Abstract
Rheumatoid arthritis (RA) and other chronic inflammatory diseases are always the major therapeutic challenges. Recent research efforts provided new insights into the molecular basis of these diseases and new opportunities for developing improved anti-inflammatory drugs. The p38 mitogen-activated protein (MAP) kinase plays a central role in the regulation of the biosynthesis and release of several proinflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Hence, inhibition of the p38 MAP kinase is regarded as a promising therapeutic strategy for controlling inflammatory diseases. A diverse range of p38α MAP kinase inhibitors have been developed as potential anti-inflammatory agents, and some of them have entered the phase II clinical trials. The imidazole derivatives are known as competitive inhibitors at the ATP binding site of the p38α MAP kinase. Modifications on the imidazole scaffold have led to a large amount of potent p38α MAP kinase inhibitors. This review will summarize the developments of small molecule p38α MAP kinase inhibitors based on the imidazole core scaffolds in recent 10 years. Variations at the N1, C2, C4 and C5 positions of imidazole were introduced, and the structure-activity relationships of these imidazole inhibitors were also discussed.
Keywords: Anti-inflammatory, p38α MAP kinase, p38α MAP kinase inhibitors, rheumatoid arthritis, tetrasubstituted imidazoles, thioimidazoles, trisubstituted imidazoles
Current Medicinal Chemistry
Title:Recent Developments of p38α MAP Kinase Inhibitors as Antiinflammatory Agents Based on the Imidazole Scaffolds
Volume: 20 Issue: 15
Author(s): Ting-Ting Kong, Cheng-Mei Zhang and Zhao-Peng Liu
Affiliation:
Keywords: Anti-inflammatory, p38α MAP kinase, p38α MAP kinase inhibitors, rheumatoid arthritis, tetrasubstituted imidazoles, thioimidazoles, trisubstituted imidazoles
Abstract: Rheumatoid arthritis (RA) and other chronic inflammatory diseases are always the major therapeutic challenges. Recent research efforts provided new insights into the molecular basis of these diseases and new opportunities for developing improved anti-inflammatory drugs. The p38 mitogen-activated protein (MAP) kinase plays a central role in the regulation of the biosynthesis and release of several proinflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Hence, inhibition of the p38 MAP kinase is regarded as a promising therapeutic strategy for controlling inflammatory diseases. A diverse range of p38α MAP kinase inhibitors have been developed as potential anti-inflammatory agents, and some of them have entered the phase II clinical trials. The imidazole derivatives are known as competitive inhibitors at the ATP binding site of the p38α MAP kinase. Modifications on the imidazole scaffold have led to a large amount of potent p38α MAP kinase inhibitors. This review will summarize the developments of small molecule p38α MAP kinase inhibitors based on the imidazole core scaffolds in recent 10 years. Variations at the N1, C2, C4 and C5 positions of imidazole were introduced, and the structure-activity relationships of these imidazole inhibitors were also discussed.
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Cite this article as:
Kong Ting-Ting, Zhang Cheng-Mei and Liu Zhao-Peng, Recent Developments of p38α MAP Kinase Inhibitors as Antiinflammatory Agents Based on the Imidazole Scaffolds, Current Medicinal Chemistry 2013; 20 (15) . https://dx.doi.org/10.2174/0929867311320150006
DOI https://dx.doi.org/10.2174/0929867311320150006 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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