Hit generation and exploration: imidazo[4,5-b]pyridine derivatives as inhibitors of Aurora kinases

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6567-71. doi: 10.1016/j.bmcl.2007.09.076. Epub 2007 Oct 22.

Abstract

A hit generation and exploration approach led to the discovery of 31 (2-(4-(6-chloro-2-(4-(dimethylamino)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide), a potent, novel inhibitor of Aurora-A, Aurora-B and Aurora-C kinases with IC(50) values of 0.042, 0.198 and 0.227microM, respectively. Compound 31 inhibits cell proliferation and has good microsomal stability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Cell Proliferation / drug effects
  • Drug Design
  • Growth Inhibitors / chemical synthesis
  • Growth Inhibitors / pharmacology
  • HCT116 Cells
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Purines / chemical synthesis*
  • Purines / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology

Substances

  • Growth Inhibitors
  • Imidazoles
  • Protein Kinase Inhibitors
  • Purines
  • Pyridines
  • 1H-imidazo(4,5-b)pyridine
  • AURKB protein, human
  • AURKC protein, human
  • Aurora Kinase B
  • Aurora Kinase C
  • Aurora Kinases
  • Protein Serine-Threonine Kinases