5-酰胺基-1H-咪唑并[5,4-b]吡啶类衍生物的合成及其血管紧张素Ⅱ受体拮抗活性研究  

Synthesis of 5-Amido-1H-imidazo\pyridine Derivatives and Their AngiotensinⅡ Receptor Antagonistic Activities

作　　者：徐进宜[1] 华维一[1] 吴晓明[1] 王秋娟[2] 胡松[2] 

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

出　　处：《高等学校化学学报》2005年第6期1067-1071,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:30371688);教育部重点基金(批准号:03089)资助.

摘　　要：在对已上市及正在临床研究阶段的非肽类血管紧张素(A)受体拮抗剂的结构参数和定量构效关系研究的基础上,应用计算机辅助药物设计、生物电子等排及结构拼合等药物设计方法,设计并合成了16个结构全新的5-酰胺基-1H-咪唑并[5,4-b]吡啶类衍生物,其结构经过IR,1HNMR和MS确证.初步生物活性研究结果表明,部分目标化合物对A引起的兔胸主动脉环收缩反应具有显著的拮抗活性.构效关系分析提示,5-酰胺基-1H-咪唑并[5,4-b]吡啶类衍生物具有良好的A受体拮抗活性,N-苯基-1H-吡咯四氮唑基团可作为新型A受体拮抗剂设计的侧链替代结构.AngiotensinⅡ(AⅡ) receptor antagonists are clinically useful for the management of cardiovascular disease. Based on the analysis of the quantitative structure-activity relationships of forty-two new compounds reported in literatures as AⅡ receptor antagonists, a series of novel 5-amido-1H-imidazo\pyridine derivatives were designed and synthesized by application of the methods of computer aided drug design and principles of bioisosterism and hybridization. All of them were first reported and their structures were confirmed by IR, ()~1H NMR and MS spectra. The results of preliminary pharmacological tests in vitro show that some target compounds have certain antagonistic activity of AⅡ receptor. Moreover, the analysis of SAR suggests that N-phenylpyrrole-2-tetrazole can be used as a substitution for future designing of novel AⅡreceptor antagonists.

关 键 词：5-酰胺基-1H-咪唑并[5 4-b]吡啶衍生物 合成 AⅡ受体拮抗活性 降压 心衰 

分 类 号：O626[理学—有机化学]