新型二氢嘧啶类化合物的合成及其抗乙型肝炎病毒活性研究  

Synthesis and Anti-HBV Activity of Novel Dihydropyrimidine Analogs

作　　者：赵国明[1] 王晓奎[1] 朱学军[1,2] 关华[1,3] 钟武[1] 王莉莉[1] 肖军海[1] 杨晓虹[2] 李松[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]吉林大学药学院,长春130021 [3]军事医学科学院放射医学研究所,北京100850

出　　处：《中国科学：生命科学》2011年第10期971-977,共7页Scientia Sinica(Vitae)

基　　金：国家“重大新药创制”科技重大专项(批准号:2009ZX09103-026)资助项目

摘　　要：以芳香氰基化合物为起始原料,经胺解、乙酰化、催化氢化、关环等步骤得到新型二氢嘧啶类化合物14个,结构通过核磁共振氢谱、质谱、元素分析确证,并利用HepG2.2.15细胞进行了体外抗HBV活性评价.结果表明部分化合物具有明显的抗HBVDNA复制作用,其中化合物5c和5n抑制HBVDNA复制的半数有效浓度分别为0.87μmol/L和0.67μmol/L.初步探讨了活性化合物的构效关系,同时运用分子排阻色谱法考察了活性化合物与病毒衣壳蛋白的相互作用.Fourteen novel dihydropyrimidine analogs were synthesized from aromatic nitriles through ammonolysis,acetylation,catalytic hydrogenation and cyclization procedures.All the compounds were characterized by 1H NMR,MS and elemental analysis and the antiviral activity was tested in transfected HepG2.2.15 cells.The results show that some compounds had effective activity.The IC50 of compounds 5c and 5n were 0.87 and 0.67 μmol/L,respectively.The structure-activity relationship of 2-heteroaryl was discussed and the interaction of active compounds with capsid was studied by size exclusion chromatography.

关 键 词：二氢嘧啶 乙型肝炎病毒 衣壳 分子排阻色谱 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]