The discovery of potent cRaf1 kinase inhibitors

Bioorg Med Chem Lett. 2000 Feb 7;10(3):223-6. doi: 10.1016/s0960-894x(99)00668-x.

Abstract

A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compounds with low nanomolar kinase enzyme inhibition and inhibited the intracellular MAPK pathway.

MeSH terms

  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • MAP Kinase Signaling System
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-raf