New NO donors with antithrombotic and vasodilating activities, part 26 amidoximes and their prodrugs

Seventeen amidoximes (2a-q) comprising aliphatic (2a-d), aromatic (2e-n), a nd bis compounds (2o-q) have been synthesized. In the Born rest 4-chlorophe nylethenecarboxamidoxime (21) was most active and inhibited the blood plate let aggregation induced by collagen with an IC50 = 3 mu M. After oral admin istration to rats (60 mg/kg) fourteen compounds significantly inhibited the formation of thrombi in arterioles and venules. The strongest effect was o bserved with ethene-bis-carboxamidoxime (2q) (31% in arterioles and 18% in venules). The O-ethoxycarbonylderivatives 3 and the corresponding 1,2, 4-ox adiazol-5-ones 4, which had been synthesized as prodrugs, showed smaller an tithrombotic effects.