Abstract
The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and 1L-1beta. Accordingly, new pyrrolo[2, 3-]pyridine derivatives 5a-d were prepared from 2-amino-3-cyanopyrroles 3a-d via the intermediate propenylaminopyrroles 4a-d. Then the compounds 5a-d were tested for their ability to inhibit the production of TNF-alpha in vivo in rats. The most potent compounds 5a and 5b possess enhanced ability to inhibit the production of TNF-alpha stimulated with bacterial lipopolysaccharide.
MeSH terms
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Administration, Oral
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Animals
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Escherichia coli / chemistry
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Escherichia coli / metabolism
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Injections, Intraperitoneal
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Lipopolysaccharides / administration & dosage
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Lipopolysaccharides / metabolism
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Male
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Molecular Structure
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Neoplasm Proteins / administration & dosage
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Neoplasm Proteins / chemical synthesis*
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Neoplasm Proteins / pharmacokinetics
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Pyridines / administration & dosage
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Pyridines / chemical synthesis*
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Pyridines / pharmacokinetics*
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Pyrroles / administration & dosage
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Pyrroles / chemical synthesis*
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Pyrroles / pharmacokinetics*
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Rats
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor Decoy Receptors
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Lipopolysaccharides
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Neoplasm Proteins
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Pyridines
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Pyrroles
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Receptors, Tumor Necrosis Factor, Type II
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Tumor Necrosis Factor Decoy Receptors
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Tumor Necrosis Factor-alpha
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pyrrolo(2, 3-b)pyridine