Identification of novel 7-amino-5-methyl-1,6-naphthyridin-2(1H)-one derivatives as potent PI3K/mTOR dual inhibitors

Bioorg Med Chem Lett. 2014 Feb 1;24(3):790-3. doi: 10.1016/j.bmcl.2013.12.112. Epub 2014 Jan 3.

Abstract

Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway is one of the most intensively studied approaches to cancer therapy. Rational design led to the identification of novel 7-amino-5-methyl-1,6-naphthyridin-2(1H)-one derivatives as potent PI3K/mTOR dual inhibitors. Design, synthesis and structure activity relationship 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

  • Animals
  • Binding Sites
  • Drug Design*
  • Enzyme Activation / drug effects
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Naphthyridines / chemistry*
  • Naphthyridines / pharmacokinetics
  • Naphthyridines / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / isolation & purification
  • Protein Kinase Inhibitors / pharmacology*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Naphthyridines
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases