Study On Design And Synthesis Of 4-methoxybenzene-1, 3-isophthalamide Derivatives And 4-methoxybenzene-1,3-disulfonamide Derivatives

The significance of studying on the platelet aggregation inhibitor and that pathogenesis and formation of thrombus and platelet was described in this paper. And mechanism and structure activity relationship of anti-platelet and anti-thrombus drugs were discussed including latest development and research. Eleven target compounds which all had not yet been reported have been designed and synthesized,and of them ,the anti-platelet aggregation activity and the acute toxicity of three target compounds have been texted.According to corresponding literature and previous works of our laboratory, to find more effective, broad-spectrum and low toxically anti-platelet inhibitors, Picotamide was chosen as a leading compound, which can simultaneously inhibit TXA₂ synthetase and antagonise TXA2/PGH2. Based on the result of CoMFA, according to combination principle, we connected this effective structure to designe and synthesis six aryl amide derivatives PN301^PN306. And according to bioisosterism principle, with the group of 4-methoxyl-1, 3-benzenedisulfonamide replacing the 4-methoxyl-1, 3-benzenedicarboxamide, we designed and synthesized five arylsulfonamide derivatives PN307^PN311. All the structures of compounds were identified by IR and 1^H-NMR.In addition, the preliminary screening to acute toxicity and their anti-platelet aggregation activity of compounds PN305,PN306 and PN311 have been tested. The results shows that three compounds had higher activity than Picotamide and low toxicity. These results provide some important references for our laboratory to research new drugs.