N-酰基-硫色烯并噻唑-2-胺类衍生物的设计、合成及其乙酰胆碱酯酶抑制活性  

Design, synthesis and activity of N-acyl-thiochromenothiazol-2-amine as acetylcholinesterase inhibitors

作　　者：马正月[1] 张元功[1] 杨琦[1] 李俊杰[1] 杨更亮[1] 

机构地区：[1]河北大学药学院,河北省药物质量分析控制重点实验室,河北保定071002

出　　处：《药学学报》2014年第9期1289-1295,共7页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09103-101-057);国家自然科学基金资助项目(21175031);河北省教育厅科研计划资助项目(ZD2010234);河北省科技厅重点基础研究专项(12276403D)

摘　　要：本文设计、合成了一类全新结构类型的N-酰基-硫色烯并噻唑-2-胺类化合物,并考察了这些化合物对乙酰胆碱酯酶活性的抑制作用。以苯硫酚为起始原料,经Hantzsch、酰化和取代反应合成了N-酰基-硫色烯并噻唑-2-胺类化合物;利用Ellman分光光度法考察了它们对乙酰胆碱酯酶(AChE)的体外抑制活性。试验结果表明目标化合物均具有一定的AChE抑制活性,其中化合物10a抑制活性最好,其IC50达到了7.92μmol·L-1,优于对照药利斯的明。N-酰基-硫色烯并噻唑-2-胺类化合物对乙酰胆碱酯酶具有较好的抑制活性,值得进一步深入研究。A series of novel N-acyl-thiochromenothiazol-2-amine derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase was investigated. N-Acyl-thiochromenothiazol-2- amines were prepared from thiophenol by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on ACHE, and the compound 10a was the best in them. The IC50 of 10a to AChE is 7.92 μmol·L^-1, and the value is better than that of rivastigmine. N-Acyl-thiochromenothiazol-2-amine derivatives showed a certain bioactivity in vitro, which were worth further investigation.

关 键 词：阿尔茨海默症 乙酰胆碱酯酶抑制剂 N-酰基.硫色烯并噻唑-2-胺 

分 类 号：R916[医药卫生—药学]