Discovery of a novel class of triazolones as checkpoint kinase inhibitors--hit to lead exploration

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5133-8. doi: 10.1016/j.bmcl.2010.07.015. Epub 2010 Jul 29.

Abstract

Checkpoint Kinase-1 (Chk1, CHK1, CHEK1) is a Ser/Thr protein kinase that mediates cellular responses to DNA-damage. A novel class of Chk1 inhibitors, triazoloquinolones/triazolones (TZ's) was identified by high throughput screening. The optimization of these hits to provide a lead series is described.

MeSH terms

  • Checkpoint Kinase 1
  • Crystallography, X-Ray
  • Drug Discovery
  • Models, Molecular
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / drug effects*
  • Structure-Activity Relationship
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • Protein Kinase Inhibitors
  • Triazoles
  • Protein Kinases
  • Checkpoint Kinase 1