First synthesis and evaluation of the inhibitory effects of aza analogues of TSAO on HIV-1 replication

J Med Chem. 2005 Jun 30;48(13):4276-84. doi: 10.1021/jm050091g.

Abstract

Aza TSAO-T derivatives bearing a dihydroisothiazole dioxide ring instead of an oxathiole dioxide ring at the C-3' position on the sugar moiety were prepared. We have synthesized four families of compounds depending on substitution at both N-3 and N-2' '. Biological evaluation showed that these compounds are HIV-1(III(B))-specific and potent reverse transcriptase inhibitors with EC(50) values between 0.13 and 3.5 microM in cell culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemical synthesis
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology*
  • Cell Line
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • HIV-2 / drug effects
  • HIV-2 / physiology
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship
  • Thymidine / analogs & derivatives*
  • Thymidine / chemical synthesis*
  • Thymidine / pharmacology*
  • Uridine / analogs & derivatives
  • Virus Replication / drug effects*

Substances

  • Aza Compounds
  • Reverse Transcriptase Inhibitors
  • Spiro Compounds
  • Thymidine
  • TSAO-T
  • Uridine