Abstract
mPGES-1 is a promising target for development of new anti-inflammatory drugs. We aimed to create mPGES-1 inhibitors by modifying the structure of NSAIDs by replacing the carboxylic acid functionality by sulfonamide moieties. Compounds were also tested for 5-LOX inhibition. The most potent mPGES-1 inhibitor was lonazolac derivative 22 (IC₅₀ = 0.16 μM), while the best 5-LOX inhibition was attained by indomethacin derivative 17 (IC₅₀ = 0.9 μM). Inhibition of COX-1 activity was completely removed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Cell Line
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Humans
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Indomethacin / analogs & derivatives
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Indomethacin / chemical synthesis
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Indomethacin / chemistry
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Indomethacin / pharmacology
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Intramolecular Oxidoreductases / antagonists & inhibitors*
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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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Microsomes / drug effects
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Microsomes / metabolism
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Prostaglandin-E Synthases
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry
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Pyrazoles / pharmacology
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Lipoxygenase Inhibitors
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Pyrazoles
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Sulfonamides
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lonazolac
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Arachidonate 5-Lipoxygenase
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Intramolecular Oxidoreductases
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PTGES protein, human
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Prostaglandin-E Synthases
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Indomethacin