Synthesis and in vitro activities on anti-platelet aggregation of N,N＇-di（2-substituted-phenyl）-4-methoxyisophthalamides and benzene- 1,3-disulfonamides

• Published in: 中国化学快报：英文版 2011, Vol.22 (10), p.1139-1142
• Main Author: Xiu Jie Liu Xin He Cheng Ling Shi Jie Meng Ying Lu Shao Hong Qiang Si Tao Hu
• Format: Article
• Language: English
• Subjects: 体外活性; 化合物; 取代苯基; 合成过程; 抗血小板聚集; 核磁共振; 空间位阻; 阿司匹林
• ISSN: 1001-8417; 1878-5964

On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs,we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives,which contain both 18 N.N＇-di（2- substitutedphenyl）-4-methoxyisophthalamides（2a-2r） of the 2 series and nine N,N＇-di（2-substitutedphenyl）-4-methoxybenzene- 1,3-disulfonamides（3a-3i） of the 3 series.The results showed that three compounds 2e,2i and 3g emerged as significant activities of antiplatelet aggregation,superior to two reference drugs picotamide and aspirin,and eight compounds 2j,2k,21,2o,2p,2q,2r and 3i merely superior to picotamide.The preliminary SAR shows that it is favorable for the 2 series to increase the activities via the steric hindrance substituents attached to the two side chain benzene rings at 2-positions.And the arylamides of the 2 series have better the activity values than the arylsulfonamides of the 3 series respective except for 3b and 3g.On the contrary,electrostatic factors would not contribute evidently to the activities of the two series.The structures of 15 compounds newly synthesized have been established by MS and ~1H NMR and been first reported in this paper.