Palladium-catalyzed synthesis and anti-AD biological activity evaluation of N -aryl-debenzeyldonepezil analogues

A series of novel -aryl-debenzeyldonepezil derivatives ( ) were designed and synthesized as cholinesterase inhibitors by the modification of anti-Alzheimer's disease drug donepezil, using Palladium catalyzed Buchwald-Hartwig cross-coupling reaction as a key chemical synthesis strategy. cholinesterase inhibition studies demonstrated that the majority of synthesized compounds exhibited high selective inhibition of AChE. Among them, analogue possessing a quinoline functional group showed the most potent AChE inhibition effect and significant neuroprotective effect against H O -induced injury in SH-SY5Y cells. Furthermore, Compound did not show significant cytotoxicity on SH-SY5Y. These results suggest that is a potential multifunctional active molecule for treating Alzheimer's disease.