NMDA受体
化学
抗惊厥药
甘氨酸
敌手
立体化学
芳基
放射性配体
化学合成
药理学
体外
受体
氨基酸
生物化学
神经科学
生物
癫痫
有机化学
烷基
作者
Zhang‐Lin Zhou,James M Navratil,Sui Xiong Cai,Edward R. Whittemore,Stephen Espitia,Jon E. Hawkinson,Minhtam Tran,Richard M. Woodward,Eckard Weber,John F. W. Keana
标识
DOI:10.1016/s0968-0896(01)00115-8
摘要
A series of 5-, 6-, 7- and 8-aza analogues of 3-aryl-4-hydroxyquinolin-2(1H)-one was synthesized and assayed as NMDA/glycine receptor antagonists. The in vitro potency of these antagonists was determined by displacement of the glycine site radioligand [3H]5,7-dicholorokynurenic acid ([3H]DCKA) in rat brain cortical membranes. Selected compounds were also tested for functional antagonism using electrophysiological assays in Xenopus oocytes expressing cloned NMDA receptor (NR) 1A/2C subunits. Among the 5-, 6-, 7-, and 8-aza-3-aryl-4-hydroxyquinoline-2(1H)-ones investigated, 5-aza-7-chloro-4-hydroxy-3-(3-phenoxyphenyl)quinolin-2-(1H)-one (13i) is the most potent antagonist, having an IC50 value of 110 nM in [3H]DCKA binding and a Kb of 11 nM in the electrophysiology assay. Compound 13i is also an active anticonvulsant when administered systemically in the mouse maximum electroshock-induced seizure test (ED50=2.3 mg/kg, IP).
科研通智能强力驱动
Strongly Powered by AbleSci AI