PREPARATION AND ANTICONVULSANT ACTIVITY OF A SERIES OF FUNCTIONALIZED ALPHA-HETEROATOM-SUBSTITUTED AMINO-ACIDS

被引：62

作者：

KOHN, H ^{[1
]}

SAWHNEY, KN ^{[1
]}

LEGALL, P ^{[1
]}

ROBERTSON, DW ^{[1
]}

LEANDER, JD ^{[1
]}

机构：

[1] ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 08期

关键词：

D O I：

10.1021/jm00112a020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent anticonvulsant activity has been reported for (R,S)-2-acetamido-N-benzyl-2-methylacetamide (2a). Select alpha-heteroatom substituted derivatives of 2a have been prepared (26 examples) in which the alpha-methyl group has been replaced by nitrogen (3a-q), oxygen (3r-u), and sulfur (3v-z) containing moieties. The functionalized amino acid derivatives were evaluated in the maximal electroshock seizure (MES) and horizontal screen (tox) tests in mice. The most active compounds were (R,S)-2-acetamido-N-benzyl-2-(methoxyamino)acetamide (31), and (R,S)-2-acetamido-N-benzyl-2-(methoxymethylamino)acetamide (3n). After ip administration, the MES ED50 values for 31 (6.2 mg/kg) and 3n (6.7 mg/kg) compared favorably with phenytoin (9.50 mg/kg).

引用

页码：2444 / 2452

页数：9

共 19 条

[1] DIFFERENTIALLY PROTECTED ALPHA-AMINOGLYCINE [J].