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

ChemMedChem. 2018 Jan 8;13(1):97-104. doi: 10.1002/cmdc.201700657. Epub 2017 Dec 12.

Abstract

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.

Keywords: antitumor agents; antiviral agents; drug discovery; nucleosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Deoxyribose / chemistry*
  • HIV-1 / drug effects
  • Humans
  • Nucleosides / chemistry*
  • Pyrroles / chemistry
  • Ribose / chemistry*
  • Structure-Activity Relationship
  • Triazines / chemistry*

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Nucleosides
  • Pyrroles
  • Triazines
  • Deoxyribose
  • Ribose