Abstract
A facile and novel synthetic route to MC-1220 was achieved by condensation of 4,6-dichloro-N,N-5-trimethylpyrimidin-2-amine (1) with the sodium salt of 2,6-difluorophenylacetonitrile, followed by methylation and strong acidic hydrolysis. The prodrugs of MC-1220 were synthesized by reaction of chlorophosphoramidate derivatives (7a-e) or α-acetobromoglucose with the sodium salt of MC-1220. The stability and anti-HIV-1 activity of phosphoramidate prodrugs turned out to be comparable to those of the parent drug MC-1220.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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Cells, Cultured
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Dose-Response Relationship, Drug
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Fluorobenzenes / chemical synthesis*
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Fluorobenzenes / chemistry
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Fluorobenzenes / pharmacology
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HIV-1 / drug effects
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Humans
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Microbial Sensitivity Tests
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Molecular Structure
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Phosphoric Acids / chemical synthesis*
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Phosphoric Acids / chemistry
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Phosphoric Acids / pharmacology
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Pyrimidinones / chemical synthesis*
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Pyrimidinones / chemistry
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Pyrimidinones / pharmacology
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Structure-Activity Relationship
Substances
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6-(1-(2,6-difluorophenyl)ethyl)-2-(dimethylamino)-5-methylpyrimidin-4(3H)-one
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Amides
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Anti-HIV Agents
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Fluorobenzenes
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Phosphoric Acids
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Prodrugs
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Pyrimidinones
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phosphoramidic acid