Synthesis and Biological Evaluation of Novel Neuroprotective Pyridazine Derivatives as Excitatory Amino Acid Transporter 2 (EAAT2) Activators
Author(s)
Chelini, A
Brogi, S
Paolino, M
Di Capua, A
Cappelli, A
Giorgi, G
Farzad, M
Di Cesare Mannelli, L
Micheli, L
Ghelardini, C
Anzini, M
Griffith University Author(s)
Year published
2017
Metadata
Show full item recordAbstract
LDN-212320 (3) was found to be a potent EAAT2 activator at a translational level, restoring the normal clearance of glutamate and providing neuronal protection. Since the pharmacologic activation of EAAT2 represents a valuable strategy to relieve neuropathic pain, we synthesized novel activators (4a–f) of EAAT2. Among them 4f, analyzed in comparison with 3 by different paradigms in a rat model of oxaliplatin-induced neuropathic pain, showed the better antihypersensitive profile being able to fully counteract the oxaliplatin-induced neuropathy.LDN-212320 (3) was found to be a potent EAAT2 activator at a translational level, restoring the normal clearance of glutamate and providing neuronal protection. Since the pharmacologic activation of EAAT2 represents a valuable strategy to relieve neuropathic pain, we synthesized novel activators (4a–f) of EAAT2. Among them 4f, analyzed in comparison with 3 by different paradigms in a rat model of oxaliplatin-induced neuropathic pain, showed the better antihypersensitive profile being able to fully counteract the oxaliplatin-induced neuropathy.
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Journal Title
Journal of Medicinal Chemistry
Volume
60
Issue
12
Subject
Medicinal and biomolecular chemistry
Medicinal and biomolecular chemistry not elsewhere classified
Organic chemistry
Pharmacology and pharmaceutical sciences