Abstract:
With the recent research advances in molecular biology and technology multiple credible hypotheses about the
progress of Alzheimer’s disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are
commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in
this work to develop muilti-functional agents, which can mainly serve as dual beta-secretase (BACE 1) and
Acetylcholinesterase (AChE) inhibitors. Series of new compounds were designed, synthesized and evaluated in this
work, from which we identified 2-((4-(1,3-dioxoisoindolin-2-yl)benzyl)amino)-2-oxoethyl-2-(4-methoxyphenyl)acetate
(1h) as a new dual cholinesterase and beta-secretase inhibitor without toxicity.
