Abstract
Hydroxylamine and hydroxamic acid derivatives of a known nonsteroidal antiinflammatory dibenzoxepine series display both cyclooxygenase (CO) and 5-lipoxygenase (5-LO) inhibitory properties. Many of these new dual CO/5-LO inhibitors also exhibit potent topical antiinflammatory activity in the arachidonic acid-induced murine ear edema model. On the basis of their promising profile of in vitro and in vivo activities, hydroxamic acids 24h, 3-(6,11-dihydro-11-oxodibenz[b,e]oxepin-2-yl)-N-hydroxy-N-++ +methylpropanamide (HP 977), and 25, 3-(6,11-dihydrodibenz[b,e]oxepin-2-yl)-N-hydroxy-N- methylpropanamide (P10294), were selected as developmental candidates for the topical treatment of inflammatory skin disorders.
MeSH terms
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3T3 Cells
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Arachidonate 5-Lipoxygenase / metabolism
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Arachidonic Acid / pharmacology
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology*
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Dibenzoxepins / chemical synthesis
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Dibenzoxepins / chemistry
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Dibenzoxepins / pharmacology*
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Dinoprostone / analysis
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Hydroxamic Acids / chemical synthesis
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Hydroxamic Acids / chemistry
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Hydroxamic Acids / pharmacology*
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Hydroxyeicosatetraenoic Acids / analysis
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Hydroxylamines / chemical synthesis
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Hydroxylamines / chemistry
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Hydroxylamines / pharmacology*
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Lipoxygenase Inhibitors / chemical synthesis
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Lipoxygenase Inhibitors / chemistry
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Lipoxygenase Inhibitors / pharmacology*
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Mice
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Molecular Structure
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase Inhibitors
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Dibenzoxepins
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HP 977
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Hydroxamic Acids
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Hydroxyeicosatetraenoic Acids
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Hydroxylamines
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Lipoxygenase Inhibitors
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P 10294
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Arachidonic Acid
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5-hydroxy-6,8,11,14-eicosatetraenoic acid
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Arachidonate 5-Lipoxygenase
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Dinoprostone