Abstract
Several new TOP1-targeting agents were prepared using as intermediates the N,N,N-trimethyl quaternary ammonium salts of either ARC-111 or its 12-aza analog (ARC-31), 3 and 4, respectively. Direct displacement of the quaternary ammonium group with water, imidazole, alkylethylenediamines, or polyhydroxylated alkylamines provides a convenient means for furthering the structure-activity relationships associated with these non-camptothecin TOP1-targeting agents.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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DNA Topoisomerases, Type I / drug effects*
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Dose-Response Relationship, Drug
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Humans
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Hydrophobic and Hydrophilic Interactions
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Mice
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Molecular Structure
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Naphthyridines / chemical synthesis*
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Naphthyridines / chemistry
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Naphthyridines / pharmacology
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Quaternary Ammonium Compounds / chemistry*
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Stereoisomerism
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Structure-Activity Relationship
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Xenograft Model Antitumor Assays
Substances
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12-aza-5H-8,9-dimethoxy-5-(2-(N,N-dimethylamino)ethyl)-2,3-methylenedioxydibenzo(c,h)(1,6)naphthyridin-6-one
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Antineoplastic Agents
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Naphthyridines
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Quaternary Ammonium Compounds
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topovale
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DNA Topoisomerases, Type I