Synthesis And In Vitro Activities On Anti-platelet Aggregation Of4-methoxy Benzene-1,3-disulfonamides

This paper reviewed the pathogenesis and harm of thrombosis and thedevelopment prospects， as well as the studying significance of anti-plateletaggregation drugs was discussed.Based on the principle of new drug design and bioisosterism and the previousresearch work in our laboratory, seventeen4-methoxybenzene-1,3-disulfonamidecompounds (P1-P17), of which ten compounds have been first reported in this paper,were designed and synthesized with the N1, N3-bis (2-acetylphenyl)-4-methoxyisophthalamide as the leader compound, which was screened with higheranti-platelet aggregation. All the target compounds have been confirmed by IR and1H-NMR spectra, and some of the compounds are confirmed by MS data.The in vitro anti-platelet aggregating activities of the target compounds (P1-P17)have been tested by the means of Born turbidimetric method. The experimental resultsshowed that eight kinds of target compounds have significant anti-platelet aggregationactivities, and were superior to the control drug Picotamide and aspirin. CompoundP13has the highest activity with IC500.46.The acute toxicity of compounds P10, P13, P15and P17were tested and theresults showed that four of the tested compounds (P10, P13, P15and P17)respectively exhibited low toxicity and have further study and development value.Cytotoxicity test of compounds P10, P13and P15on L929cell showed that all of thethree tested compounds in middle and high dose have high survival rate, relatively.According to the pharmacology results, preliminary structure-activity relationship oftarget compounds was summarized and provided a new basis and reference for thefuture research work of our laboratory.