Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7326-9. doi: 10.1016/j.bmcl.2012.10.084. Epub 2012 Oct 23.

Abstract

Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based on a benzothiazole derivative that was discovered from high-throughput screening of our compound library. As a result, we identified potent, selective, and orally bioavailable ASK1 inhibitors for wide range of therapeutic targets.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Design*
  • High-Throughput Screening Assays
  • MAP Kinase Kinase Kinase 5 / antagonists & inhibitors*
  • MAP Kinase Kinase Kinase 5 / metabolism
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Protein Kinase Inhibitors
  • Pyridines
  • MAP Kinase Kinase Kinase 5
  • imidazo(1,2-a)pyridine