Synthesis And In Vitro Activities Evaluation Of4-ethoxyisophthalamide Derivaties

This subject is to verify the results of CoMFA and to obtain some innovative drugs ofanti-platelet aggregation. Based on the previous works of4-methoxyisophthalamidesderivatives in our laboratory and according to the results of CoMFA that increase the volumeof4-position substituents of parent benzene is benefit to the activities of compounds, wereplaced the4-position methoxy with an ethoxy, to study the influence of the substituentschanges to the activities of anti-platelet aggregation. This article focuses on further researchthe SAR of the4-ethoxyisophthalamides, a total of15unreported target compounds(PN450-PN464) has been designed and synthesized, the structures of all compounds wereidentified by MS,1H-NMR, and IR. Melting points were also determined and thethermometer was uncorrected.The in vitro inhibiting ADP-induced platelet aggregation activities of target compoundshave been tested by Born turbidimetric methods. The results revealed that three compounds(PN450,PN452,PN454) have higher inhibition rate than the positive control drugs picotamideand aspirin. Compound PN450exhibited the lowest IC50value, whose pharmacologicalactivity superior to two reference drugs. While IC50value of PN452was similar to tworeference drugs. So two target compounds PN450and PN452have a promising future asantithrombotic drugs.Screening three target compounds (PN450,PN452,PN454) with higher activities furtherstudy on their acute toxicity, taking picotamide and aspirin as the positive control drugs. Thetest results showed that the overall toxicity quite minor was far lower than aspirin and near topicotamide. In addition, taken picotamide as reference drugs, chosen two compounds (PN450,PN452) with ideal pharmacological activity and acute toxicity to study their cell toxicity, byresearching the interaction of target compounds with L929cells. Cytotoxicity test ofcompounds PN450and PN452on L929cells showed that two tested compounds in high andgeneral doses have low toxicities on cells, similar to reference drugs picotamide.Finally, the preliminary structure-activity relationship of target compounds was summari-zed according to the pharmacology results and new data provided support for the laboratoryresearch in the future.