INTRODUCTION: The hepatitis B virus (HBV) core protein is a significant therapeutic target due to its essential role in HBV replication. Over the past five years, numerous structurally unique CpAMs have been patented. However, no compounds have been approved due to various issues such as poor pharmacokinetics (PK) and hepatotoxicity. As a result, there is an urgent need to develop novel CpAMs without these limitations. AREAS COVERED: This review provides a comprehensive analysis of patents related to CpAMs from 2019 to the present, with the aim of delineating the chemical evolution that has occurred in the pursuit of more promising CpAMs. The sources of patent information included databases of the European Patent Office, the China Patent Office and the U.S.A. Patent Office, while relevant research articles were accessed through PubMed. EXPERT OPINION: During the optimization of CpAMs, striking a good balance between activity and druggability usually poses a certain challenge while the emergence of drug resistance issues further complicates the development process. A comprehensive analysis of the structural features of CpAMs and identification of essential patterns in chemical evolution can reveal common principles that improve pharmacodynamic (PD) and PK profiles, thereby facilitating the discovery of next-generation CpAMs.