Abstract
In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the anilino moiety, showed COX-1-selective inhibition. Moreover compound 11f, which is the most potent compound in this study showed more potent analgesic activity than that of aspirin at 30 mg/kg by po. The anti-inflammatory activity and gastric damage, however, were very weak or not detectably different from aspirin. Since the structure of our COX-1 inhibitors are very simple, they may be useful as lead compounds for superior COX-1 inhibitors as analgesic agents without gastric disturbance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / pharmacology*
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Analgesics / toxicity
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Anilides / chemical synthesis*
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Anilides / pharmacology*
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Anilides / toxicity
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Animals
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Benzenesulfonates / chemical synthesis*
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Benzenesulfonates / pharmacology*
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Benzenesulfonates / toxicity
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Carrageenan
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Colorimetry
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Crystallography, X-Ray
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Cyclooxygenase 1 / metabolism*
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / pharmacology*
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Cyclooxygenase Inhibitors / toxicity
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Drug Design
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Edema / chemically induced
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Edema / prevention & control
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Gastric Mucosa / pathology
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Indicators and Reagents
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Indomethacin / toxicity
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Kinetics
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Male
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Mice
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Molecular Conformation
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Rats
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Sheep
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Stomach Ulcer / chemically induced*
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Stomach Ulcer / pathology
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Structure-Activity Relationship
Substances
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Analgesics
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Anilides
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Benzenesulfonates
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Cyclooxygenase Inhibitors
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Indicators and Reagents
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Carrageenan
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Cyclooxygenase 1
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Indomethacin