Design and synthesis of an orally active matrix metalloproteinase inhibitor

Bioorg Med Chem. 2006 Sep 15;14(18):6383-403. doi: 10.1016/j.bmc.2006.05.040. Epub 2006 Jun 9.

Abstract

A series of 4-(4-phenoxy)benzoylamino-4-methoxymethyloxymethyl butyric acid hydroxamates, which were derived from l-glutamic acid, were synthesized and evaluated as matrix metalloproteinase inhibitors. Most of the compounds listed in exhibited strong inhibitory activity against MMP-2 and MMP-9, as well as even stronger inhibitory activity against MMP-3, but showed relatively weak inhibition of MMP-1. Structure-activity relationships are discussed.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzamides* / chemical synthesis
  • Benzamides* / chemistry
  • Benzamides* / pharmacology
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Enzyme Activation / drug effects
  • Glutamic Acid / chemistry
  • Guinea Pigs
  • Hydroxamic Acids* / chemical synthesis
  • Hydroxamic Acids* / chemistry
  • Hydroxamic Acids* / pharmacology
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Molecular Conformation
  • Protease Inhibitors* / administration & dosage
  • Protease Inhibitors* / chemical synthesis
  • Protease Inhibitors* / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Benzamides
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Glutamic Acid