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

Autor: 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., 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., Rørsted EM; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark., Pedersen H; Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark., Jensen AA; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark., Clausen RP; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark., Vital P; Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark., Glibstrup E; Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark., Jessing M; Molecular Discovery and Innovation, H. Lundbeck A/S, Ottiliavej 9, Valby 2500, Denmark., Kristensen JL; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen 2100, Denmark.
Jazyk: angličtina
Zdroj: The Journal of organic chemistry [J Org Chem] 2021 Jun 18; Vol. 86 (12), pp. 8248-8262. Date of Electronic Publication: 2021 Jun 01.
DOI: 10.1021/acs.joc.1c00707
Abstrakt: 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.
Databáze: MEDLINE
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