Abstract
From a high-throughput screening (HTS) hit with inhibitory activity against virus-induced cytophathic in the low micromolar range, we have developed a potent anti-influenza lead through careful optimization without compromising the drug-like properties of the compound. An orally bioavailable compound was identified as a lead agent with nanomolar activity against influenza, representing a 140-fold improvement over the initial hit.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / chemistry*
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Antiviral Agents / pharmacokinetics
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Antiviral Agents / pharmacology*
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Cell Line
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Drug Discovery
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Humans
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Influenza A Virus, H1N1 Subtype / drug effects*
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Influenza, Human / drug therapy
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Male
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Orthomyxoviridae Infections / drug therapy
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Quinolines / chemistry*
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Quinolines / pharmacokinetics
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Quinolines / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
Substances
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Antiviral Agents
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Quinolines