Journal article
Synthesis of 4-oxotetrahydropyrimidine-1(2H)-carboxamides derivatives as capsid assembly modulators of hepatitis B virus
Medicinal chemistry research, v 30(2), pp 459-472
2021
PMID: 33456291
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We report herein the synthesis and evaluation of phenyl ureas derived from 4-oxotetrahydropyrimidine as novel capsid assembly modulators of hepatitis B virus (HBV). Among the derivatives, compound 27 (58031) and several analogs showed an activity of submicromolar EC50 against HBV and low cytotoxicities (>50 mu M). Structure-activity relationship studies revealed a tolerance for an additional group at position 5 of 4-oxotetrahydropyrimidine. The mechanism study indicates that compound 27 (58031) is a type II core protein allosteric modulator (CpAMs), which induces core protein dimers to assemble empty capsids with fast electrophoresis mobility in native agarose gel. These compounds may thus serve as leads for future developments of novel antivirals against HBV.
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Details
- Title
- Synthesis of 4-oxotetrahydropyrimidine-1(2H)-carboxamides derivatives as capsid assembly modulators of hepatitis B virus
- Creators
- Nicky Hwang - Baruch S. Blumberg InstituteHaiqun Ban - Renji HospitalJunjun Chen - Baruch S. Blumberg InstituteJulia Ma - Baruch S. Blumberg InstituteHui Liu - Peking UniversityPatrick Lam - Baruch S. Blumberg InstituteJohn Kulp - Baruch S. Blumberg InstituteStephan Menne - Georgetown University Medical CenterJinhong Chang - Baruch S. Blumberg InstituteJu-Tao Guo - Baruch S. Blumberg InstituteYanming Du - Baruch S. Blumberg Institute
- Publication Details
- Medicinal chemistry research, v 30(2), pp 459-472
- Publisher
- Springer Nature
- Number of pages
- 14
- 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:000607009000001
- Scopus ID
- 2-s2.0-85099308129
- Other Identifier
- 991020547438204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Chemistry, Medicinal