Abstract
The excitatory neurotransmitter glutamate interacts with ionotropic and metabotropic receptors that mediate a variety of normal signalling processes in the brain. However, excessive stimulation of these receptors appears to be involved in neurodegenerative processes, at least in animal models. Ionotropic glutamate receptors can be divided into NMDA and non-NMDA (AMPA and KA) subtypes on the basis of t heir preferential affinities for the synthetic excitatory aminoacids N-methyl-D-aspartic acid (NMDA) or 2-amino-3- (3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA), respectively. Although most of the early evidence favoured a role for NMDA receptors in the excitotoxic processes, it has been recognised that AMPA receptors may also be significantly involved in neuronal death. As a consequence, the synthesis of specific AMPA antagonists has raised much interest as source of potential drugs for epilepsy and acute and chronic neurodegenerative diseases. The discovery of RPR117824, a potent and selective AMPA receptors antagonist endowed with anticonvulsant and neuroprotective properties, induced growing interest on dihydro-4-oxo-4Himidazo[ 1,2-a]indeno[1,2-e]pyrazine series. This review covers the main chemical course leading to the most promising compounds as well as the pharmacological properties of this original class of AMPA receptor antagonists.
Keywords: Dihydro-4-oxo-4HImidazo, propionic acid (AMPA), 3-hydroxy-5-methylisoxazol-4-yl
Mini-Reviews in Medicinal Chemistry
Title: Synthesis and Structure-Activity Relationships of 4,10-Dihydro-4-oxo-4HImidazo[ 1,2-a]Indeno[1,2-e]Pyrazine Derivatives: Highly Potent and Selective AMPA Receptor Antagonists with In Vivo Activity
Volume: 4 Issue: 2
Author(s): Jean-Marie Stutzmann, Marc Vuilhorgne and Serge Mignani
Affiliation:
Keywords: Dihydro-4-oxo-4HImidazo, propionic acid (AMPA), 3-hydroxy-5-methylisoxazol-4-yl
Abstract: The excitatory neurotransmitter glutamate interacts with ionotropic and metabotropic receptors that mediate a variety of normal signalling processes in the brain. However, excessive stimulation of these receptors appears to be involved in neurodegenerative processes, at least in animal models. Ionotropic glutamate receptors can be divided into NMDA and non-NMDA (AMPA and KA) subtypes on the basis of t heir preferential affinities for the synthetic excitatory aminoacids N-methyl-D-aspartic acid (NMDA) or 2-amino-3- (3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA), respectively. Although most of the early evidence favoured a role for NMDA receptors in the excitotoxic processes, it has been recognised that AMPA receptors may also be significantly involved in neuronal death. As a consequence, the synthesis of specific AMPA antagonists has raised much interest as source of potential drugs for epilepsy and acute and chronic neurodegenerative diseases. The discovery of RPR117824, a potent and selective AMPA receptors antagonist endowed with anticonvulsant and neuroprotective properties, induced growing interest on dihydro-4-oxo-4Himidazo[ 1,2-a]indeno[1,2-e]pyrazine series. This review covers the main chemical course leading to the most promising compounds as well as the pharmacological properties of this original class of AMPA receptor antagonists.
Export Options
About this article
Cite this article as:
Stutzmann Jean-Marie, Vuilhorgne Marc and Mignani Serge, Synthesis and Structure-Activity Relationships of 4,10-Dihydro-4-oxo-4HImidazo[ 1,2-a]Indeno[1,2-e]Pyrazine Derivatives: Highly Potent and Selective AMPA Receptor Antagonists with In Vivo Activity, Mini-Reviews in Medicinal Chemistry 2004; 4 (2) . https://dx.doi.org/10.2174/1389557043487411
DOI https://dx.doi.org/10.2174/1389557043487411 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
Related Articles
-
Role of Pharmacogenomics in Antiepileptic Drug Therapy: Current Status and Future Perspectives
Current Pharmaceutical Design Astroglial Connexins in Neurological and Neuropsychological Disorders and Radiation Exposure
Current Medicinal Chemistry Histamine H3 Receptor: A Potential Drug Target for the Treatment of Central Nervous System Disorders
Current Drug Targets - CNS & Neurological Disorders Patent Selections
Recent Patents on CNS Drug Discovery (Discontinued) Endocannabinoid System: A Multi-Facet Therapeutic Target
Current Clinical Pharmacology Curcumin: Not So Spicy After All
Mini-Reviews in Medicinal Chemistry Principles and Applications of Diffuse Optical Imaging for the Brain
Current Medical Imaging Mouse Models of Genomic Syndromes as Tools for Understanding the Basis of Complex Traits: An Example with the Smith-Magenis and the Potocki-Lupski Syndromes
Current Genomics Evolution of the Human Ion Channel Set
Combinatorial Chemistry & High Throughput Screening Anticonvulsant Activity of A Novel Series of 2,5-Disubstituted 1,3,4-Oxadiazoles: Semicarbazones Based Pharmacophoric Model Studies
Letters in Drug Design & Discovery Tackling the Elusive Challenges Relevant to Conquering the 100-Plus Year Old Problem of Alzheimer’s Disease
Current Alzheimer Research Chemistry and Biology of Cyperus scariosus: An Overview
Current Chemical Biology Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology Metabotropic Glutamate Receptors Modulate Periaqueductal Grey Descending Analgesic System
Central Nervous System Agents in Medicinal Chemistry Understanding Abnormal c-JNK/p38MAPK Signaling in Amyotrophic Lateral Sclerosis: Potential Drug Targets and Influences on Neurological Disorders
CNS & Neurological Disorders - Drug Targets The Role of Folate-supplementation in Depression: A Narrative Review
Current Psychopharmacology Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review
Current Medicinal Chemistry PET/MR Tomographs: A Review with Technical, Radiochemical and Clinical Perspectives
Current Radiopharmaceuticals Severe Preeclampsia
Current Women`s Health Reviews Pharmacological Characterisation and Modulation of Neuroplasticity in Humans
Current Neuropharmacology