Design, synthesis and biological evaluation of pyridin-3-yl pyrimidines as potent Bcr-Abl inhibitors

Chem Biol Drug Des. 2014 May;83(5):592-9. doi: 10.1111/cbdd.12272. Epub 2014 Mar 14.

Abstract

A series of pyridin-3-yl pyrimidines was synthesized and evaluated for their Bcr-Abl inhibitory and anticancer activity. The preliminary results indicated that some compounds were promising anticancer agents. Compounds A2, A8, and A9 exhibited potent Bcr-Abl inhibitory activity, suggesting that aniline containing halogen substituents might be important for biological activity. Molecular docking was carried out to investigate the binding mode of them with Bcr-Abl. Details of synthesis and SAR studies of these compounds are described.

Keywords: 3D-QSAR; Bcr-Abl; anticancer; leukemia cell; pyridin-3-yl pyrimidines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Cell Proliferation / drug effects
  • Drug Design*
  • Fusion Proteins, bcr-abl / antagonists & inhibitors*
  • Humans
  • K562 Cells
  • Molecular Docking Simulation
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / toxicity
  • Protein Structure, Tertiary
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / toxicity
  • Quantitative Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Fusion Proteins, bcr-abl