Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycarbonylimidazol-1-ylmethyl)decahydroiso-quinoline-3-carboxylic ester:: A prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine

被引：46

作者：

Filla, SA ^{[1
]}

Winter, MA

Johnson, KW

Bleakman, D

Bell, MG

Bleisch, TJ

Castaño, AM

Clemens-Smith, A

del Prado, M

Dieckman, DK

Dominguez, E

Escribano, A

Ho, KH

Hudziak, KJ

Katofiasc, MA

Martinez-Perez, JA

Mateo, A

Mathes, BM

Mattiuz, EL

Ogden, AML

Phebus, LA

Stack, DR

Stratford, RE

Ornstein, PL

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

[2] Ctr Invest Lilly, Madrid 28108, Spain

[3] Allelix Biopharmaceut, Mississauga, ON L4V 1P1, Canada

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 20期

关键词：

D O I：

10.1021/jm025548q

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.

引用

页码：4383 / 4386

页数：4

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