Synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors

Bioorg Med Chem Lett. 2016 Apr 1;26(7):1762-6. doi: 10.1016/j.bmcl.2016.02.039. Epub 2016 Feb 16.

Abstract

α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26μM, 1.88±0.35μM and 1.52±0.31μM, respectively) and favorable CC50 values (CC50>100μM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor.

Keywords: 3C protease; Enterovirus 71; Inhibitor; Structure activity relationship; α-Keto amide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amides / pharmacology
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Enterovirus A, Human / drug effects*
  • Enterovirus A, Human / enzymology*
  • Enterovirus Infections / drug therapy
  • Enterovirus Infections / virology
  • Humans
  • Models, Molecular
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors

Substances

  • Amides
  • Antiviral Agents
  • Protease Inhibitors
  • Viral Proteins