Synthesis And Study On Antiiplatelet Activity&Toxicity Of 4-ethoxydisulfonamides

The anti-thrombotic drugs,the body's pathogenesis of thrombosis and anti-platelet aggregation drug research were described in this paper.Based on the previous work,twenty five new 4-ethoxy?sulfonamide?target compounds have been designed and synthesized based on the principle of electronic isotype.The structure of the obtained target product was confirmed by IR,¹H-NMR,¹³C-NMR and ESI-MS spectroscopy.Born turbidimetric method was used to screen the target compounds in vitro against platelet aggregation.The target compound with better activity was selected and L929 cells were used for in vitro cytotoxicity experiments.Based on the pharmacological experimental data,the structure-activity relationship of the target compounds was preliminarily estimated.Anisole was used as the starting material to react with chlorosulfonic acid to form 4-meth-oxy-1,3-benzenedisulfonyl chloride,which was reacted with different aromatic amines respectively to generate six target 4-methoxy-1,3-benzene disulfonamides?PN740-745?.Phenetole as the starting material,react with chlorosulfonic acid to generate the intermediate4-ethoxy-1,3-benzenedisulfonyl chloride and continue to react with different aromatic amines to produce ninteen target 4-ethoxy-1,3-benzene disulfonamides?PN721-739??The resulting target compounds were subjected to an anti-platelet aggregation activity test in vitro using Born turbidimetry.The experimental results showed that ten target compounds?PN723,PN725,PN729,PN731,PN733,PN735,PN736,PN742,PN743,PN744?exhibited higher in vitro anti-platelet aggregation activity.The other 8 target compounds?PN721,PN722,PN724,PN726,PN727,PN728,PN730,PN732?showed comparable or slightly lower activity to Picotamide and aspirin,and 7 target compounds?PN734,PN737,PN738,PN739,PN740,PN741,PN745?showed the opposite activity to the positive control drugs Picotamide and aspirin,that is,they could promote platelet aggregation.Through screening experiments,five compounds PN723,PN725,PN729,PN731 and PN743 were picked for toxicity test.Experimental results,and the mouse fibroblasts L929were used.The experimental results show that the target compound PN731 L929 cell survival rate of more than 80%,less effect on the cells or less toxic.Pharmacological experimental data analysis showed that the initial speculation of the structure-activity relationship of the target compound.In the side chain benzene ring,the same substituent to replace the different positions,the activity of the sort:ortho substitution>meta replacement>para substitution.The order of activities of different substituents for ortho substitution is:electron withdrawing group>donating electron group.Extending the carbon number of aromatic amine chain,is conducive to anti-platelet aggregation activity increased.