Pyridazinoquinolinetriones as NMDA Glycine-Site Antagonists with Oral Antinociceptive Activity in a Model of Neuropathic Pain
| Autor: | Edward P. Vacek, Thomas Michael Bare, Martin C. Dyroff, Kathy L. Neilson, Rebecca Urbanek, J. Empfield, Alan S. Kirschner, Christine Barlaam, Joseph Lewis, Chi-Ming C. Lee, Wenhua Xiao, Megan Murphy, Vernon Alford, Janet Marie Forst, Gary Steelman, Shephali Trivedi, Richard A. Keith, Frances M. Mclaren, Dean G. Brown, Keith John Herzog, Horchler Carey |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Pyridines Stereochemistry Analgesic Administration Oral Pain Constriction Pathologic Pharmacology Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley Radioligand Assay Structure-Activity Relationship Receptors Glycine Oral administration Drug Discovery Animals Glycine receptor Analgesics Chemistry Antagonist Brain Peripheral Nervous System Diseases Sciatic Nerve Rats Bioavailability Pyridazines Alkynes Chronic Disease Neuropathic pain Glycine Quinolines Molecular Medicine NMDA receptor |
| Zdroj: | Journal of Medicinal Chemistry. 50:3113-3131 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm060212s |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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