MK-8325: A silyl proline-containing NS5A inhibitor with pan-genotype activity for treatment of HCV

Bioorg Med Chem Lett. 2018 Jun 1;28(10):1954-1957. doi: 10.1016/j.bmcl.2018.03.049. Epub 2018 Mar 20.

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 regimen. Herein, we describe the discovery and characterization of silyl proline-containing HCV NS5A inhibitor MK-8325 with good pan-genotype activity and acceptable pharmacokinetic properties.

Keywords: Antiviral; HCV; NS5A; Silyl proline.

MeSH terms

  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology
  • Cytochrome P-450 Enzyme System / metabolism
  • Dogs
  • Genotype
  • Half-Life
  • Haplorhini
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Heterocyclic Compounds, 4 or More Rings / pharmacokinetics
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Proline / chemistry*
  • Rats
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Heterocyclic Compounds, 4 or More Rings
  • MK-8325
  • Viral Nonstructural Proteins
  • Cytochrome P-450 Enzyme System
  • Proline
  • NS-5 protein, hepatitis C virus