Novel acetylcholine and carbamoylcholine analogues: Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Novel acetylcholine and carbamoylcholine analogues : Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist. / Hansen, Camilla Petrycer; Jensen, Anders Asbjørn; Christensen, Jeppe K.; Balle, Thomas; Liljefors, Tommy; Frølund, Bente Flensborg.

In: Journal of Medicinal Chemistry, Vol. 51, No. 23, 2008, p. 7380-7395.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hansen, CP, Jensen, AA, Christensen, JK, Balle, T, Liljefors, T & Frølund, BF 2008, 'Novel acetylcholine and carbamoylcholine analogues: Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist', Journal of Medicinal Chemistry, vol. 51, no. 23, pp. 7380-7395. https://doi.org/10.1021/jm701625v

APA

Hansen, C. P., Jensen, A. A., Christensen, J. K., Balle, T., Liljefors, T., & Frølund, B. F. (2008). Novel acetylcholine and carbamoylcholine analogues: Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist. Journal of Medicinal Chemistry, 51(23), 7380-7395. https://doi.org/10.1021/jm701625v

Vancouver

Hansen CP, Jensen AA, Christensen JK, Balle T, Liljefors T, Frølund BF. Novel acetylcholine and carbamoylcholine analogues: Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist. Journal of Medicinal Chemistry. 2008;51(23):7380-7395. https://doi.org/10.1021/jm701625v

Author

Hansen, Camilla Petrycer ; Jensen, Anders Asbjørn ; Christensen, Jeppe K. ; Balle, Thomas ; Liljefors, Tommy ; Frølund, Bente Flensborg. / Novel acetylcholine and carbamoylcholine analogues : Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 23. pp. 7380-7395.

Bibtex

@article{92191d60e95e11ddbf70000ea68e967b,
title = "Novel acetylcholine and carbamoylcholine analogues: Development of a functionally selective a4{\ss}2 nicotinic acetylcholine receptor agonist",
abstract = "A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity for this subtype over alpha 3beta 4, alpha 4beta 4, and alpha 7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha 4beta 2 selectivities exhibited by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha 4beta 2 nAChR agonist with negligible activities at the alpha 3beta 4 and alpha 7 subtypes, thus being one of the few truly functionally selective alpha 4beta 2 nAChR agonists published to date. Ligand-protein docking experiments using homology models of the amino-terminal domains of alpha 4beta 2 and alpha 3beta 4 nAChRs identified residues Val111(beta 2)/Ile113(beta 4), Phe119(beta 2)/Gln121(beta 4), and Thr155(alpha 4)/Ser150(alpha 3) as possible key determinants of the alpha 4beta 2/alpha 3beta 4-selectivity displayed by the analogues.",
keywords = "Former Faculty of Pharmaceutical Sciences",
author = "Hansen, {Camilla Petrycer} and Jensen, {Anders Asbj{\o}rn} and Christensen, {Jeppe K.} and Thomas Balle and Tommy Liljefors and Fr{\o}lund, {Bente Flensborg}",
year = "2008",
doi = "10.1021/jm701625v",
language = "English",
volume = "51",
pages = "7380--7395",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Novel acetylcholine and carbamoylcholine analogues

T2 - Development of a functionally selective a4ß2 nicotinic acetylcholine receptor agonist

AU - Hansen, Camilla Petrycer

AU - Jensen, Anders Asbjørn

AU - Christensen, Jeppe K.

AU - Balle, Thomas

AU - Liljefors, Tommy

AU - Frølund, Bente Flensborg

PY - 2008

Y1 - 2008

N2 - A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity for this subtype over alpha 3beta 4, alpha 4beta 4, and alpha 7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha 4beta 2 selectivities exhibited by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha 4beta 2 nAChR agonist with negligible activities at the alpha 3beta 4 and alpha 7 subtypes, thus being one of the few truly functionally selective alpha 4beta 2 nAChR agonists published to date. Ligand-protein docking experiments using homology models of the amino-terminal domains of alpha 4beta 2 and alpha 3beta 4 nAChRs identified residues Val111(beta 2)/Ile113(beta 4), Phe119(beta 2)/Gln121(beta 4), and Thr155(alpha 4)/Ser150(alpha 3) as possible key determinants of the alpha 4beta 2/alpha 3beta 4-selectivity displayed by the analogues.

AB - A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha 4beta 2 nAChR and pronounced selectivity for this subtype over alpha 3beta 4, alpha 4beta 4, and alpha 7 nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha 4beta 2 selectivities exhibited by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha 4beta 2 nAChR agonist with negligible activities at the alpha 3beta 4 and alpha 7 subtypes, thus being one of the few truly functionally selective alpha 4beta 2 nAChR agonists published to date. Ligand-protein docking experiments using homology models of the amino-terminal domains of alpha 4beta 2 and alpha 3beta 4 nAChRs identified residues Val111(beta 2)/Ile113(beta 4), Phe119(beta 2)/Gln121(beta 4), and Thr155(alpha 4)/Ser150(alpha 3) as possible key determinants of the alpha 4beta 2/alpha 3beta 4-selectivity displayed by the analogues.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/jm701625v

DO - 10.1021/jm701625v

M3 - Journal article

C2 - 18989912

VL - 51

SP - 7380

EP - 7395

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -

ID: 9914377