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 lowering 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 mesenteric 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 (approximately 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.
Institut für Pharmazie I, Freie Universität Berlin, Germany.
K
K
Satyanarayana
K
K
Rehse
D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000627:therapeutic use
D001386:Azides; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide