Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors

  • Bioorg Med Chem Lett. 2004 Feb 9;14(3):805-8. doi: 10.1016/j.bmcl.2003.10.064.
Yongxin Han  1 ,  André Giroux ,  Erich L Grimm ,  Renée Aspiotis ,  Sébastien Francoeur ,  Christopher I Bayly ,  Daniel J Mckay ,  Sophie Roy ,  Steve Xanthoudakis ,  John P Vaillancourt ,  Dita M Rasper ,  John Tam ,  Paul Tawa ,  Nancy A Thornberry ,  Erin P Paterson ,  Margarita Garcia-Calvo ,  Joseph W Becker ,  Jennifer Rotonda ,  Donald W Nicholson ,  Robert J Zamboni
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada & Co, PO Box 1005, Pointe-Claire-Dorval, Québec, Canada H9R 4P8. [email protected]
PMID: 14741294 DOI: 10.1016/j.bmcl.2003.10.064
Abstract

The discovery of a series of potent, selective and reversible dipeptidyl Caspase-3 inhibitors are reported. The iterative discovery process of using combinatorial chemistry, parallel synthesis, moleculare modelling and structural biology will be discussed.