Identification of [(naphthalene-1-carbonyl)-amino]-acetic acid derivatives as nonnucleoside inhibitors of HCV NS5B RNA dependent RNA polymerase

Bioorg Med Chem Lett. 2004 Aug 16;14(16):4221-4. doi: 10.1016/j.bmcl.2004.06.013.

Abstract

A novel series of HCV NS5B RNA dependent RNA polymerase inhibitors containing a naphthalene carboxamide scaffold were identified by high throughput screening. Optimization of substituents by parallel synthesis and the iterative design towards understanding structure-activity relationship to improve potency are described. Tetra substituted naphthalene 31 displayed potent activity with IC(50) of 120 nM against HCV NS5B enzyme and was selective over a panel of polymerases.

MeSH terms

  • Acetates / chemistry*
  • Acetates / pharmacology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Acetates
  • Enzyme Inhibitors
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • RNA-Dependent RNA Polymerase