Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease.

Abstract

Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 portion led to the identification of compounds, such as 26, that have a unique selectivity profile against other cysteine proteases and offering new opportunities for safer treatment of Chagas disease.

• Authors: Christian Beaulieu, Elise Isabel, Angélique Fortier, Frédéric Massé, Christophe Mellon, Nathalie Méthot, Momar Ndao, Deborah Nicoll-Griffith, Doris Lee, Hyeram Park, W Cameron Black
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 20 Issue 24 Pg. 7444-9 (Dec 15 2010) ISSN: 1464-3405 [Electronic] England
• PMID: 21041084 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Biphenyl Compounds
• Cysteine Proteinase Inhibitors
• Protozoan Proteins
• Cathepsins
• Cysteine Proteases
• Cysteine Endopeptidases
• cruzipain
• Valine

Topics

• Biphenyl Compounds (chemical synthesis, chemistry, therapeutic use)
• Cathepsins (antagonists & inhibitors, metabolism)
• Chagas Disease (drug therapy)
• Cysteine Endopeptidases (chemistry, metabolism)
• Cysteine Proteases (chemistry, metabolism)
• Cysteine Proteinase Inhibitors (chemical synthesis, chemistry, therapeutic use)
• Humans
• Protozoan Proteins
• Structure-Activity Relationship
• Valine (analogs & derivatives, chemical synthesis, chemistry, therapeutic use)