4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3121-4. doi: 10.1016/j.bmcl.2006.03.059. Epub 2006 Apr 5.

Abstract

CHK-1 is one of the key enzymes regulating checkpoints in cellular growth cycles. Novel 4-(amino-alkylamino)-3-benzimidazole-quinolinones were prepared and assayed for their ability to inhibit CHK-1. These compounds are potent cell permeable CHK-1 inhibitors and showed synergistic effect with a DNA-damaging agent, camptothecin.

MeSH terms

  • Alkylation
  • Amination
  • Benzimidazoles / chemistry*
  • Cell Line, Tumor
  • Checkpoint Kinase 1
  • Crystallography, X-Ray
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Quinolones / chemical synthesis
  • Quinolones / chemistry*
  • Quinolones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Quinolones
  • benzimidazole
  • Protein Kinases
  • Checkpoint Kinase 1

Associated data

  • PDB/2GDO