A comparative molecular field analysis study of N-benzylpiperidines as acetylcholinesterase inhibitors.

doi:10.1021/JM950704X

Paper

A comparative molecular field analysis study of N-benzylpiperidines as acetylcholinesterase inhibitors.

Published Jan 19, 1996 · W. Tong, E. R. Collantes, Y. Chen

Journal of medicinal chemistry

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60

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0

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Abstract

A series of 1-benzyl-4-[2-(N-benzoylamino)ethyl]piperidine derivatives and of N-benzylpiperidine benzisoxazoles has been investigated using the comparative molecular field analysis (CoMFA) approach. These compounds have been found to inhibit the metabolic breakdown of the neurotransmitter acetylcholine (ACh) by the enzyme acetylcholinesterase (AChE) and hence alleviate memory deficits in patients with Alzheimer's Disease by potentiating cholinergic transmission. Development of the CoMFA model considered two separate alignments: (i) alignment I which emphasized the electrostatic fitting of the subject compounds and (ii) alignment II which emphasized their steric fitting. In addition, the inhibitor compounds were considered both as neutral species and as N-piperidine-protonated species. The resulting 3D-QSAR indicates a strong correlation between the inhibitory activity of these N-benzylpiperidines and the steric and electronic factors which modulate their biochemical activity. A CoMFA model with considerable predictive ability was obtained.

Study Snapshot

N-benzylpiperidines effectively inhibit acetylcholinesterase, alleviating memory deficits in Alzheimer's patients, with a strong correlation between their inhibitory activity and steric and electronic factors.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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A comparative molecular field analysis study of N-benzylpiperidines as acetylcholinesterase inhibitors.

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References

Citations

Synthesis, Docking and Acetylcholinesterase Inhibitory Evaluation of 1,3,4-Thiadiazole Derivatives as Potential Anti-Alzheimer Agents

1,3,4-thiadiazole derivatives show remarkable anticholinesterase activity, suggesting potential as anti-Alzheimer agents.

Synthesis and molecular docking study of thiophene-bearing thiourea derivatives as potential acetylcholinesterase, and butyrylcholinesterase inhibitors

Thiophene-bearing thiourea derivatives show potential as potent acetylcholinesterase and butyrylcholinesterase inhibitors, with compounds 3, 5, 7, 9, and 10 showing many folds better activity than standard drug donepezil.

Validation of Acetylcholinesterase Inhibition Machine Learning Models for Multiple Species

Machine learning models can accurately predict acetylcholinesterase inhibition activity in various species, aiding in identifying potential toxins and aiding in in vitro testing.

Design, Green Synthesis, and Biological Evaluation of New Substituted Tetrahydropyrimidine Derivatives as Acetylcholinesterase Inhibitors

Novel tetrahydropyrimidine derivatives show potent butyrylcholinesterase inhibitory activity and acetylcholinesterase inhibitory effects comparable to donepezil, with 4-methyl substituted derivative 6d showing the best results.

Synthesis, characterization, UV–Vis absorption and cholinesterase inhibition properties of bis-indolyl imine ligand systems

Bis-indolyl imine ligand systems show promising anticholinesterase properties, with compound 9 showing the highest inhibition of acetylcholinesterase and butyrylcholinesterase enzymes compared to standard Galantamine.

The design of novel 4,6-dimethoxyindole based hydrazide-hydrazones: Molecular modeling, synthesis and anticholinesterase activity

Novel 4,6-dimethoxyindole hydrazide-hydrazones show promising anticholinesterase activity, with compound 11b showing the highest inhibition of acetyl- and butrylcholinesterase enzymes.

Chromatographic fingerprint analysis, antioxidant properties, and inhibition of cholinergic enzymes (acetylcholinesterase and butyrylcholinesterase) of phenolic extracts from Irvingia gabonensis (Aubry-Lecomte ex O’Rorke) Baill bark

Irvingia gabonensis stem bark phenolic extracts show potential anti-Alzheimer's activity by inhibiting cholinesterase activities and suppressing oxidative-stress-induced neurodegeneration.

In Silico Studies in Drug Research Against Neurodegenerative Diseases

In silico drug design methods can help reduce the number of ligands tested in experimental assays, promoting a multi-target therapeutic strategy for neurodegenerative diseases.

3D-QSAR studies of some reversible Acetyl cholinesterase inhibitors based on CoMFA and ligand protein interaction fingerprints using PC-LS-SVM and PLS-LS-SVM

The field descriptor-based QSAR model is more applicable and predictive for predicting binding modes of piperidine acetylcholinesterase inhibitors, making it suitable for future 3D-QSAR softwares.