Structure-activity relationships within a series of caspase inhibitors. Part 2: Heterocyclic warheads

Bioorg Med Chem Lett. 2005 Aug 1;15(15):3632-6. doi: 10.1016/j.bmcl.2005.05.036.

Abstract

Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp backbone have been prepared. A study of their structure-activity relationship (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a cellular model of cell death is also discussed. Potent broad-spectrum caspase inhibitors have been identified.

MeSH terms

  • Animals
  • Aspartic Acid / chemistry
  • Caspase Inhibitors*
  • Cell Death / drug effects*
  • Cells, Cultured
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / pharmacology*
  • Ketones / chemical synthesis
  • Ketones / pharmacology*
  • Mice
  • Models, Biological
  • Naphthols / chemistry
  • Structure-Activity Relationship
  • Valine / chemistry

Substances

  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Heterocyclic Compounds
  • Ketones
  • Naphthols
  • naphthyl acetate
  • Aspartic Acid
  • Valine