New NO-donors with antithrombotic and vasodilating activities, V: Oligonitroso sydnone imines

Article abstract of DOI:10.1002/ardp.19943270610

Nine 4,4'-bis- and four 4,4'-tris-N-nitroso sydnone imines were synthesized. The sydnone imine moiety is connected either by aromatic 1,3-phenylene or 1,3,5-benzene or aliphatic methylene or propylene bridges. Compared to the corresponding sydnone imines the collagen induced platelet aggregation inhibiting activity is increased by several orders of magnitude by the nitroso derivatives. The most potent compound bears a hexyl substituent in 3-position (1d: IC₅₀ = 0.05 μmol/L). These data show that aromatic bridges (1d, 2d) are more favourable than aliphatic ones (4b). This indicates the mutual influence of the nitroso-imino moieties via the aromatic bridges. In the series of 3,3'-bis-nitrososydnone imines (13 compounds) mostly additive effects of the nitroso groups are seen. The activities range from IC₅₀ = 0.2 μmol/L (5i; 1,3-xylene bridge) to IC₅₀ = 8 μmol/L (5b; trimethylene bridge). The differences suggest different affinities to the platelet membrane.