Potent aza-peptide derived inhibitors of HCV NS3 protease

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4760-3. doi: 10.1016/j.bmcl.2009.06.060. Epub 2009 Jun 17.

Abstract

Chronic hepatitis C infection is the primary cause for cirrhosis of the liver and hepatocellular carcinoma leading to liver failure and transplantation. The etiological agent hepatitis C virus produces a single positive strand RNA that is processed further with the help of NS3 serine protease to produce mature virus. Inhibition of this protease can potentially be used to develop drugs for HCV infections. Boceprevir is a ketoamide derived novel inhibitor of HCV NS3 protease that has been progressed to clinical trials and proven to be efficacious in humans. Herein, we report our efforts in identifying an aza-peptide derivative as a potential second generation compound, that lacks electrophilic ketoamide group and are potent in enzyme and replicon assay.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Aza Compounds / chemical synthesis
  • Aza Compounds / chemistry*
  • Aza Compounds / pharmacology
  • Hepacivirus / enzymology*
  • Hepatitis C / drug therapy
  • Humans
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / pharmacology
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / chemistry*
  • Serine Proteinase Inhibitors / pharmacology
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antiviral Agents
  • Aza Compounds
  • NS3 protein, hepatitis C virus
  • Peptides
  • Serine Proteinase Inhibitors
  • Viral Nonstructural Proteins