SYNTHESIS AND ANTICONVULSANT ACTIVITY OF IMIDOOXY DERIVATIVES

被引：44

作者：

EDAFIOGHO, IO ^{[1
]}

SCOTT, KR ^{[1
]}

MOORE, JA ^{[1
]}

FARRAR, VA ^{[1
]}

NICHOLSON, JM ^{[1
]}

机构：

[1] HOWARD UNIV,GRAD SCH ARTS & SCI,DEPT CHEM,WASHINGTON,DC 20059

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 01期

关键词：

POTENTIAL ANTICONVULSANTS; AMINOOXYACETIC ACID; CONVULSANT; ANALOGS;

D O I：

10.1021/jm00105a059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Previous results of anticonvulsant activity in several imidooxy carboxylates related to (aminooxy)acetic acid in young chicks, prompted an in-depth reinvestigation of these analogues in mice. A series of 22 succinimidooxy, phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated for anticonvulsant activity by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d), ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which were initially found to be active as anticonvulsants in young chicks were uniformly inactive in the Phase I seizure tests involving maximal electroshock (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)-2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h) evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione (5b), which displayed anti-MES activity and a protective index (TD50/ED50) of > 4.5.

引用

页码：387 / 392

页数：6

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