Synthesis and anti-HIV-1 activity of novel TSAO-T derivatives modified at the 2'- and 5'-positions of the sugar moiety.
Novel analogues of the anti-HIV-1 agent TSAO-T, [1-[2',5'-bis-O-(tert- butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5"-(4"-amino- 1",2"-oxathiole-2",2"-dioxide) and its 3-methyl counterpart TSAO-m3T were obtained by modifications at positions 2' or 5' of the sugar moiety. These compounds were evaluated for their inhibitory effect on HIV-1 and HIV-2 replication in cell culture. Introduction of new groups at the 5'-position (i.e. esters, benzylether and silylethers) resulted in compounds that were either inactive or less active than the parent compounds (TSAO-T and TSAO-m3T). Attempts to introduce small silyl ether groups at this position were not successful since these products decomposed during purification. Similar modifications at the 2'-position had a much less pronounced influence on the anti-HIV-1 activity.
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Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
Pérez-Pérez
M J
MJ
De Clercq
E
E
Balzarini
J
J
Camarasa
M J
MJ
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002241:Carbohydrates / Q000737:chemistry*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D002241:Carbohydrates; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine