Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7317-22. doi: 10.1016/j.bmcl.2010.10.071. Epub 2010 Oct 21.

Abstract

We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2∗ groups. P2∗ 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein.

MeSH terms

  • Administration, Oral
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacokinetics
  • Hepacivirus / enzymology*
  • Isoquinolines / chemistry
  • Macrocyclic Compounds / chemical synthesis
  • Macrocyclic Compounds / chemistry*
  • Macrocyclic Compounds / pharmacokinetics
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacokinetics
  • Rats
  • Structure-Activity Relationship
  • Thiazoles / chemistry
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antiviral Agents
  • Isoquinolines
  • Macrocyclic Compounds
  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Thiazoles
  • Viral Nonstructural Proteins
  • isoquinoline