Synthesis and structure-activity relationship of 2-arylamino-4-aryl-pyrimidines as potent PAK1 inhibitors

Bioorg Med Chem Lett. 2013 Jul 15;23(14):4072-5. doi: 10.1016/j.bmcl.2013.05.059. Epub 2013 May 28.

Abstract

2-Arylamino-4-aryl-pyrimidines were found to be potent inhibitors of PAK1 kinase. The synthesis and SAR are described. The incorporation of a bromide at the 5-position of the pyrimidine core and in combination with a 1,2-dimethylpiperazine pendant domain yielded a lead compound with potent PAK1 inhibition and anti-proliferative activity in various colon cancer cell lines.

MeSH terms

  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Aniline Compounds / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / toxicity
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / chemistry
  • Pyrimidinones / toxicity
  • Structure-Activity Relationship
  • p21-Activated Kinases / antagonists & inhibitors*
  • p21-Activated Kinases / metabolism

Substances

  • Aniline Compounds
  • Protein Kinase Inhibitors
  • Pyrimidinones
  • p21-Activated Kinases