Abstract
A series of sulfonimidamide analogs of the oncolytic diarylsulfonylureas was synthesized and evaluated for (1) in vitro cytotoxicity against CEM cells, (2) in vivo antitumor activity against subaxillary implanted 6C3HED lymphosarcoma, and (3) metabolic breakdown to the o-sulfate of p-chloroaniline. The separated enantiomers of one sulfonimidamide analog displayed very different activities in the in vivo screening model. In general, several analogs demonstrated excellent growth inhibitory activity in the 6C3HED model when dosed orally or intraperitoneally. A correlative structure-activity relationship to the oncolytic sulfonylureas was not apparent.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Cell Division / drug effects
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Drug Screening Assays, Antitumor
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Inbred C3H
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Molecular Structure
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Phenylurea Compounds / chemical synthesis
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Phenylurea Compounds / metabolism
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Phenylurea Compounds / pharmacology*
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Sarcoma, Experimental / drug therapy
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Sulfonylurea Compounds / chemical synthesis
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Sulfonylurea Compounds / chemistry
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Sulfonylurea Compounds / metabolism
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Sulfonylurea Compounds / pharmacology*
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Phenylurea Compounds
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Sulfonylurea Compounds
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LY 181984
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sulofenur