[Synthesis and anti-retroviral activity of various new 2',3'-dideoxynucleoside analogs].
About 40 new 2',3'-dideoxynucleoside analogues with different basic structures have been synthetized with the aim of finding more potent and selective inhibitors of HIV and the associated pathogenicity. Some new synthesis techniques were developed and existing ones were used for the preparation of these analogues. Among the 3'-fluorinated 2',3'-dideoxynucleosides several potent inhibitors of HIV were found and especially 3'-fluoro-2',3'-dideoxy-5-chloro-uridine (81) is endowed with a high selectivity index, comparable to the selectivity displayed by 3'-azido-3'-deoxythymidine (AZT). Because of its substantially reduced toxicity profile compared to AZT, this compound deserves further evaluation as a possible alternative for the treatment of AIDS. Likewise, the 5-chlorinated cytidine analogues 102 and 103 should be further examined because of their lack of toxicity in vitro.
Van Aerschot
A
A
Laboratorium voor Farmaceutische Scheikunde, Katholieke Universiteit Leuven.
D015224:Dideoxynucleosides / Q000737:chemistry / Q000494:pharmacology; D006678:HIV / Q000201:enzymology; D006801:Humans; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine
Synthese en antiretrovirale activiteit van enige nieuwe 2', 3'-dideoxynucleoside analogen.