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Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2008 Jan 01; Vol. 18 (1), pp. 179-83. Date of Electronic Publication: 2007 Nov 01. - Publication Year :
- 2008
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 18039577
- Full Text :
- https://doi.org/10.1016/j.bmcl.2007.10.106