5-aryl-pyrazolo[3,4-b]pyridazines: potent inhibitors of glycogen synthase kinase-3 (GSK-3)

Bioorg Med Chem Lett. 2003 May 5;13(9):1581-4. doi: 10.1016/s0960-894x(03)00135-5.

Abstract

Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography.

Publication types

  • Comparative Study

MeSH terms

  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Models, Molecular
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Structure-Activity Relationship

Substances

  • Pyrazoles
  • Pyridazines
  • Glycogen Synthase Kinase 3