Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

Research output: Contribution to journalJournal articleResearchpeer-review

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Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists. / Crestey, François; Jensen, Anders A.; Borch, Morten; Andreasen T., Jesper; Andersen, Jacob; Balle, Thomas; Kristensen, Jesper Langgaard.

In: Journal of Medicinal Chemistry, Vol. 56, No. 23, 2013, p. 9673-9682.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Crestey, F, Jensen, AA, Borch, M, Andreasen T., J, Andersen, J, Balle, T & Kristensen, JL 2013, 'Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists' Journal of Medicinal Chemistry, vol. 56, no. 23, pp. 9673-9682. https://doi.org/10.1021/jm4013592

APA

Crestey, F., Jensen, A. A., Borch, M., Andreasen T., J., Andersen, J., Balle, T., & Kristensen, J. L. (2013). Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists. Journal of Medicinal Chemistry, 56(23), 9673-9682. https://doi.org/10.1021/jm4013592

Vancouver

Crestey F, Jensen AA, Borch M, Andreasen T. J, Andersen J, Balle T et al. Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists. Journal of Medicinal Chemistry. 2013;56(23):9673-9682. https://doi.org/10.1021/jm4013592

Author

Crestey, François ; Jensen, Anders A. ; Borch, Morten ; Andreasen T., Jesper ; Andersen, Jacob ; Balle, Thomas ; Kristensen, Jesper Langgaard. / Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 23. pp. 9673-9682.

Bibtex

@article{4724187472e640928d36d154d97f750c,
title = "Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists",
abstract = "The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype-selective antagonists for the nAChRs and thereby probe the potential of using these natural products as scaffolds for further ligand optimization. The most selective and potent nAChR ligand to come from the series, 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (3c) (also a natural product by the name of O-methylcorypalline), displayed submicromolar binding affinity toward the α4β2 nAChR with more than 300-fold selectivity over α4β4, α3β4, and α7. Furthermore, this lead structure (which also has inhibitory activity at monoamine oxidases A and B and at the serotonin and norepinephrine transporters) showed antidepressant-like effect in the mouse forced swim test at 30 mg/kg.",
author = "Fran{\cc}ois Crestey and Jensen, {Anders A.} and Morten Borch and {Andreasen T.}, Jesper and Jacob Andersen and Thomas Balle and Kristensen, {Jesper Langgaard}",
year = "2013",
doi = "10.1021/jm4013592",
language = "Dansk",
volume = "56",
pages = "9673--9682",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Design, synthesis and biological evaluation of Erythrina alkaloid analogues as neuronal nicotinic acetylcholine receptor antagonists

AU - Crestey, François

AU - Jensen, Anders A.

AU - Borch, Morten

AU - Andreasen T., Jesper

AU - Andersen, Jacob

AU - Balle, Thomas

AU - Kristensen, Jesper Langgaard

PY - 2013

Y1 - 2013

N2 - The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype-selective antagonists for the nAChRs and thereby probe the potential of using these natural products as scaffolds for further ligand optimization. The most selective and potent nAChR ligand to come from the series, 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (3c) (also a natural product by the name of O-methylcorypalline), displayed submicromolar binding affinity toward the α4β2 nAChR with more than 300-fold selectivity over α4β4, α3β4, and α7. Furthermore, this lead structure (which also has inhibitory activity at monoamine oxidases A and B and at the serotonin and norepinephrine transporters) showed antidepressant-like effect in the mouse forced swim test at 30 mg/kg.

AB - The synthesis of a new series of Erythrina alkaloid analogues and their pharmacological characterization at various nicotine acetylcholine receptor (nAChR) subtypes are described. The compounds were designed to be simplified analogues of aromatic erythrinanes with the aim of obtaining subtype-selective antagonists for the nAChRs and thereby probe the potential of using these natural products as scaffolds for further ligand optimization. The most selective and potent nAChR ligand to come from the series, 6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (3c) (also a natural product by the name of O-methylcorypalline), displayed submicromolar binding affinity toward the α4β2 nAChR with more than 300-fold selectivity over α4β4, α3β4, and α7. Furthermore, this lead structure (which also has inhibitory activity at monoamine oxidases A and B and at the serotonin and norepinephrine transporters) showed antidepressant-like effect in the mouse forced swim test at 30 mg/kg.

U2 - 10.1021/jm4013592

DO - 10.1021/jm4013592

M3 - Tidsskriftartikel

VL - 56

SP - 9673

EP - 9682

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 62033998