Abstract
Exploration of the chemical space of known influenza polymerase PB2 inhibitor Pimodivir, was performed by our group. We synthesized and identified compounds 16a and 16b, two novel thienopyrimidine derivatives displaying anti-influenza A activity in the single digit nanomolar range in cell culture. Binding of these unique compounds in the influenza polymerase PB2 pocket was also determined using molecular modeling.
Keywords:
Antiviral; Flu; Influenza A; Virus.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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A549 Cells
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Amino Acid Sequence
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Animals
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Antiviral Agents / chemistry*
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Antiviral Agents / pharmacology
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Drug Discovery
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Humans
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Influenza A virus / drug effects*
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Influenza, Human / drug therapy*
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Models, Molecular
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Molecular Structure
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Protein Binding
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Pyridines / chemistry*
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Pyridines / pharmacology
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology
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Pyrroles / chemistry*
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Pyrroles / pharmacology
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RNA-Dependent RNA Polymerase / metabolism*
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Structure-Activity Relationship
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Viral Proteins / metabolism*
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Virus Replication / drug effects
Substances
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Antiviral Agents
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PB2 protein, Influenzavirus A
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Pyridines
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Pyrimidines
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Pyrroles
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Viral Proteins
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pimodivir
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RNA-Dependent RNA Polymerase