Abstract
Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system (CNS), design and synthesis of a hydrophilic analogue is considered to be one approach to improving the side-effect profile of Ariflo 1. Water-soluble piperidine derivatives were found to possess therapeutic potential.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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3',5'-Cyclic-AMP Phosphodiesterases / metabolism
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Animals
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Bronchoconstriction / drug effects
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Bronchoconstriction / physiology
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Cyclohexanecarboxylic Acids / adverse effects
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Cyclohexanecarboxylic Acids / chemistry
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Gastric Emptying / drug effects
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Gastric Emptying / physiology
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Guinea Pigs
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Humans
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Nitriles
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Phosphodiesterase Inhibitors / chemistry*
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Phosphodiesterase Inhibitors / pharmacology
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Phosphodiesterase Inhibitors / therapeutic use*
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Piperidines / chemistry
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Piperidines / pharmacology
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Rats
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Tumor Necrosis Factor-alpha / biosynthesis
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U937 Cells
Substances
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Cyclohexanecarboxylic Acids
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Nitriles
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Phosphodiesterase Inhibitors
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Piperidines
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Tumor Necrosis Factor-alpha
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Cilomilast
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4