Abstract
A number of dioxolane, dioxane, and dioxepine quinazoline derivatives have been synthetized and evaluated as EGFR inhibitors. Their cytotoxic activity has been tested against two cell lines overexpressing and not expressing EGFR. Most derivatives were able to counteract EGF-induced EGFR phosphorylation, and their potency was comparable to the reference compound PD153035. The size of the fused dioxygenated ring was crucial for the biological activity, the dioxane derivatives being the most promising class of this series.
Publication types
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Research Support, Non-U.S. Gov't
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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Dioxanes / chemical synthesis*
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Dioxanes / chemistry
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Dioxanes / pharmacology
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Dioxolanes / chemical synthesis*
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Dioxolanes / chemistry
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Dioxolanes / pharmacology
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Drug Screening Assays, Antitumor
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / biosynthesis
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Heterocyclic Compounds, 3-Ring / chemical synthesis*
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Heterocyclic Compounds, 3-Ring / chemistry
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Heterocyclic Compounds, 3-Ring / pharmacology
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Humans
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Mice
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NIH 3T3 Cells
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Oxepins / chemical synthesis*
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Oxepins / chemistry
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Oxepins / pharmacology
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Phosphorylation
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Quinazolines / chemical synthesis*
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Quinazolines / chemistry
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Quinazolines / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Dioxanes
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Dioxolanes
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Heterocyclic Compounds, 3-Ring
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Oxepins
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Quinazolines
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ErbB Receptors