Synthesis and biological evaluation of trisubstituted imidazole derivatives as inhibitors of p38alpha mitogen-activated protein kinase

Bioorg Med Chem Lett. 2008 Jul 15;18(14):4006-10. doi: 10.1016/j.bmcl.2008.06.007. Epub 2008 Jun 6.

Abstract

A series of trisubstituted imidazole derivatives containing a 4-fluorophenyl group, a pyrimidine ring, and a CN- or CONH(2)-substituted benzyl moiety have been synthesized and evaluated for p38alpha MAP kinase inhibitory activity. Among them, compounds 22c, 27b, and 28b inhibited p38alpha MAP kinase with IC(50) values 27.6, 28, and 31 nM, respectively.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Inhibitory Concentration 50
  • MAP Kinase Signaling System
  • Models, Chemical
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Pyrimidines / chemistry
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Imidazoles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Recombinant Proteins
  • p38 Mitogen-Activated Protein Kinases