Fluoro carbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluoro carbocyclic pyrimidine nucleosides including carbocyclic 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil and carbocyclic 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil

J Med Chem. 1990 Jan;33(1):179-86. doi: 10.1021/jm00163a030.

Abstract

The racemic carbocyclic 2'-fluoroarabinosyl pyrimidine nucleosides 8, 9 (C-FIAU), 12, and 13 (C-FMAU) and the 2'-fluororibosyl pyrimidine nucleosides 17, 20, and 21 were prepared from their respective protected 2'-fluoro amino diols 5 and 14. The carbocyclic 2'-2'-difluorothymidine analogue 27 was obtained from the protected difluoro amino diol 24 which was prepared from the ketone 23 and (diethylamino)sulfur trifluoride (DAST). The chiral carbocyclic 2'-deoxy-6'-fluorouridines 33, 34, 38, and 39 were synthesized from the protected 6'-fluoro amino diols 30 and 36, which were prepared by reduction of the azides 28 and 35. C-FMAU (13) and C-FIAU (9) were active in vitro against HSV-1 with ID50 values of 4.4 and 11 micrograms/mL, respectively, but they were inactive against HSV-2. The cytidine analogues 12 and 20 displayed modest activity in vitro against HSV-1 and HSV-2 but were inactive against human influenza A virus.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiviral Agents*
  • Cell Line
  • Chemical Phenomena
  • Chemistry
  • Crystallography
  • Influenza A virus / drug effects
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Structure
  • Pyrimidine Nucleosides / chemical synthesis
  • Pyrimidine Nucleosides / pharmacology*
  • Simplexvirus / drug effects*
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Pyrimidine Nucleosides
  • 1-((1,2,3,4)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopentyl)-5-methyl-2,4-(1H,3H)-pyrimidinedione
  • 1-((1,2,3,4)-2-fluoro-3-hydroxy-4-( hydroxymethyl)cyclopentyl)-5-iodo-2,4(1H,3H)-pyrimidinedione