Synthesis and Biological Evaluation of Pyrrolo[2,1-f][1,2,4]triazine C-Nucleosides with a Ribose, 2'-Deoxyribose, and 2',3'-Dideoxyribose Sugar Moiety.

The synthesis of hitherto unknown pyrrolo[2,1-f][1,2,4]triazine C-nucleosides is described. Structural variations (chlorine, bromine, iodine, and cyano groups) were introduced at position 7 of 4-aza-7,9-dideazaadenine. In addition, pyrrolo[2,1-f][1,2,4]triazine C-nucleosides bearing a 2'-deoxy-, 2',3'-dideoxy-, and 2',3'-dehydrodideoxyribose moiety were also prepared. Among these analogues, the pyrrolo[2,1-f][1,2,4]triazine C-ribonucleosides with either a hydrogen atom or cyano group at position 7 of the nucleobase displayed potent cytotoxic activity in a panel of various cancer cell lines.