitric oxide splitting at physiological pH values. The effect of the synthesized compounds on human platelet soluble guanylate cyclase activity and ADP-induced human platelets aggregation were studied. Four of 7 derivatives studied exhibited a distinct correlation between the intensity of platelet guanylate cyclase activation, inhibition of platelets aggregation and acceleration of their disaggregation. The NO-dependent mechanism of guanylate cyclase activation and intraplatelet cGMP accumulation are suggested to be responsible for antiaggregatory/disaggregatory properties of the compounds used. Data presented allow us to regard 1,2-diazetidine-di-N-oxide derivatives as antiaggregatory agents of a new class.