Design and synthesis of quinolin-2(1H)-one derivatives as potent CDK5 inhibitors

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5384-9. doi: 10.1016/j.bmcl.2007.07.045. Epub 2007 Aug 6.

Abstract

Cyclin-dependent kinase 5 (CDK5) is a serine/threonine protein kinase and its deregulation is implicated in a number of neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. Using active site homology modeling between CDK5 and CDK2, we explored several different chemical series of potent CDK5 inhibitors. In this report, we describe the design, synthesis, and CDK5 inhibitory activities of quinolin-2(1H)-one derivatives.

MeSH terms

  • Binding Sites
  • Cyclin-Dependent Kinase 2 / chemistry
  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 5 / chemistry
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Indicators and Reagents
  • Models, Molecular
  • Protein Binding
  • Quinolines / chemical synthesis*
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Indicators and Reagents
  • Quinolines
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinase 2