Biomaterial Database

Synthesis and Biological Evaluation of Novel Neuroprotective Pyridazine Derivatives as Excitatory Amino Acid Transporter 2 (EAAT2) Activators. 2017

Alessia Chelini, and Simone Brogi, and Marco Paolino, and Angela Di Capua, and Andrea Cappelli, and Gianluca Giorgi, and Mersedeh Farzad, and Lorenzo Di Cesare Mannelli, and Laura Micheli, and Carla Ghelardini, and Maurizio Anzini

Dipartimento di Biotecnologie, Chimica e Farmacia, Università di Siena , Via A. Moro 2, 53100 Siena, Italy.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009437	Neuralgia	Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.	Nerve Pain,Neurodynia,Paroxysmal Nerve Pain,Neuralgia, Atypical,Neuralgia, Iliohypogastric Nerve,Neuralgia, Ilioinguinal,Neuralgia, Perineal,Neuralgia, Stump,Neuralgia, Supraorbital,Neuralgia, Vidian,Neuropathic Pain,Atypical Neuralgia,Atypical Neuralgias,Iliohypogastric Nerve Neuralgia,Iliohypogastric Nerve Neuralgias,Ilioinguinal Neuralgia,Ilioinguinal Neuralgias,Nerve Neuralgia, Iliohypogastric,Nerve Neuralgias, Iliohypogastric,Nerve Pain, Paroxysmal,Nerve Pains,Nerve Pains, Paroxysmal,Neuralgias,Neuralgias, Atypical,Neuralgias, Iliohypogastric Nerve,Neuralgias, Ilioinguinal,Neuralgias, Perineal,Neuralgias, Stump,Neuralgias, Supraorbital,Neuralgias, Vidian,Neurodynias,Neuropathic Pains,Pain, Nerve,Pain, Neuropathic,Pain, Paroxysmal Nerve,Pains, Nerve,Pains, Neuropathic,Pains, Paroxysmal Nerve,Paroxysmal Nerve Pains,Perineal Neuralgia,Perineal Neuralgias,Stump Neuralgia,Stump Neuralgias,Supraorbital Neuralgia,Supraorbital Neuralgias,Vidian Neuralgia,Vidian Neuralgias
D009944	Organoplatinum Compounds	Organic compounds which contain platinum as an integral part of the molecule.	Compounds, Organoplatinum
D011724	Pyridazines	Six-membered rings with two adjacent nitrogen atoms also called 1,2-diazine.
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D004353	Drug Evaluation, Preclinical	Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.	Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D000077150	Oxaliplatin	An organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane, and with an oxalate ligand which is displaced to yield active oxaliplatin derivatives. These derivatives form inter- and intra-strand DNA crosslinks that inhibit DNA replication and transcription. Oxaliplatin is an antineoplastic agent that is often administered with FLUOROURACIL and FOLINIC ACID in the treatment of metastatic COLORECTAL NEOPLASMS.	Platinum(2+) ethanedioate (1R,2R)-1,2-cyclohexanediamine (1:1:1),1,2-Diaminocyclohexane Platinum Oxalate,1,2-Diamminocyclohexane(trans-1)oxolatoplatinum(II),ACT 078,ACT-078,Cis-oxalato-(trans-l)-1,2-diaminocyclohexane-platinum(II),Eloxatin,Eloxatine,L-OHP Cpd,Oxalato-(1,2-cyclohexanediamine)platinum II,Oxaliplatin, (SP-4-2-(1R-trans))-isomer,Oxaliplatin, (SP-4-2-(1S-trans))-isomer,Oxaliplatin, (SP-4-3-(cis))-isomer,Oxaliplatine,Platinum(II)-1,2-cyclohexanediamine Oxalate,1,2 Diaminocyclohexane Platinum Oxalate,ACT078
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D050491	Glutamate Plasma Membrane Transport Proteins	A family of plasma membrane neurotransmitter transporter proteins that couple the uptake of GLUTAMATE with the import of SODIUM ions and PROTONS and the export of POTASSIUM ions. In the CENTRAL NERVOUS SYSTEM they regulate neurotransmission through synaptic reuptake of the excitatory neurotransmitter glutamate. Outside the central nervous system they function as signal mediators and regulators of glutamate metabolism.	Neurotransmitter Transport Proteins, Glutamate-Specific,Neurotransmitter Transporters, Glutamate-Specific,EAAT Proteins,Excitatory Amino Acid Transport Proteins,Excitatory Amino Acid Transporter Proteins,Glutamate Plasma Membrane Transporter Proteins,Sodium-Glutamate Cotransporter,Sodium-Glutamate Transporter,Cotransporter, Sodium-Glutamate,Glutamate-Specific Neurotransmitter Transporters,Neurotransmitter Transport Proteins, Glutamate Specific,Neurotransmitter Transporters, Glutamate Specific,Sodium Glutamate Cotransporter,Sodium Glutamate Transporter,Transporters, Glutamate-Specific Neurotransmitter