New NO-donors with antithrombotic and vasodilating activities .13. Pyrazol-4-one 1,2-dioxides and 4-hydroxyiminopyrazole 1,2-dioxides

Twenty pyrazol-4-one 1,2-dioxides and eleven 4-hydroxyimino-pyrazole 1,2-dioxides were prepared and tested for their anti-platelet activity (Born test with collagen). Six compounds which al belong to the pyrazolone series inhibited the platelet aggregation half-maximally in submicromolar concentrations (200-800 nmol/L). In positions 3 and 5, these compounds bear at least one (15, 16, 24, 31) or two substituents (7, 29) with electron-withdrawing groups. Among them are aromatic moieties like 4-hydroxysulfonylphenyl (7), 4-cyanophenyl (16), 4-chlorophenyl (15), phenyl (24) or carboxylic acid esters (29). Two compounds were investigated in an in vivo thrombosis model (1, 31). 2h after oral administration of 60 mg/kg 1 to rats in arterioles 69% inhibition of thrombus formation (venules 40%) was observed.