Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole

J Med Chem. 2009 Dec 24;52(24):7938-41. doi: 10.1021/jm901383u.

Abstract

The synthesis and characterization of a novel polycyclic azaindole based derivative is disclosed, and its binding to JAK2 is described. The compound is further evaluated for its ability to block the EPO/JAK2 signaling cascade in vitro and in vivo.

MeSH terms

  • Animals
  • Aza Compounds / chemical synthesis
  • Aza Compounds / chemistry*
  • Aza Compounds / pharmacokinetics
  • Aza Compounds / pharmacology*
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Erythropoietin / metabolism
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Indoles / pharmacology*
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / metabolism
  • Lactams, Macrocyclic / chemical synthesis
  • Lactams, Macrocyclic / chemistry
  • Lactams, Macrocyclic / pharmacokinetics
  • Lactams, Macrocyclic / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Models, Molecular
  • Molecular Conformation
  • Protein Conformation
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • Aza Compounds
  • Indoles
  • Lactams, Macrocyclic
  • Protein Kinase Inhibitors
  • Erythropoietin
  • Janus Kinase 2