Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2-]Pyrimidines as New Acetylcholinesterase Inhibitors.

A new series of thiazolo[3,2-]pyrimidine bromide salt derivatives - were synthesized from 3,4-dihydropyrimidinethione precursors. The target compounds were fully characterized by 1D- and 2D-NMR, high resolution ESI-MS/MS and single crystal X-ray diffraction analysis, which confirmed a regioselective 5 cyclization of the dihydropyrimidinethiones. All target compounds were evaluated in vitro as human acetylcholinesterase (AChE) inhibitors via an Ellman-based colorimetric assay and showed good inhibition activities (better than 70% at 10 µM and IC values in the 1 µM range). Molecular docking simulations for all target products into AChE were performed and confirmed strong binding to the enzyme. These results provide a promising and new starting point to improve acetylcholinesterase inhibitors and explore novel treatment options against Alzheimer's disease.