A new class of selective, non-basic 5-HT2A receptor antagonists

Bioorganic & Medicinal Chemistry Letters
Tammy LadduwahettyAngus M MacLeod

Abstract

Based on an existing series of 5-HT2A receptor ligands containing a basic nitrogen, we designed a non-basic lead that had reduced affinity for both the 5-HT2A receptor and the IKr potassium channel. The present paper describes the development of this lead to a novel series of non-basic piperidine sulfonamides and amides that have high affinity for the 5-HT2A receptor, whilst maintaining excellent selectivity over off target activities such as the IKr channel. This work has shown that the proposed pharmacophore model for the 5-HT2A receptor which suggests that a basic nitrogen is required for the binding of ligands is questionable.

References

Aug 7, 1998·Journal of Psychopharmacology·P Schloss, D C Williams
Feb 15, 2001·Journal of Medicinal Chemistry·M RowleyP H Hutson
Jun 8, 2002·Current Topics in Medicinal Chemistry·Richard B Westkaemper, Richard A Glennon
Jan 27, 2004·Bioorganic & Medicinal Chemistry Letters·Christopher G ThomsonJanusz J Kulagowski
Aug 25, 2004·Bioorganic & Medicinal Chemistry Letters·Lü-Pei DuLin Xia
Jul 5, 2005·Bioorganic & Medicinal Chemistry Letters·L Rebecca FishAngus M MacLeod
Jan 1, 1998·International Journal of Psychiatry in Clinical Practice·J Fritze, B Bandelow

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Citations

Mar 14, 2008·Chemical Communications : Chem Comm·Emilie VardelleJérôme Marrot
Oct 1, 2010·European Journal of Medicinal Chemistry·Nicolas RenaultAmaury Farce
Oct 30, 2009·Organic & Biomolecular Chemistry·Fei LiuSébastien Thibaudeau
May 6, 2017·Scientific Reports·Adam S HogendorfAndrzej J Bojarski
Dec 18, 2020·European Journal of Medicinal Chemistry·Jakub StarońAndrzej J Bojarski
Jan 27, 2021·International Journal of Molecular Sciences·Sabina PodlewskaJadwiga Handzlik

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