Study On Design, And Synthesis And Activity Of 4-Methoxybenzene-1, 3-disulfonamide Derivatives

The significance of studying the platelet aggregation inhibitor was described in this thesis. And the structure activity relationship of anti-platelet aggregation drugs was discussed. The design, synthesis and anti-platelet aggregation activity of fourteen target compounds have been reported.According to corresponding literature and the previous works of our laboratory, Picotamide was chosen as a leading compound, which can simultaneously inhibit TXA₂ synthetase and antagonise TXA₂/PGH₂. Based on the result of CoMFA, fourteen arylsulfonamide derivatives were designed by bioisosterism and combination principle. All the compounds were synthesized and identified by IR and ¹H-NMR. They all had not yet been reported. Through Born turbidity method, the anti-platelet aggregation activity was tested. Among these compounds, ten had higher activity than Picotamide and four had equivalent or lower activity. According to pharmacology results, the structure activity relationship of target compounds was summarized.In addition, through orthogonal experimentation design method, the process of 4-methoxybenzene-1,3-disulfonyl dichloride, core intermediate of target compounds, was improved, which has provided advantage for the synthesis of target compounds.