Exploring the role of the 5'-position of TSAO-T. Synthesis and anti-HIV evaluation of novel TSAO-T derivatives

Antiviral Res. 2001 Jun;50(3):207-22. doi: 10.1016/s0166-3542(01)00145-0.

Abstract

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have been synthesized in which the 5'-TBDMS group has been replaced by alkyl-, alkenyl- or aromatic ether groups, substituted amines, carbamoyl or (thio)acyl groups.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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology
  • Cell Line
  • Drug Design
  • HIV-1 / drug effects*
  • HIV-2 / drug effects*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship
  • Thymidine / analogs & derivatives
  • Thymidine / chemistry
  • Thymidine / pharmacology
  • Thymine / chemistry
  • Uridine / analogs & derivatives
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
  • Spiro Compounds
  • Thymine
  • Thymidine
  • TSAO-T
  • Uridine