2. Academic Validation
  3. Synthesis of [(11)C]GSK1482160 as a new PET agent for targeting P2X(7) receptor

Synthesis of [(11)C]GSK1482160 as a new PET agent for targeting P2X(7) receptor

  • Bioorg Med Chem Lett. 2015 May 1;25(9):1965-70. doi: 10.1016/j.bmcl.2015.03.021.
Mingzhang Gao 1,  Min Wang 1,  Mark A Green 1,  Gary D Hutchins 1,  Qi-Huang Zheng 2
Affiliations

Affiliations

  • 1 Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
  • 2 Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: [email protected].
PMID: 25819093 DOI: 10.1016/j.bmcl.2015.03.021
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. [(11)C]GSK1482160 was prepared from either desmethyl-GSK1482160 or Boc-protected desmethyl-GSK1482160 with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with SPE in 40-50% and 30-40% radiochemical yield, respectively, based on [(11)C]CO2 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.

Keywords

Neuroinflammation; P2X(7) receptor; Positron emission tomography (PET); Radiosynthesis; [(11)C]GSK1482160.

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