Synthesis and biological evaluation of 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4566-9. doi: 10.1016/j.bmcl.2009.06.099. Epub 2009 Jul 3.

Abstract

The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC(50) (microM) DYRK1A=11; CDK5=0.41; GSK-3=1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Binding Sites
  • Computer Simulation
  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 5 / metabolism
  • Dyrk Kinases
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 / metabolism
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / metabolism
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology

Substances

  • 3,6-diamino-1H-pyrazolo(3,4-b)pyridine
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Cyclin-Dependent Kinase 5
  • Protein Serine-Threonine Kinases
  • Glycogen Synthase Kinase 3