1. A new class of selective, non-basic 5-HT2A receptor antagonists
- Author
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Caroline Quin, Kerry L. Chapman, Andrew Mitchinson, Smita Patel, Amanda Louise Boase, T. Ladduwahetty, and Angus Murray Macleod
- Subjects
Molecular Structure ,Chemistry ,Stereochemistry ,Ligand ,medicine.drug_class ,Organic Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Carboxamide ,Biochemistry ,Chemical synthesis ,Potassium channel ,chemistry.chemical_compound ,Structure-Activity Relationship ,Drug Discovery ,medicine ,Serotonin 5-HT2 Receptor Antagonists ,Molecular Medicine ,Humans ,Receptor, Serotonin, 5-HT2A ,Piperidine ,Receptor ,Selectivity ,Molecular Biology ,5-HT receptor - Abstract
Based on an existing series of 5-HT 2A receptor ligands containing a basic nitrogen, we designed a non-basic lead that had reduced affinity for both the 5-HT 2A 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-HT 2A receptor, whilst maintaining excellent selectivity over off target activities such as the IKr channel. This work has shown that the proposed pharmacaphore model for the 5-HT 2A receptor which suggests that a basic nitrogen is required for the binding of ligands is questionable.
- Published
- 2006