Discovery and design of benzimidazolone based inhibitors of p38 MAP kinase

Bioorg Med Chem Lett. 2006 Dec 15;16(24):6316-20. doi: 10.1016/j.bmcl.2006.09.014. Epub 2006 Sep 28.

Abstract

A new class of benzimidazolone p38 MAP kinase inhibitors was discovered through high-throughput screening. X-ray crystallographic data of the lead molecule with p38 were used to design analogues with improved binding affinity and potency in a cell assay of LPS-induced TNFalpha production. Herein, we report the SAR of this new class of p38 inhibitors.

MeSH terms

  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology*
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Protein Conformation
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / chemistry*

Substances

  • Benzimidazoles
  • Enzyme Inhibitors
  • benzimidazole
  • p38 Mitogen-Activated Protein Kinases