Structure-driven HtL: design and synthesis of novel aminoindazole inhibitors of c-Jun N-terminal kinase activity

Bioorg Med Chem Lett. 2005 Jul 15;15(14):3459-62. doi: 10.1016/j.bmcl.2005.05.008.

Abstract

The design and synthesis of a new series of c-Jun N-terminal kinase inhibitors are reported. The novel series of substituted amino indazoles were designed based on a combination of hits from high-throughput screening and X-ray crystal structure information of the compounds crystallised into the JNK-1 ATP binding site.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Indazoles / chemical synthesis*
  • Indazoles / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Indazoles
  • Adenosine Triphosphate
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 8