Synthesis and biological evaluation of dinucleoside methylphosphonates of 3'-azido-3'-deoxythymidine and 2', 3'-dideoxycytidine.
The 5'----5' dinucleoside methylphosphonates of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC) were prepared and evaluated for their inhibitory properties against different viruses, including human immunodeficiency virus (HIV). The synthesis of the compounds was achieved by reaction of AZT or N4-(4-monomethoxytrityl)-2',3'-dideoxycytidine with in situ prepared methylphosphonic bis (triazolide), followed in the latter case by an acidic treatment. The two title compounds showed in vitro anti-HIV activity, that was 200- to 450-fold less pronounced that that shown by the corresponding monomeric nucleosides AZT and DDC. The decreased antiviral activity may be ascribed to nuclease resistance of the methylphosphonate linkage.
Puech
F
F
Laboratoire de Chimie Bio-organique, Université des Sciences et Techniques du Languedoc, Montpellier, France.
Gosselin
G
G
Balzarini
J
J
Good
S S
SS
Rideout
J L
JL
De Clercq
E
E
Imbach
J L
JL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003845:Deoxycytosine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D006868:Hydrolysis; D051379:Mice; D008809:Mice, Inbred C3H; D008980:Moloney murine sarcoma virus / Q000187:drug effects / Q000254:growth & development; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000138:chemical synthesis* / Q000494:pharmacology; D015215:Zidovudine / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D003845:Deoxycytosine Nucleotides; D013942:Thymine Nucleotides; D015215:Zidovudine; D016047:Zalcitabine