Anti-HIV pronucleotides: decomposition pathways and correlation with biological activities.
The purpose of the present study was to compare the decomposition pathways in CEM cell extracts of various phenyl phosphoramidate derivatives of AZT. In addition, the structures of their metabolites were identified. Correlations with their anti-HIV activities in a thymidine kinase deficient (TK-) CEM cell line have been established with a rationale of designing phosphoramidate pronucleotides capable of delivering intracellularly their respective 5'-nucleoside monophosphate derivatives.
Egron
D
D
Laboratoire de Chimie Bioorganique, UMR CNRS-USTL 5625, Université Montpellier II, France.
Lefebvre
I
I
Périgaud
C
C
Beltran
T
T
Pompon
A
A
Gosselin
G
G
Aubertin
A M
AM
Imbach
J L
JL
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000172:deficiency; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D019380:Anti-HIV Agents; D007202:Indicators and Reagents; D011355:Prodrugs; D015215:Zidovudine; D013937:Thymidine Kinase