Palladium-Catalyzed Synthesis, Acetylcholinesterase Inhibition, and Neuroprotective Activities of -Aryl Galantamine Analogues.

A series of new -aryl galantamine analogues (-) were designed and synthesized by modification of galantamine, using Pd-catalyzed Buchwald-Hartwig cross-coupling reaction in good to excellent yields. The cholinesterase inhibitory and neuroprotective activities of -aryl derivatives of galantamine were evaluated. Among the synthesized compounds, the 4-methoxylpyridine-galantamine derivative () (IC = 0.19 μM) exhibited excellent acetylcholinesterase inhibition activity, as well as significant neuroprotective effect against HO-induced injury in SH-SY5Y cells. Molecular docking, staining, and Western blotting analyses were performed to demonstrate the mechanism of action of . Derivative would be a promising multifunctional lead compound for the treatment of Alzheimer's disease.