Abstract
A series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the ViroPharma small molecule collection. Using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioavailable first-in-class inhibitor of orthopoxvirus egress from infected cells. Compound 14 has shown comparable efficaciousness in three murine orthopoxvirus models and has entered Phase I clinical trials.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Administration, Oral
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Animals
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / pharmacokinetics
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Antiviral Agents / pharmacology
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Benzamides / chemical synthesis*
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Benzamides / pharmacokinetics
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Benzamides / pharmacology
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Biological Availability
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Cell Line
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Crystallography, X-Ray
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Humans
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In Vitro Techniques
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Indoles / chemical synthesis*
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Indoles / pharmacokinetics
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Indoles / pharmacology
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Isoindoles
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Macaca fascicularis
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Mice
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Molecular Structure
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Orthopoxvirus / drug effects*
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Orthopoxvirus / physiology
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Rats
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antiviral Agents
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Benzamides
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Indoles
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Isoindoles
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tecovirimat