Cyanobiphenyls: Novel H
Acetylcholinesterase
/ metabolism
Alzheimer Disease
/ drug therapy
Animals
Biphenyl Compounds
/ chemical synthesis
Butyrylcholinesterase
/ metabolism
Cholinesterase Inhibitors
/ chemical synthesis
Dose-Response Relationship, Drug
Electrophorus
Horses
Humans
Ligands
Molecular Structure
Monoamine Oxidase
/ metabolism
Monoamine Oxidase Inhibitors
/ chemical synthesis
Receptors, Histamine H3
/ metabolism
Structure-Activity Relationship
Alzheimer’s disease
Biphenyl derivatives
Cholinesterase inhibitors
Histamine H(3) receptor ligands
Monoamine oxidase B inhibitors
Multi-target-directed ligands
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
09
03
2021
revised:
23
06
2021
accepted:
24
06
2021
pubmed:
5
7
2021
medline:
15
12
2021
entrez:
4
7
2021
Statut:
ppublish
Résumé
Alzheimer's disease (AD) is a complex and incurable illness that requires the urgent approval of new effective drugs. However, since 2003, no new molecules have shown successful results in clinical trials, thereby making the common "one compound - one target" paradigm questionable. Recently, the multitarget-directed ligand (MTDL) approach has gained popularity, as compounds targeting at least two biological targets may be potentially more effective in treating AD. On the basis of these findings, we designed, synthesized, and evaluated through biological assays a series of derivatives of alicyclic amines linked by an alkoxy bridge to an aromatic lipophilic moiety of [1,1'-biphenyl]-4-carbonitrile. The research results revealed promising biological activity of the obtained compounds toward the chosen targets involved in AD pathophysiology; the compounds showed high affinity (mostly low nanomolar range of K
Identifiants
pubmed: 34217977
pii: S0045-2068(21)00506-X
doi: 10.1016/j.bioorg.2021.105129
pii:
doi:
Substances chimiques
Biphenyl Compounds
0
Cholinesterase Inhibitors
0
Ligands
0
Monoamine Oxidase Inhibitors
0
Receptors, Histamine H3
0
Monoamine Oxidase
EC 1.4.3.4
Acetylcholinesterase
EC 3.1.1.7
Butyrylcholinesterase
EC 3.1.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105129Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.