Discovery of a potent respiratory syncytial virus RNA polymerase inhibitor

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6789-93. doi: 10.1016/j.bmcl.2013.10.018. Epub 2013 Oct 16.

Abstract

Targeting viral polymerases has been a proven and attractive strategy for antiviral drug discovery. Herein we describe our effort in improving the antiviral activity and physical properties of a series of benzothienoazepine compounds as respiratory syncytial virus (RSV) RNA polymerase inhibitors. The antiviral activity and spectrum of this class was significantly improved by exploring the amino substitution of the pyridine ring, resulting in the discovery of the most potent RSV A polymerase inhibitors reported to date.

Keywords: Antiviral; Polymerase inhibitor; Respiratory syncytial virus.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Azepines / chemical synthesis
  • Azepines / chemistry
  • Azepines / pharmacology
  • Cell Line
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • DNA-Directed RNA Polymerases / metabolism
  • Drug Evaluation, Preclinical
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Respiratory Syncytial Viruses / enzymology*
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Azepines
  • Enzyme Inhibitors
  • Viral Proteins
  • DNA-Directed RNA Polymerases