Abstract
Two series of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB). Extensive structure-activity relationships (SAR) were studied within these series. Several compounds were found to be novel and selective COX-2 inhibitors. Among them, the most potent and selective was 4-(3-carboxy-4-hydroxy-benzylideneamino)benzenesulfonamide (20, LA2135), (IC(50)'s for COX-1: 85.13 microM; COX-2: 0.74 microM; SI: 114.5), being more active COX-2 selective than celecoxib.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amination
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Benzenesulfonamides
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Benzylidene Compounds / chemical synthesis*
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Benzylidene Compounds / chemistry
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Benzylidene Compounds / pharmacology*
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Blood Platelets / drug effects
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Blood Platelets / enzymology
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / chemical synthesis*
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Humans
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Imines / chemistry*
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Methylation
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Molecular Structure
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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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Benzylidene Compounds
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Cyclooxygenase 2 Inhibitors
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Imines
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Sulfonamides
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Cyclooxygenase 2