Abstract
(6,7-Disubstituted-quinolin-4-yloxy-phenyl)(4-substituted-phenyl)amine derivatives were synthesized and evaluated by a cellular autophosphorylation assay for FGF-R2 in the human scirrhous gastric carcinoma cell line, OCUM-2MD3. We also performed metabolic stability studies showing that substitutions at the 7-position of quinoline affect its biological stability. In this study, we achieved a remarkable improvement in the solubility and metabolic stability of the diphenylamine derivative. The most promising compound 15e showed a significant decrease in tumor volume when orally administered.
MeSH terms
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Administration, Oral
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Animals
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Antineoplastic Agents / pharmacology*
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Cell Division / drug effects
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Cell Line, Tumor
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Diphenylamine / analogs & derivatives
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Diphenylamine / metabolism
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Diphenylamine / pharmacology*
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Drug Screening Assays, Antitumor
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Humans
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Molecular Structure
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Phosphorylation
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Rats
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
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Receptor, Fibroblast Growth Factor, Type 2
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Receptors, Fibroblast Growth Factor / antagonists & inhibitors*
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Stomach Neoplasms / drug therapy
Substances
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Antineoplastic Agents
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Receptors, Fibroblast Growth Factor
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Diphenylamine
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FGFR2 protein, human
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Fgfr2 protein, rat
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Receptor Protein-Tyrosine Kinases
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Receptor, Fibroblast Growth Factor, Type 2