Pyridazinoquinolinetriones as NMDA glycine-site antagonists with oral antinociceptive activity in a model of neuropathic pain

TM Bare, DG Brown, CL Horchler… - Journal of medicinal …, 2007 - ACS Publications
TM Bare, DG Brown, CL Horchler, M Murphy, RA Urbanek, V Alford, C Barlaam, MC Dyroff…
Journal of medicinal chemistry, 2007ACS Publications
A series of 7-chloro-2, 3-dihydro-2-[1-(pyridinyl) alkyl]-pyridazino [4, 5-b] quinoline-1, 4, 10
(5 H)-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 …
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.
ACS Publications
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