1. Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties.
- Author
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Mader M, de Dios A, Shih C, Bonjouklian R, Li T, White W, López de Uralde B, Sánchez-Martinez C, del Prado M, Jaramillo C, de Diego E, Martín Cabrejas LM, Dominguez C, Montero C, Shepherd T, Dally R, Toth JE, Chatterjee A, Pleite S, Blanco-Urgoiti J, Perez L, Barberis M, Lorite MJ, Jambrina E, Nevill CR Jr, Lee PA, Schultz RC, Wolos JA, Li LC, Campbell RM, and Anderson BD
- Subjects
- Adenosine Triphosphate analogs & derivatives, Adenosine Triphosphate metabolism, Animals, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacokinetics, Benzimidazoles chemistry, Benzimidazoles pharmacokinetics, Benzimidazoles pharmacology, Edema drug therapy, ErbB Receptors metabolism, Humans, Imidazoles chemistry, Imidazoles pharmacokinetics, Mice, Mice, Inbred BALB C, Peptide Fragments metabolism, Pyridines chemistry, Pyridines pharmacokinetics, Rats, Structure-Activity Relationship, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents pharmacology, Imidazoles pharmacology, Mitogen-Activated Protein Kinase 14 antagonists & inhibitors, Pyridines pharmacology
- 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.
- Published
- 2008
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