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
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
-
The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration
Current Neuropharmacology Anti-Inflammatory Activity of Tetracyclines: Applications to Human Disease
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Clinical Applications of Non-Antimicrobial Actions of Tetracyclines in Inflammatory Diseases
Current Drug Therapy Immune Functions of Glia and Neurons in the Central Nervous System
Current Immunology Reviews (Discontinued) Editorial (Thematic Issue: Neurodegeneration, Oxidative Stress, Metabolic Syndrome, Drug Design and Development: Clinical Implications)
CNS & Neurological Disorders - Drug Targets Prevention and Treatment for Chemotherapy-Induced Peripheral Neuropathy: Therapies Based on CIPN Mechanisms
Current Neuropharmacology Experimental Research on Nitric Oxide and the Therapy of Alzheimer Disease: A Challenging Bridge
CNS & Neurological Disorders - Drug Targets Emerging and Alternative Therapies For Parkinson Disease: An Updated Review
Current Pharmaceutical Design The Paths to Neurodegeneration in Genetic Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Common SAR Derived from Linear and Non-linear QSAR Studies on AChE Inhibitors used in the Treatment of Alzheimer's Disease
Current Neuropharmacology Cyclic Nucleotides Signaling and Phosphodiesterase Inhibition: Defying Alzheimer’s Disease
Current Drug Targets Role of Catechol-O-Methyltransferase (COMT)-Dependent Processes in Parkinson’s Disease and L-DOPA Treatment
CNS & Neurological Disorders - Drug Targets Evaluation of the Performance of Manganese Phthalocyanines as Superoxide Dismutase Mimics
Current Analytical Chemistry Current View from Alzheimer Disease to Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Drp1 in Ischemic Neuronal Death: An Unusual Suspect
Current Medicinal Chemistry Heat Shock Proteins as Suppressors of Accumulation of Toxic Prefibrillar Intermediates and Misfolded Proteins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Probenecid: An Emerging Tool for Neuroprotection
CNS & Neurological Disorders - Drug Targets High Throughput Screening for Neurodegeneration and Complex Disease Phenotypes
Combinatorial Chemistry & High Throughput Screening Human Platelet Acetylcholinesterase Inhibition by Cyclophosphamide: A Combined Experimental and Computational Approach
CNS & Neurological Disorders - Drug Targets Self-Assembling Peptide Nanofibrous Scaffolds for Tissue Engineering: Novel Approaches and Strategies for Effective Functional Regeneration
Current Protein & Peptide Science