Bernhard Lesch, Alexander Birkmann, Susanne Bonsmann, Alastair Donald, Florian Engel, Thomas Goldner, Kamal Kumar, Tamara Pfaff, Andreas Urban, Holger Zimmermann, Alexandra E. Bosnidou, Estefanía del Castillo, Félix Cuevas, Elena Detta, Daniel Font, Jordi González García, Justine Raymond, Maria Ángeles Sarmentero, Arjen Cnossen, Wessel Sinnige, Jack C. Slootweg, Anita Wegert, Helmut Buschmann
{"title":"Discovery of AIC263282, a Hepatitis B Virus Capsid Assembly Modulator Ready for Candidate Profiling","authors":"Bernhard Lesch, Alexander Birkmann, Susanne Bonsmann, Alastair Donald, Florian Engel, Thomas Goldner, Kamal Kumar, Tamara Pfaff, Andreas Urban, Holger Zimmermann, Alexandra E. Bosnidou, Estefanía del Castillo, Félix Cuevas, Elena Detta, Daniel Font, Jordi González García, Justine Raymond, Maria Ángeles Sarmentero, Arjen Cnossen, Wessel Sinnige, Jack C. Slootweg, Anita Wegert, Helmut Buschmann","doi":"10.1021/acs.jmedchem.4c02838","DOIUrl":null,"url":null,"abstract":"Hepatitis B Virus (HBV) infections remain a threat to the global public health. Nucleoside analogues remain the mainstay of therapy despite their discouraging cure rates achieved. Capsid assembly modulators (CAMs) have been at the center of HBV research, but despite having shown clinical efficacy on viral load in clinical studies, market entry has been elusive. Herein, we present the optimization program of our lead series. Setting our focus on potency, solubility, and hERG liability, these studies resulted in AIC263282, a new, potent capsid assembly modulator with improved physicochemical properties, which is ready for profiling as a preclinical candidate.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"5 1","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c02838","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Hepatitis B Virus (HBV) infections remain a threat to the global public health. Nucleoside analogues remain the mainstay of therapy despite their discouraging cure rates achieved. Capsid assembly modulators (CAMs) have been at the center of HBV research, but despite having shown clinical efficacy on viral load in clinical studies, market entry has been elusive. Herein, we present the optimization program of our lead series. Setting our focus on potency, solubility, and hERG liability, these studies resulted in AIC263282, a new, potent capsid assembly modulator with improved physicochemical properties, which is ready for profiling as a preclinical candidate.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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