Synthesis and evaluation of novel prodrugs of caspase inhibitors

Bioorg Med Chem Lett. 2012 Jan 1;22(1):485-8. doi: 10.1016/j.bmcl.2011.10.102. Epub 2011 Nov 6.

Abstract

A novel type of caspase inhibitor prodrug that improves systemic exposure after oral administration in rats has been designed. Such a prodrug, based on a 6,6a-dihydrofuro[3,2-d]oxazol-5(3aH)-one motif, has the advantage of rapidly liberating the active inhibitor without producing any cleavage by-product. Prodrugs 6-8, are synthesised in a high yielding one-step transformation from the active parents with high diastereomeric excess.

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis
  • Area Under Curve
  • Caspase Inhibitors
  • Cell Line
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydrolysis
  • Models, Chemical
  • Molecular Conformation
  • Peptides / chemistry
  • Peptidomimetics
  • Prodrugs / chemical synthesis*
  • Prodrugs / pharmacology*
  • Rats
  • Stereoisomerism

Substances

  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Peptides
  • Peptidomimetics
  • Prodrugs