Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer

Min Wang, Reynaldo Tzintzun, Mingzhang Gao, Zhidong Xu, Qi Huang Zheng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Abstract The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29-49% and 24-32% overall chemical yield, respectively. The target tracer [<sup>11</sup>C]CX-6258 {(E)-5-chloro-3-((5-(3-(4-[<sup>11</sup>C]methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, [<sup>11</sup>C]4a} was prepared from N-desmethyl-CX-6258 (5) with [<sup>11</sup>C]CH<inf>3</inf>OTf under basic condition (2 N NaOH) through N-[<sup>11</sup>C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [<sup>11</sup>C]CO<inf>2</inf> and decay corrected to end of bombardment (EOB) with 370-1110 GBq/μmol specific activity at EOB.

Original languageEnglish (US)
Article number22950
Pages (from-to)3831-3835
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number18
DOIs
StatePublished - Aug 17 2015

Fingerprint

Imaging techniques
Furaldehyde
Neoplasms
Methylation
Acids
Solid Phase Extraction
1,4-diazepane
proto-oncogene proteins pim
furan
CX-6258
High Pressure Liquid Chromatography
indolin-2-one

Keywords

  • Cancer
  • Pim kinases
  • Positron emission tomography (PET)
  • Radiosynthesis
  • [<sup>11</sup>C]CX-6258

ASJC Scopus subject areas

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

Cite this

Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer. / Wang, Min; Tzintzun, Reynaldo; Gao, Mingzhang; Xu, Zhidong; Zheng, Qi Huang.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 18, 22950, 17.08.2015, p. 3831-3835.

Research output: Contribution to journalArticle

Wang, Min ; Tzintzun, Reynaldo ; Gao, Mingzhang ; Xu, Zhidong ; Zheng, Qi Huang. / Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer. In: Bioorganic and Medicinal Chemistry Letters. 2015 ; Vol. 25, No. 18. pp. 3831-3835.
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abstract = "Abstract The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29-49{\%} and 24-32{\%} overall chemical yield, respectively. The target tracer [11C]CX-6258 {(E)-5-chloro-3-((5-(3-(4-[11C]methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, [11C]4a} was prepared from N-desmethyl-CX-6258 (5) with [11C]CH3OTf under basic condition (2 N NaOH) through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50{\%} radiochemical yield based on [11C]CO2 and decay corrected to end of bombardment (EOB) with 370-1110 GBq/μmol specific activity at EOB.",
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AU - Wang, Min

AU - Tzintzun, Reynaldo

AU - Gao, Mingzhang

AU - Xu, Zhidong

AU - Zheng, Qi Huang

PY - 2015/8/17

Y1 - 2015/8/17

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AB - Abstract The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29-49% and 24-32% overall chemical yield, respectively. The target tracer [11C]CX-6258 {(E)-5-chloro-3-((5-(3-(4-[11C]methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, [11C]4a} was prepared from N-desmethyl-CX-6258 (5) with [11C]CH3OTf under basic condition (2 N NaOH) through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [11C]CO2 and decay corrected to end of bombardment (EOB) with 370-1110 GBq/μmol specific activity at EOB.

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KW - Pim kinases

KW - Positron emission tomography (PET)

KW - Radiosynthesis

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