Discovery and optimizing polycyclic pyridone compounds as anti-HBV agents

ABSTRACT

Introduction

Hepatitis B disease is caused by the hepatitis B virus (HBV), which is a DNA virus that belongs to the Hepadnaviridae family. It is a considerable health burden, with 257 million active cases globally. Long-standing infection may create a fundamental cause of liver disease and chronic infections, including cirrhosis, hepatocellular, and carcinoma liver failure. There is an urgent need to develop novel, safe, and effective drug candidates with a novel mechanism of action, improved activity, efficacy, and cure rate.

Areas covered

Herein, the authors provide a concise report focusing on a general and cutting-edge overview of the current state of polycyclic pyridone-related anti-HBV agent patents from 2016 to 2018 and some future perspectives.

Expert opinion

In medicinal chemistry, high-throughput screening (HTS), hit-to-lead optimization (H2L), bioisosteric replacement, and scaffold hopping approaches are playing a major role in the discovery and development of HBV inhibitors. Developing polycyclic pyridone-related anti-HBV agents that could target host factors has attracted significant interest and attention in recent years.

KEYWORDS:

• Polycyclic pyridone
• HBV inhibitors
• medicinal chemistry
• high-throughput screening
• hit-to-lead optimization
• scaffold hopping
• drug design

Article highlights

• None of the current standard therapies for chronic hepatitis B have a satisfactory clinical cure rate due to the difficulty of eradicating cccDNA.

• A significant rise of interest in host drug targets has propelled the development of anti-HBV inhibitors to reduce HBsAg levels and restore virus-specific immune responsiveness.

• The scaffold of polycyclic pyridone-related anti-HBV agent holds the potential for antiviral development.

• Bioisosteric replacement and scaffold hopping approach, etc., are promising strategies to achieve safe and effective anti-HBV agents with novel mechanisms of action.

This box summarizes key points contained in the article.

Author contributions

All the authors made significant contributions in the conception, study design, execution, and acquisition of data, analysis and interpretation more or less and they are ranked by their contribution to the manuscript. Also, all authors reviewed and agreed to submit this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have nothing to disclose.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Financial support from the Key Project of NSFC for International Cooperation (No.81420108027), the National Natural Science Foundation of China (NSFC Nos. 81273354, 81573347), Young Scholars Program of Shandong University (YSPSDU No. 2016WLJH32), Key research and development project of Shandong Province (No. 2019JZZY021011, 2017CXGC1401) is gratefully acknowledged.