Facile and high-yield synthesis of N-(4-diethylamino)benzyl-4-[¹¹C]methoxy-N-(p-tolyl)benzenesulfonamide as a new potential PET selective CB2 radioligand.
The reference standard N-(4-diethylamino)benzyl-4-methoxy-N-(p-tolyl)benzenesulfonamide (3c) (CB2, Ki=0.5 nM; CB1, Ki=1297 nM; selectivity CB1/CB2=2594) and its corresponding precursor N-(4-diethylamino)benzyl-4-hydroxy-N-(p-tolyl)benzenesulfonamide (3d) were synthesized from 4-(diethylamino)benzaldehyde and p-toluidine in 3 steps with 75-84% overall chemical yield. The target tracer N-(4-diethylamino)benzyl-4-[(11)C]methoxy-N-(p-tolyl)benzenesulfonamide ([(11)C]3c) was synthesized from the phenol hydroxyl precursor by O-[(11)C]-methylation with [(11)C]CH3OTf, followed by HPLC combined with SPE purification in 40-50% decay corrected radiochemical yields with 370-740 GBq/μmol specific activity at the end of bombardment (EOB).
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-202, Indianapolis, IN 46202-2111, USA.
Mingzhang
M
Gao
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-202, Indianapolis, IN 46202-2111, USA.
Julie
J
Xu
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-202, Indianapolis, IN 46202-2111, USA.
Min
M
Wang
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, L3-202, Indianapolis, IN 46202-2111, USA. Electronic address: qzheng@iupui.edu.
Qi-Huang
QH
Zheng
D002250:Carbon Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry*; D013449:Sulfonamides / Q000138:chemical synthesis*; D000096926:Benzenesulfonamides
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D000096926:Benzenesulfonamides
Cancer; Cannabinoid receptor 2 (CB2); N-(4-Diethylamino)benzyl-4-[(11)C]methoxy-N-(p-tolyl)benzenesulfonamide; Neurological disorders; Positron emission tomography (PET); Radiosynthesis