NO donors with antithrombotic and vasodilating activities, Part 23: Organic azides

Twenty eight organic azides were synthesized and tested for their antithrombotic and blood pressure towering activities in rats (60 mg/kg, p.o.). In fifteen compounds significant antithrombotic effects were observed. In thirteen cases a significant lowering of the blood pressure of spontaneously hypertensive rats (SHR) was seen. The peak activities in both systems were found for hexyl azide (4), 2-phenylethyl azide (14), and 4- pyridinecarboxylic acid azide (23). In these compounds the inhibition of thrombus formation in meserteric arterioles was >20%. The lowering of blood pressure was > 10% and long lasting (> 6 h) in 4 and 14 while 23 had a shorter duration of action (~ 4 h). In two classes of azides, namely branched aliphatic azides (e.g. 2-azidopentane 9) and aliphatic carbonyl derivatives (e.g. benzoyl-azido-methane 17), only antithrombotic properties were observed. A lack of endothelial metabolism is suggested to be the reason for this therapeutically favorable behaviour.