Discovery of hydroxyaniline amides as selective Extracellular Regulated Kinase (Erk) inhibitors

Bioorg Med Chem Lett. 2015 Apr 1;25(7):1627-9. doi: 10.1016/j.bmcl.2015.01.049. Epub 2015 Feb 4.

Abstract

Starting from weak μM hits identified through affinity based Automated Ligand Identification System (ALIS) screenings, double digit nM hydroxyaniline amide Erk inhibitors were discovered. This class of compounds had the unique dual mechanism of inhibiting activated and non-activated forms of Erk. They generally had high degree of selectivity in kinase panel tested.

Keywords: ALIS; Erk; Extracellular regulated kinase; MAPK; NeoMorph.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Aminophenols / chemical synthesis
  • Aminophenols / chemistry
  • Aminophenols / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amides
  • Aminophenols
  • Protein Kinase Inhibitors
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1