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Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents
- Source :
- Bioorg Med Chem
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Chronic hepatitis B viral infection is a significant health problem world-wide, and currently available antiviral agents suppress HBV infections, but rarely cure this disease. It is presumed that antiviral agents that target the viral nuclear reservoir of transcriptionally active cccDNA may eliminate HBV infection. Through a series of chemical optimization, we identified a new series of glyoxamide derivatives affecting HBV nucleocapsid formation and cccDNA maintenance at low nanomolar levels. Among all the compounds synthesized, GLP-26 displays a major effect on HBV DNA, HBeAg secretion and cccDNA amplification. In addition, GLP-26 shows a promising pre-clinical profile and long-term effect on viral loads in a humanized mouse model.
- Subjects :
- Hepatitis B virus
Clinical Biochemistry
Pharmaceutical Science
Microbial Sensitivity Tests
medicine.disease_cause
Antiviral Agents
Biochemistry
Article
Structure-Activity Relationship
Drug Discovery
medicine
Structure–activity relationship
Secretion
Molecular Biology
Dose-Response Relationship, Drug
Molecular Structure
Chemistry
Organic Chemistry
cccDNA
Virology
Sulfonylurea Compounds
Capsid
HBeAg
Humanized mouse
Molecular Medicine
Viral load
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....6ad73c90faa516e774c005401223a0f2