From 2-Triethylammonium Ethyl Ether of 4-Stilbenol (MG624) to Selective Small-Molecule Antagonists of Human α9α10 Nicotinic Receptor by Modifications at the Ammonium Ethyl Residue.


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
28 07 2022
Historique:
pubmed: 15 7 2022
medline: 30 7 2022
entrez: 14 7 2022
Statut: ppublish

Résumé

Nicotinic acetylcholine receptors containing α9 subunits (α9*-nAChRs) are potential druggable targets arousing great interest for pain treatment alternative to opioids. Nonpeptidic small molecules selectively acting as α9*-nAChRs antagonists still remain an unattained goal. Here, through modifications of the cationic head and the ethylene linker, we have converted the 2-triethylammonium ethyl ether of 4-stilbenol (MG624), a well-known α7- and α9*-nAChRs antagonist, into some selective antagonists of human α9*-nAChR. Among these, the compound with cyclohexyldimethylammonium head (

Identifiants

pubmed: 35834819
doi: 10.1021/acs.jmedchem.2c00746
pmc: PMC9339509
mid: NIHMS1824089
doi:

Substances chimiques

Ammonium Compounds 0
Nicotinic Antagonists 0
Quaternary Ammonium Compounds 0
Receptors, Nicotinic 0
Stilbenes 0
Ether 0F5N573A2Y
triethyl-(beta-4-stilbenoxyethyl)ammonium 2551-76-0
4-hydroxystilbene 3839-46-1

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

10079-10097

Subventions

Organisme : NIDA NIH HHS
ID : R01 DA042749
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA043567
Pays : United States

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Auteurs

Francesco Bavo (F)

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via Mangiagalli 25, I-20133 Milano, Italy.
Department of Drug Design and Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark.

Marco Pallavicini (M)

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via Mangiagalli 25, I-20133 Milano, Italy.

Susanna Pucci (S)

Institute of Neuroscience, CNR, via Vanvitelli 32, I-20129 Milano, Italy.
NeuroMi Milan Center for Neuroscience, University of Milano Bicocca, piazza Ateneo Nuovo 1, I-20126 Milano, Italy.

Rebecca Appiani (R)

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via Mangiagalli 25, I-20133 Milano, Italy.

Alessandro Giraudo (A)

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via Mangiagalli 25, I-20133 Milano, Italy.

Brek Eaton (B)

Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona 85013, United States.

Linda Lucero (L)

Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona 85013, United States.

Cecilia Gotti (C)

Institute of Neuroscience, CNR, via Vanvitelli 32, I-20129 Milano, Italy.

Milena Moretti (M)

Institute of Neuroscience, CNR, via Vanvitelli 32, I-20129 Milano, Italy.
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, via Vanvitelli 32, I-20129 Milano, Italy.

Paul Whiteaker (P)

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298, United States.

Cristiano Bolchi (C)

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, via Mangiagalli 25, I-20133 Milano, Italy.

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Classifications MeSH