Xiu Jie Liu
Abstract
Introduction Platelet aggregation is one of the most significant factors in the development of thrombotic disorders, which plays a central role in thrombosis (clot formation). Picotamide (Figure 1), also known as N,N’-bis(3-pycolyl)-4-methoxylisophthalamide, is an antiplatelet drug with a dual inhibitory action, which inhibits both thromboxane A (TXA2 ) receptors and TXA2 synthase and at variance with aspirin, does not interfere by endothelial prostacylin (PGI2) production. On the purpose of searching for novel antiplatelet aggregating drugs, since 2000,we have carried out the antiplatelet aggregating activity studies of various series of isophthalamides of series 1 (Figure 1), which are the structural analogues of Picotamide and was synthesized via replacing the two 3-pycolyl groups in picotamide with two substituted phenyl groups attached to the nitrogen atoms. And in which some compounds exhibited higher antiplatelet aggregation activities than picotamide. After 2005, in continuation of our interest on the synthesis of related compounds N,N’-disubstitutedphenyl-4-methoxyl-benzene-1,3-disulfonamidesseries of series 2 (Figure 1) , it is based on that benzene-1,3-disulfonamide is the isostere of isophthalamide. In order to further study the structure-activity relationship (SAR) of the benzene-1,3-disulfonamides in antiplatelet aggregation, especially the influence of different meta-position substitutedphenyl groups on anti-platelet aggregation activities, 18 N,N’-di(3-substitutedphenyl)-4-methoxybenzene-1,3-disulfonamides were synthesized and their in vitro anti-platelet aggregation activities were screened induced by adenosine diphosphate (ADP) using the Born’s method in this article. Besides, comparison of the in vitro anti-platelet aggregation activities of the same substitutions attached to the same positions of the two side chain benzene rings between series 1 and series 2, respectively. The chemical structures of these target compounds were confirmed by IR, 1H-NMR and M (Figure 1). Figure 1. Structures of Picotamide (1), Isophthalamides (2) and Benzene-1,3-disulfonamides (3).