Activity of acyclic 6-(phenylselenenyl)pyrimidine nucleosides against human immunodeficiency viruses in primary lymphocytes.
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.
Goudgaon
N M
NM
Veterans Affairs Medical Center, Atlanta, Georgia 30033.
Schinazi
R F
RF
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000382:microbiology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects; D013329:Structure-Activity Relationship; D014709:Vero Cells / Q000187:drug effects
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; D012194:RNA-Directed DNA Polymerase