Design and synthesis of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6591-4. doi: 10.1016/j.bmcl.2009.10.027. Epub 2009 Oct 13.

Abstract

Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Using active site homology and previous structure-activity relationships, a new series of potent CDK5 inhibitors was designed. This report describes the optimization of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors.

MeSH terms

  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors*
  • Drug Design*
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Protein Kinase Inhibitors
  • Pyridones
  • Cyclin-Dependent Kinase 5