Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists

Charlotte Grube Jørgensen; Bente Flensborg Frølund; Jan Kehler; Anders Asbjørn Jensen

doi:10.1002/cmdc.201000444

Discovery of benzamide analogues as a novel class of 5-HT₃ receptor agonists

Charlotte Grube Jørgensen, Bente Flensborg Frølund, Jan Kehler, Anders Asbjørn Jensen

11 Citationer (Scopus)

Abstract

A 5-HT(3) receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT(3) A receptor yielded substantial information concerning the analogues as 5-HT(3) receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT(3) receptor agonist, as it does not possess a positively charged functionality, which is essential for the binding of all orthosteric ligands to the receptor. Preliminary investigations suggest that the compounds may exert their effects on 5-HT(3) receptors by binding to an allosteric site in the receptor complex.

Originalsprog	Engelsk
Tidsskrift	ChemMedChem
Vol/bind	6
Udgave nummer	4
Sider (fra-til)	725-736
ISSN	1860-7179
DOI	https://doi.org/10.1002/cmdc.201000444
Status	Udgivet - 4 apr. 2011

Emneord

Det tidligere Farmaceutiske Fakultet

Adgang til dokumentet

10.1002/cmdc.201000444

Citationsformater

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title = "Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists",

abstract = "A 5-HT(3) receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT(3) A receptor yielded substantial information concerning the analogues as 5-HT(3) receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT(3) receptor agonist, as it does not possess a positively charged functionality, which is essential for the binding of all orthosteric ligands to the receptor. Preliminary investigations suggest that the compounds may exert their effects on 5-HT(3) receptors by binding to an allosteric site in the receptor complex.",

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author = "J{\o}rgensen, {Charlotte Grube} and Fr{\o}lund, {Bente Flensborg} and Jan Kehler and Jensen, {Anders Asbj{\o}rn}",

note = "Keywords: agonists, allosterism, benzamides, ion channels, serotonin type 3 receptors",

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AU - Jørgensen, Charlotte Grube

AU - Frølund, Bente Flensborg

AU - Kehler, Jan

AU - Jensen, Anders Asbjørn

N1 - Keywords: agonists, allosterism, benzamides, ion channels, serotonin type 3 receptors

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AB - A 5-HT(3) receptor agonist based on a benzamide scaffold was identified in a screening of a small commercial compound library, and an elaborate SAR study originating from this hit was performed. The design, synthesis, and functional characterisation of benzamide analogues at the 5-HT(3) A receptor yielded substantial information concerning the analogues as 5-HT(3) receptor agonists. However, the potencies of the derived analogues were not significantly improved over that of the initial hit. The benzamide scaffold constitutes a novel type of 5-HT(3) receptor agonist, as it does not possess a positively charged functionality, which is essential for the binding of all orthosteric ligands to the receptor. Preliminary investigations suggest that the compounds may exert their effects on 5-HT(3) receptors by binding to an allosteric site in the receptor complex.

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