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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Therapeutic Implications of Immune-endocrine Interactions in the Critically Ill Patients
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Contribution of Dietary Factors to Peroxisome Proliferator-Activated Receptor-Mediated Inflammatory Signaling in Arthritic Diseases
Current Rheumatology Reviews Effect of Alpha-1-Acid Glycoprotein Binding on Pharmacokinetics and Pharmacodynamics
Current Drug Metabolism Lipoxins, The Novel Mediators of Gastroprotection and Gastric Adaptation to Ulcerogenic action of Aspirin
Current Pharmaceutical Design Patent Annotations
Recent Patents on Anti-Cancer Drug Discovery The Role of Progenitor Cells in Osteoarthritis Development and Progression
Current Stem Cell Research & Therapy Chronic Non-bacterial Osteomyelitis in Childhood – a Comprehensive Review
Current Rheumatology Reviews Modifying Toll-like Receptor 9 Signaling for Therapeutic Use
Mini-Reviews in Medicinal Chemistry Atypical Chemokine Receptors in Inflammatory Disease
Current Molecular Medicine Beyond Rodent Models of Pain: Non-Human Primate Models for Evaluating Novel Analgesic Therapeutics and Elaborating Pain Mechanisms
CNS & Neurological Disorders - Drug Targets Regulation of Protective and Pathogenic Th17 Responses
Current Immunology Reviews (Discontinued) Frailty of Older Age: The Role of the Endocrine - Immune Interaction
Current Pharmaceutical Design Combined Anticancer Therapies: An Overview of the Latest Applications
Anti-Cancer Agents in Medicinal Chemistry Post-Wortmannin Era: Novel Phosphoinositide 3-Kinase Inhibitors with Potential Therapeutic Applications
Current Enzyme Inhibition Cytotoxicity and Anti-Inflammatory Effects of Polyherbal Formulations, Joint Pain Spl and Rumalaya Forte on Lipopolysaccharide Induced Inflammation in IC-21 Macrophages
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Alzheimer Research Endogenous Repair System of Oxidative Damage of DNA
Current Chemical Biology Immune Aging and Autoimmune Diseases in Children
Current Immunology Reviews (Discontinued) Targeting BLyS in Systemic Lupus Erythematosus
Recent Patents on Inflammation & Allergy Drug Discovery