Abstract
Derivatization of rolipram led to the identification of 3-[4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxo-pyrrolidin-1-yl]-5-( 3- methoxybenzyloxy)-benzoic acid N',N'-dimethylhydrazide (4), a potent and selective inhibitor of PDE4, which inhibits the activation of human leukocytes with pIC50 values in the range of 7.3-7.8, and blocks antigen induced eosinophilia in Brown Norway rats at a dose of 1 mg/kg (i.t.).
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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Animals
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Anti-Asthmatic Agents / chemical synthesis*
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Anti-Asthmatic Agents / pharmacology
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Humans
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Leukocytes / drug effects
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Phosphodiesterase Inhibitors / chemical synthesis*
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Phosphodiesterase Inhibitors / pharmacology
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Pyrrolidinones / chemical synthesis*
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Pyrrolidinones / pharmacology
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Rats
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Rats, Inbred BN
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Rolipram
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Structure-Activity Relationship
Substances
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Anti-Asthmatic Agents
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Rolipram