The discovery of anthranilic acid-based MMP inhibitors. Part 3: incorporation of basic amines

Bioorg Med Chem Lett. 2001 Nov 19;11(22):2975-8. doi: 10.1016/s0960-894x(01)00601-1.

Abstract

Anthranilic acid derivatives bearing basic amines were prepared and evaluated in vitro and in vivo as inhibitors of MMP-1, MMP-9, MMP-13, and TACE. Piperazine 4u has been identified as a potent, selective, orally active inhibitor of MMP-9 and MMP-13.

MeSH terms

  • ADAM Proteins
  • ADAM17 Protein
  • Amines / chemistry*
  • Animals
  • Binding Sites
  • Collagenases / metabolism
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydroxamic Acids / chemistry
  • Interleukin-1
  • Interleukin-1beta
  • Magnetic Resonance Spectroscopy
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Metalloendopeptidases
  • Mice
  • Models, Molecular
  • Osteoarthritis / drug therapy
  • Rats
  • Structure-Activity Relationship
  • ortho-Aminobenzoates / chemical synthesis
  • ortho-Aminobenzoates / chemistry
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Amines
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Interleukin-1
  • Interleukin-1beta
  • Matrix Metalloproteinase Inhibitors
  • ortho-Aminobenzoates
  • ADAM Proteins
  • Collagenases
  • Matrix Metalloproteinase 13
  • Metalloendopeptidases
  • Mmp13 protein, mouse
  • Mmp13 protein, rat
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1
  • ADAM17 Protein
  • Adam17 protein, mouse
  • Adam17 protein, rat