Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent β isoform selective phosphatidylinositol 3-kinase inhibitors

Bioorg Med Chem Lett. 2012 May 1;22(9):3198-202. doi: 10.1016/j.bmcl.2012.03.039. Epub 2012 Mar 16.

Abstract

A series of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones with excellent enzyme inhibition, improved isoform selectivity, and excellent inhibition of downstream phosphorylation of AKT has been identified. Several compounds in the series demonstrated potent (∼ 0.100 μM IC(50)) growth inhibition in a PTEN deficient cancer cell line.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • PTEN Phosphohydrolase / deficiency
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Isoforms / antagonists & inhibitors
  • Protein Kinase Inhibitors / chemistry*
  • Pyrimidines
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Isoforms
  • Protein Kinase Inhibitors
  • Pyrimidines
  • PTEN Phosphohydrolase