Highly efficient and versatile synthesis of libraries of constrained beta-strand mimetics

Bioorg Med Chem Lett. 1998 Sep 8;8(17):2321-6. doi: 10.1016/s0960-894x(98)00420-x.

Abstract

The general approach of using a bicyclic template to produce inhibitors of the protease superfamily of enzymes has been investigated. The Diels Alder cycloaddition reaction on solid support has been found to be highly efficient for the synthesis of libraries of compounds that mimic the beta-strand secondary structure of proteins. Several potent and selective inhibitors of proteases have been discovered.

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Chymases
  • Indicators and Reagents
  • Kallikreins / antagonists & inhibitors
  • Kinetics
  • Models, Molecular
  • Peptide Library*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology
  • Protein Structure, Secondary*
  • Serine Endopeptidases / metabolism
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors
  • Trypsin Inhibitors / chemical synthesis
  • Trypsin Inhibitors / chemistry
  • Trypsin Inhibitors / pharmacology
  • Tryptases

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Indicators and Reagents
  • Peptide Library
  • Protease Inhibitors
  • Serine Proteinase Inhibitors
  • Trypsin Inhibitors
  • Kallikreins
  • Serine Endopeptidases
  • chymase 2
  • Chymases
  • Thrombin
  • Tryptases