Exploring the role of the 5'-position of TSAO-T. Synthesis and anti-HIV evaluation of novel TSAO-T derivatives.
Various 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) have been synthesized in which the 5'-TBDMS group has been replaced by alkyl-, alkenyl- or aromatic ether groups, substituted amines, carbamoyl or (thio)acyl groups. The compounds synthesized were evaluated for their inhibitory effect on HIV-1 and HIV-2 replication in cell culture. Replacement of the 5'-TBDMS group by an acyl, aromatic or a cyclic moiety markedly diminish or even eliminate the anti-HIV activity. However, the presence at that position of an alkyl or alkenyl chain, partially retain antiviral activity. These observations suggest that the 5'-TBDMS group of the TSAO molecule plays a crucial role.
Chamorro
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Instituto de Química Médica (C.S.I.C.), C/Juan de la Cierva 3, E-28006, Madrid, Spain.
Pérez-Pérez
M J
MJ
Rodríguez-Barrios
F
F
Gago
F
F
De Clercq
E
E
Balzarini
J
J
San-Félix
A
A
Camarasa
M J
MJ
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013941:Thymine / Q000737:chemistry; D014529:Uridine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D013941:Thymine; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine