Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1)

Bioorg Med Chem Lett. 2001 Feb 26;11(4):571-4. doi: 10.1016/s0960-894x(00)00720-4.

Abstract

Structure activity relationships are described for a series of succinyl hydroxamic acids 4a-o as potent and selective inhibitors of matrix metalloprotease-3 (stromelysin-1). Optimisation of P1' and P3' groups gave compound 4j (MMP-3 IC50=5.9nM) which was >140-fold less potent against MMP-1 (IC50=51,000nM), MMP-2 (IC50=1790nM), MMP-9 (IC50=840nM) and MMP-14 (IC50=1900nM).

MeSH terms

  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / pharmacology*
  • Matrix Metalloproteinase Inhibitors*
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors