CRCU

Chemical Research in Chinese Universities ›› 2009, Vol. 25 ›› Issue (3): 332-337.

• Articles • Previous Articles     Next Articles

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

ZHI Hui1, CHEN Lan-mei1, ZHANG Lin-lin1, LIU Si-jie1, David Chi Cheong WAN2, LIN Huang-quan2 and HU Chun1*   

  1. 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
  • Received:2008-04-07 Revised:2008-04-22 Online:2009-05-25 Published:2009-08-07
  • Contact: HU Chun, E-mail: chunhu@syphu.edu.cn

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Abstract:

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 10 μmol/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.

Key words: Acetylcholinesterase inhibitor; Docking screening; Heterocycle; Biological activity; 5H-Thiazolo[3,2-a] pyrimidine-6-carboxylic acid ethyl ester derivative