Synthesis, Characterization, and Cholinesterase Inhibitory Activity of 2‐Aminothiazole Derivatives

ABSTRACT To find novel acetylcholinesterase inhibitors for the treatment of Alzheimer's disease, eighteen 2‐amino thiazole derivatives were synthesized by combining ethyl 2‐aminothiazole‐4‐carboxylate with alcohols, phenols, or acid substituents through chloroacetyl chloride. The structures of the target compounds ( 4a ‐ 4r ) were confirmed by FT‐IR, 1 H‐NMR, 13 C‐NMR, and HRMS. The acetylcholinesterase inhibitory activities of those compounds were evaluated by Ellman's method. Most of the compounds showed potent inhibitory activities against acetylcholinesterase. Compound 4m had the best acetylcholinesterase inhibitory activity with an IC 50 of 1.48 ± 0.28 µM. The inhibitory activity of the compound increased with the increase in concentration. The results of molecular docking showed that compound 4m binds to both the catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase. In addition, ADME results showed that these compounds had good trafficability. In summary, compound 4m shows a strong potential as an acetylcholinesterase inhibitor, which is expected to be further studied for the treatment of Alzheimer's disease.