Azetidines and spiro azetidines as novel P2 units in hepatitis C virus NS3 protease inhibitors

Herein, we report the synthesis and structure–activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the discovery of a potent hepatitis C protease inhibit...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2013-12, Vol.23 (23), p.6325-6330
Hauptverfasser:	Bondada, Lavanya, Rondla, Ramu, Pradere, Ugo, Liu, Peng, Li, Chengwei, Bobeck, Drew, McBrayer, Tamara, Tharnish, Philip, Courcambeck, Jerome, Halfon, Philippe, Whitaker, Tony, Amblard, Franck, Coats, Steven J., Schinazi, Raymond F.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antiviral Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Azetidines - chemistry Azetidines - pharmacology Drug Design HCV hepatitis C Hepatitis C - drug therapy Hepatitis C virus Humans Models, Molecular Protease inhibitor Protease Inhibitors - chemical synthesis Protease Inhibitors - chemistry Protease Inhibitors - pharmacology proteinase inhibitors Structure-Activity Relationship structure-activity relationships Viral Nonstructural Proteins - antagonists & inhibitors Viral Nonstructural Proteins - chemistry
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Beschreibung
Zusammenfassung:	Herein, we report the synthesis and structure–activity relationship studies of new analogs of boceprevir 1 and telaprevir 2. Introduction of azetidine and spiroazetidines as a P2 substituent that replaced the pyrrolidine moiety of 1 and 2 led to the discovery of a potent hepatitis C protease inhibitor 37c (EC50=0.8μM).
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2013.09.068