Structure-activity relationships of proline modifications around the tetracyclic-indole class of NS5A inhibitors

Bioorg Med Chem Lett. 2016 Nov 1;26(21):5354-5360. doi: 10.1016/j.bmcl.2016.08.097. Epub 2016 Sep 2.

Abstract

We describe the impact of proline modifications, in our tetracyclic-indole based series of nonstructural protein 5A (NS5A) inhibitors, to their replicon profiles. This work identified NS5A inhibitors with an improved and flattened resistance profiles.

Keywords: Direct-acting antiviral agents; Elbasvir; HCV NS5A inhibitor; HCV infection treatment; Indole based tetracyclic core; MK-8742.

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Indoles / chemistry*
  • Proline / chemistry*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Benzofurans
  • Imidazoles
  • Indoles
  • Viral Nonstructural Proteins
  • elbasvir
  • Proline
  • NS-5 protein, hepatitis C virus