Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3

Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9. doi: 10.1016/j.bmcl.2005.06.083.

Abstract

The structure-based design and synthesis of a new series of c-Jun N-terminal kinase-3 inhibitors with selectivity against JNK1 and p38alpha is reported. The novel series of substituted 6-anilinoindazoles were designed based on a combination of hits from high throughput screening and X-ray crystal structure information of the compounds crystallized into the JNK3 ATP binding active site.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design*
  • Indazoles / chemical synthesis
  • Indazoles / chemistry*
  • Indazoles / pharmacology*
  • Inhibitory Concentration 50
  • Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 10 / metabolism
  • Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 14 / metabolism
  • Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Structure, Tertiary
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Indazoles
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase 10
  • Mitogen-Activated Protein Kinase 14
  • Mitogen-Activated Protein Kinase 8