Activity of acyclic 6-(phenylselenenyl)pyrimidine nucleosides against human immunodeficiency viruses in primary lymphocytes

J Med Chem. 1991 Nov;34(11):3305-9. doi: 10.1021/jm00115a022.


Several 6-phenylselenenyl-substituted acyclouridine derivatives were prepared for evaluation as antiviral agents. Lithiation of the tert-butyldimethylsilyl-protected acyclonucleosides 4a-f with lithium diisopropylamide at -78 degrees C, followed by reaction with diphenyl diselenide as an electrophile, and subsequent removal of the protecting group with tetra n-butylammonium fluoride gave 1-[(2-hydroxyethoxy)methyl]-6-(phenylselenenyl)uracils 6a-f in 50-70% overall yield. The potency and spectrum of activity of compounds 6a-f against HIV-1 in vitro was similar to HEPT (1), a related 6-phenylthio acyclonucleoside. However, whereas HEPT inhibited HIV-1 reverse transcriptase, the selenium-containing derivatives were ineffective, suggesting a different mechanism of action. Of significance was the finding that the 6-phenylselenenyl acyclonucleosides inhibited also HIV-2 in primary human lymphocytes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • HIV-1 / drug effects*
  • HIV-2 / drug effects
  • Humans
  • Lymphocytes / drug effects
  • Lymphocytes / microbiology
  • Pyrimidine Nucleosides / chemical synthesis*
  • Pyrimidine Nucleosides / pharmacology
  • RNA-Directed DNA Polymerase / drug effects
  • Structure-Activity Relationship
  • Vero Cells / drug effects


  • Antiviral Agents
  • Pyrimidine Nucleosides
  • RNA-Directed DNA Polymerase