Toward Biophysical Probes for the 5-HT3 Receptor: Structure−Activity Relationship Study of Granisetron Derivatives

This report describes the synthesis and biological characterization of novel granisetron derivatives that are antagonists of the human serotonin (5-HT3A) receptor. Some of these substituted granisetron derivatives showed low nanomolar binding affinity and allowed the identification of positions on t...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2010-03, Vol.53 (5), p.2324-2328
Main Authors: Vernekar, Sanjeev Kumar V, Hallaq, Hasan Y, Clarkson, Guy, Thompson, Andrew J, Silvestri, Linda, Lummis, Sarah C. R, Lochner, Martin
Format: Article
Language:English
Subjects:
Binding, Competitive
Boron Compounds - chemistry
Brief
Cell Line
Granisetron - analogs & derivatives
Granisetron - chemical synthesis
Granisetron - chemistry
Granisetron - pharmacology
Humans
Magnetic Resonance Spectroscopy
Radioligand Assay
Receptors, Serotonin, 5-HT3 - metabolism
Serotonin 5-HT3 Receptor Antagonists
Serotonin Antagonists - chemical synthesis
Serotonin Antagonists - chemistry
Serotonin Antagonists - pharmacology
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship
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Summary:This report describes the synthesis and biological characterization of novel granisetron derivatives that are antagonists of the human serotonin (5-HT3A) receptor. Some of these substituted granisetron derivatives showed low nanomolar binding affinity and allowed the identification of positions on the granisetron core that might be used as attachment points for biophysical tags. A BODIPY fluorophore was appended to one such position and specifically bound to 5-HT3A receptors in mammalian cells.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm901827x