New NO-donors with antithrombotic and vasodilating activities, Part 14. 1,3,4-Triazol-1-oles

Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl substituents in 2,5-position were synthesized and tested for their antithrombotic properties. The 2,5-dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a-inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 mumol/L.