Design,Synthesis And In Vitro Activities On Anti-Platelet Aggregation Of 4-Ethoxybenzene-1,3-Disulfonamides

The significance of research the platelet aggregation inhibitor was explained in this thesis.And we have discussed the structure activity relationship of anti-platelet aggregation drugs.The design,synthesis and anti-platelet aggregation activity of fourteen target compounds have been reported.According to corresponding literatures and the previous works of our laboratory,We chose Picotamide was chosen as leading compound,which can simultaneously inhibit TXA₂synthetase and antagonise TXA₂/PGH₂.Based on the result of Co MFA,fourteen arylsulfon-amide and disulfonamides were designed according to bioisosterism and combination principle.In continuation of our interest on the synthesis of related compounds N,N’-disub-stitutedphenyl-4-ethoxy-benzene-1,3-disulfonamides,it is based on that benzene-1,3-disulfon-amide is an isosteres of isophthalamide.At last we get the products（PN623,PN624,PN626,PN627,PN651,PN656,PN657,PN680 and PN682）by replacing the 4-methoxy with4-ethoxy.All the compounds were synthesized and identified by IR,MS and 1H-NMR.They all have not yet been reported.Through Born turbidity method,their anti-platelet aggregation activity was tested.Among these compounds,compounds PN547,PN548,PN627 and PN623have very obviously anti-platelet aggregation activities,and compounds PN651,PN657&PN549 have good anti-platelet aggregation activities.According to pharmacology results,the structure activity relationship of target compounds was summarized.Otherwise four lowest acute toxicity compounds PN548,PN623,PN627 and PN627 were picked out to carry L-929Cytotoxicity test and the result showed that PN627 has lower toxicity,but each of them are higher than that of the Picotamide’s..