Ethyl-for-methyl substitution enhances the subtype specificity of mecamylamine analogues

David Mangan; Neasa Mcnabola; Emily H. Clark; Isabel Bermudez; Susan Wonnacott; J. Mike Southern

doi:10.1039/c9ob01993f

Ethyl-for-methyl substitution enhances the subtype specificity of mecamylamine analogues

David Mangan, Neasa Mcnabola, Emily H. Clark, Isabel Bermudez, Susan Wonnacott, J. Mike Southern

Department of Life Sciences

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

Abstract

The synthesis of novel mecamylamine analogues is described in which one, two or three of the methyl groups of mecamylamine have been systematically replaced with ethyl groups. Assessment of the compounds highlights that simple ethyl for methyl changes changes to the parent structure can dramatically enhance activity and selectivity towards either the α₄β₂ (at the expense of α₃β₄) or the α₃β₄ (at the expense of α₄β₂) nicotinic acetylcholine receptor sub-type as compared to the parent compound.

Original language	English
Pages (from-to)	9892-9905
Number of pages	14
Journal	Organic and Biomolecular Chemistry
Volume	17
Issue number	46
Early online date	6 Nov 2019
DOIs	https://doi.org/10.1039/c9ob01993f
Publication status	Published - 14 Dec 2019

Bibliographical note

Funding Information:
This work was supported by The Irish Research Council (DM) and The School of Chemistry, Trinity College, Dublin (NMN).

Publisher Copyright:
© 2019 The Royal Society of Chemistry.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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abstract = "The synthesis of novel mecamylamine analogues is described in which one, two or three of the methyl groups of mecamylamine have been systematically replaced with ethyl groups. Assessment of the compounds highlights that simple ethyl for methyl changes changes to the parent structure can dramatically enhance activity and selectivity towards either the α4β2 (at the expense of α3β4) or the α3β4 (at the expense of α4β2) nicotinic acetylcholine receptor sub-type as compared to the parent compound.",

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AU - Mcnabola, Neasa

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AU - Bermudez, Isabel

AU - Wonnacott, Susan

AU - Southern, J. Mike

N1 - Funding Information: This work was supported by The Irish Research Council (DM) and The School of Chemistry, Trinity College, Dublin (NMN). Publisher Copyright: © 2019 The Royal Society of Chemistry. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

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AB - The synthesis of novel mecamylamine analogues is described in which one, two or three of the methyl groups of mecamylamine have been systematically replaced with ethyl groups. Assessment of the compounds highlights that simple ethyl for methyl changes changes to the parent structure can dramatically enhance activity and selectivity towards either the α4β2 (at the expense of α3β4) or the α3β4 (at the expense of α4β2) nicotinic acetylcholine receptor sub-type as compared to the parent compound.

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Ethyl-for-methyl substitution enhances the subtype specificity of mecamylamine analogues

Abstract

Bibliographical note

ASJC Scopus subject areas

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