Discovery of novel conformationally restricted diazocan peptidomimetics as inhibitors of interleukin-1beta synthesis

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4291-4. doi: 10.1016/j.bmcl.2005.06.050.

Abstract

A novel diazocan containing dipeptide mimetic was synthesized via reductive N-N bond cleavage of a pyrazolidino-pyrazolidine using Raney-Ni and evaluated as an ICE inhibitor. This versatile 8-membered ring containing scaffold possesses an N-5 ring nitrogen that was used to explore structure-activity relationships in a cell-based assay measuring inhibition of interleukin-1beta.

MeSH terms

  • Caspase Inhibitors
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology
  • Drug Evaluation, Preclinical
  • Inhibitory Concentration 50
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / biosynthesis
  • Molecular Conformation
  • Molecular Mimicry
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology
  • Pyrazoles / chemistry
  • Structure-Activity Relationship

Substances

  • Caspase Inhibitors
  • Dipeptides
  • Interleukin-1
  • Peptides, Cyclic
  • Pyrazoles
  • diazocan