Enantioselective synthesis of derivatives and structure-activity relationship study in the development of NA255 as a novel host-targeting anti-HCV agent

Bioorg Med Chem Lett. 2013 Jan 1;23(1):336-9. doi: 10.1016/j.bmcl.2012.10.083. Epub 2012 Oct 30.

Abstract

Hepatitis C virus (HCV) infection represents a serious health-care problem. Previously we reported the identification of NA255 from our natural products library using a HCV sub-genomic replicon cell culture system. Herein, we report how the absolute stereochemistry of NA255 was determined and an enantioselective synthetic method for NA255 derivatives was developed. The structure-activity relationship of the NA255 derivatives and rat pharmacokinetic profiles of the representative compounds are disclosed.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / toxicity
  • Cell Line
  • Cell Survival / drug effects
  • Citrates / chemistry*
  • Citrates / pharmacokinetics
  • Citrates / toxicity
  • Half-Life
  • Hepacivirus / drug effects
  • Hepacivirus / growth & development*
  • Humans
  • Phenylpropionates / chemistry*
  • Phenylpropionates / pharmacokinetics
  • Phenylpropionates / toxicity
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Citrates
  • NA 255
  • Phenylpropionates