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

Jeremiah P Malerich; Jennifer S Lam; Barry Hart; Richard M Fine; Boris Klebansky; Mary J Tanga; Annalisa D'Andrea

doi:10.1016/j.bmcl.2010.10.026

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.

Authors

Jeremiah P Malerich¹, Jennifer S Lam, Barry Hart, Richard M Fine, Boris Klebansky, Mary J Tanga, Annalisa D'Andrea

Affiliation

¹ SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.

PMID: 21106455
DOI: 10.1016/j.bmcl.2010.10.026

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