Abstract
A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones were synthesized and found to have potent activity at the glycine site of the NMDA receptor. In some cases, these compounds possessed poor aqueous solubility that may have contributed to poor rat oral bioavailability. Subsequently, compounds have been identified with improved aqueous solubility and oral bioavailability. Several of these compounds were examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and found to have potent activity when dosed orally.
MeSH terms
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Administration, Oral
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Alkynes / chemical synthesis
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Alkynes / chemistry
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Alkynes / pharmacology
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Analgesics / chemical synthesis*
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Analgesics / chemistry
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Analgesics / pharmacology
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Animals
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Brain / metabolism
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Chronic Disease
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Constriction, Pathologic / complications
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Male
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Pain / drug therapy*
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Pain / etiology
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Peripheral Nervous System Diseases / drug therapy*
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Peripheral Nervous System Diseases / etiology
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology
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Pyridines / chemical synthesis
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Pyridines / chemistry
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Pyridines / pharmacology
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Quinolines / chemical synthesis*
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Quinolines / chemistry
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Quinolines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptors, Glycine / antagonists & inhibitors*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
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Sciatic Nerve / pathology
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Structure-Activity Relationship
Substances
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Alkynes
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Analgesics
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Pyridazines
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Pyridines
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Quinolines
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Receptors, Glycine
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Receptors, N-Methyl-D-Aspartate