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ID: ALA1148517

Journal: Bioorg Med Chem Lett

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

Authors: Ladduwahetty T, Boase AL, Mitchinson A, Quin C, Patel S, Chapman K, MacLeod AM.

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.

CiteXplore: 16632354

DOI: 10.1016/j.bmcl.2006.03.050