The discovery of tricyclic pyridone JAK2 inhibitors. Part 1: hit to lead

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7421-5. doi: 10.1016/j.bmcl.2010.10.031. Epub 2010 Oct 12.

Abstract

This paper describes the discovery and design of a novel class of JAK2 inhibitors. Furthermore, we detail the optimization of a screening hit using ligand binding efficiency and log D. These efforts led to the identification of compound 41, which demonstrates in vivo activity in our study.

MeSH terms

  • Animals
  • Binding Sites
  • Computer Simulation
  • Cyclization
  • Drug Evaluation, Preclinical
  • Heterocyclic Compounds, 3-Ring / chemical synthesis
  • Heterocyclic Compounds, 3-Ring / chemistry*
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pyridones / chemical synthesis
  • Pyridones / chemistry*
  • Pyridones / pharmacology
  • STAT5 Transcription Factor / metabolism
  • Structure-Activity Relationship

Substances

  • Heterocyclic Compounds, 3-Ring
  • Pyridones
  • STAT5 Transcription Factor
  • Janus Kinase 2