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

  • Bioorg Med Chem Lett. 2013 Dec 1;23(23):6325-30. doi: 10.1016/j.bmcl.2013.09.068.
Lavanya Bondada  1 ,  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
Affiliations
  • 1. Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Veterans Affairs Medical Center, 1670 Haygood Drive, NE, Atlanta, GA 30322, USA.
PMID: 24135727 DOI: 10.1016/j.bmcl.2013.09.068
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).

Keywords
Antiviral; HCV; Protease inhibitor.