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-pyrazo le-3-carboxamide ((11C)JHU75575)

摘要

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. Copyright 2006 John Wiley & Sons, Ltd.