SYNTHESIS AND ACTIVITY OF SPIROISOINDOLINES AS NOVEL NONCOMPETITIVE NMDA ANTAGONISTS

被引：24
作者：
BARE, TM
DRAPER, CW
MCLAREN, CD
PULLAN, LM
PATEL, J
PATEL, JB
机构：
[1] ICI Pharmaceuticals Group, A Business Unit, ICI Americas Inc., Wilmington
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1993年 / 3卷 / 01期
关键词：
D O I：
10.1016/S0960-894X(00)80091-8
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of novel spiroisoindolines was designed and synthesized as potential noncompetitive NMDA antagonists. Affinities of these compounds for the noncompetitive NMDA binding site were determined using [H-3]TCP and found to possess IC50s ranging from 0.065 to 17 muM. In vivo testing of 2'-methylspiro-[4,5,6,7-tetrahydrobenzothiophene-4,1'-(1,3-dihydroisoindole)] (43) showed it to antagonize NMDA-induced convulsions, to be neuroprotective in a gerbil model of ischemia, and not to generalize to MK-801 in a drug discrimination paradigm.
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页码：55 / 60
页数：6
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