Synthesis and structure-activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3β

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5948-51. doi: 10.1016/j.bmcl.2011.07.073. Epub 2011 Aug 5.

Abstract

The synthesis, GSK-3β inhibitory activity, and anti-microbial activity of bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3-carboxylic acid scaffold were studied. Kinase selectivity profiling indicated that members of this class were potent and highly selective GSK-3 inhibitors.

MeSH terms

  • 4-Quinolones / chemistry
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Clinical Trials as Topic
  • Drug Design
  • Drug Evaluation, Preclinical
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • HL-60 Cells
  • High-Throughput Screening Assays
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • 4-Quinolones
  • Anti-Bacterial Agents
  • Isoenzymes
  • Protein Kinase Inhibitors
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3