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 vit ro), antithrombotic, and blood pressure lowering activities. Nine of them i nhibited the aggregation of blood platelets (Born test, inducer collagen) w ith IC50 values between 10 and 50 mu M The most active compounds i.e, azido -4-nitrophenylbenzaldoxime (2h) had an IC50 = 2 mu M. Nine azide oximes exh ibited significant antithrombotic properties. The most active compounds wer e 2h and 2c (azido-4-methylphenylbenzaldoxime) with an inhibition of thromb us formation above 20% in arterioles after a single p.o. dose of 60 mg/kg. Both compounds lowered the blood pressure in spontaneously hypertensive rat s by 11% (2h) or 5% (2c), respectively. Seven azide oximes were rearranged to the title tetrazolol 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 similar to 10% . h (-1)) and nitrosohydrogen (conversion rate similar to 2% . h(-1)). This mak es it appear probable that the above effects are mediated by these molecule s.