Bis-ketol nucleoside triesters as prodrugs of the antiviral nucleoside triphosphate analogues of 3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine.
Derivatives of 3'-deoxythymidine (ddT) and 3'-deoxy-2',3'-didehydrothymidine (d4T) were prepared in which the 5'-hydroxyl group of the nucleoside was esterified to a bis-ketol phosphate. The resulting phosphate triesters are postulated to be prodrugs of the corresponding 5'-mononucleotides, which are formed intracellularly by the hydrolysis of the two ketol ester groups. The triesters were tested for anti-HIV activity with the result that those derived from ddT showed enhanced antiviral activity when compared to the parent nucleoside.
Calvo
Kim C
KC
Department of Chemistry, The University of Akron, Akron, Ohio 44325-3601, USA. kimcalvo@uakron.edu
Wang
Xiaohong
X
Koser
Gerald F
GF
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D004952:Esters / Q000737:chemistry* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry*; D018119:Stavudine / Q000737:chemistry* / Q000494:pharmacology; D013936:Thymidine / Q000031:analogs & derivatives*
D019380:Anti-HIV Agents; D004952:Esters; D009705:Nucleosides; D011355:Prodrugs; D018119:Stavudine; D013936:Thymidine