Synthesis and antiviral activity of some 5'-N-phthaloyl-3'-azido-2',3'-dideoxythymidine analogues.
A variety of substituted 5'-N-phthaloyl-3'-azido-2',3'-dideoxythymidine derivatives has been evaluated for their activity against HIV-1, HIV-2 and Moloney murine sarcoma virus (MSV) in cell culture. Most of the 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine) derivatives showed antiviral activity in the lower micromolar concentration range and there was a close correlation between their anti-HIV and anti-MSV activity (r = 0.99). The adamantyl phthaloyl derivative was active at submicromolar concentrations. None of the compounds showed marked cytostatic activity. They did not inhibit recombinant HIV-1 reverse transcriptase. All compounds were inactive against HIV in thymidine kinase-deficient cells, pointing to the compounds' requirement to release free AZT to afford antiviral efficacy.
Balzarini
Jan
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
De Clercq
Erik
E
Kaminska
Beata
B
Orzeszko
Andrzej
A
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects; D006801:Humans; D007094:Imides / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D009053:Sarcoma Viruses, Murine / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D019380:Anti-HIV Agents; D007094:Imides; D011355:Prodrugs; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine