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

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 4; pp. 904 - 910
• Main Authors: Boucle, Sebastien, Lu, Xiao, Bassit, Leda, Ozturk, Tugba, Russell, Olivia Ollinger, Amblard, Franck, Coats, Steven J., Schinazi, Raymond F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-02-2017
• Subjects: Animals; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Capsid assembly effectors; Capsid Proteins - chemistry; Capsid Proteins - metabolism; Cell Line; Cell Survival - drug effects; Cercopithecus aethiops; HAP; HBV; Hep G2 Cells; Hepatitis B virus - physiology; Heteroarylpyrimidine; Humans; Pyridines - chemistry; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Vero Cells; Virus Replication - drug effects; Heteroarylpyrimidine; HBV; Capsid assembly effectors; HAP
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.01.010

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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.