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Journal article
4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators
Bioorganic & medicinal chemistry letters, v 58, pp 128518-128518
15 Feb 2022
PMID: 34979256
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Hepatitis B virus (HBV) core protein, the building block of the HBV capsid, plays multiple roles in viral replication, and is an attractive target for development of antiviral agents with a new mechanism of action. In addition to the heteroaryldihydropyrimidines (HAPs), sulfamoylbenzamides (SBAs), dibenzothiazepine derivatives (DBTs), and sulfamoylpyrrolamides (SPAs) that inhibit HBV replication by modulation of viral capsid assembly and are currently under clinical trials for the treatment of chronic hepatitis B (CHB), other chemical structures with activity to modulate HBV capsid assembly have also been explored. Here we describe our continued optimization of a benzamide originating from our high throughput screening. A new bicyclic carboxamide lead featuring an electron deficient non-planar core structure was discovered. Evaluations of its ADMET (absorption, distribution, metabolism, excretion and toxicity) and pharmacokinetic (PK) profiles demonstrate improved metabolic stability and good bioavailability.
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Details
- Title
- 4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators
- Creators
- Nicky Hwang - Baruch S. Blumberg InstituteHaiqun Ban - Baruch S. Blumberg InstituteShuo Wu - Baruch S. Blumberg InstituteKelly McGuire - Temple UniversityEllen Hernandez - Delaware Valley Univ, 700 Butler Ave, Doylestown, PA 18901 USAJunjun Chen - Baruch S. Blumberg InstituteQiong Zhao - Baruch S. Blumberg InstituteManasa Suresh - Georgetown Univ, Med Ctr, 3900 Reservoir Rd, Washington, DC 20057 USABenjamin Blass - Temple UniversityUsha Viswanathan - Baruch S. Blumberg InstituteJohn Kulp - Baruch S. Blumberg InstituteJinhong Chang - Baruch S. Blumberg InstituteJason Clement - Baruch S. Blumberg InstituteStephan Menne - Georgetown Univ, Med Ctr, 3900 Reservoir Rd, Washington, DC 20057 USAJu-Tao Guo - Baruch S. Blumberg InstituteYanming Du - Baruch S. Blumberg Institute
- Publication Details
- Bioorganic & medicinal chemistry letters, v 58, pp 128518-128518
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- Commonwealth of Pennsylvania through the Hepatitis B Foundation AI113267 / National Institutes of Health, USA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Pharmacology and Physiology
- Web of Science ID
- WOS:000783518600009
- Scopus ID
- 2-s2.0-85122250932
- Other Identifier
- 991020547318604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal
- Chemistry, Organic