title: 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.
abstract: Synthesis and in vitro evaluation of [O-methyl-(11)C]1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-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.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. dk2038@columbia.edu
authors.forename: J S Dileep
authors.initials: JS
authors.lastname: Kumar
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.forename: Mark D
authors.initials: MD
authors.lastname: Underwood
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.forename: Suham A
authors.initials: SA
authors.lastname: Kassir
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Van Heertum
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D001345:Autoradiography; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D006801:Humans; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D043884:Receptor, Cannabinoid, CB1 / Q000032:analysis* / Q000737:chemistry
chemical_list: C494033:(O-methyl-11C)1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide; D002250:Carbon Radioisotopes; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1