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

Abstract

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=0.8 μM).

• Authors: Lavanya Bondada, Ramu Rondla, Ugo Pradere, Peng Liu, Chengwei Li, Drew Bobeck, Tamara McBrayer, Philip Tharnish, Jerome Courcambeck, Philippe Halfon, Tony Whitaker, Franck Amblard, Steven J Coats, Raymond F Schinazi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 23 Pg. 6325-30 (Dec 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 24135727 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antiviral Agents
• Azetidines
• NS3 protein, hepatitis C virus
• Protease Inhibitors
• Viral Nonstructural Proteins

Topics

• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Azetidines (chemistry, pharmacology)
• Drug Design
• Hepatitis C (drug therapy)
• Humans
• Models, Molecular
• Protease Inhibitors (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Viral Nonstructural Proteins (antagonists & inhibitors, chemistry)