Identification and structure-activity relationships of substituted pyridones as inhibitors of Pim-1 kinase

Bioorg Med Chem Lett. 2007 Mar 15;17(6):1679-83. doi: 10.1016/j.bmcl.2006.12.086. Epub 2007 Jan 4.


A novel series of highly potent substituted pyridone Pim-1 kinase inhibitors is described. Structural requirements for in vitro activity are outlined as well as a complex crystal structure with the most potent Pim-1 inhibitor reported (IC(50)=50 nM). A hydrogen bond matrix involving the Pim-1 inhibitor, two water molecules, and the catalytic core, together with a potential weak hydrogen bond between an aromatic hydrogen on the R(1) phenyl ring and a main-chain carbonyl of Pim-1, accounts for the overall potency of this inhibitor.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrogen Bonding
  • Indicators and Reagents
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-pim-1 / chemical synthesis
  • Proto-Oncogene Proteins c-pim-1 / genetics
  • Pyridones / chemical synthesis*
  • Pyridones / pharmacology*
  • Recombinant Proteins / chemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Indicators and Reagents
  • Pyridones
  • Recombinant Proteins
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins c-pim-1