An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFRα and kit

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4579-84. doi: 10.1016/j.bmcl.2012.05.107. Epub 2012 Jun 6.

Abstract

Here we describe the synthesis and characterization of a number of 3-amino-1H-indazol-6-yl-benzamides that were designed to target the 'DFG-out' conformation of the kinase activation loop. Several compounds such as 4 and 11 exhibit single-digit nanomolar EC(50)s against FLT3, c-Kit and the gatekeeper T674M mutant of PDGFRα.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Indazoles / chemical synthesis*
  • Indazoles / pharmacology
  • Mice
  • Models, Molecular
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors*
  • Receptor, Platelet-Derived Growth Factor alpha / antagonists & inhibitors*
  • Structure-Activity Relationship
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*

Substances

  • Indazoles
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • fms-Like Tyrosine Kinase 3