Discovery of GS-9256: a novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1394-6. doi: 10.1016/j.bmcl.2011.12.038. Epub 2011 Dec 13.

Abstract

A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.

MeSH terms

  • Animals
  • Carrier Proteins / antagonists & inhibitors*
  • Dogs
  • Drug Discovery*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Humans
  • Inhibitory Concentration 50
  • Intracellular Signaling Peptides and Proteins
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology
  • Phosphinic Acids / chemical synthesis
  • Phosphinic Acids / chemistry*
  • Phosphinic Acids / pharmacology
  • Swine
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Carrier Proteins
  • Enzyme Inhibitors
  • GS-9256
  • Intracellular Signaling Peptides and Proteins
  • NS3 protein, hepatitis C virus
  • NS4A cofactor peptide, Hepatitis C virus
  • Peptides, Cyclic
  • Phosphinic Acids
  • Viral Nonstructural Proteins