Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7454-7. doi: 10.1016/j.bmcl.2010.10.026. Epub 2010 Oct 13.

Abstract

Tyrosine kinase 2 (TYK2) is required for signaling of interleukin-23 (IL-23), which plays a key role in rheumatoid arthritis. Presented is the design and synthesis of 1,2,4-triazoles, and the evaluation of their inhibitory activity against the Janus associated kinases TYK2 and JAKs 1-3.

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Humans
  • Interleukin-23 / metabolism
  • Janus Kinase 1 / antagonists & inhibitors*
  • Janus Kinase 1 / metabolism
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / metabolism
  • Janus Kinase 3 / antagonists & inhibitors*
  • Janus Kinase 3 / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • TYK2 Kinase / antagonists & inhibitors*
  • TYK2 Kinase / metabolism
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology

Substances

  • Interleukin-23
  • Protein Kinase Inhibitors
  • Triazoles
  • 1,2,4-triazole
  • Janus Kinase 1
  • Janus Kinase 2
  • Janus Kinase 3
  • TYK2 Kinase