Abstract
Compound 4k N-[5-(4-fluoro)phenoxythien-2-yl]methanesulfonamide is representative of a new class of potent inhibitors of 5-lipoxygenase (5-LO). These versatile compounds exhibit dose-dependent inhibition of 5-LO with IC50s ranging from 20-100 nM in the rat basophilic leukemia (RBL-1) cell homogenate assay and submicromolar IC50s in both the RBL-1 and human peripheral blood leukocyte (PBL) whole cell assays. Compound 4k also showed significant anti-inflammatory activity in the adjuvant arthritic rat at an oral dose of 3 mg/kg.
MeSH terms
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Administration, Oral
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Alkylation
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Animals
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Anti-Inflammatory Agents / administration & dosage
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use
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Arthritis, Experimental / drug therapy
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Ethers / chemical synthesis
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Humans
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Leukemia, Basophilic, Acute / enzymology
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Leukemia, Basophilic, Acute / pathology
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / drug effects
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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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Lipoxygenase Inhibitors / therapeutic use
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Male
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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Sulfides / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use
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Thiophenes / chemistry
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Tumor Cells, Cultured
Substances
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Anti-Inflammatory Agents
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Ethers
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Lipoxygenase Inhibitors
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Sulfides
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Sulfonamides
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Thiophenes