Synthesis and in vitro biological evaluation of new P2X7R radioligands [11C]halo-GSK1482160 analogs

Bioorg Med Chem Lett. 2019 Jun 15;29(12):1476-1480. doi: 10.1016/j.bmcl.2019.04.018. Epub 2019 Apr 10.


The reference standards halo-GSK1482160 (F-, Br-, and I-) and their corresponding precursors desmethyl-halo-GSK1482160 (F-, Br-, and I-) were synthesized from (S)-1-methyl-5-oxopyrrolidine-2-carboxylic acid or (S)-5-oxopyrrolidine-2-carboxylic acid and 2-halo-3-(trifluoromethyl)benzylamine (F-, Br-, and I-) in one step with 45-93% yields. The target tracers [11C]halo-GSK1482160 (F-, Br-, and I-) were prepared from desmethyl-halo-GSK1482160 (F-, Br-, and I-) with [11C]CH3OTf under basic conditions (NaOH-Na2CO3, solid, w/w 1:2) through N-[11C]methylation and isolated by HPLC combined with SPE in 40-50% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity (AM) at end of bombardment (EOB) was 370-740 GBq/μmol. The potency of halo-GSK1482160 (F-, Br-, and I-) in comparison with GSK1482160 (Cl-) was determined by a radioligand competitive binding assay using [11C]GSK1482160, and the binding affinity Ki values for halo-GSK1482160 (F-, Br-, and I-) and GSK1482160 (Cl-) are 54.2, 2.5, 1.9 and 3.1 nM, respectively.

Keywords: Competitive binding assay; Positron emission tomography (PET); Purinergic P2X7 receptor (P2X7R); Radiosynthesis; [(11)C]Halo-GSK1482160 (F-, Br-, and I-).

Publication types

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

MeSH terms

  • Humans
  • Radioligand Assay / methods*
  • Radiopharmaceuticals / chemical synthesis*


  • Radiopharmaceuticals