Pelayo Camps

TL;DR: A novel series of donepezil-tacrine hybrids designed to simultaneously interact with the active, peripheral and midgorge binding sites of acetylcholinesterase have been synthesized and tested, exhibiting IC50 values in the subnanomolar or low nanomolar range in most cases.

TL;DR: Molecular modeling simulations of the AChE-inhibitor complex provided a basis to explain the differences in inhibitory activity of these compounds and supported the tight-binding character of compounds (-)-20 and (-)-30 and showed their ability to cross the blood-brain barrier.

TL;DR: Two isomeric series of dual binding site acetylcholinesterase (AChE) inhibitors that retain the potent and selective human AChE inhibitory activity of the parent 6-chlorotacrine while exhibiting a significant in vitro inhibitoryActivity toward the AChe-induced and self-induced Abeta aggregation and toward BACE-1, as well as ability to enter the central nervous system, which makes them promising anti-Alzheimer lead compounds.

TL;DR: Huprine X is a novel acetylcholinesterase (AChE) inhibitor, with one of the highest affinities reported for a reversible inhibitor, a synthetic hybrid that contains the 4-aminoquinoline substructure of one anti-Alzheimer drug, tacrine, and a carbobicyclic moiety resembling that of another AChE inhibitor, (-)-huperzine A.

TL;DR: This work reviews from a structural point of view the main classes of dimeric or hybrid compounds developed for the treatment of Alzheimer's disease, along with the pharmacological profile of the most active compounds.