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

Bioorg Med Chem. 2006 Dec 15;14(24):8599-607. doi: 10.1016/j.bmc.2006.08.026. Epub 2006 Sep 8.

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 H(2)/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-[(11)C]6b, 4-[(11)C]11c, 3-[(11)C]11c, 5-[(11)C]11f, 4-[(11)C]11f, 4-[(11)C]11i, 3-[(11)C]11i, 5-[(11)C]11l, and 4-[(11)C]11l) were prepared by O-[(11)C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [(11)C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30-55% radiochemical yields.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzothiazoles / chemical synthesis*
  • Benzothiazoles / chemistry
  • Carbon Radioisotopes*
  • Humans
  • Neoplasms / diagnostic imaging*
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Tomography, Emission-Computed

Substances

  • 4-fluoro-2-(3,4-dimethoxyphenyl)benzothiazole
  • 4-fluoro-2-(3-benzyloxy-4-methoxyphenyl)benzothiazole
  • Benzothiazoles
  • Carbon Radioisotopes
  • Radiopharmaceuticals
  • benzothiazole