Design, synthesis and evaluation of novel sulfonyl pyrrolidine derivatives as matrix metalloproteinase inhibitors

Bioorg Med Chem. 2008 May 15;16(10):5398-404. doi: 10.1016/j.bmc.2008.04.027. Epub 2008 Apr 15.

Abstract

A series of novel sulfonyl pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. Compounds 6a-d were more potent MMP-2 inhibitors than the positive control LY52. The structure-activity relationships were also briefly discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / drug effects
  • CD13 Antigens / antagonists & inhibitors
  • Computer Simulation
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Matrix Metalloproteinase Inhibitors*
  • Models, Molecular
  • Molecular Conformation
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfones / chemistry*

Substances

  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • Pyrrolidines
  • Sulfones
  • CD13 Antigens