Synthesis and structure-activity relationships of PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives

Bioorg Med Chem Lett. 2014 Sep 15;24(18):4538-4541. doi: 10.1016/j.bmcl.2014.07.073. Epub 2014 Aug 7.

Abstract

Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway by PI3K/mTOR dual inhibitors provides a promising new approach to the treatment of cancers. In this Letter, we identified structurally novel and potent PI3K/mTOR dual inhibitors from a series of 2-amino-4-methylpyrido[2,3-d]pyrimidine derivatives. Their synthesis and structure-activity relationships are reported.

Keywords: Anti-tumor activity; Dual inhibitor; Mammalian target of rapamycin; Phosphoinositide 3-kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • 2-amino-4-methylpyrido(2,3-d)pyrimidine
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • Pyrimidines
  • TOR Serine-Threonine Kinases