Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists
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Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists. / Jørgensen, Charlotte Grube; Frølund, Bente Flensborg; Kehler, Jan; Jensen, Anders Asbjørn.
I: ChemMedChem, Bind 6, Nr. 4, 04.04.2011, s. 725-736.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Discovery of benzamide analogues as a novel class of 5-HT3 receptor agonists
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
PY - 2011/4/4
Y1 - 2011/4/4
N2 - 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.
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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1002/cmdc.201000444
DO - 10.1002/cmdc.201000444
M3 - Journal article
C2 - 21246737
VL - 6
SP - 725
EP - 736
JO - Farmaco
JF - Farmaco
SN - 1860-7179
IS - 4
ER -
ID: 33253259