Abstract
A2B adenosine receptors have been investigated in recent years as potential target for the treatment of different pathologies. The involvement of this receptor in processes such as interleukins secretion, Ca2+ mobilization, hepatic glucose regulation, tumor vascularisation, and cardioprotection have stimulated many researchers to develop specific agonists and antagonists. For many years, the lack of potent and selective A2B ligands precluded a deep exploration of their therapeutic prospective; at present, much progress in the field of antagonists led to preclinical studies for different compounds. Less populated is the universe of A2B agonists, but really promising for the involvement in ischemic preconditioning. A summary of the most significant advancements in the synthesis of new compounds and of the principal structure activity relationships is reported. The xanthine-based A2B antagonists currently show the better profile of affinity and selectivity, as CVT-6883 (CVT-Therapeutics: Ki(A2B)=22 nM, and selectivity higher than 50-fold over other subtypes), MRE-2029-F20 (Baraldis group: Ki(A2B)=5.5 nM, selectivity > 180 fold), LAS38096 (Almirall Prodesfarma: Ki(A2B)=17 nM, selectivity > 60 fold), OSIP339391 (OSI Pharmaceuticals: Ki(A2B)=0.5 nM, selectivity > 80 fold), PSB601 (Bonn University: Ki(A2B)=3.6 nM, selectivity > 140 fold) and the deazaxanthine 32 of Carottis group (Ki(A2B)=11 nM, selectivity > 90 fold). Other recently emerging scaffolds with promising biological profiles are described. With regard to the agonists, many research groups are involved in the discovery of useful agonist radioligands, but the only example of potent and rather selective A2B agonists are compound 65, recently synthesized, and BAY-60-6583, that is under preclinical phase investigation.
Keywords: A2B, A2B antagonist, A2B agonist, A2B receptor, CVT-6883, MRE-2029-F20, LAS38096, OSIP339391, PSB601, BAY-60-6583, Asthma, inflammation, angiogenic diseases, atherosclerosis, cardioprotection, tumor
Current Topics in Medicinal Chemistry
Title: A2B Receptor Ligands: Past, Present and Future Trends
Volume: 10 Issue: 9
Author(s): G. Ortore and A. Martinelli
Affiliation:
Keywords: A2B, A2B antagonist, A2B agonist, A2B receptor, CVT-6883, MRE-2029-F20, LAS38096, OSIP339391, PSB601, BAY-60-6583, Asthma, inflammation, angiogenic diseases, atherosclerosis, cardioprotection, tumor
Abstract: A2B adenosine receptors have been investigated in recent years as potential target for the treatment of different pathologies. The involvement of this receptor in processes such as interleukins secretion, Ca2+ mobilization, hepatic glucose regulation, tumor vascularisation, and cardioprotection have stimulated many researchers to develop specific agonists and antagonists. For many years, the lack of potent and selective A2B ligands precluded a deep exploration of their therapeutic prospective; at present, much progress in the field of antagonists led to preclinical studies for different compounds. Less populated is the universe of A2B agonists, but really promising for the involvement in ischemic preconditioning. A summary of the most significant advancements in the synthesis of new compounds and of the principal structure activity relationships is reported. The xanthine-based A2B antagonists currently show the better profile of affinity and selectivity, as CVT-6883 (CVT-Therapeutics: Ki(A2B)=22 nM, and selectivity higher than 50-fold over other subtypes), MRE-2029-F20 (Baraldis group: Ki(A2B)=5.5 nM, selectivity > 180 fold), LAS38096 (Almirall Prodesfarma: Ki(A2B)=17 nM, selectivity > 60 fold), OSIP339391 (OSI Pharmaceuticals: Ki(A2B)=0.5 nM, selectivity > 80 fold), PSB601 (Bonn University: Ki(A2B)=3.6 nM, selectivity > 140 fold) and the deazaxanthine 32 of Carottis group (Ki(A2B)=11 nM, selectivity > 90 fold). Other recently emerging scaffolds with promising biological profiles are described. With regard to the agonists, many research groups are involved in the discovery of useful agonist radioligands, but the only example of potent and rather selective A2B agonists are compound 65, recently synthesized, and BAY-60-6583, that is under preclinical phase investigation.
Export Options
About this article
Cite this article as:
Ortore G. and Martinelli A., A2B Receptor Ligands: Past, Present and Future Trends, Current Topics in Medicinal Chemistry 2010; 10 (9) . https://dx.doi.org/10.2174/156802610791268747
DOI https://dx.doi.org/10.2174/156802610791268747 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Understanding the Multifaceted Role of Inflammatory Mediators in Ischemic Stroke
Current Medicinal Chemistry Macrophage Polarization as a Therapeutic Target in Myocardial Infarction
Current Drug Targets Editorial [Hot Topic: Nitric Oxide (Guest Editor: Greg Thatcher)]
Current Topics in Medicinal Chemistry 23Na Magnetic Resonance Imaging for the Determination of Myocardial Viability: The Status and the Challenges
Current Vascular Pharmacology The Bax Inhibitor-1 (BI-1) Family in Apoptosis and Tumorigenesis
Current Molecular Medicine Enkephalin-Fentanyl Multifunctional Opioids as Potential Neuroprotectants for Ischemic Stroke Treatment
Current Pharmaceutical Design Management of Inflammation by Natural Polyphenols: A Comprehensive Mechanistic Update
Current Medicinal Chemistry Remote Preconditioning- Endocrine Factors in Organ Protection Against Ischemic Injury
Endocrine, Metabolic & Immune Disorders - Drug Targets Iron and Iron Chelators: A Review on Potential Effects on Skin Aging
Current Aging Science MicroRNAs in the Blood-Brain Barrier in Hypoxic-Ischemic Brain Injury
Current Neuropharmacology Targeting Stenosis with Nucleotide-Hydrolyzing Enzymes
Current Pharmaceutical Biotechnology Synthesis and Biological Activity of Prostaglandin Analogs Containing Heteroatoms in the Cyclopentane Ring
Current Organic Chemistry Brainstem Neuropeptides and Vagal Protection of the Gastric Mucosal Against Injury: Role of Prostaglandins, Nitric Oxide and Calcitonin-Gene Related Peptide in Capsaicin Afferents
Current Medicinal Chemistry PI-3 Kinase-PTEN Signaling Node: An Intercept Point for the Control of Angiogenesis
Current Pharmaceutical Design Marrow Stromal Cells: Implications in Health and Disease in the Nervous System
Current Molecular Medicine The Activation and Function of Autophagy in Alcoholic Liver Disease
Current Molecular Pharmacology Out-of-Hospital Cardiac Arrest –Optimal Management
Current Cardiology Reviews Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca<sup>2+</sup> Sensitivity
Current Vascular Pharmacology Chemokines and Atherosclerotic Plaque Progression: Towards Therapeutic Targeting?
Current Pharmaceutical Design Subcutaneous Immunoglobulins: A Promising Alternative for Immunomodulation?
Current Pharmaceutical Design