Highly potent fluorescence-tagged nonimidazole histamine H3 receptor ligands.
Different (3-phenoxypropyl)piperidine derivatives have been coupled to fluorescent moieties (5-dimethylaminonaphthalene-1-sulfonyl, carbazol-9-ylcarbonyl, 2-cyanoisoindol-1-yl, 2-cyanobenzo[f]isoindol-1-yl, 2,4-dinitrobenzen-1-yl, 2,4-diaminophenyl, 7-nitrobenzofurazan-4-yl, 7-aminosulfonylbenzofurazan-4-yl, 4-methylcoumarin-6-yl) as novel histamine H(3) receptor ligands. They have been synthesised starting from piperidine in a few steps. The compounds display good to excellent histamine hH(3) receptor affinities with K(i) values ranging from 13.4 to 0.048 nM. Some of the new compounds belong to the most potent ligands known so far and may act as tools for identification and understanding of the binding site on the histamine H(3) receptor. In vivo screening on selected derivatives of Sanger's reagent showed antagonist potencies with ED(50) values from 7.9 to 0.39 mg kg(-1), p.o.
Amon
Michael
M
Institut für Pharmazeutische Chemie, Johann Wolfgang Goethe-Universität, ZAFES/CMP, Biozentrum, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
Ligneau
Xavier
X
Camelin
Jean-Claude
JC
Berrebi-Bertrand
Isabelle
I
Schwartz
Jean-Charles
JC
Stark
Holger
H
D005453:Fluorescence; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D008024:Ligands; D018100:Receptors, Histamine H3