New NO-donors with antithrombotic and vasodilating activities, I: 3-arylalkyl-N-nitroso-5-sydnone imines

Article abstract of DOI:10.1002/ardp.19933260811

Nine nitrosimino title compounds were prepared. They inhibit the aggregation of human platelets induced by collagen with an IC₅₀ = 0.7-33 μmol/L. The most active substance is the 3-phenylethyl derivtive 6b. The in vitro effect is mediated by an active metabolite which is formed by a photochemical reaction in the aggregometer. As the corresponding and so far unknown sydnone-5-cyanimines have no effect on platelets the metabolite is most certainly a NO-species. The activity of the sydnone-5-nitrimine 5b is in the same order of magnitude (IC₅₀ = 7.5 μmol/L) as in the nitrosimines of type 6. The most active compound 6b was investigated for antithrombotic properties in a thrombosis model, where the thrombus formation was induced by a laser beam. 2 h after oral administration of 60 mg/kg of 6b to rats in venoles a 28% inhibition of thrombin formation was found. In arterioles this effect is more evident and a 48% inhibition is seen (the thrombus formation index is 2.6 and 3.9, respectively). These results suggest that the active metabolite is formed as well in vivo.