Molecular modelling, synthesis and acetylcholinesterase inhibition of ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate

Elena Soriano; Abdelouahid Samadi; Mourad Chioua; Cristóbal de los Ríos; José Marco-Contelles

doi:10.1016/j.bmcl.2010.03.010

Molecular modelling, synthesis and acetylcholinesterase inhibition of ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate

Bioorg Med Chem Lett. 2010 May 1;20(9):2950-3. doi: 10.1016/j.bmcl.2010.03.010. Epub 2010 Mar 4.

Authors

Elena Soriano¹, Abdelouahid Samadi, Mourad Chioua, Cristóbal de los Ríos, José Marco-Contelles

Affiliation

¹ Laboratorio de Radicales Libres y Química Computacional (LRL-QC, IQOG, CSIC), C/Juan de la Cierva 3, 28006-Madrid, Spain.

PMID: 20350807
DOI: 10.1016/j.bmcl.2010.03.010

Abstract

In silico analysis of ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate (2) predicts that this molecule should be successfully docked in the PAS, and easily accommodated in the CAS of AChE. The synthesis and the AChE/BuChE inhibition studies are reported, confirming that compound 2 is a potent and selective AChE inhibitor, and consequently, a new lead compound for further development into new dual CAS/PAS cholinergic agents for the treatment of Alzheimer's disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / chemistry*
Acetylcholinesterase / metabolism
Binding Sites
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology
Computer Simulation
Crystallography, X-Ray
Models, Chemical*
Models, Molecular*
Molecular Dynamics Simulation
Naphthyridines / chemical synthesis
Naphthyridines / chemistry*
Naphthyridines / pharmacology

Substances

Cholinesterase Inhibitors
Naphthyridines
ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo(b)(1,8)naphthyridine-3-carboxylate
Acetylcholinesterase