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

Tammy Ladduwahetty·Amanda L Boase·Andrew Mitchinson·Caroline Quin·Smita Patel·Kerry Chapman·Angus M MacLeod
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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.

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HumansMolecular StructureReceptor, Serotonin, 5-HT2ASerotonin 5-HT2 Receptor AntagonistsStructure-Activity RelationshipJournal Article

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Tammy Ladduwahetty, Amanda L Boase, Andrew Mitchinson, Caroline Quin, Smita Patel, Kerry Chapman, Angus M MacLeod. 2006-05-02. A new class of selective, non-basic 5-HT2A receptor antagonists.. https://doi.org/10.1016/j.bmcl.2006.03.050

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