Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6325-30. doi: 10.1016/j.bmcl.2013.09.068. Epub 2013 Sep 30.

Abstract

Herein, we report the synthesis and structure-activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the discovery of a potent hepatitis C protease inhibitor 37c (EC50=0.8 μM).

Keywords: Antiviral; HCV; Protease inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Azetidines / chemistry*
  • Azetidines / pharmacology*
  • Drug Design
  • Hepatitis C / drug therapy*
  • Humans
  • Models, Molecular
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / chemistry*

Substances

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