The synthesis and biochemical evaluation of thymidine analogues substituted with nido carborane at the N-3 position

Youngjoo Byun, Junhua Yan, Ashraf Al Madhoun, Jayaseharan Johnsamuel, Weilian Yang, Rolf F. Barth, Staffan Eriksson, Werner Tjarks

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Several thymidine analogues substituted with closo- and nido-carborane at the N-3 position were synthesized. The nido-carboranyl thymidine analogues were designed to be effective substrates for human thymidine kinase 1 in combination with an increased water solubility sufficient for clinical application in boron neutron capture therapy. This was done because N-3 substituted closo-carboranyl thymidine analogues previously synthesized in our laboratories were good TK1 substrates but were poorly water-soluble. Newly synthesized zwitterionic amino nido- and the corresponding neutral closo-m-carboranyl thymidine analogues exhibited excellent TK1 phosphorylation rates up to 75% relative to thymidine, indicating that these compounds were good substrates for thymidine kinase 1. Thin layer chromatographic studies were indicative of increased hydrophilicity of the synthesized nido-carboranyl thymidine analogues compared with their closo-carboranyl counterparts and previously reported closo-carboranyl thymidine analogues.

Original languageEnglish
Pages (from-to)1125-1130
Number of pages6
JournalApplied Radiation and Isotopes
Issue number5
Publication statusPublished - 1 Nov 2004



  • BNCT
  • Boc
  • Boron neutron capture therapy
  • Closo-carborane
  • High resolution mass spectrometry
  • HRMS
  • Monophosphate
  • MP
  • N-tert-Butoxycarbonyl
  • Nido-carborane
  • NMR
  • Nuclear magnetic resonance
  • Reversed phase
  • RP
  • TBAF
  • Thymidine kinase 1

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