Solid-phase synthesis of azidomethylene inhibitors targeting cysteine proteases

Org Lett. 2008 May 15;10(10):1881-4. doi: 10.1021/ol800575z. Epub 2008 Apr 12.

Abstract

An efficient strategy for the solid-phase synthesis of azidomethylene inhibitors targeting cysteine proteases is described. The method is highlighted by its compatibility with readily available building blocks, as well as its ability to accommodate different functional groups. A 249-member library has thus far been successfully synthesized, characterized, and screened against Caspase-1, -3 and -7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azides / chemical synthesis*
  • Azides / chemistry
  • Azides / pharmacology
  • Caspase 1 / chemistry
  • Caspase 3 / chemistry
  • Caspase 7 / chemistry
  • Caspase Inhibitors
  • Combinatorial Chemistry Techniques*
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / drug effects
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology
  • Drug Evaluation, Preclinical
  • Methane / analogs & derivatives*
  • Methane / chemical synthesis*
  • Methane / chemistry
  • Methane / pharmacology
  • Molecular Structure
  • Small Molecule Libraries
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Azides
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Small Molecule Libraries
  • Caspase 3
  • Caspase 7
  • Cysteine Endopeptidases
  • Caspase 1
  • Methane