Abstract
A novel series of potent blockers of the monocarboxylate transporter, MCT1, is disclosed. From very potent but lipophilic lead compounds, systematic changes to all parts of the molecule, targeting reduction in log D, afforded compounds with significantly improved overall properties. These compounds show potent immunomodulatory activity.
MeSH terms
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Animals
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Aryl Hydrocarbon Hydroxylases / immunology
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Aryl Hydrocarbon Hydroxylases / metabolism*
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Cytochrome P-450 CYP2C9
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme System / immunology
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Cytochrome P-450 Enzyme System / metabolism*
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Graft vs Host Disease / immunology
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Herpesviridae / drug effects*
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Herpesviridae / immunology
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Herpesviridae / metabolism
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Humans
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Immunologic Factors / chemistry
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Immunologic Factors / pharmacology*
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Monocarboxylic Acid Transporters / antagonists & inhibitors*
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Monocarboxylic Acid Transporters / immunology
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Monocarboxylic Acid Transporters / metabolism
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Symporters / antagonists & inhibitors*
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Symporters / immunology
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Symporters / metabolism
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T-Lymphocytes / drug effects*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Immunologic Factors
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Monocarboxylic Acid Transporters
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Symporters
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monocarboxylate transport protein 1
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Cytochrome P-450 Enzyme System
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CYP2C9 protein, human
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Cytochrome P-450 CYP2C9
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Aryl Hydrocarbon Hydroxylases
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CYP3A protein, human
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Cytochrome P-450 CYP3A