Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13)

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6. doi: 10.1016/j.bmcl.2004.12.016.

Abstract

Computer aided drug design led to a new class of spiro-barbiturates (e.g., 4a, MMP-13 K(i)=4.7 nM) that are potent inhibitors of MMP-13.

MeSH terms

  • Barbiturates / chemical synthesis*
  • Barbiturates / pharmacology
  • Computer Simulation
  • Computer-Aided Design
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Kinetics
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase Inhibitors*
  • Models, Molecular
  • Osteoarthritis / drug therapy
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Barbiturates
  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Spiro Compounds
  • MMP13 protein, human
  • Matrix Metalloproteinase 13