Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine nucleotide analogues with a carbamoyl linker

Bioorg Med Chem. 2013 Mar 1;21(5):1097-108. doi: 10.1016/j.bmc.2013.01.007. Epub 2013 Jan 16.

Abstract

5-Arylcarbamoyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesised from N-methyl-C-diethoxyphosphorylnitrone and N-arylacrylamides in good yields. cis- and trans-isoxazolidine phosphonates obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. Isoxazolidines having phenyl substituted with halogen (Ar=2-F-C(6)H(4); 3-Br-C(6)H(4); and 4-Br-C(6)H(4)) have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC(50) in the 100-170 μM range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / toxicity
  • Carbamates / chemistry
  • Cell Line
  • Cell Proliferation / drug effects
  • Cytostatic Agents / chemical synthesis*
  • Cytostatic Agents / chemistry
  • Cytostatic Agents / toxicity
  • DNA Viruses / drug effects
  • Drug Design*
  • HeLa Cells
  • Humans
  • Isoxazoles / chemistry
  • Nucleotides / chemical synthesis
  • Nucleotides / chemistry*
  • Nucleotides / toxicity
  • RNA Viruses / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Carbamates
  • Cytostatic Agents
  • Isoxazoles
  • Nucleotides