New carbocyclic N(6)-substituted adenine and pyrimidine nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, antiviral, anticancer activity and X-ray crystallography

Bioorg Med Chem. 2015 Oct 1;23(19):6346-54. doi: 10.1016/j.bmc.2015.08.033. Epub 2015 Sep 1.


New nucleoside analogues with an optically active bicyclo[2.2.1]heptane skeleton as sugar moiety and 6-substituted adenine were synthesized by alkylation of 6-chloropurine intermediate. Thymine and uracil analogs were synthesized by building the pyrimidine ring on amine 1. X-ray crystallography confirmed an exo-coupling of the thymine to the ring and an L configuration of the nucleoside analogue. The library of compounds was tested for their inhibitory activity against influenza virus A∖California/07/09 (H1N1)pdm09 and coxsackievirus B4 in cell culture. Compounds 13a and 13d are the most promising for their antiviral activity against influenza, and compound 3c against coxsackievirus B4. Compounds 3b and 3g were tested for anticancer activity.

Keywords: Anticancer; Antiviral activity; Bicyclo[2.2.1]heptane nucleosides; Chloropurine; Pyrimidine nucleosides; X-ray-crystallography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / chemistry*
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Bridged Bicyclo Compounds / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Crystallography, X-Ray
  • Dogs
  • Drug Screening Assays, Antitumor
  • Enterovirus B, Human / drug effects
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Madin Darby Canine Kidney Cells
  • Molecular Conformation
  • Pyrimidine Nucleosides / chemistry*
  • Structure-Activity Relationship
  • Vero Cells


  • Adenine Nucleotides
  • Antineoplastic Agents
  • Antiviral Agents
  • Bridged Bicyclo Compounds
  • Pyrimidine Nucleosides
  • bicyclo(2.2.1)heptene