Highly potent, non-basic 5-HT sub(6) ligands. Site mutagenesis evidence for a second binding mode at 5-HT sub(6) for antagonism

A series of 5-HT sub(6) ligands derived from (R)-1-(amino)methyl-6-(phenyl)sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure-activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all c...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-06, Vol.20 (11), p.3436-3440
Main Authors: Harris, Ralph N, Stabler, Russel S, Repke, David B, Kress, James M, Walker, Keith A, Martin, Renee S, Brothers, Julie M, Ilnicka, Mariola, Lee, Simon W, Mirzadegan, Tara
Format: Article
Language:English
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Summary:A series of 5-HT sub(6) ligands derived from (R)-1-(amino)methyl-6-(phenyl)sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure-activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all combined to reveal a new alternative binding mode to 5-HT sub(6) for antagonism.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2010.03.110