Design and synthesis of dipeptidyl nitriles as potent, selective, and reversible inhibitors of cathepsin C

A series of dipeptide nitriles with a thienyl alanine in P2 were identified as potent and selective cathepsin C inhibitors. Incorporation of a substituted cyclopropyl moiety in P1 effectively protects these derivatives against hydrolase activity in whole blood.

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Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-09, Vol.19 (18), p.5392-5396
Hauptverfasser:	Guay, Daniel, Beaulieu, Christian, Jagadeeswar Reddy, T., Zamboni, Robert, Methot, Nathalie, Rubin, Joel, Ethier, Diane, David Percival, M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cathepsin C Cathepsin C - antagonists & inhibitors Cathepsin C - metabolism Cell Line Dipeptide nitrile Dipeptides - blood Dipeptides - chemical synthesis Dipeptides - chemistry Dipeptides - pharmacology Dipeptidyl peptidase I Humans Medical sciences Nitriles - blood Nitriles - chemical synthesis Nitriles - chemistry Nitriles - pharmacology Pharmacology. Drug treatments Rats Structure-Activity Relationship
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Beschreibung
Zusammenfassung:	A series of dipeptide nitriles with a thienyl alanine in P2 were identified as potent and selective cathepsin C inhibitors. Incorporation of a substituted cyclopropyl moiety in P1 effectively protects these derivatives against hydrolase activity in whole blood.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2009.07.114