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

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.