Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors

Zhuang Jin; Pasha Khan; Youseung Shin; Jingyi Wang; Li Lin; Michael D. Cameron; Jon M. Lindstrom; Paul J. Kenny; Theodore M. Kamenecka

doi:10.1016/j.bmcl.2013.11.049

Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors

Zhuang Jin, Pasha Khan, Youseung Shin, Jingyi Wang, Li Lin, Michael D. Cameron, Jon M. Lindstrom, Paul J. Kenny, Theodore M. Kamenecka

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

17 Scopus citations

Abstract

The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2- yl)benzonitrile (5k) and 3,3′-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered.

Original language	English
Pages (from-to)	674-678
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2013.11.049
State	Published - 15 Jan 2014
Externally published	Yes

Keywords

Positive allosteric modulators
Substituted heteroaromatics
α4β2α5

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10.1016/j.bmcl.2013.11.049

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title = "Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors",

abstract = "The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2- yl)benzonitrile (5k) and 3,3′-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered.",

keywords = "Positive allosteric modulators, Substituted heteroaromatics, α4β2α5",

author = "Zhuang Jin and Pasha Khan and Youseung Shin and Jingyi Wang and Li Lin and Cameron, {Michael D.} and Lindstrom, {Jon M.} and Kenny, {Paul J.} and Kamenecka, {Theodore M.}",

note = "Funding Information: Supported by the National Institute on Drug Abuse ( DA030929 to P.J.K. and J.M.L.). ",

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doi = "10.1016/j.bmcl.2013.11.049",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors

AU - Jin, Zhuang

AU - Khan, Pasha

AU - Shin, Youseung

AU - Wang, Jingyi

AU - Lin, Li

AU - Cameron, Michael D.

AU - Lindstrom, Jon M.

AU - Kenny, Paul J.

AU - Kamenecka, Theodore M.

N1 - Funding Information: Supported by the National Institute on Drug Abuse ( DA030929 to P.J.K. and J.M.L.).

PY - 2014/1/15

Y1 - 2014/1/15

N2 - The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2- yl)benzonitrile (5k) and 3,3′-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered.

AB - The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2- yl)benzonitrile (5k) and 3,3′-(2H-tetrazole-2,5-diyl)dipyridine (12h) with good in vitro efficacy were discovered.

KW - Positive allosteric modulators

KW - Substituted heteroaromatics

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JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors

Abstract

Keywords

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