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), and bis compounds (2o-q) have been synthesized. In the Born test 4-chlorophenylethenecarboxamidoxime (21) was most active and inhibited the blood platelet aggregation induced by collagen with an IC50 = 3 microM. After oral administration to rats (60 mg/kg) fourteen compounds significantly inhibited the formation of thrombi in arterioles and venules. The strongest effect was observed with ethene-bis-carboxamidoxime (2q) (31% in arterioles and 18% in venules). The O-ethoxycarbonylderivatives 3 and the corresponding 1,2,4-oxadiazol-5-ones 4, which had been synthesized as prodrugs, showed smaller antithrombotic effects.