Synthesis and Cytostatic and Antiviral Profiling of Thieno-Fused 7-Deazapurine Ribonucleosides

J Med Chem. 2017 Mar 23;60(6):2411-2424. doi: 10.1021/acs.jmedchem.6b01766. Epub 2017 Mar 3.


Two isomeric series of new thieno-fused 7-deazapurine ribonucleosides (derived from 4-substituted thieno[2',3':4,5]pyrrolo[2,3-d]pyrimidines and thieno[3',2':4,5]pyrrolo[2,3-d]pyrimidines) were synthesized by a sequence involving Negishi coupling of 4,6-dichloropyrimidine with iodothiophenes, nucleophilic azidation, and cyclization of tetrazolopyrimidines, followed by glycosylation and cross-couplings or nucleophilic substitutions at position 4. Most nucleosides (from both isomeric series) exerted low micromolar or submicromolar in vitro cytostatic activities against a broad panel of cancer and leukemia cell lines and some antiviral activity against HCV. The most active were the 6-methoxy, 6-methylsulfanyl, and 6-methyl derivatives, which were highly active to cancer cells and less toxic or nontoxic to fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Hepacivirus / drug effects
  • Hepatitis C / drug therapy
  • Humans
  • Neoplasms / drug therapy
  • Purines / chemical synthesis
  • Purines / chemistry*
  • Purines / pharmacology*
  • Ribonucleosides / chemical synthesis
  • Ribonucleosides / chemistry
  • Ribonucleosides / pharmacology


  • 7-deazapurine
  • Antineoplastic Agents
  • Antiviral Agents
  • Purines
  • Ribonucleosides