Design, synthesis, and biological evaluation of 5H-thiazolo[3,2-a]pyrimidine derivatives as a new type of acetylcholinesterase inhibitors

Acetylcholinesterase(AChE) inhibitors are important research topics because of their wide range of associated health implications, especially for the treatment of Alzheimer's disease. The finding of novel AChE inhibitors is presented here. A docking screening model of AChE inhibitor was used to evaluate a series of 5H-thiazolo[3,2-a]pyrimidine derivatives. The virtual screening hits were analyzed in drug likeness and physical-chemical features, therefore were focused to those compounds in the present article. To investigate the relationship between the bioactivities and the structures, 10 target compounds with the 5H-thiazolo[3,2-a]pyrimidine scaffold were synthesized as potential AChE inhibitors, and the pharmacological assay result also conformed, some compounds displayed considerable inhibitory effects with inhibition rates above 50% at 10 mu M, and all their core structures are very different from those of known AChE inhibitors. The results demonstrate the effectiveness and validity of the virtual screening approach especially of the docking screening approach, and provide a starting point for the development of novel drugs to treat Alzheimer's disease.