Enantiomeric 2',3'-dideoxycytidine derivatives are potent human immunodeficiency virus inhibitors in cell cultures.
2',3'-dideoxy-beta-L-cytidine (beta-L-DDC) and its 5-fluoro derivative (beta-L-5-F-DDC) have been stereospecifically synthesized by a multi-step reaction sequence from L-xylose and their anti-HIV properties examined. Among these two L-enantiomers, the hitherto unknown beta-L-5-F-DDC emerged as a potent anti-HIV-1 and HIV-2 compound in different cell culture systems, with selectivity indices similar or superior to those of the currently licensed drug DDC which has the natural beta-D configuration.
Gosselin
G
G
Laboratoire de Chimie Bioorganique, URA CNRS 488, Université de Montpellier-II, Sciences et Techniques du Languedoc, Montpellier, France.
Mathé
C
C
Bergogne
M C
MC
Aubertin
A M
AM
Kirn
A
A
Schinazi
R F
RF
Sommadossi
J P
JP
Imbach
J L
JL
D002478:Cells, Cultured; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D008968:Molecular Conformation; D013237:Stereoisomerism; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
C085719:2',3'-dideoxy-beta-5-fluorocytidine; D016047:Zalcitabine