Synthesis of (Z)-2-((1H-indazol-3-yl)methylene)-6-[¹¹C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one as a new potential PET probe for imaging of the enzyme PIM1

Bioorg Med Chem Lett. 2013 Aug 1;23(15):4342-6. doi: 10.1016/j.bmcl.2013.05.091. Epub 2013 Jun 6.

Abstract

(Z)-2-((1H-Indazol-3-yl)methylene)-6-methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one is a potent and selective proviral integration site in moloney murine leukemia virus kinase 1 (PIM1) inhibitor with an IC₅₀ value of 3 nM. (Z)-2-((1H-Indazol-3-yl)methylene)-6-[(11)C]methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one, a new potential PET probe for imaging of the enzyme PIM1, was first designed and synthesized in 20-30% decay corrected radiochemical yield and 370-740 GBq/μmol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled Boc-protected intermediate followed by a quick acidic de-protection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzofurans / chemical synthesis*
  • Benzofurans / chemistry*
  • Carbon Isotopes / chemistry
  • Fungal Proteins
  • Humans
  • Indazoles / chemical synthesis*
  • Indazoles / chemistry
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasms / diagnostic imaging
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Positron-Emission Tomography
  • Protein Kinase Inhibitors / chemical synthesis
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry

Substances

  • (Z)-2-((1H-indazol-3-yl)methylene)-6-((11)C)methoxy-7-(piperazin-1-ylmethyl)benzofuran-3(2H)-one
  • Benzofurans
  • Carbon Isotopes
  • Fungal Proteins
  • Indazoles
  • Piperazines
  • Protein Kinase Inhibitors
  • Radiopharmaceuticals
  • Mitogen-Activated Protein Kinases
  • Pim1 protein, Pichia pastoris
  • benzofuran