Highly potent fluorescence-tagged nonimidazole histamine H3 receptor ligands

ChemMedChem. 2007 May;2(5):708-16. doi: 10.1002/cmdc.200600270.


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.

MeSH terms

  • Fluorescence
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Receptors, Histamine H3 / metabolism*
  • Spectrometry, Mass, Electrospray Ionization


  • Ligands
  • Receptors, Histamine H3