Synthesis And Study On The Activities Of N,N'-dihalophenyl-1,3-Benzenedisulfonamides

Thrombosis refers to abnormal blood clots formed in the blood circulation under some inducement conditions,or massive spots come away from the walls either cardiovascular and cerebrovascular vessels.Antithromboxane therapy is a benefit therapy method especialy aimed at thrombin and platelet two links.Of which,anti-platelet drug is one very impotant kind drug to prevent and treat the formation of coronary or cerebrovascular thrombosis.In order to develop new anti-platelet aggregation drugs of more broad spectrum,high efficiency and less side effects,take the Picotamide as the leader compound in this paper,which have dual roles of inhibition of TXA2 synthase and antagonism of TXA2 / PGH2 receptor.According to the principle of bioelectrical isotopes,we resembled the structure features and remarked its two side chains on N1-and N3-positions of Picotamide by instead of isophthalamide groups with benzene-1,3-sulfonamide groups.On the basis of computer-aided drug design from the MDQSAR,17 target 4-Methoxybenzene-1,3-disulfonamides(PN217-222,PN566-574,PN577,PN578)were designed and synthesized..And their structures have been confirmed by1H-NMR,13C-NMR,mass spectrometry and infrared spectroscopy.In vitro induced by ADP,the anti-platelet aggregation activities of each target compound were tested and assessed by Born's method on rabbits.The pharmacological data showed,among seventeen compounds,that the in vitro activities at the density of 10-6mol/L,seven showed higher activities than that of the positive control drug Picotamide,while three compounds PN217,PN220 and PN568,their inhibition rates were 41.8%,43.1 % and 48.6%respectively,higher than another positive control drug Aspirin's 38.6%,and the activities of other four compounds PN566,PN570,PN574 and PN578 are close to Aspirin at the same density.On the basis of the pharmacology results,the preliminary SAR(structure-activity relationship)was summarized and provided a new reference for the laboratory research in near future.