Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7283-7. doi: 10.1016/j.bmcl.2010.10.081. Epub 2010 Oct 23.

Abstract

Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles.

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM Proteins / metabolism
  • ADAM17 Protein
  • Acetylene / analogs & derivatives
  • Acetylene / pharmacokinetics
  • Acetylene / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Dogs
  • Haplorhini
  • Humans
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / therapeutic use
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Protease Inhibitors
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human
  • Adam17 protein, rat
  • Acetylene