Abstract
Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands of the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 7-[18F]fluoro-6-cyano-QX ([18F]FCQX) with radiochemical yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyanoand nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7- dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.
Keywords: AMPA receptor, fluorine-18, glutamate receptor, positron emission tomography, quinoxalinedione, radiofluorination.
Graphical Abstract
Medicinal Chemistry
Title:Synthesis and First Evaluation of [18F]Fluorocyano- and [18F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists
Volume: 11 Issue: 1
Author(s): Sebastian Olma, Johannes Ermert, Wiebke Sihver and Heinz H. Coenen
Affiliation:
Keywords: AMPA receptor, fluorine-18, glutamate receptor, positron emission tomography, quinoxalinedione, radiofluorination.
Abstract: Derivatives of quinoxalinedione (QX) were chosen as chemical lead for the development of new radioligands of the AMPA receptor, since there are several examples of QX-derivatives with high affinity. The radiosyntheses of the new compounds 6-[18F]fluoro-7-nitro-QX ([18F]FNQX) and 7-[18F]fluoro-6-cyano-QX ([18F]FCQX) with radiochemical yields of 8 ± 2 and 3 ± 2 %, respectively, as well as the evaluation of their binding properties to the AMPA-receptor were performed. A comparison of the Ki-values of the new QX-derivatives FCQX and FNQX with mono-substituted cyanoand nitro-QX shows negligibly small differences of affinity (within the range of 1.4 to 5 µM), but exhibits a tenfold lower affinity than derivatives with two electron withdrawing groups like the 7-cyano-6-nitro-compound CNQX and the 6,7- dinitro compound DNQX. Thus, with respect to the low affinity and a high non-specific binding with in vitro and ex vivo autoradiographic studies, the new compounds do not lend themselves for in vivo imaging.
Export Options
About this article
Cite this article as:
Olma Sebastian, Ermert Johannes, Sihver Wiebke and Coenen H. Heinz, Synthesis and First Evaluation of [18F]Fluorocyano- and [18F]Fluoronitroquinoxalinedione as Putative AMPA Receptor Antagonists, Medicinal Chemistry 2015; 11 (1) . https://dx.doi.org/10.2174/1573406410666140428151318
DOI https://dx.doi.org/10.2174/1573406410666140428151318 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
How Accurate is Subjective Reporting of Childhood Sleep Patterns? A Review of the Literature and Implications for Practice
Current Pediatric Reviews Synaptic Potentiation and Sleep Need: Clues from Molecular and Electrophysiological Studies
Current Topics in Medicinal Chemistry Overview of Pediatric Epilepsy
Current Pediatric Reviews Chemo-botanical and Neurological Accounts of Some Ayurvedic Plants Useful in Mental Health
The Natural Products Journal ABC Transporters in Neurological Disorders: An Important Gateway for Botanical Compounds Mediated Neuro-Therapeutics
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: Measurements of ABC Transporters at the Blood-Brain Barrier: Novel Methods and Applications)
Current Pharmaceutical Design <i>In Vivo</i> Longitudinal Monitoring of Changes in the Corpus Callosum Integrity During Disease Progression in a Mouse Model of Alzheimer’s Disease
Current Alzheimer Research Growth Inhibition of Human Non-Small Lung Cancer Cells H460 By Green Tea and Ginger Polyphenols
Anti-Cancer Agents in Medicinal Chemistry Food Selectivity, Gastrointestinal Symptoms and Urine Organic Acids in Autism Spectrum Disorder: A Pilot Study
Current Nutrition & Food Science Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A New Route in the Fight Against COVID-19?
Current Pharmaceutical Design Age-Specific Impairment of Morris Water Maze Performance Following Neonatal Exposure to Magnetic Resonance Image in Rats
Current Neurovascular Research Comparative Studies on Phospholipase A2 as a Marker for Gut Microbiota- liver-brain Axis in a rodent Model of Autism
Current Proteomics MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)
Current Neurovascular Research Editorial [Hot topic: The Urokinase Receptor System as Strategic Therapeutic Target: Challenges for the 21st Century (Executive Guest Editor: Bernard Degryse)]
Current Pharmaceutical Design Malononitrile as a Key Reagent in Multicomponent Reactions for the Synthesis of Pharmaceutically Important Pyridines
Current Organic Chemistry Editorial (Thematic Issue: GABAergic Modulation as Treatment Strategy: Consideration of Several Diseases)
Current Pharmaceutical Design Heart Rate Variability Based Prediction of Personalized Drug Therapeutic Response: The Present Status and the Perspectives
Current Topics in Medicinal Chemistry The Benefit of Prescribing Vitamin D as Add on Therapy on the Electrocardiographic Changes in Epileptic Patients
Current Clinical Pharmacology Piroxicam: Source for Synthesis of Central Nervous System (CNS) Acting Drugs
Central Nervous System Agents in Medicinal Chemistry Glycoconjugates: Roles in Neural Diseases Caused by Exogenous Pathogens
CNS & Neurological Disorders - Drug Targets