The 4',4'-difluoro analog of 5'-noraristeromycin: a new structural prototype for possible antiviral drug development toward orthopoxvirus and cytomegalovirus

Bioorg Med Chem. 2005 Jul 15;13(14):4443-9. doi: 10.1016/j.bmc.2005.04.044.

Abstract

As a surrogate for 4'-hydroxy-5'-noraristeromycin and related carbocyclic nucleosides, an efficient, enantiodivergent synthetic route to both enantiomers of 5-(6-amino-9H-purin-9-yl)-3,3-difluorocyclopentane-1,2-diol (6 and ent-6) has been developed from a common starting material ((+)-(1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate, 10). Both compounds were assayed versus a series of viruses. The only response found was for compound 6 toward vaccinia and cowpox (EC50 of 143 and 94 microM, respectively) and human cytomegalovirus (EC50 of 6.2 microM). Both compounds were non-cytotoxic. While not as active as cidofovir toward the orthopox viruses and ganciclovir toward cytomegalovirus, compound 6 offers a new structural prototype upon which to build for uncovering new agents effective against these viral types.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / growth & development
  • Humans
  • Magnetic Resonance Spectroscopy
  • Microbial Sensitivity Tests
  • Orthopoxvirus / drug effects*
  • Orthopoxvirus / growth & development
  • Vero Cells
  • Viral Plaque Assay

Substances

  • Antiviral Agents
  • 5'-noraristeromycin
  • Adenosine