Pyridazinoquinolinetriones as NMDA Glycine-Site Antagonists with Oral Antinociceptive Activity in a Model of Neuropathic Pain
journal contribution
posted on 2007-06-28, 00:00 authored by Thomas M. Bare, Dean G. Brown, Carey L. Horchler, Megan Murphy, Rebecca A. Urbanek, Vernon Alford, Christine Barlaam, Martin C. Dyroff, James B. Empfield, Janet M. Forst, Keith J. Herzog, Richard A. Keith, Alan S. Kirschner, Chi-Ming C. Lee, Joseph Lewis, Frances M. McLaren, Kathy L. Neilson, Gary B. Steelman, Shephali Trivedi, Edward P. Vacek, Wenhua XiaoA 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.
