Design,Synthesis,and Biological Evaluation of 5H-Thiazolo[3,2-a]pyrimidine-6-carboxylic Acid Ethyl Ester Derivatives as a Novel Series of Acetylcholinesterase Inhibitors  

作　　者：ZHI Hui CHEN Lan-mei ZHANG Lin-lin LIU Si-jie David Chi Cheong WAN LIN Huang-quan HU Chun 

机构地区：[1]School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China [2]Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong SAR, P. R. China

出　　处：《Chemical Research in Chinese Universities》2009年第3期332-337,共6页高等学校化学研究（英文版）

摘　　要：Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.

关 键 词：Acetylcholinesterase inhibitor Docking screening HETEROCYCLE Biological activity 5H-Thiazolo[3 2-a] pyrimidine-6-carboxylic acid ethyl ester derivative 

分 类 号：O623.624[理学—有机化学] TQ455.43[理学—化学]