Structure Design And Synthesis Of 4-Ethoxy-1,3-Benzenedisulfonamide Derivatives And Anti-Platelet Aggregation Activity In Vitro

This paper concisely describes the latest development of thrombosis diseases and treatment of the classification and action mechanism of thrombosis diseases drugs,using the related theories,15 compounds have been designed and synthesized,all of which have been carried a series of related pharmacological research.12 early compounds(*)were selected as a comparative object,explored the preliminary structure-activity relationship(SAR).Based on the pharmacological activities of Picotamide,combined with the earlier work of laboratory,15 4-ethoxybenzene-1,3-disulfnamides have been designed and synthesized.All the target compounds were confirmed by Melting point,ESI-MS,1H-NMR,IR and13C-NMR.Firstly,ADP,used as a inducer,the anti-platelet aggregation test in vitro of 15 target compounds were experimented by Born turbidimetry.The experiment found that the anti-platelet activities of PN604,PN618 and PN700 are better than Picotamide and Aspirin.Among of them,PN618 has the highest activity and minimum IC50.Then,collagen and arachidonic acid were choosed as inducers for the further experiments.The results showed PN612 has the highest activity induced by collagen and PN617 has the highest activity induced by arachidonic acid,all of them were higher than Aspirin and Picotamide.In the end,the compounds of PN604,PN612,PN617,PN618 and PN700 were tested with L-929 cells,because of their better activities.The experimental results showed that whether in high drug concentration(100 ?mol/L),or in low dose concentration(10 ?mol/L),PN612 always has higher cell survival rate than Aspirin and Picotamide.In addition,the cell survival rate of PN618 was about the same as Aspirin.The compound of PN612 showed high activity of anti-platelet aggregation in vitro,especially induced by collagen,its activity was highest.Moreover,in L-929 cell toxicity experiment,under the different drug concentrations,the relative cell survival rates of PN612 were higher than controlled drugs,showed lower toxicity.Above all,PN612 has the meaning of further study.