Tying up nicotine: New selective competitive antagonist of the neuronal nicotinic acetylcholine receptors

Ida Nymann Petersen; François Crestey; Anders A. Jensen; Dinesh C. Indurthi; Henrik Pedersen; Jesper T. Andreasen; Thomas Balle; Jesper L. Kristensen

doi:10.1021/acsmedchemlett.5b00028

Tying up nicotine: New selective competitive antagonist of the neuronal nicotinic acetylcholine receptors

Ida Nymann Petersen
, François Crestey
, Anders A. Jensen
, Dinesh C. Indurthi
, Henrik Pedersen
, Jesper T. Andreasen
, Thomas Balle
, Jesper L. Kristensen

Biochemistry

University of Copenhagen
H. Lundbeck A/S
The University of Sydney

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers, and determination of absolute configuration via enantioselective synthesis showed that the pharmacological activity resided almost exclusively in the (R)-enantiomer.

Original language	English
Pages (from-to)	472-475
Number of pages	4
Journal	ACS Medicinal Chemistry Letters
Volume	6
Issue number	4
DOIs	https://doi.org/10.1021/acsmedchemlett.5b00028
State	Published - Apr 9 2015

Keywords

Bridged-nicotine analogue
nAChRs
Negishi cross-coupling reaction
oocyte
selective antagonist

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10.1021/acsmedchemlett.5b00028

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title = "Tying up nicotine: New selective competitive antagonist of the neuronal nicotinic acetylcholine receptors",

abstract = "Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers, and determination of absolute configuration via enantioselective synthesis showed that the pharmacological activity resided almost exclusively in the (R)-enantiomer.",

keywords = "Bridged-nicotine analogue, nAChRs, Negishi cross-coupling reaction, oocyte, selective antagonist",

author = "Petersen, \{Ida Nymann\} and Fran{\c c}ois Crestey and Jensen, \{Anders A.\} and Indurthi, \{Dinesh C.\} and Henrik Pedersen and Andreasen, \{Jesper T.\} and Thomas Balle and Kristensen, \{Jesper L.\}",

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doi = "10.1021/acsmedchemlett.5b00028",

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T2 - New selective competitive antagonist of the neuronal nicotinic acetylcholine receptors

AU - Petersen, Ida Nymann

AU - Crestey, François

AU - Jensen, Anders A.

AU - Indurthi, Dinesh C.

AU - Pedersen, Henrik

AU - Andreasen, Jesper T.

AU - Balle, Thomas

AU - Kristensen, Jesper L.

PY - 2015/4/9

Y1 - 2015/4/9

N2 - Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers, and determination of absolute configuration via enantioselective synthesis showed that the pharmacological activity resided almost exclusively in the (R)-enantiomer.

AB - Conformational restriction of the pyrrolidine nitrogen in nicotine by the introduction of an ethylene bridge provided a potent and selective antagonist of the α4β2-subtype of the nicotinic acetylcholine receptors. Resolution by chiral SFC, pharmacological characterization of the two enantiomers, and determination of absolute configuration via enantioselective synthesis showed that the pharmacological activity resided almost exclusively in the (R)-enantiomer.

KW - Bridged-nicotine analogue

KW - nAChRs

KW - Negishi cross-coupling reaction

KW - oocyte

KW - selective antagonist

UR - https://www.scopus.com/pages/publications/84927655266

U2 - 10.1021/acsmedchemlett.5b00028

DO - 10.1021/acsmedchemlett.5b00028

M3 - Article

AN - SCOPUS:84927655266

SN - 1948-5875

VL - 6

SP - 472

EP - 475

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 4

ER -

Tying up nicotine: New selective competitive antagonist of the neuronal nicotinic acetylcholine receptors

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Keywords

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