Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer’s drugs. A series of 6-acetyl-
5H-thiazolo[3,2-a]pyrimidine derivatives as the novel acetylcholinesterase inhibitors were designed based on virtual
screening methods. The target compounds which are not reported in the literature 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
showed most of the target compounds exhibited varying inhibition at 10 µM using the Ellman method. The results
provide a starting point for the development of novel drugs to treat Alzheimer’s disease, and a foundation in search for
improved acetylcholinesterase inhibitors with the novel scaffolds. The preliminary structure-activity relationships were
the 2-hydroxyethoxy group at the phenyl ring at C4 position of the parent nucleus played significant roles in the AChE inhibitory
activity of the target compounds.
Keywords: Acetylcholinesterase inhibitor, 6-Acetyl-5H-thiazolo[3, 2-a]pyrimidine derivatives, Biological activity, Docking
screening, Heterocycles, Synthesis.
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