Synthesis and evaluation of NS5A inhibitors containing diverse heteroaromatic cores

Bioorg Med Chem Lett. 2015 Feb 15;25(4):948-51. doi: 10.1016/j.bmcl.2014.12.042. Epub 2014 Dec 22.


Inhibitors of the HCV NS5A nonstructural protein are showing promising clinical potential in the treatment of hepatitis C when used in combination with other direct-acting antiviral agents. Current NS5A clinical candidates such as daclatasvir, ledipasvir, and ombitasvir share a common pharmacophore that features a pair of (S)-methoxycarbonylvaline capped pyrrolidines linked to various cores by amides, imidazoles and/or benzimidazoles. In this Letter, we describe the evaluation of NS5A inhibitors which contain alternative heteroaromatic replacements for these amide mimetics. The SAR knowledge gleaned in the optimization of scaffolds containing benzoxazoles was parlayed toward the identification of potent NS5A inhibitors containing other heteroaromatic replacements such as indoles and imidazopyridines.

Keywords: HCV; Hepatitis C; NS5A.

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Hepacivirus / drug effects*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*


  • Antiviral Agents
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus