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 journalArticle

8 Citations (Scopus)

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

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Methylation
Competitive Binding
Leucine
Assays
High Pressure Liquid Chromatography
Ligands
Acids
Experiments
V28 receptor

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

Cite this

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

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 12, 2017, p. 2727-2730.

Research output: Contribution to journalArticle

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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.",
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",
author = "Mingzhang Gao and Min Wang and Meyer, {Jill A.} and Peters, {Jonathan S.} and Hamideh Zarrinmayeh and Paul Territo and Gary Hutchins and Qi-Huang Zheng",
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T1 - 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)

AU - Gao, Mingzhang

AU - Wang, Min

AU - Meyer, Jill A.

AU - Peters, Jonathan S.

AU - Zarrinmayeh, Hamideh

AU - Territo, Paul

AU - Hutchins, Gary

AU - Zheng, Qi-Huang

PY - 2017

Y1 - 2017

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AB - 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.

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