Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors

Zhi Liang Wei; Yingxian Xiao; Kenneth J. Kellar; Alan P. Kozikowski

doi:10.1016/j.bmcl.2003.10.071

Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors

Zhi Liang Wei, Yingxian Xiao, Kenneth J. Kellar, Alan P. Kozikowski

School of Medicine

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

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Abstract

A series of bivalent ligands 6a-d of epibatidine were synthesized. All four ligands showed nanomolar binding affinities at six neuronal nicotinic acetylcholine receptor (nAChR) subtypes in competition binding assays. In contrast to epibatidine, these bivalent ligands are weak partial agonists at the α3β4 nAChR as shown by functional assays.

Original language	English (US)
Pages (from-to)	1855-1858
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2003.10.071
State	Published - Apr 19 2004

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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title = "Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors",

abstract = "A series of bivalent ligands 6a-d of epibatidine were synthesized. All four ligands showed nanomolar binding affinities at six neuronal nicotinic acetylcholine receptor (nAChR) subtypes in competition binding assays. In contrast to epibatidine, these bivalent ligands are weak partial agonists at the α3β4 nAChR as shown by functional assays.",

author = "Wei, {Zhi Liang} and Yingxian Xiao and Kellar, {Kenneth J.} and Kozikowski, {Alan P.}",

note = "Funding Information: We are indebted to NIH (R01 DA17980) for support of this work. We thank Maryna Baydyuk and Haizhu P. Wang for their assistance with tissue culture and ligand binding assays, and Dr. Werner T{\"u}ckmantel for proofreading the manuscript.",

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T1 - Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors

AU - Wei, Zhi Liang

AU - Xiao, Yingxian

AU - Kellar, Kenneth J.

AU - Kozikowski, Alan P.

N1 - Funding Information: We are indebted to NIH (R01 DA17980) for support of this work. We thank Maryna Baydyuk and Haizhu P. Wang for their assistance with tissue culture and ligand binding assays, and Dr. Werner Tückmantel for proofreading the manuscript.

PY - 2004/4/19

Y1 - 2004/4/19

N2 - A series of bivalent ligands 6a-d of epibatidine were synthesized. All four ligands showed nanomolar binding affinities at six neuronal nicotinic acetylcholine receptor (nAChR) subtypes in competition binding assays. In contrast to epibatidine, these bivalent ligands are weak partial agonists at the α3β4 nAChR as shown by functional assays.

AB - A series of bivalent ligands 6a-d of epibatidine were synthesized. All four ligands showed nanomolar binding affinities at six neuronal nicotinic acetylcholine receptor (nAChR) subtypes in competition binding assays. In contrast to epibatidine, these bivalent ligands are weak partial agonists at the α3β4 nAChR as shown by functional assays.

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Synthesis and pharmacological characterization of bivalent ligands of epibatidine at neuronal nicotinic acetylcholine receptors

Abstract

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