Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors

作者：Costanzo Paola; Cariati Luca; Desiderio Doriana; Sgammato Roberta; Lamberti Anna; Arcone Rosaria; Salerno Raffaele; Nardi Monica; Masullo Mariorosario; Oliverio Manuela^*

来源：ACS Medicinal Chemistry Letters, 2016, 7(5): 470-475.

DOI：10.1021/acsmedchemlett.5b00483

• Alzheimer's disease
• donepezil analogues
• indanones
• aldol condensation
• acethylcholinesterase

An ecofriendly synthetic pathway for the synthesis of donepezil precursors is described. Alternative energy sources were used for the total synthesis in order to improve yields, regioselectively, and rate of each synthetic step and to reduce the coproduction of waste at the same time. For all products, characterized by an improved structural rigidity respect to donepezil, the inhibitor activity on AChE, the selectivity vs BuChE, the side-activity on BACE-1, and the effect on SHSY-5Y neuroblastoma cells viability were tested. Two potential new lead compounds for a dual therapeutic strategy against Alzheimer's disease were envisaged.

• 出版日期2016-5