Synthesis and anti-enterovirus activity of new analogues of MDL-860

Bioorg Med Chem Lett. 2017 Oct 1;27(19):4540-4543. doi: 10.1016/j.bmcl.2017.08.056. Epub 2017 Aug 30.

Abstract

A series of twelve novel compounds, analogues of antiviral agent MDL-860 were synthesized and their antiviral activity was evaluated in vitro against enteroviruses poliovirus 1 (PV1), Coxsackieviruses B1 (CVB1) and Coxsackieviruses B3 (CVB3). Compounds 14, 24 and 25 manifested strong antiviral effects against CVB1 and PV1 (SI values of 405 and 118 for CVB1 and PV1 respectively). In contrast to the wide anti-enteroviral activity of MDL-860, these three compounds were inactive against CVB3. Compounds 14, 24 and 25 along with MDL-860 were tested in vivo in mice infected with CVB1. Marked protective effects of compounds 14 and 24 were established, PI values of 50% and 33.3%, respectively. In addition, almost all of the tested compounds manifested very low toxicity.

Keywords: Coxsackieviruses; Diarylethers; Enterovirus; MDL-860; Polio.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enterovirus / drug effects*
  • Enterovirus Infections / drug therapy*
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nitriles / chemical synthesis
  • Nitriles / chemistry
  • Nitriles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Nitriles
  • 2-(3,4-dichlorophenoxy)-5-nitrobenzonitrile