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-HT(3)A) 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-HT(3)A receptors in mammalian cells.
Vernekar
Sanjeev Kumar V
SK
Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
Hallaq
Hasan Y
HY
Clarkson
Guy
G
Thompson
Andrew J
AJ
Silvestri
Linda
L
Lummis
Sarah C R
SC
Lochner
Martin
M
D001667:Binding, Competitive; D001896:Boron Compounds / Q000737:chemistry; D002460:Cell Line; D017829:Granisetron / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011869:Radioligand Assay; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D001896:Boron Compounds; D017829:Granisetron; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene