Synthesis and p38 Inhibitory Activity of Some Novel Substituted N,N'-Diarylurea Derivatives

Molecules. 2016 May 23;21(5):677. doi: 10.3390/molecules21050677.

Abstract

We have identified a novel series of substituted N,N'-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 × 10(-8) and appears to be the most promising one in the series.

Keywords: BIRB-796; P38 MAPK; SPR; TNF-α.

MeSH terms

  • Cell Line, Tumor
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Ligands
  • Lipopolysaccharides / chemistry
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / metabolism
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / chemistry
  • Urea / administration & dosage*
  • Urea / analogs & derivatives
  • Urea / chemistry
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / chemistry
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Urea
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases