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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