Investigations of nucleoside H-phosphonamidate in the design of nucleotide prodrug.
The synthesis, anti-HIV activity and stability studies of a H-phosphonamidate derivative of 3'-azido-2',3'-dideoxythymidine (AZT) incorporating a N,N-diisopropylamino residue as first model of alkylamino group are reported. The results demonstrate that such phosphorylated structure exerts its biological effects via chemical hydrolysis into the corresponding H-phosphonate, precursor of the parent nucleoside.
Egron
D
D
Université Montpellier II, UMR 5625 CNRS, Montpellier, France.
Imbach
J L
JL
Gosselin
G
G
Aubertin
A M
AM
Périgaud
C
C
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D002460:Cell Line; D015195:Drug Design; D004355:Drug Stability; D006678:HIV / Q000187:drug effects*; D006801:Humans; D006868:Hydrolysis; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis*; D009711:Nucleotides / Q000138:chemical synthesis*; D063065:Organophosphonates; D011355:Prodrugs / Q000138:chemical synthesis*; D013601:T-Lymphocytes; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D019380:Anti-HIV Agents; D009705:Nucleosides; D009711:Nucleotides; D063065:Organophosphonates; D011355:Prodrugs; D015215:Zidovudine