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

Autor:	Christophe Mellon, Nathalie Méthot, Deborah A. Nicoll-Griffith, Momar Ndao, Frédéric Massé, Christian Beaulieu, Angélique Fortier, Hyeram Park, W. Cameron Black, Elise Isabel, Doris Lee
Rok vydání:	2010
Předmět:	Chagas disease Proteases Clinical Biochemistry Protozoan Proteins Pharmaceutical Science Cruzipain Cysteine Proteinase Inhibitors Biochemistry Structure-Activity Relationship Cysteine Proteases Drug Discovery medicine Humans Structure–activity relationship Chagas Disease Trypanosoma cruzi Molecular Biology biology Chemistry Biphenyl Compounds Organic Chemistry Kinetoplastida Valine biology.organism_classification medicine.disease Cathepsins Cysteine protease Cysteine Endopeptidases Drug development Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:7444-7449
ISSN:	0960-894X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6582e07a38a94405e3fdc8c323756d1 https://doi.org/10.1016/j.bmcl.2010.10.015 Zobrazit plný text záznamu Full Text from ScienceDirect