Synthesis and biological evaluation of 3-ethylidene-1,3-dihydro-indol-2-ones as novel checkpoint 1 inhibitors

Bioorg Med Chem Lett. 2006 Jan 15;16(2):421-6. doi: 10.1016/j.bmcl.2005.09.064. Epub 2005 Oct 18.

Abstract

Chk1 inhibitors have emerged as a novel class of neoplastic agents for abrogating the G2 DNA damage checkpoint arrest. Analogs of the Chk1 inhibitor, 3-ethylidene-1,3-dihydro-indol-2-one, were synthesized and tested in vitro for their inhibitory activities. The most promising compound identified from this series is analog 28, which possesses potent enzymatic and cellular activities.

MeSH terms

  • Cell Proliferation / drug effects
  • Checkpoint Kinase 1
  • Crystallography, X-Ray
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Kinases / drug effects*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1