SYNTHESIS AND PLATELET AGGREGATION INHIBITORY ACTIVITY OF 6-(4′-SUBSTITUTED ACYLAMINOPHENYL)-4,5-DIHYDRO-3-(2H)-PYRIDAZINONES

AIM: To study the synthesis and antiplatelet aggregation activity of 6-(4′-substituted acyl aminophenyl)-4,5-dihydro-3(2H)-pyridazinones. METHODS: The title compounds were synthesized by acylation of twelve acyl chlorides and two intermediates prepared by Friedel-Crafts reaction, lengthening of carbon chain, hydrolysis and cyclization; the antiplatelet aggregation activity of the title compounds was measured by Born′s method. RESULTS: Twenty four 6-(4′-substituted acyl aminophenyl)-4,5-dihydro-3(2H)-pyridazinones were designed and synthesized. Of them, 22 were first reported. The chemical structures of all the compounds were determined by IR, 1HNMR and elementary analysis. The intermediate, 6-(4′-aminophenyl)-4,5-dihydro-3(2H)-pyridazinones, was synthesized by two methods. Preliminary pharmacological tests showed that all of the title compounds inhibited ADP induced platelet aggregation to a certain extent. Compounds II showed more potent inhibition than did compounds I. The inhibitory activities of I₁, I₃, II₁, II₃, II₄, II₆ and II₉, were more potent than that of the control compound CI-930. The inhibitory effect of II1 and II3 against platelet aggregation were about ten times of that of CI-930. CONCLUSION: Some of the title compounds showed potent activity of antiplatelet aggregation and should be studied further.