'Reverse' alpha-ketoamide-based p38 MAP kinase inhibitors

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5456-9. doi: 10.1016/j.bmcl.2008.09.028. Epub 2008 Sep 11.

Abstract

We have identified a second series of potent p38 inhibitors. As with our first generation series, these compounds are based on an alpha-ketoamide scaffold. The reversal of the ketoamide order, however, introduces more chemical flexibility and in addition results in improve potencies against p38.

MeSH terms

  • Allosteric Site
  • Amides / chemistry*
  • Anti-Inflammatory Agents / pharmacology
  • Chemistry, Pharmaceutical / methods
  • Cytokines / metabolism
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inflammation / drug therapy
  • Inhibitory Concentration 50
  • Ketones / chemistry*
  • Models, Chemical
  • Models, Molecular
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*

Substances

  • Amides
  • Anti-Inflammatory Agents
  • Cytokines
  • Enzyme Inhibitors
  • Ketones
  • p38 Mitogen-Activated Protein Kinases