1-Phenyl-5-pyrazolyl ureas: potent and selective p38 kinase inhibitors

Bioorg Med Chem Lett. 2000 Sep 18;10(18):2051-4. doi: 10.1016/s0960-894x(00)00272-9.

Abstract

Inhibitors of the MAP kinase p38 are potentially useful for the treatment of arthritis and osteoporosis. Several 2,3-dichlorophenyl ureas were identified as small-molecule inhibitors of p38 by a combinatorial chemistry effort. Optimization for cellular potency led to the discovery of a new class of potent and selective p38 kinase inhibitors, exemplified by the 1-phenyl-5-pyrazolyl urea 7 (IC50 = 13 nM).

MeSH terms

  • Antirheumatic Agents / chemical synthesis
  • Antirheumatic Agents / chemistry
  • Combinatorial Chemistry Techniques
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Heterocyclic Compounds / chemistry
  • Humans
  • Hydrocarbons, Chlorinated / chemistry
  • Inhibitory Concentration 50
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Osteoporosis / drug therapy
  • Phenylurea Compounds* / chemical synthesis
  • Phenylurea Compounds* / pharmacology
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Solubility
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis*
  • Urea / pharmacology*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Antirheumatic Agents
  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • Hydrocarbons, Chlorinated
  • Phenylurea Compounds
  • Pyrazoles
  • Urea
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases