Malonyl alpha-mercaptoketones and alpha-mercaptoalcohols, a new class of matrix metalloproteinase inhibitors

Bioorg Med Chem Lett. 1998 May 19;8(10):1157-62. doi: 10.1016/s0960-894x(98)00185-1.

Abstract

A novel series of matrix metalloproteinase (MMP) inhibitors is described. Incorporation of a terminal alpha-mercaptoketone or alpha-mercaptoalcohol in the zinc binding domain of a series of inhibitors led to compounds exhibiting low nanomolar activity against collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).

Publication types

  • Comparative Study

MeSH terms

  • Alcohols / chemical synthesis
  • Alcohols / chemistry*
  • Alcohols / pharmacology
  • Binding Sites
  • Drug Design
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Ketones / chemical synthesis
  • Ketones / chemistry*
  • Ketones / pharmacology
  • Kinetics
  • Matrix Metalloproteinase 1
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / antagonists & inhibitors*
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemical synthesis
  • Sulfhydryl Compounds / chemistry*
  • Sulfhydryl Compounds / pharmacology
  • Zinc / metabolism

Substances

  • Alcohols
  • Hydroxamic Acids
  • Ketones
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Sulfhydryl Compounds
  • marimastat
  • Metalloendopeptidases
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1
  • Zinc