N-{[(硫色满-4-酮-3-基)-苯基]-甲基}乙酰胺类化合物的合成、α-葡萄糖苷酶抑制活性评价及分子对接研究  

Synthesis, biological activity and molecular docking research of N-{[(4-oxo-thiochroman-3-yl)phenyl]-methyl}acetamide derivatives as α-glucosidase inhibitors

作　　者：周冠[1,2] 梁国超[1,2] 韩晓燕[1,2] 钟一凡[1,2] 董芸芳 罗晓聪 金宏威[4] 宋亚丽[1,2] 

机构地区：[1]河北大学药学院,河北省药品质量控制重点实验室,河北保定071002 [2]河北大学药物化学与分子诊断教育部重点实验室,河北保定071002 [3]永信药品工业(昆山)有限公司,江苏苏州215300 [4]北京大学药学院,天然药物及仿生药物国家重点实验室,北京100191

出　　处：《药学学报》2016年第1期93-99,共7页Acta Pharmaceutica Sinica

基　　金：河北大学自然科学基金资助项目(2010-194);河北省药物质量分析控制重点实验室开放基金资助课题

摘　　要：利用Dakin-West反应"一锅法"合成了12个N-{[(硫色满-4-酮-3-基)-苯基]-甲基}乙酰胺衍生物。所合成的化合物经~1H NMR、^(13)C NMR、IR和HR-MS等方法进行了结构表征。葡萄糖氧化酶法测试结果表明,大多数目标分子表现出α-葡萄糖苷酶抑制活性,其中化合物4k抑制作用最强(在浓度为5.39 mmol·L^(-1)时,绝对抑制活性达到87.3%)。根据活性测试结果对合成化合物的构效关系进行了讨论。用分子对接方法研究了化合物4k与α-葡萄糖苷酶的作用模式,为进一步的研究提供了依据。In order to develop potent antidiabetic agents that have inhibitory effect to α-glucosidase, twelve β-acetamido ketone derivatives such as N-{[（substituted-4-oxo-thiochroman-3-yl）phenyl]-methyl}acetamide are designed and synthesized through one-pot Dakin-West reaction. Their chemical structures are confirmed by ^1H NMR, ^13C NMR, IR and HR-MS. In vitro α-glucosidase inhibition assays of compounds 4a-4l were carried out using glucose oxidase method. The result indicated that most of them possess inhibitory activity in vitro. Compound 4k showed the most potent inhibitory activity with 87.3% inhibition of α-glucosidase at the concentration of 5.39 mmol·L^-1. The structure-activity relationship of these β-acetamido ketone derivatives was discussed preliminarily. Moreover, the molecular docking method was used to study the interaction mode of compound 4k and α-glucosidase. Our results will be helpful for designing of α-glucosidase inhibitors in the future.

关 键 词：硫色满酮 Α-葡萄糖苷酶抑制剂 一锅法 β-乙酰氨基酮 

分 类 号：R916[医药卫生—药学]