Synthesis and SAR of piperazinyl-N-phenylbenzamides as inhibitors of hepatitis C virus RNA replication in cell culture

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1779-83. doi: 10.1016/j.bmcl.2009.01.066. Epub 2009 Jan 27.

Abstract

The RNA replication machinery of HCV is a multi-subunit membrane-associated complex. NS5A has emerged as an active component of HCV replicase, possibly involved in regulation of viral replication and resistance to the antiviral effect of interferon. We report here substituted piperazinyl-N-(aryl)benzamides as potent inhibitors of HCV replication exerted via modulation of the dimerization of NS5A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Benzamides / chemical synthesis*
  • Benzamides / pharmacology
  • Crystallography, X-Ray / methods
  • Dimerization
  • Hepacivirus / genetics*
  • Hepacivirus / physiology
  • Hepatitis C / drug therapy*
  • Humans
  • Interferons / chemistry
  • Models, Chemical
  • Molecular Conformation
  • Mutation
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / chemistry*

Substances

  • Antiviral Agents
  • Benzamides
  • Viral Nonstructural Proteins
  • Interferons
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase