Discovery and optimization of pyrazoline compounds as B-Raf inhibitors

Bioorg Med Chem Lett. 2010 Aug 15;20(16):4800-4. doi: 10.1016/j.bmcl.2010.06.113. Epub 2010 Jun 25.

Abstract

The discovery of novel pyrazoline derivatives as B-Raf (V600E) inhibitors is described in this report. Chemical modification of the pyrazoline scaffold led to the development of SAR and identified potent and selective inhibitors of B-Raf (V600E). Determination of the pharmacokinetic properties of selected inhibitors is also reported.

MeSH terms

  • Amino Acid Substitution
  • Binding Sites
  • Computer Simulation
  • Drug Evaluation, Preclinical
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacokinetics
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Recombinant Proteins
  • Proto-Oncogene Proteins B-raf