Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) Inhibitor of Insulin-Like Growth Factor I Receptor Kinase With in Vivo Antitumor Activity

J Med Chem. 2005 Sep 8;48(18):5639-43. doi: 10.1021/jm050392q.

Abstract

Compound 3 (BMS-536924), a novel small-molecule inhibitor of the insulin-like growth factor receptor kinase with equal potency against the insulin receptor is described. The in vitro and in vivo biological activity of this interesting compound is also reported.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Biological Availability
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Haplorhini
  • Humans
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Molecular Structure
  • Neoplasm Transplantation
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology
  • Rats
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, Insulin / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • BMS 536924
  • Benzimidazoles
  • Pyridines
  • Pyridones
  • Receptor, IGF Type 1
  • Receptor, Insulin