Abstract
Herein we report investigations into the p38alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation.
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / metabolism
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Animals
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacokinetics
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Anti-Inflammatory Agents / pharmacology*
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Benzimidazoles / chemistry
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Benzimidazoles / pharmacokinetics
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Benzimidazoles / pharmacology
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Edema / drug therapy
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ErbB Receptors / metabolism
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Humans
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Imidazoles / chemistry
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology*
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Mice
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Mice, Inbred BALB C
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Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
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Peptide Fragments / metabolism
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Pyridines / chemistry
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Pyridines / pharmacokinetics
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Pyridines / pharmacology*
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Rats
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents
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Benzimidazoles
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Imidazoles
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Peptide Fragments
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Pyridines
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Tumor Necrosis Factor-alpha
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Adenosine Triphosphate
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ErbB Receptors
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Mitogen-Activated Protein Kinase 14