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

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

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.
Original languageEnglish
JournalChemMedChem
Volume6
Issue number4
Pages (from-to)725-736
ISSN1860-7179
DOIs
Publication statusPublished - 4 Apr 2011

ID: 33253259