Abstract
This communication describes the synthesis and in vitro PDE4 inhibitory activity of a novel series of imidazol-2-one and 2-cyanoiminoimidazole derivatives. The compounds described were also tested in in vivo models to evaluate their anti-inflammatory activity after topical administration as well as their gastro-intestinal side effects. Several compounds proved to be potent PDE4 inhibitors and some 2-cyanoiminoimidazoles showed less pronounced gastro-intestinal side effects than reference compounds but maintained anti-inflammatory activity after topical administration.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
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Administration, Topical
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Animals
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Anti-Inflammatory Agents / administration & dosage
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / pharmacology
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Ear Diseases / drug therapy
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Humans
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Imidazoles / administration & dosage
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Imidazoles / chemical synthesis
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Imidazoles / pharmacology*
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Inflammation / drug therapy
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Inhibitory Concentration 50
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Rats
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Enzyme Inhibitors
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Imidazoles
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imidazolone
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4