Synthesis of 1-(2,4-dichlorophenyl)-4-cyano-5-(4[11C]methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide ([11C]JHU75528) and 1-(2bromophenyl)-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

Two novel ligands for cerebral cannabinoid receptor (CBI), 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 CBI selective antagonist, and AM281, the only available ligand for emission tomography imaging of CBI in human subjects. Radiolabeled [C-11]JHU75528 and [C-11]JHU75575 were prepared by reaction of [C-11]methyl iodide with nor-methyl precursors. The average radiochemical yield, specific radioactivity, and radiochemical purity of [C-11]JHU75528 were 16%, 235 GBq/mu mol (6360 mCi/mu mol), and 99%, respectively; those of [C-11]JHU75575 were 8%, 196 GBq/mu mol (5308 mCi/mu mol), and 99%, respectively. Both ligands hold promise as PET radioligands for imaging CBI receptor. (c) Copyright 2006 John Wiley & Sons, Ltd.