取代苯甲酰胍与曲美他嗪偶联物的合成及对Na^+/H^+交换器-1的抑制活性  

Synthesis and Na^+/H^+ exchanger 1 inhibitory activity of substituted benzoylguanidine-trimetazidine conjugates

作　　者：杜萍[1] 张迪[1] 张国敏[2] 任淑娟[1] 龚国清[2] 徐云根[1] 

机构地区：[1]中国药科大学药物化学教研室,南京210009 [2]中国药科大学药理学教研室,南京210009

出　　处：《中国药科大学学报》2011年第1期22-28,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30672512)~~

摘　　要：为了寻找对心肌缺血再灌注损伤具有保护作用的药物,并探索不同基团修饰对苯甲酰胍与曲美他嗪偶联物活性的影响,将苯甲酰胍的4位通过亚甲基与曲美他嗪进行偶联,并在苯环的3位引入不同的取代苯甲酰胺基,设计合成了12个未见文献报道的目标化合物。其结构经过IR,1H NMR和MS确证。体外血小板肿胀模型(PSA)试验结果表明,化合物9b和9c抑制Na+/H+交换器-1(NHE1)的IC50分别为2.55和2.80 nmol/L,其活性是卡立泊来德(IC50=12.1 nmol/L)的4.7和4.3倍。In order to search for drugs with protective effects against myocardial ischemic-reperfusion injury,and study the structure-activity relationship of benzoylguanidine derivatives,a novel series of 4-[4-（2,3,4-trimethoxybenzyl）piperazin-1-yl]-methyl and 4-{1-[4-（2,3,4-trimethoxy-benzyl）piperazin-1-yl]}-ethyl benzoylguanidine derivatives were designed and synthesized,and their structures were characterized by MS,IR,1H NMR.Na＋/H＋ exchanger 1（NHE1） inhibitory activity of twelve target compounds was evaluated in a rat platelet swelling assay.Among all the tested compounds,the IC50 values of compounds 9b and 9c were 4.7 and 4.3 times more potent than cariporide（IC50=12.1 nmol/L）,respectively.

关 键 词：苯甲酰胍衍生物 缺血再灌注损伤 合成 NHE1抑制活性 

分 类 号：R914[医药卫生—药物化学]