Pyrazolo[3,4-d]pyrimidines as potent inhibitors of the insulin-like growth factor receptor (IGF-IR)

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5406-9. doi: 10.1016/j.bmcl.2007.07.037. Epub 2007 Jul 25.

Abstract

A high throughput screen of Abbott's compound repository revealed that the pyrazolo[3,4-d]pyrimidine class of kinase inhibitors possessed moderate potency for IGF-IR, a promising target for cancer chemotherapy. The synthesis and subsequent optimization of this class of compounds led to the discovery of 14, a compound that possesses in vivo IGF-IR inhibitory activity.

MeSH terms

  • Administration, Oral
  • Animals
  • Drug Design
  • Drug Evaluation, Preclinical
  • Injections, Intravenous
  • Mice
  • Phosphorylation
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptors, Somatomedin / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Pyrazoles
  • Pyrimidines
  • Receptors, Somatomedin
  • pyrazolo(3,4-d)pyrimidine
  • Receptor Protein-Tyrosine Kinases