Discovery of potent dual ligands for dopamine D4 and σ1 receptors.
Dopamine D4
Hybrids
Molecular dynamics
Molecular modelling
Piperidine
Polypharmacology
Receptor
Sigma1
Triazole
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
25
02
2022
revised:
04
05
2022
accepted:
20
05
2022
pubmed:
27
6
2022
medline:
14
7
2022
entrez:
26
6
2022
Statut:
ppublish
Résumé
During our work on exploration of molecules with some piperidine-triazole scaffolds, we realized that our compounds display chemical similarity with some σ, as well as dopaminergic receptor ligands. Here we show that this series of molecules has indeed strong affinity both for σ1 and dopamine D4 receptors. Moreover, they appear selective towards σ2, dopamine paralogues D1, D2, D3 and D5 receptors and hERG channel. Extensive molecular dynamics with our lead compound AVRM-13 were carried out on σ1, supporting agonist activity of the ligand. Unexpectedly, several observations suggested the existence of a cation binding domain, a probable regulatory site for calcium.
Identifiants
pubmed: 35753263
pii: S0968-0896(22)00243-7
doi: 10.1016/j.bmc.2022.116851
pii:
doi:
Substances chimiques
Ligands
0
Receptors, Dopamine D1
0
Receptors, Dopamine D2
0
Receptors, Dopamine D3
0
Receptors, sigma
0
Receptors, Dopamine D4
137750-34-6
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116851Informations de copyright
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