Novel imidazolopyrimidines as dual PI3-Kinase/mTOR inhibitors

Bioorg Med Chem Lett. 2010 Jan 15;20(2):653-6. doi: 10.1016/j.bmcl.2009.11.057. Epub 2009 Dec 1.

Abstract

This article describes the syntheses and SAR of a series of imidazolopyrimidine derivatives, which are evaluated as inhibitors of PI3-Kinase (PI3K) and mTOR. These compounds were found to be ATP competitive with good tumor cell growth inhibition, and suppression of pathway specific biomakers such as phosphorylation of Akt at T308.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Binding, Competitive
  • Cell Line, Tumor
  • Computer Simulation
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Phosphorylation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • TOR Serine-Threonine Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Adenosine Triphosphate
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases