Dioxo-triazines as a novel series of cathepsin K inhibitors

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1488-90. doi: 10.1016/j.bmcl.2010.01.116. Epub 2010 Jan 25.

Abstract

A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC(50) values of 17nM against catK and >10,000nM in catL, catB and catS assays.

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Cathepsin K / antagonists & inhibitors*
  • Cathepsin K / metabolism
  • Crystallography, X-Ray
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology
  • High-Throughput Screening Assays
  • Humans
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry*
  • Triazines / pharmacology
  • Uracil / analogs & derivatives
  • Uracil / chemical synthesis
  • Uracil / chemistry
  • Uracil / pharmacology

Substances

  • Cysteine Proteinase Inhibitors
  • Triazines
  • Uracil
  • Cathepsin K