Erythrina Alkaloid Analogues as nAChR Antagonists-A Flexible Platform for Leads in Drug Discovery.


Journal

The Journal of organic chemistry
ISSN: 1520-6904
Titre abrégé: J Org Chem
Pays: United States
ID NLM: 2985193R

Informations de publication

Date de publication:
18 06 2021
Historique:
pubmed: 2 6 2021
medline: 8 7 2021
entrez: 1 6 2021
Statut: ppublish

Résumé

Erythrina alkaloids and their central nervous system effects have been studied for over a century, mainly due to their potent antagonistic actions at β2-containing nicotinic acetylcholine receptors (nAChRs). In the present work, we report a synthetic approach giving access to a diverse set of Erythrina natural product analogues and present the enantioselective total synthesis of (+)-Cocculine and (+)-Cocculidine, both found to be potent antagonists of the β2-containing nAChRs.

Identifiants

pubmed: 34061521
doi: 10.1021/acs.joc.1c00707
doi:

Substances chimiques

Alkaloids 0
Indolizines 0
Receptors, Nicotinic 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

8248-8262

Auteurs

Sebastian Clementson (S)

Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

Sergio Armentia Matheu (SA)

Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

Emil Märcher Rørsted (EM)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

Henrik Pedersen (H)

Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.

Anders A Jensen (AA)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

Rasmus P Clausen (RP)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

Paulo Vital (P)

Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.

Emil Glibstrup (E)

Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.

Mikkel Jessing (M)

Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark.

Jesper L Kristensen (JL)

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.

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Classifications MeSH