In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors

Bioorg Med Chem Lett. 2011 May 15;21(10):2958-61. doi: 10.1016/j.bmcl.2011.03.053. Epub 2011 Mar 21.

Abstract

Synthesis and biological evaluation of a series of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochemical screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, physical properties and pharmacodynamic effects.

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Inhibitory Concentration 50
  • Janus Kinase 2 / antagonists & inhibitors*
  • Mice
  • Molecular Structure
  • Nitriles / chemical synthesis*
  • Nitriles / chemistry
  • Nitriles / pharmacokinetics
  • Nitriles / pharmacology*
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemistry*
  • Pyridines / chemistry*
  • Rats
  • Structure-Activity Relationship

Substances

  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Janus Kinase 2