alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1

Bioorg Med Chem Lett. 2001 Oct 22;11(20):2723-5. doi: 10.1016/s0960-894x(01)00557-1.

Abstract

A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable.

MeSH terms

  • Alkanes / chemistry
  • Alkanes / pharmacology*
  • Collagenases / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Inhibitory Concentration 50
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Structure-Activity Relationship

Substances

  • Alkanes
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Collagenases
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 1