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.
Kofi A Oppong  1 ,  Christopher D Ellis ,  Michael C Laufersweiler ,  Steven V O'Neil ,  Yili Wang ,  David L Soper ,  Mark W Baize ,  John A Wos ,  Biswanath De ,  Gregory K Bosch ,  Amy N Fancher ,  Wei Lu ,  Maureen K Suchanek ,  Richard L Wang ,  Thomas P Demuth Jr
Affiliations
  • 1. Procter & Gamble Pharmaceuticals, Inc., 8700 Mason-Montgomery Road, Mason, OH 45040, USA. [email protected]
PMID: 16046125 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.