N-酰基-4-苯基噻唑-2-胺类衍生物的设计、合成及其乙酰胆碱酯酶抑制活性的研究  

Design, synthesis and evaluation of N-acyl-4-phenylthiazole-2-amines as acetylcholinesterase inhibitors

作　　者：马正月[1] 杨琦[1] 张元功[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6期813-818,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：以α-溴代苯乙酮作为原料,经过3步反应,合成了N-酰基-4-苯基噻唑-2-胺类化合物。采用Ellman分光光度法测试了化合物对乙酰胆碱酯酶的体外抑制活性,结果表明,目标化合物具有一定的乙酰胆碱酯酶抑制活性,其中化合物8c的抑制活性最好,其IC50达到了0.51μmol·L-1,优于利斯的明和石杉碱甲。N-酰基-4-苯基噻唑-2-胺对乙酰胆碱酯酶的抑制活性值得进一步研究。N-Acyl-4-phenylthiazole-2-amines were designed and synthesized, moreover their effects on acetylcholinesterase activities were tested. N-Acyl-4-phenylthiazole-2-amines were prepared from substituted 2-bromo-1-acetophenones by three steps reaction, and their AChE inhibitory activities were measured by Ellman method in vitro. The results showed that the target compounds had a certain inhibitory activity on AChE in vitro. Among them, 8c was the best, and IC50 of 8e was 0.51 μmol·L-1, better than that of rivastigmine and Huperzine-A. The inhibitory activities of N-acyl-4-phenylthiazole-2-amines on acetylcholinesterase are worth while to be further studied.

关 键 词：N-酰基-4-苯基噻唑-2-胺 乙酰胆碱酯酶抑制剂 阿尔兹海默症 

分 类 号：R916[医药卫生—药学]