Synthesis and evaluation of non-dimeric HCV NS5A inhibitors

• Type of Material: Article
• Authors: Franck Amblard, Emory University; HongWang Zhang, Emory University; Longhu Zhou, Emory University; Junxing Shi, Emory University; Drew R. Bobeck, RFS Pharma, LLC; James H Nettles, Emory University; Satish Chavre, Emory University; Tamara R. McBrayer, RFS Pharma, LLC; Philip Tharnish, RFS Pharma, LLC; Tony Whitaker, RFS Pharma, LLC; Steven Coats, Emory University; Raymond F Schinazi, Emory University
• Language: English
• Date: 2013-04-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bmcl.2013.02.023
• Title of Journal or Parent Work: Bioorganic and Medicinal Chemistry Letters
• ISSN: 0960-894X
• Volume: 23
• Issue: 7
• Start Page: 2031
• End Page: 2034
• Keywords: HCV; Science & Technology; Physical Sciences; Pharmacology & Pharmacy; Chemistry, Organic; NS5A; Chemistry, Medicinal; Life Sciences & Biomedicine; Antiviral agent; HEPATITIS-C; Chemistry
• Research Categories: Chemistry, Pharmaceutical; Biology, Virology; Health Sciences, Medicine and Surgery

Abstract

Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).