Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release

Zhenfa Zhang; Guangrong Zheng; Marharyta Pivavarchyk; A. Gabriela Deaciuc; Linda P. Dwoskin; Peter A. Crooks

doi:10.1016/j.bmcl.2010.11.070

Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release

Zhenfa Zhang, Guangrong Zheng, Marharyta Pivavarchyk, A. Gabriela Deaciuc, Linda P. Dwoskin, Peter A. Crooks

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

7 Scopus citations

Abstract

A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, represent drug-like inhibitors of α6-containing nicotinic acetylcholine receptors. The bis-tertiary amine analog 7 exhibited an IC ₅₀ of 0.95 nM, while the tris-tertiary amine analog 19 had an IC ₅₀ of 0.35 nM at nAChRs mediating nicotine-evoked dopamine release.

Original language	English
Pages (from-to)	88-91
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2010.11.070
State	Published - Jan 1 2011

Bibliographical note

Funding Information:
This work was supported by NIH . (Grant U19DA017548 )

Keywords

Smoking cessation
Tobacco dependency
nAChR antagonists

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2010.11.070

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abstract = "A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, represent drug-like inhibitors of α6-containing nicotinic acetylcholine receptors. The bis-tertiary amine analog 7 exhibited an IC 50 of 0.95 nM, while the tris-tertiary amine analog 19 had an IC 50 of 0.35 nM at nAChRs mediating nicotine-evoked dopamine release.",

keywords = "Smoking cessation, Tobacco dependency, nAChR antagonists",

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AU - Zheng, Guangrong

AU - Pivavarchyk, Marharyta

AU - Deaciuc, A. Gabriela

AU - Dwoskin, Linda P.

AU - Crooks, Peter A.

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KW - Tobacco dependency

KW - nAChR antagonists

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Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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