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.
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.
Kumar
J S Dileep
JS
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. dk2038@columbia.edu
Prabhakaran
Jaya
J
Arango
Victoria
V
Parsey
Ramin V
RV
Underwood
Mark D
MD
Simpson
Norman R
NR
Kassir
Suham A
SA
Majo
Vattoly J
VJ
Van Heertum
Ronald L
RL
Mann
J John
JJ
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
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