New NO-donors with antithrombotic and vasodilating activities, Part 19. Pseudonitroles and their dimeric azodioxides

Thirteen geminally substituted nitro-nitroso compounds (pseudonitroles) have been synthesized, four of them for the first time. In the solid state the pseudonitroles are dimerized to azodioxides. This is proved by IR spectroscopy, with the dimeric N-O valence vibration being observed between 1293 and 1306 cm-1. Only 1,3-diphenyl-2-nitro-2-nitrosopropane is monomeric even when solid. This is backed by its blue color and an IR band at 1574 cm-1. When dissolved in chloroform these azodioxides dissociate completely to the blue monomers (lambda max approximately 650 nm). Eight pseudonitroles inhibited the aggregation of blood platelets half-maximally at concentrations below 10 microM (Born test, collagen). When administered orally to rats (60 mg/kg) the thrombus formation in mesenteric arterioles and venules was inhibited up to 25 percent (k; 1-nitro-1-nitrosocyclohexane). When kept in aqueous media at 37 degrees C nitric oxide and its reduced from, i.e. nitrosohydrogen, are released. This suggests that the above biological effects arise from an NO dependent mechanism. The lack of influence on the blood pressure of spontaneously hypertensive rats, however, strongly suggests that an enzyme supported rather than a thermal formation of NO occurs in vivo.