Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine derivatives as potent gelatinase inhibitors

Bioorg Med Chem. 2006 Dec 15;14(24):8286-94. doi: 10.1016/j.bmc.2006.09.015. Epub 2006 Sep 27.

Abstract

A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on the l-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and -9) and APN were tested. Structure-activity relationship studies showed that the side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory activities on gelatinase than aliphatic side chain. Most compounds exhibited poor activities on APN compared with MMP-2. Within this series, three compounds, A8, B9 and C10, have the good potency (IC(50)=5.2-9.7nM) and could be used as lead compounds in the future.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caffeic Acids / chemistry
  • Cinnamates / chemistry*
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Matrix Metalloproteinase Inhibitors*
  • Molecular Structure
  • Pyrrolidines / chemical synthesis*
  • Pyrrolidines / pharmacology
  • Structure-Activity Relationship
  • Trinitrobenzenesulfonic Acid / metabolism

Substances

  • Caffeic Acids
  • Cinnamates
  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Pyrrolidines
  • cinnamic acid
  • Trinitrobenzenesulfonic Acid
  • pyrrolidine
  • caffeic acid