New NO donors with antithrombotic and vasodilating activities, Part 27. Azide oximes and 1-hydroxytetrazoles

Eleven azide oximes were prepared and tested for their antiplatelet (in vitro), antithrombotic, and blood pressure lowering activities. Nine of them inhibited the aggregation of blood platelets (Born test, inducer collagen) with IC50 values between 10 and 50 microM. The most active compounds i.e. azido-4-nitrophenylbenzaldoxime (2h) had an IC50 = 2 microM. Nine azide oximes exhibited significant antithrombotic properties. The most active compounds were 2h and 2c (azido-4-methylphenylbenzaldoxime) with an inhibition of thrombus formation above 20% in arterioles after a single p.o. dose of 60 mg/kg. Both compounds lowered the blood pressure in spontaneously hypertensive rats by 11% (2h) or 5% (2c), respectively. Seven azide oximes were rearranged to the title tetrazololes which however showed smaller antithrombotic effects. In separate in vitro experiments at 37 degrees C it could be demonstrated that azide oximes release nitric oxide (conversion rate approximately 10%.h-1) and nitrosohydrogen (conversion rate approximately 2%.h-1). This makes it appear probable that the above effects are mediated by these molecules.