@article {502,
	title = {Novel huprine derivatives with inhibitory activity toward beta-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates},
	journal = {ChemMedChem},
	volume = {5},
	year = {2010},
	month = {2010/11/08/},
	pages = {1855 - 1870},
	abstract = {A new family of dual binding site acetylcholinesterase (AChE) inhibitors has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced beta-amyloid (Abeta) aggregation and beta-secretase (BACE-1), and to cross the blood-brain barrier. The new heterodimers consist of a unit of racemic or enantiopure huprine Y or X and a donepezil-related 5,6-dimethoxy-2-[(4-piperidinyl)methyl]indane moiety as the active site and peripheral site to mid-gorge-interacting moieties, respectively, connected through a short oligomethylene linker. Molecular dynamics simulations and kinetics studies support the dual site binding to AChE. The new heterodimers are potent inhibitors of human AChE and moderately potent inhibitors of human BChE, AChE-induced and self-induced Abeta aggregation, and BACE-1, and are predicted to be able to enter the central nervous system (CNS), thus constituting promising multitarget anti-Alzheimer drug candidates with the potential to modify the natural course of this disease.},
	keywords = {\&, 4, Alzheimer, Aminoquinolines/chemistry/pharmacology/therapeutic, Amyloid, beta-Peptides/antagonists, Binding, Butyrylcholinesterase/metabolism;, Cholinesterase, Compounds, Disease/drug, Dynamics, Heterocyclic, Humans;, Indans/chemistry/pharmacology/therapeutic, Inhibitors/chemistry/pharmacology/therapeutic, inhibitors/metabolism;, Kinetics;, Molecular, More, or, Precursor, Protein, Relationship, Rings/chemistry/pharmacology/therapeutic, Secretases/antagonists, Simulation;, Sites;, Structure-Activity, therapy/metabolism/pathology;, use;, with},
	author = {Viayna,E. and Gomez,T. and Galdeano,C. and Ramirez,L. and Ratia,M. and Badia,A. and Clos,M. V. and Verdaguer,E. and Junyent,F. and Camins,A. and Pallas,M. and Bartolini,M. and Mancini,F. and Andrisano,V. and Arce,M. P. and Rodriguez-Franco,M. I. and A. Bidon-Chanal and F. J. Luque and Camps,P. and Munoz-Torrero,D.}
}
