Synthesis of (O-methyl-11C)1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole- 3-carboxylic acid piperidin-1-ylamide: a potential PET ligand for CB1 receptors.

摘要

Synthesis and in vitro evaluation of [O-methyl-(11)C]1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazol e-3-carboxylic acid piperidin-1-ylamide ([(11)C]-1), a potential imaging agent for CB(1) receptors using PET is described. 1-(2-Chlorophenyl)-5-(4-hydroxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (5), the precursor for radiolabeling, was synthesized from 4-OTBDPS-propiophenone (2) in five steps with 30% overall yield. The reaction of alcohol 5 with [(11)C]MeOTf at 60 degrees C afforded [(11)C]-1 with an average radiochemical yield of 14.5% (EOS) and >2000 Ci/mmol specific activity. The radiotracer was found to selectively label CB(1) receptors in slide-mounted sections of postmortem human brain containing prefrontal cortex as demonstrated by in vitro autoradiography using phosphor imaging.