Abstract
New oleanane triterpenoids with various substituents at the C-17 position of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) and methyl 2-carboxy-3,12-dioxooleana-1,9(11)-dien-28-oate were synthesized. Among them, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile shows extremely high inhibitory activity (IC(50)=1 pM level) against production of nitric oxide induced by interferon-gamma in mouse macrophages. This potency is about 100 times and 30 times more potent than CDDO and dexamethasone, respectively.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Dexamethasone / pharmacology
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Interferon-gamma / pharmacology
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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Molecular Structure
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Nitric Oxide / antagonists & inhibitors*
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Nitric Oxide / biosynthesis
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Nitriles / chemical synthesis*
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Nitriles / chemistry
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Nitriles / pharmacology*
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Oleanolic Acid / analogs & derivatives*
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Oleanolic Acid / chemical synthesis*
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Oleanolic Acid / chemistry
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Oleanolic Acid / pharmacology
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Structure-Activity Relationship
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Triterpenes / chemical synthesis*
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Triterpenes / chemistry
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Triterpenes / pharmacology*
Substances
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Nitriles
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Triterpenes
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Nitric Oxide
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cyanogen
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Oleanolic Acid
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Dexamethasone
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Interferon-gamma