Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors

Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors

[Display omitted] New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iod...

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Published in:Bioorganic & medicinal chemistry letters Vol. 27; no. 4; pp. 904 - 910
Main Authors: Boucle, Sebastien, Lu, Xiao, Bassit, Leda, Ozturk, Tugba, Russell, Olivia Ollinger, Amblard, Franck, Coats, Steven J., Schinazi, Raymond F.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 15-02-2017
Subjects:
Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Capsid assembly effectors
Capsid Proteins - chemistry
Capsid Proteins - metabolism
Cell Line
Cell Survival - drug effects
Cercopithecus aethiops
HAP
HBV
Hep G2 Cells
Hepatitis B virus - physiology
Heteroarylpyrimidine
Humans
Pyridines - chemistry
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
Structure-Activity Relationship
Vero Cells
Virus Replication - drug effects
Heteroarylpyrimidine
HBV
Capsid assembly effectors
HAP
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Abstract [Display omitted] New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.
AbstractList New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.
[Display omitted] New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV activity in the HepAD38 system, and cytotoxicity profiles of each of the new compounds has been assessed. Among them, five new iodo- and bromo-heteroarylpyrimidines analogs displayed anti-HBV activity in the low micromolar range.
Author Boucle, Sebastien
Schinazi, Raymond F.
Lu, Xiao
Ozturk, Tugba
Russell, Olivia Ollinger
Amblard, Franck
Coats, Steven J.
Bassit, Leda
AuthorAffiliation b Cocrystal Pharma, Inc., 1860 Montreal Road, Tucker, GA 30084, USA
a Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
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  givenname: Xiao
  surname: Lu
  fullname: Lu, Xiao
  organization: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
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  surname: Schinazi
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  email: rschina@emory.edu
  organization: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
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Keywords Heteroarylpyrimidine
HBV
Capsid assembly effectors
HAP
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Snippet [Display omitted] New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored....
New modifications to the scaffold of previously reported HBV capsid assembly effectors such as BAY 41-4109, HAP-12 and GLS4 were explored. The anti-HBV...
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SubjectTerms Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Capsid assembly effectors
Capsid Proteins - chemistry
Capsid Proteins - metabolism
Cell Line
Cell Survival - drug effects
Cercopithecus aethiops
HAP
HBV
Hep G2 Cells
Hepatitis B virus - physiology
Heteroarylpyrimidine
Humans
Pyridines - chemistry
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacology
Structure-Activity Relationship
Vero Cells
Virus Replication - drug effects
Title Synthesis and antiviral evaluation of novel heteroarylpyrimidines analogs as HBV capsid effectors
URI https://dx.doi.org/10.1016/j.bmcl.2017.01.010
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