Synthesis and structure-activity relationship of a novel, non-hydroxamate series of TNF-alpha converting enzyme inhibitors

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4678-82. doi: 10.1016/j.bmcl.2007.05.100. Epub 2007 Jun 7.

Abstract

A novel series of TNF-alpha converting enzyme (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds use a triazolethione moiety as the zinc binding ligand and exhibit IC50 values from 1.5 to 100 nM in a porcine TACE assay. They also have excellent selectivities over other MMPs.

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM17 Protein
  • Binding Sites
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacology*
  • Molecular Structure
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Heterocyclic Compounds
  • ADAM Proteins
  • ADAM17 Protein