Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors

• Type of Material: Article
• Authors: Sebastien Rene Louis Boucle, Emory University; Xiao Lu, Emory University; Leda C. Bassit, Emory University; Tugba Ozturk, Emory University; Olivia Ollinger Russell, Emory University; Franck Amblard, Emory University; Steven J. Coats, Cocrystal Pharma Inc; Raymond F Schinazi, Emory University
• Language: English
• Date: 2017-02-15
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bmcl.2017.01.010
• Title of Journal or Parent Work: Bioorganic and Medicinal Chemistry Letters
• ISSN: 0960-894X
• Volume: 27
• Issue: 4
• Start Page: 904
• End Page: 910
• Grant/Funding Information: This work was supported in part by NIH grant 5P30-AI-50409 (CFAR), and the National Center for Advancing Translational Sciences of the National Institutes of Health UL1TR000454.
• Keywords: Science & Technology; Chemistry; Physical Sciences; HAP; Life Sciences & Biomedicine; INHIBITORS; Chemistry, Medicinal; HBV; REPLICATION; Pharmacology & Pharmacy; Chemistry, Organic; Capsid assembly effectors; Heteroarylpyrimidine
• Research Categories: Health Sciences, Pharmacology

Abstract

New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.