Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid.

Abstract

Prolonged hepatitis C infection is the leading cause for cirrhosis of the liver and hepatocellular carcinoma. The etiological agent HCV virus codes a single polyprotein of approximately 3000 amino acids that is processed with the help of a serine protease NS3A to produce structural and non-structural proteins required for viral replication. Inhibition of NS3 protease can potentially be used to develop drugs for treatment of HCV infections. Herein, we report the development of a series of novel NS3 serine protease inhibitors derived from 2-aza-bicyclo[2.2.1]-heptane carboxylic acid with potential therapeutic use for treatment of HCV infections.

• Authors: Srikanth Venkatraman, F George Njoroge, Wanli Wu, Viyyoor Girijavallabhan, Andrew J Prongay, Nancy Butkiewicz, John Pichardo
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 6 Pg. 1628-32 (Mar 15 2006) ISSN: 0960-894X [Print] England
• PMID: 16413182 (Publication Type: Journal Article)

Chemical References

• 2-azabicyclo(2.2.1)heptane-3-carboxylic acid
• Bridged Bicyclo Compounds
• NS3 protein, hepatitis C virus
• Serine Proteinase Inhibitors
• Viral Nonstructural Proteins

Topics

• Binding Sites
• Bridged Bicyclo Compounds (chemical synthesis, chemistry, pharmacology)
• Hepacivirus (chemistry, drug effects, enzymology)
• Molecular Structure
• Protein Binding
• Replicon (drug effects)
• Serine Proteinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Viral Nonstructural Proteins (antagonists & inhibitors, chemistry)
• X-Ray Diffraction