Abstract
Due to the clearly demonstrated receptor-receptor interaction between adenosine A2A and dopamine D2 receptors in the basal ganglia, the discovery and development of potent and selective A2A adenosine receptor antagonists became, in the last ten years, an attractive field of research to discovery new drugs for the treatment of neurodegenerative disorders, such as Parkinsons disease. Different compounds have been deeply investigated as A2A adenosine receptor antagonists, which could be classified in two great families: xanthine derivatives and nitrogen poliheterocyclic systems. These studies led to the discovery of some highly potent and selective A2A adenosine receptor antagonists such as ZM241385, SCH58261 and some xanthine derivatives (KW6002), which have been used as pharmacological tools for studying this receptor subtype. However, those compounds showed some problems that do not permit their use in clinical studies, such as poor water solubility (SCH58261, and xanthine derivatives) or good affinity for A2B adenosine receptor subtype (ZM241385). In the last few years great efforts have been made to overcome these problems, trying to optimize not only the pharmacological profile but also the pharmacokinetic character of this class of compounds. The aim of this report is to briefly summarize the recent progress made in this attractive field of research.
Keywords: adenosine receptors, antagonists, xanthine derivatives, heterocyclic derivatives, neurodegenerative disorders
Current Topics in Medicinal Chemistry
Title: Medicinal Chemistry of A2A Adenosine Receptor Antagonists
Volume: 3 Issue: 4
Author(s): Barbara Cacciari, Giorgia Pastorin and Giampiero Spalluto
Affiliation:
Keywords: adenosine receptors, antagonists, xanthine derivatives, heterocyclic derivatives, neurodegenerative disorders
Abstract: Due to the clearly demonstrated receptor-receptor interaction between adenosine A2A and dopamine D2 receptors in the basal ganglia, the discovery and development of potent and selective A2A adenosine receptor antagonists became, in the last ten years, an attractive field of research to discovery new drugs for the treatment of neurodegenerative disorders, such as Parkinsons disease. Different compounds have been deeply investigated as A2A adenosine receptor antagonists, which could be classified in two great families: xanthine derivatives and nitrogen poliheterocyclic systems. These studies led to the discovery of some highly potent and selective A2A adenosine receptor antagonists such as ZM241385, SCH58261 and some xanthine derivatives (KW6002), which have been used as pharmacological tools for studying this receptor subtype. However, those compounds showed some problems that do not permit their use in clinical studies, such as poor water solubility (SCH58261, and xanthine derivatives) or good affinity for A2B adenosine receptor subtype (ZM241385). In the last few years great efforts have been made to overcome these problems, trying to optimize not only the pharmacological profile but also the pharmacokinetic character of this class of compounds. The aim of this report is to briefly summarize the recent progress made in this attractive field of research.
Export Options
About this article
Cite this article as:
Cacciari Barbara, Pastorin Giorgia and Spalluto Giampiero, Medicinal Chemistry of A2A Adenosine Receptor Antagonists, Current Topics in Medicinal Chemistry 2003; 3 (4) . https://dx.doi.org/10.2174/1568026033392183
DOI https://dx.doi.org/10.2174/1568026033392183 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Medicinal Chemistry Advancement in Life-Threatening Diseases
The current issue will highlight concise reports that specify ground-breaking insights, including the novel discovery of drug targets and their action mechanism or drugs of novel classes. These are projected to encourage medicinal chemistry future efforts to address the most challenging medical needs. The current issue highlights further efforts to ...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
-
Tau Pathology and Future Therapeutics
Current Alzheimer Research Glial Cell: A Potential Target for Cellular and Drug Based Therapy in Various CNS Diseases
Current Pharmaceutical Design Patents on Therapeutic and Cosmetic Applications of Bioactives of Crocus Sativus L. and their Production through Synthetic Biology Methods: A Review
Recent Patents on Biotechnology Protein Misfolding and Aggregation in Alzheimer's Disease and Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Retinal Degenerations: From Cell Signaling to Cell Therapy; Pre-Clinical and Clinical Issues
Current Gene Therapy Nanotechnology and Alzheimer's Disease: What has been Done and What to Do'
Current Medicinal Chemistry Prediction of Gene Co-Expression by Quantifying Heterogeneous Features
Current Bioinformatics Innate Immune Surveillance in the Central Nervous System Following Legionella pneumophila Infection
CNS & Neurological Disorders - Drug Targets Effects of Coenzyme Q and Creatine Supplementation on Brain Energy Metabolism in Rats Exposed to Chronic Cerebral Hypoperfusion
Current Alzheimer Research Patent Annotations
Recent Patents on CNS Drug Discovery (Discontinued) Lipids at the Cross-road of Autoimmunity in Multiple Sclerosis
Current Medicinal Chemistry In silico Modeling Studies of 5-HT2B Antagonistic Activity of 2-(2- phenylethyl)chromone Derivatives from Cucumis melo Seeds
Letters in Drug Design & Discovery The Concept of “Neuroprotection” in Neurological Diseases
Current Neuropharmacology New Technologies for Drug Delivery Across the Blood Brain Barrier
Current Pharmaceutical Design Metabolomic-Driven Elucidation of Serum Disturbances Associated with Alzheimer's Disease and Mild Cognitive Impairment
Current Alzheimer Research Nuclear Factor Erythroid 2 - Related Factor 2 Signaling in Parkinson Disease: A Promising Multi Therapeutic Target Against Oxidative Stress, Neuroinflammation and Cell Death
CNS & Neurological Disorders - Drug Targets Glutamate Transporter 1: Target for the Treatment of Alcohol Dependence
Current Medicinal Chemistry The Animal Models of Dementia and Alzheimer’s Disease for Pre-Clinical Testing and Clinical Translation
Current Alzheimer Research The Proinflammatory Cytokine GITRL Contributes to TRAIL-mediated Neurotoxicity in the HCN-2 Human Neuronal Cell Line
Current Alzheimer Research Structural and Molecular Basis of Carbohydrate-Protein Interaction Systems as Potential Therapeutic Targets
Current Pharmaceutical Design