Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4-[11C] methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([ 11C]JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4-[ 11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor

Hong Fan, Hayden T. Ravert, Daniel P. Holt, Robert F. Dannals, Andrew G. Horti

Research output: Contribution to journalArticlepeer-review

Abstract

Two novel ligands for cerebral cannabinoid receptor (CB1), 1-(2,4-dichlorophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl) -1H-pyrazole-3-carboxamide (JHU75528) and 1-(2-bromophenyl)-4-cyano-5-(4- methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (JHU75575) have been synthesized. Both JHU75528 and JHU75575 display a combination of higher binding affinity and lower lipophilicity than those of Rimonabant (SR141716), a high affinity CB1 selective antagonist, and AM281, the only available ligand for emission tomography imaging of CB1 in human subjects. Radiolabeled [ 11C]JHU75528 and [11C]JHU75575 were prepared by reaction of [11C]methyl iodide with nor-methyl precursors. The average radiochemical yield, specific radioactivity, and radiochemical purity of [ 11C]JHU75528 were 16%, 235 GBq/μmol (6360 mCi/μmol), and 99%, respectively; those of [11C]JHU75575 were 8%, 196 GBq/μmol (5308 mCi/μmol), and 99%, respectively. Both ligands hold promise as PET radioligands for imaging CB1 receptor.

Original languageEnglish (US)
Pages (from-to)1021-1036
Number of pages16
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume49
Issue number12
DOIs
StatePublished - Oct 30 2006

Keywords

  • Cannabinoid receptor
  • Carbon-11
  • Positron emission tomography
  • Rimonabant
  • SR141716

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

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