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Synthesis of 1‐(2,4‐dichlorophenyl)‐4‐cyano‐5‐(4‐[ 11 C]methoxyphenyl)‐ N ‐(piperidin‐1‐yl)‐1 H ‐pyrazole‐3‐carboxamide ([ 11 C]JHU75528) and 1‐(2‐bromophenyl)‐4‐cyano‐5‐(4‐[ 11 C]methoxyphenyl)‐ N ‐(piperidin‐1‐yl)‐1 H ‐pyrazole‐3‐carboxamide ([ 11 C]JHU75575) as potential radioligands for PET imaging of cerebral cannabinoid receptor
Author(s) -
Fan Hong,
Ravert Hayden T.,
Holt Daniel P.,
Dannals Robert F.,
Horti Andrew G.
Publication year - 2006
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.1125
Subject(s) - chemistry , carboxamide , rimonabant , pyrazole , lipophilicity , ligand (biochemistry) , cannabinoid receptor , antagonist , stereochemistry , methyl iodide , cannabinoid , medicinal chemistry , receptor , biochemistry
Abstract Two novel ligands for cerebral cannabinoid receptor (CB1), 1‐(2,4‐dichlorophenyl)‐4‐cyano‐5‐(4‐methoxyphenyl)‐ N ‐(piperidin‐1‐yl)‐1 H ‐pyrazole‐3‐carboxamide (JHU75528) and 1‐(2‐bromophenyl)‐4‐cyano‐5‐(4‐methoxyphenyl)‐ N ‐(piperidin‐1‐yl)‐1 H ‐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 [ 11 C]JHU75528 and [ 11 C]JHU75575 were prepared by reaction of [ 11 C]methyl iodide with nor‐methyl precursors. The average radiochemical yield, specific radioactivity, and radiochemical purity of [ 11 C]JHU75528 were 16%, 235 GBq/µmol (6360 mCi/µmol), and 99%, respectively; those of [ 11 C]JHU75575 were 8%, 196 GBq/µmol (5308 mCi/µmol), and 99%, respectively. Both ligands hold promise as PET radioligands for imaging CB1 receptor. Copyright © 2006 John Wiley & Sons, Ltd.