Synthesis and preliminary biological evaluation of [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-D-leucinate for the fractalkine receptor (CX3CR1)

Mingzhang Gao, Min Wang, Jill A. Meyer, Jonathan S. Peters, Hamideh Zarrinmayeh, Paul Territo, Gary Hutchins, Qi-Huang Zheng

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-D-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-D-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-D-leucinate ([11C]5) was prepared from the acid precursor with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [11C]CO2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110 GBq/μmol with a total synthesis time of ∼40-min from EOB. The radioligand depletion experiment of [11C]5 did not display specific binding to CX3CR1, and the competitive binding assay of ligand 5 found much lower CX3CR1 binding affinity.

Original languageEnglish (US)
Pages (from-to)2727-2730
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number12
DOIs
StatePublished - 2017

Keywords

  • Competitive binding assay
  • Fractalkine receptor (CXCR1)
  • Positron emission tomography (PET)
  • Radioligand depletion experiment
  • Radiosynthesis
  • [C]Methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-D-leucinate

ASJC Scopus subject areas

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

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