Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors

Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100. doi: 10.1016/j.bmcl.2006.03.065. Epub 2006 May 2.

Abstract

A series of novel carboxylic acid-based alpha-sulfone MMP inhibitors have been synthesized and the in vitro enzyme SAR is discussed. A potential binding mode in the active site of the MMP-9 homology model was highlighted. These compounds are potent MMP-9 inhibitors and are selective over MMP-1.

MeSH terms

  • Animals
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry*
  • Carboxylic Acids / pharmacology*
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase Inhibitors*
  • Matrix Metalloproteinases / chemistry
  • Matrix Metalloproteinases / metabolism
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Sulfur / chemistry*

Substances

  • Carboxylic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Sulfur
  • Matrix Metalloproteinases