ChemMedChem

Cover image for Vol. 12 Issue 18

Editorial Board Chairs: Karl-Heinz Altmann, Antonello Mai, Rainer Metternich. Editor: David Peralta

Impact Factor: 3.225

ISI Journal Citation Reports © Ranking: 2016: 17/60 (Chemistry Medicinal); 73/256 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

November 04, 2011

VIP: Huprine Derivatives as Sub-Nanomolar Human Acetylcholinesterase Inhibitors: From Rational Design to Validation by X-ray Crystallography

VIP: Huprine Derivatives as Sub-Nanomolar Human Acetylcholinesterase Inhibitors: From Rational Design to Validation by X-ray CrystallographyCyril Ronco, Eugénie Carletti, Jacques-Philippe Colletier, Martin Weik, Florian Nachon, Ludovic Jean, Pierre-Yves Renard*

Acetylcholinesterase (AChE) plays a central role in nerve signal transmission. Its inhibition was the first strategy in the palliative treatment of Alzheimer’s disease (AD). Therefore, over the past decades, medicinal chemists have focused on the discovery of potent and selective reversible inhibitors of human AChE. Prof. Pierre-Yves Renard at the University of Rouen (France) and his collaborators at the Institut de Biologie Structurale and Institut de Recherche Biomédicale des Armées in Grenoble (France) carried out a complete study, from rational design to validation by X-ray structure, that allowed the prediction of inhibitory potency and led to the synthesis of two huprine derivatives with excellent inhibitory activity. These molecules are among the best human AChE inhibitors reported to date. The multifactorial and complex etiology of AD requires medicinal chemists to develop multifunctional drugs that can target two or more of the pathogenic mechanisms involved in AD. In this context, the two molecules developed by Renard and his collaborators are a good starting point for the preparation of new, potentially multi-target treatments for AD.

Received September 19, 2011; published online November 4, 2011, DOI: 10.1002/cmdc.201100438.

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