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

Appl Radiat Isot. 2014 Aug:90:181-6. doi: 10.1016/j.apradiso.2014.03.029. Epub 2014 Apr 5.

Abstract

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).

Keywords: Cancer; Cannabinoid receptor 2 (CB2); N-(4-Diethylamino)benzyl-4-[(11)C]methoxy-N-(p-tolyl)benzenesulfonamide; Neurological disorders; Positron emission tomography (PET); Radiosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzenesulfonamides
  • Carbon Radioisotopes / chemistry*
  • Isotope Labeling / methods
  • Positron-Emission Tomography / methods*
  • Protein Binding
  • Radiopharmaceuticals / chemical synthesis
  • Receptor, Cannabinoid, CB2 / chemistry*
  • Sulfonamides / chemical synthesis*

Substances

  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • Receptor, Cannabinoid, CB2
  • Sulfonamides
  • Benzenesulfonamides