Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors

TY - JOUR

T1 - Tying up Nicotine: 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.

U2 - 10.1021/acsmedchemlett.5b00028

DO - 10.1021/acsmedchemlett.5b00028

M3 - Journal article

C2 - 25941557

SN - 1948-5875

VL - 6

SP - 472

EP - 475

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 4

ER -