Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents

Min Wang, Mingzhang Gao, Bruce H. Mock, Kathy D. Miller, George W. Sledge, Gary D. Hutchins, Qi Huang Zheng

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

Fluorinated 2-arylbenzothiazoles are new potential antitumor drugs, which show potent and selective inhibitory activity against breast, lung, and colon cancer cell lines. Carbon-11 labeled fluorinated 2-arylbenzothiazoles may serve as novel probes for positron emission tomography (PET) to image tyrosine kinase in cancers. The preparation of 4-fluorinated 2-arylbenzothiazoles 4-fluoro-2-(3-benzloxy-4-methoxyphenyl)benzothiazole (6a) and 4-fluoro-2-(3,4-dimethoxyphenyl)benzothiazole (6b) was achieved by a modification of Jacobson thioanilide radical cyclization chemistry. Hydrogenolytic cleavage of the benzyl ether group of compound 6a using H2/Pd-C provided the precursor 4-fluoro-2-(3-hydroxy-4-methoxyphenyl)benzothiazole (7) for radiolabeling. Synthesis of radiolabeling precursors and the reference standards 5- and 6-fluorinated arylbenzothiazoles (11c-n) was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. The target radiotracers carbon-11 labeled 4-, 5-, and 6-fluorinated arylbenzothiazoles (3-[11C]6b, 4-[11C]11c, 3-[11C]11c, 5-[11C]11f, 4-[11C]11f, 4-[11C]11i, 3-[11C]11i, 5-[11C]11l, and 4-[11C]11l) were prepared by O-[11C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.

Original languageEnglish (US)
Pages (from-to)8599-8607
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number24
DOIs
StatePublished - Dec 15 2006

Keywords

  • Cancer imaging
  • Carbon-11
  • Fluorinated 2-arylbenzothiazoles
  • Positron emission tomography (PET)
  • Tyrosine kinase

ASJC Scopus subject areas

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

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