[A new class of soluble guanylate cyclase activators, generating nitric oxide]

Derivatives of diazetidine-di-N-oxides have been found capable nonenzymatic generation of nitric oxide by a principally new mechanism of nitric oxide splitting at physiological values of pH. The effects of the synthesized compounds on human platelet soluble guanylate cyclase activity have been studied. Four of seven derivatives exhibited a distinct correlation between the ability of being decomposed with nitric oxide formation and soluble guanylate cyclase activation. Among those, 3-bromo-4-methyl-3.4-tetramethylene-diazetidine-di-N-oxide proved to be the most effective activator, its spasmolytic effect being commensurate with the glyceryl trinitrate activity. The data obtained open up new opportunities for a search into new vasodilatory agents among compound whose chemical structure provides nitric oxide generation and guanylate cyclase activation in human tissues. Besides, they provide evidence that 1.2-diazetidine-1.2-di-N-oxide derivatives are perspective objects for creating new vasodilatory drugs.