Synthesis and biological activity of piperazine-based dual MMP-13 and TNF-alpha converting enzyme inhibitors

Bioorg Med Chem Lett. 2003 Oct 6;13(19):3243-6. doi: 10.1016/s0960-894x(03)00666-8.

Abstract

A series of novel MMP-13 and TNF-alpha converting enzyme inhibitors based on piperazine 2-hydroxamic acid scaffolds are described. The TACE, MMP-1 and MMP-13 activity of these inhibitors as well as the effect of substitution of the piperazine nitrogen and the P-1' benzyloxy tailpiece is discussed. Moderate in vivo activity is observed with several members of this group.

MeSH terms

  • ADAM Proteins
  • ADAM17 Protein
  • Animals
  • Collagenases / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase Inhibitors*
  • Metalloendopeptidases / antagonists & inhibitors*
  • Metalloendopeptidases / metabolism
  • Piperazines / chemical synthesis*
  • Piperazines / pharmacology
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Piperazines
  • Tumor Necrosis Factor-alpha
  • ADAM Proteins
  • Collagenases
  • Matrix Metalloproteinase 13
  • Metalloendopeptidases
  • Mmp13 protein, rat
  • ADAM17 Protein
  • Adam17 protein, rat