Discovery of 2,4-bis-arylamino-1,3-pyrimidines as insulin-like growth factor-1 receptor (IGF-1R) inhibitors

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2394-9. doi: 10.1016/j.bmcl.2011.02.075. Epub 2011 Feb 23.

Abstract

The insulin-like growth factor-1 receptor (IGF-1R) plays an important role in the regulation of cell growth and differentiation, and in protection from apoptosis. IGF-1R has been shown to be an appealing target for the treatment of human cancer. Herein, we report the synthesis, structure-activity relationships (SAR), X-ray cocrystal structure and in vivo tumor study results for a series of 2,4-bis-arylamino-1,3-pyrimidines.

MeSH terms

  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Evaluation, Preclinical
  • Humans
  • Mice
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacokinetics
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacokinetics
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / metabolism
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Quinolines
  • Receptor, IGF Type 1