Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays

Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. doi: 10.1016/j.bmcl.2006.11.006. Epub 2006 Nov 7.

Abstract

We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cytochrome P-450 Enzyme Inhibitors
  • Dogs
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Half-Life
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Lung Neoplasms / drug therapy
  • Mice
  • Mice, Nude
  • Models, Molecular
  • Molecular Conformation
  • Neoplasm Transplantation
  • Protein Binding
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Triazines / chemical synthesis*
  • Triazines / pharmacology
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • (7-(2,6-dichlorophenyl)-5-methylbenzo(1,2,4)triazin-3-yl)-(4-(2-pyrrolidin-1-ylethoxy)phenyl)amine
  • Antineoplastic Agents
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Pyrrolidines
  • Triazines
  • src-Family Kinases