Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1475-9. doi: 10.1016/j.bmcl.2016.01.050. Epub 2016 Jan 19.

Abstract

HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties.

Keywords: HCV; NS5a; Pan-genotype.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Proline / analogs & derivatives*
  • Silanes / chemistry*
  • Silanes / pharmacology
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / genetics
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • NS-5 protein, hepatitis C virus
  • Silanes
  • Viral Nonstructural Proteins
  • Proline