Abstract
New derivatives with electron-withdrawing substituents at the C-2 position of 3-oxoolean-1-en-28-oic acid were synthesized. Among them, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) was 400 times more potent than previous compounds we have made as an inhibitor of production of nitric oxide induced by interferon-gamma in mouse macrophages (IC50, 0.4 nM). The potency of CDDO was similar to that of dexamethasone, although CDDO does not act through the glucocorticoid receptor.
Publication types
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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.
MeSH terms
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Animals
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / pharmacology
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Dexamethasone / pharmacology
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Glucocorticoids / pharmacology
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Interferon-gamma / pharmacology
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Isoenzymes / biosynthesis
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Macrophages / drug effects*
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Macrophages / metabolism*
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Mice
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase Type II
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Oleanolic Acid / analogs & derivatives*
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Oleanolic Acid / chemical synthesis
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Oleanolic Acid / pharmacology
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Prostaglandin-Endoperoxide Synthases / biosynthesis
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Structure-Activity Relationship
Substances
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2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Enzyme Inhibitors
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Glucocorticoids
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Isoenzymes
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Nitric Oxide
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Oleanolic Acid
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Dexamethasone
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Interferon-gamma
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases