Identification of novel ligands for the gabapentin binding site on the α2δ subunit of a calcium channel and their evaluation as anticonvulsant agents

被引：77

作者：

Bryans, JS ^{[1
]}

Davies, N ^{[1
]}

Gee, NS ^{[1
]}

Dissanayake, VUK ^{[1
]}

Ratcliffe, GS ^{[1
]}

Horwell, DC ^{[1
]}

Kneen, CO ^{[1
]}

Morrell, AI ^{[1
]}

Oles, RJ ^{[1
]}

O'Toole, JC ^{[1
]}

Perkins, GM ^{[1
]}

Singh, L ^{[1
]}

Suman-Chauhan, N ^{[1
]}

O'Neill, JA ^{[1
]}

机构：

[1] Parke Davis Neurosci Res Ctr, Cambridge CB2 2QB, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 11期

关键词：

D O I：

10.1021/jm970649n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

As part of a program to investigate the structure-activity relationships of Gabapentin (Neurontin), a number of alkylated analogues were synthesized and evaluated in vitro for binding to the Gabapentin binding site located on the alpha(2) delta subunit of a calcium channel. A number of other bridged and heterocyclic analogues are also reported along with their in vitro data. Two compounds showing higher affinity than Gabapentin were selected for evaluation in an animal model of epilepsy. One of these compounds, cis-(1S,3R)-(1-(aminomethyl)-3-methylcyclohexyl)acetic acid hydrochloride (19), was shown to be effective in this model with a profile similar to that of Gabapentin itself.

引用

页码：1838 / 1845

页数：8

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