Synthesis Of N-acyl Thiazole Derivatives And Their Inhibitory Activity To Acetylcholinesterase

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by aprogressive loss of cognitive and memory abilities associated with various behavioraldisturbances. AD has drawn extensive attention due to its high prevalence in older people,underscored in a rapidly aging world population. One pharmacological approach is to restoreacetylcholine level by inhibiting acetylcholinesterase (AChE) with reversible inhibitors, thushelping to improve the cognitive and memory symptoms of the disease.In this paper, we designed and synthesized14new2-amino-4-phenylthiazole’sderivatives and they were confirmed by1H-NMR, MS and IR. We carried out the inhibiton ofAChE activity in vitro experiments which had not been studied before. The experimentsshowed that8a had a better AChE inhibition activity with IC50=3.54μmol/L. Meanwhile, wesynthesized18new N-Acyl-thiochromenothiazol-2-amine compounds and they wereconfirmed by1H-NMR, MS and IR. In vitro inhibition of AChE activity test,21a had the bestAChE inhibitory activity with IC50=7.92μmol/L. The activity of8a and21a are superior tothe compared rivastigmine.To study the mechanism of the compounds on acetylcholinesterase, the enzymatickinetics study of compound8a which held the best activity was carried out. Theexperimental results showed that machanism of the compound had a mixed competitiveinhibition type, meanwhile it may act on the two active sites ofAChE.