Synthesis and biological activity of macrocyclic inhibitors of hepatitis C virus (HCV) NS3 protease

Bioorg Med Chem Lett. 2005 Oct 15;15(20):4475-8. doi: 10.1016/j.bmcl.2005.07.033.

Abstract

The 17-membered phenylalanine-based macrocycle 6 was prepared starting from 3-iodo-phenylalanine. Macrocyclization of alkene phenyl iodide 5 was effected through a palladium-catalyzed Heck reaction. The macrocyclic alpha-ketoamides were active inhibitors of the HCV NS3 protease, with the C-terminal acids and amides being more potent than tert-butyl esters.

MeSH terms

  • Crystallography, X-Ray
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • NS3 protein, hepatitis C virus
  • Protease Inhibitors
  • Viral Nonstructural Proteins