Abstract
Tamiflu, the ethyl ester form of oseltamivir carboxylic acid (OC), is the first orally available anti-influenza drug for the front-line therapeutic option. In this study, the OC-hydroxamates, OC-sulfonamides and their guanidino congeners (GOC) were synthesized. Among them, an OC-hydroxamate 7d bearing an O-(2-indolyl)propyl substituent showed potent NA inhibition (IC50 = 6.4 nM) and good anti-influenza activity (EC50 = 60.1 nM) against the wild-type H1N1 virus. Two GOC-hydroxamates (9b and 9d) and one GOC-sulfonamide (12a) were active to the tamiflu-resistant H275Y virus (EC50 = 2.3-6.9 μM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / chemical synthesis
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Influenza A Virus, H1N1 Subtype / drug effects*
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Influenza A Virus, H1N1 Subtype / enzymology
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Neuraminidase / antagonists & inhibitors*
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Neuraminidase / metabolism
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Oseltamivir / analogs & derivatives*
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Oseltamivir / chemical synthesis
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Oseltamivir / chemistry
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Oseltamivir / pharmacology
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
Substances
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Antiviral Agents
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Enzyme Inhibitors
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N-(3-(1H-Indol-2-yl)propoxy) 4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexenecarboxamide
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N-methoxy 4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexenecarboxamide
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N-methylsulfonyl 4-acetamido-5-guanidino-3-(1-ethylpropoxy)-1-cyclohexenecarboxamide
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Sulfonamides
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Oseltamivir
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Neuraminidase