N-Aryl sulfonyl homocysteine hydroxamate inhibitors of matrix metalloproteinases: further probing of the S(1), S(1)', and S(2)' pockets

J Med Chem. 2001 Sep 13;44(19):3066-73. doi: 10.1021/jm010097f.

Abstract

A series of N-arylsulfonyl S-alkyl homocysteine hydroxamic acids were synthesized with variations in three subsites corresponding to P(1), P(1)', and P(2)'. Enzyme assays with a variety of MMPs revealed activity at the low nanomolar level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Collagenases / chemistry
  • Homocysteine / analogs & derivatives*
  • Homocysteine / chemical synthesis*
  • Homocysteine / chemistry
  • Hydroxamic Acids / chemical synthesis*
  • Hydroxamic Acids / chemistry
  • Matrix Metalloproteinase 1 / chemistry
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 2 / chemistry
  • Matrix Metalloproteinase 3 / chemistry
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / antagonists & inhibitors*
  • Metalloendopeptidases / chemistry
  • Models, Molecular
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Homocysteine
  • Collagenases
  • Matrix Metalloproteinase 13
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1