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 IC 50 = 15 μmol/L.