Abstract
This paper describes the synthesis and anti-inflammatory activity of new N-phenyl-phthalimide sulfonamides (3a-e) and the isosters N-phenyl-phthalimide amides (4a-e), designed as hybrids of thalidomide (1) and aryl sulfonamide phosphodiesterase inhibitor (2). In these series, compound 3e (LASSBio 468), having a sulfonyl-thiomorpholine moiety, showed potent inhibitory activity on LPS-induced neutrophil recruitment with ED(50)=2.5mg kg(-1), which was correlated with its inhibitory effect on TNF-alpha level.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / pharmacology
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Bronchoalveolar Lavage Fluid
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Cyclic Nucleotide Phosphodiesterases, Type 3
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Dose-Response Relationship, Drug
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Lipopolysaccharides / pharmacology
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Male
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Mice
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Mice, Inbred BALB C
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Neutrophil Infiltration / drug effects
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Phthalimides / chemical synthesis*
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Phthalimides / pharmacology
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Structure-Activity Relationship
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Thalidomide / analogs & derivatives*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
Substances
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Anti-Inflammatory Agents
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Lipopolysaccharides
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Phthalimides
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Tumor Necrosis Factor-alpha
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Thalidomide
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 3
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Cyclic Nucleotide Phosphodiesterases, Type 4