Thieno[2,3-d]pyrimidines as Novel Scaffolds for Acetylcholinesterase Inhibitors: Synthesis, Biological Activity, and Molecular Studies

inhibitory activity as potential anti-Alzheimer’s agents. The synthesized compounds were characterized through various spectroscopic techniques. Improved activity was observed in molecules containing hydrogen-bond donors and electron-donating moieties, as indicated by SAR findings. Compound 6 showed the highest potency with an IC50 of 0.199 µM. Molecular docking studies demonstrated strong π–π stacking and hydrogen bonding interactions between 6 and key residues in the AChE active site. In silico ADME profiling confirmed drug-like properties in accordance with Lipinski’s rule of five. These results suggest thieno[2,3-d]pyrimidines as promising scaffolds for the development of novel AChE inhibitors.