Synthesis of [11C]GSK1482160 as a new PET agent for targeting P2X7 receptor

Mingzhang Gao, Min Wang, Mark A. Green, Gary D. Hutchins, Qi Huang Zheng

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The authentic standards GSK1482160 and its isomer, as well as the radiolabeling precursors desmethyl-GSK1482160 and Boc-protected desmethyl-GSK1482160 were synthesized from l-pyroglutamic acid, methyl l-pyroglutamate and 2-chloro-3-(trifluoromethyl)benzylamine with overall chemical yield 27-28% in 3 steps, 58% in 4 steps, 76% in 1 step and 33% in 2 steps, respectively. [<sup>11</sup>C]GSK1482160 was prepared from either desmethyl-GSK1482160 or Boc-protected desmethyl-GSK1482160 with [<sup>11</sup>C]CH<inf>3</inf>OTf through N-[<sup>11</sup>C]methylation and isolated by HPLC combined with SPE in 40-50% and 30-40% radiochemical yield, respectively, based on [<sup>11</sup>C]CO<inf>2</inf> and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity at EOB was 370-1110 GBq/μmol with a total synthesis time of ∼40-min from EOB.

Original languageEnglish (US)
Pages (from-to)1965-1970
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number9
DOIs
StatePublished - May 1 2015

Keywords

  • Neuroinflammation
  • P2X<inf>7</inf> receptor
  • Positron emission tomography (PET)
  • Radiosynthesis
  • [<sup>11</sup>C]GSK1482160

ASJC Scopus subject areas

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

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