Design,Synthesis and Anticoagulant Activity of Butylphthalide-Pyridazinone Derivatives
In order to improve the antiplatelet agglutination activity of butylphthalide,6-aminobutylphthalide was used as the starting material,twenty novel butylphthalide-pyridazinone derivatives were synthesized by diazotization/reduction,cyclization,hydrolysis,dechlorination,etherification and sulfonation acylation.Their structures were confirmed by 1H NMR,13C NMR and HRMS.The results of antiplatelet agglutination activity test in vitro show that compounds 6a,6b and 6k exhibite better inhibitory activity(IC50=44.9～180.0 μmol/L)against ADP-induced platelet aggregation than the lead compound butylphthalide(IC50=1252μmol/L)and positive control aspirin(IC50=1140 μmol/L).Meanwhile,compound 6b(IC50=63.6 μmol/L)and 6k(IC50=191.9 μmol/L)also possess significant inhibitory activity against AA-induced platelet aggregation.This study provides a theoretical reference for the study of butylphthalide-pyridazinone skeleton in the treatment of ischemic stroke.
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