Structure-based design and parallel synthesis of N-benzyl isatin oximes as JNK3 MAP kinase inhibitors

Bioorg Med Chem Lett. 2009 May 15;19(10):2891-5. doi: 10.1016/j.bmcl.2009.03.043. Epub 2009 Mar 17.

Abstract

A series of N-benzylated isatin oximes were developed as inhibitors of the mitogen-activated kinase, JNK3. X-ray crystallographic structures aided in the design and synthesis of novel, selective compounds, that inhibit JNK3, but not p38 MAP kinase and provided key insights into understanding the behavior of gatekeeper residue methionine-146 in determining target selectivity for this series.

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Drug Design
  • Isatin / chemical synthesis
  • Isatin / chemistry*
  • Mitogen-Activated Protein Kinase 10 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 10 / metabolism
  • Oximes / chemical synthesis
  • Oximes / chemistry*
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Structure-Activity Relationship

Substances

  • Oximes
  • Protein Kinase Inhibitors
  • Isatin
  • Mitogen-Activated Protein Kinase 10