Synthesis and biological profiling of 6-or 7-(het)aryl-7-deazapurine 4 '-C-methylribonucleosides

Abstrakt

The synthesis and biological activity profiling of a large series of diverse pyrrolo[2,3-d]pyrimidine 4 '-C-methylribonucleosides bearing an (het) aryl group at position 4 or 5 is reported as well as the synthesis of several phosphoramidate prodrugs. These compounds are 4 '-C-methyl derivatives of previously reported cytostatic hetaryl-7-deazapurine ribonucleosides.

The synthesis is based on glycosylation of halogenated 7-deazapurine bases with 1,2-di-O-acetyl-3,5-di-O-benzyl-4-C-methyl-beta-D-ribofuranose followed by cross-coupling and nucleophilic substitution reactions. The final compounds showed low cytotoxicity and several derivatives exerted antiviral activity against HCV or Dengue viruses at micromolar concentrations.

Klíčová slova

• Nucleosides
• 4 '-C-Methyl-ribonucleosides
• Branched nucleosides
• Nucleoside antivirals
• Prodrugs