3-Hydroxy-4-arylsulfonyltetrahydropyranyl-3-hydroxamic acids are novel inhibitors of MMP-13 and aggrecanase

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4727-30. doi: 10.1016/j.bmcl.2004.06.081.

Abstract

N-Hydroxy-3-hydroxy-4-arylsulfonyltetrahydropyranyl-3-carboxamides were designed as novel inhibitors of MMP-13 and aggrecanase based on known endocyclic hydroxamate inhibitors of matrix metalloproteinases. These compounds offer favorable physicochemical properties and low metabolic clearance. Synthesis and structure-activity relationships are reported.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Collagenases / chemistry
  • Endopeptidases / chemistry
  • Endopeptidases / metabolism*
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacokinetics
  • Matrix Metalloproteinase 1 / chemistry
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase Inhibitors*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacokinetics
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry
  • Pyrans / pharmacokinetics
  • Rats
  • Structure-Activity Relationship

Substances

  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Pyrans
  • Endopeptidases
  • Collagenases
  • Matrix Metalloproteinase 13
  • Mmp13 protein, rat
  • Matrix Metalloproteinase 1
  • aggrecanase