2. Academic Validation
  3. Xylo-C-nucleosides with a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base: Synthesis and antiproliferative properties

Xylo-C-nucleosides with a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base: Synthesis and antiproliferative properties

  • Bioorg Med Chem Lett. 2019 Jun 15;29(12):1450-1453. doi: 10.1016/j.bmcl.2019.04.023.
Peng Nie 1,  Elisabetta Groaz 1,  Dirk Daelemans 2,  Piet Herdewijn 3
Affiliations

Affiliations

  • 1 Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49-box 1041, Leuven 3000, Belgium.
  • 2 Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, KU Leuven, Herestraat 49-box 1043, Leuven 3000, Belgium.
  • 3 Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49-box 1041, Leuven 3000, Belgium. Electronic address: [email protected].
PMID: 31005446 DOI: 10.1016/j.bmcl.2019.04.023
Abstract

The synthesis of a xylo-C-nucleoside containing pyrrolo[2,1-f][1,2,4]triazin-4-amine as nucleobase along with that of its 1'-cyano analogue is described. Among different experimental conditions explored in order to optimize a key debenzylation step in the presented synthetic route, it was found that palladium catalyzed hydrogen transfer allowed for obtaining the target compounds in good yields. The resulting mixture of epimers was separated and each was characterized by NOESY NMR experiments. In vitro antiproliferative assays showed that the 1'-unsubstituted analogue was active against a panel of tumor cell lines such as the human leukemia HL-60 (IC50 = 1.9 µM) and lung Cancer NCI-H460 (IC50 = 2.0 µM) cells.

Keywords

Antitumor agents; C-nucleosides; Nucleoside analogues; Xylo-nucleosides.

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