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

Mingzhang Gao, Min Wang, Jill A. Meyer, Paul R. Territo, Gary D. Hutchins, Hamideh Zarrinmayeh, Qi Huang Zheng

Research output: Contribution to journalArticle

3 Scopus citations


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 [ 11 C]halo-GSK1482160 (F-, Br-, and I-) were prepared from desmethyl-halo-GSK1482160 (F-, Br-, and I-) with [ 11 C]CH 3 OTf under basic conditions (NaOH-Na 2 CO 3 , solid, w/w 1:2) through N-[ 11 C]methylation and isolated by HPLC combined with SPE in 40–50% decay corrected radiochemical yield. The radiochemical purity was >99%, and the molar activity (A M ) 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 [ 11 C]GSK1482160, and the binding affinity K i values for halo-GSK1482160 (F-, Br-, and I-) and GSK1482160 (Cl-) are 54.2, 2.5, 1.9 and 3.1 nM, respectively.

Original languageEnglish (US)
Pages (from-to)1476-1480
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number12
StatePublished - Jun 15 2019


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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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