A novel series of highly selective inhibitors of MMP-3

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6750-3. doi: 10.1016/j.bmcl.2007.10.042. Epub 2007 Oct 17.

Abstract

The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described. Substitution of a 4-biaryl piperidine sulfonamide core, which binds at the S1' subsite of MMP-3, was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. Compounds 26 and 27 were identified as having the best balance of pharmacology and properties required for topical drug delivery.

MeSH terms

  • Amino Acids / chemistry
  • Combinatorial Chemistry Techniques
  • Drug Delivery Systems
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Matrix Metalloproteinase Inhibitors*
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Amino Acids
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Sulfonamides