Synthesis and antiviral activity of purine 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl nucleosides.
9-(2',3'-Dideoxy-2',3'-difluoro-beta-D-arabinofuranosyl)adenine (20), 2-chloro-9-(2',3'-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)adenine (22), as well as their respective alpha-anomers 21 and 23, were synthesized by the nucleobase anion glycosylation of intermediate 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-alpha-D-arabinofuranosyl bromide (13) starting from methyl 5-O-benzyl-3-deoxy-3-fluoro-alpha-D-ribofuranoside (3) and methyl 5-O-benzoyl-alpha-D-xylofuranoside (10). These compounds were evaluated as potential inhibitors of HIV-1 and hepatitis C virus in human PBM and Huh-7 Replicon cells, respectively. The adenosine analog 20 demonstrated potent activity against HIV-1 in primary human lymphocytes with no apparent cytotoxicity. Conformation of pentofuranose ring of nucleoside 20 in solution was studied by PSEUROT calculations.
Sivets
Grigorii G
GG
Institute of Bioorganic Chemistry, National Academy of Sciences, Minsk, Belarus.
Kalinichenko
Elena N
EN
Mikhailopulo
Igor A
IA
Detorio
Mervi A
MA
McBrayer
Tami R
TR
Whitaker
Tony
T
Schinazi
Raymond F
RF
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017611:Fluorine Compounds / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008968:Molecular Conformation; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000998:Antiviral Agents; D017611:Fluorine Compounds; D011684:Purine Nucleosides