Xylo-C-nucleosides with a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base: Synthesis and antiproliferative properties.
Nie P, Groaz E, Daelemans D, Herdewijn P.
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 (IC<sub>50</sub> = 1.9 µM) and lung cancer NCI-H460 (IC<sub>50</sub> = 2.0 µM) cells.