Pyridazinoquinolinetriones as NMDA Glycine-Site Antagonists with Oral Antinociceptive Activity in a Model of Neuropathic Pain
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- 作者：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. K
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：June 28, 2007
- 年：2007
- 卷：50
- 期：13
- 页码：3113 - 3131
- 全文大小：297K
- 年卷期：v.50,no.13(June 28, 2007)
- ISSN：1520-4804
文摘
A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones weresynthesized 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 neuropathicpain and found to have potent activity when dosed orally.