新型乙酰胆碱酯酶抑制剂的设计、合成与活性研究  

Design, synthesis and evaluation of new 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3期346-351,共6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(11966411D)

摘　　要：本文设计、合成了一类全新结构类型的2-氨基-4-苯基噻唑类化合物,并考察了这些化合物对乙酰胆碱酯酶活性的抑制作用。以α-溴代苯乙酮为起始原料,经Hantzsch、酰化和取代反应合成了2-氨基-4-苯基噻唑类化合物,并利用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。实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8a抑制活性最好,其IC50达到了3.54μmol·L-1,优于对照药利斯的明。2-氨基-4-苯基噻唑类化合物对乙酰胆碱酯酶具有较好的抑制活性,需要进一步深入研究。A series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase were investigated. 2-Amino-4-phenylthiazoles were prepared from a-bromoacetophenones 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 8a was the best of them. The IC50 of 8a to AChE is 3.54 μmol·L^-1, and the value was better than that of rivastigmine. 2-Amino- 4-phenylthiazole derivatives showed a certain bioactivity in vitro, which were worth further investigation.

关 键 词：2-氨基-4-苯基噻唑 乙酰胆碱酯酶抑制剂 阿尔茨海默病 

分 类 号：R916[医药卫生—药学]