Novel 8-arylated purines as inhibitors of glycogen synthase kinase

Eur J Med Chem. 2010 Aug;45(8):3389-93. doi: 10.1016/j.ejmech.2010.04.026. Epub 2010 Apr 28.

Abstract

A series of 8-arylated purine derivatives bearing either an aniline or an alkyl amide at position 6 were found to inhibit glycogen synthase kinase-3, with good selectivity over ten kinases. Molecular modeling studies indicated that the most active compounds (8a and 8e), adopt a planar conformation, close to the shape of AMPPNP in the crystal structure of GSK-3. These compounds are stabilized by hydrophobic contacts between the 8-aromatic group and the protein adenine pocket and by electrostatic contacts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Glycogen Synthase Kinases / antagonists & inhibitors*
  • Glycogen Synthase Kinases / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Purines / chemical synthesis
  • Purines / chemistry*
  • Purines / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Purines
  • Glycogen Synthase Kinases