Progress in acetylcholinesterase inhibitors for Alzheimer's disease: an update

Background: To date, the pharmacotherapy of Alzheimer's disease (AD) has been based on acetylcholinesterase inhibitors (AChEls), and more recently on an N-methyl-D-aspartate receptor antagonist. By increasing acetylcholine concentration in the brain, AChEls slow behavioral and functional impairments, improving cognitive function. Objective: The review provides an update on novel analogs of approved AChEls, their combination with other anti-AD agents, natural AChEls, and modern multitarget-directed ligands (MTDLs) able to hit different biological targets. Methods: We reviewed patents filed during 2005 - 2007 dealing with new AChEls and their potential application for AD treatment. We point out new chemical structures and scaffolds for designing new AD therapeutic agents as well as new combinations or MTDLs. Results and conclusions: Compared to the limited number of novel commercially available AChEl analogs, many new natural compounds were patented for AD treatment. These might represent a starting point for the rational design of new MTDLs.