Synthesis, preliminary biological evaluation and molecular modeling of some new heterocyclic inhibitors of TACE

Eur J Med Chem. 2011 Nov;46(11):5549-55. doi: 10.1016/j.ejmech.2011.09.018. Epub 2011 Sep 21.

Abstract

Central heteroaryl ring analogues belonging to a series of potent hydroxamate TACE inhibitors were synthesized. The TACE inhibitory activities of these compounds were evaluated by in vitro WBA and in silico molecular modeling studies using crystal structure of human TACE. Compound 14 showed very good in vitro inhibition, supported by the in silico docking studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / antagonists & inhibitors*
  • ADAM Proteins / chemistry
  • ADAM Proteins / metabolism
  • ADAM17 Protein
  • Chemistry Techniques, Synthetic*
  • Drug Discovery
  • Humans
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Models, Molecular*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Protein Conformation
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Hydroxamic Acids
  • Protease Inhibitors
  • Tumor Necrosis Factor-alpha
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human