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Discovery of Benzamide Analogues as a Novel Class of 5‐HT 3 Receptor Agonists
Author(s) -
Jørgensen Charlotte G.,
Frølund Bente,
Kehler Jan,
Jensen Anders A.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000444
Subject(s) - benzamide , agonist , allosteric regulation , receptor , chemistry , pharmacology , enzyme linked receptor , stereochemistry , biochemistry , biology
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.