Lacosamide has been submitted for regulatory approval in the United States and Europe for the treatment of epilepsy. Previous synthetic methods did not permit the elaboration of the structure-activity relationship (SAR) for the 3-oxy site in lacosamide. We report an expedient five-step stereospecific synthesis for N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide analogs beginning with D-serine methyl ester. The procedure incorporated alkyl (e.g. methyl, primary, secondary, and tertiary) and aryl groups at this position. The SAR for the 3-oxy site showed maximal activity in animal seizure models for small 3-alkoxy substituents.

中文翻译：

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N-苄基 (2R)-2-乙酰氨基-3-氧取代丙酰胺衍生物的合成和抗惊厥活性。

拉考沙胺已在美国和欧洲提交监管部门批准用于治疗癫痫。以前的合成方法不允许详细说明拉科酰胺中 3-氧位点的构效关系 (SAR)。我们报告了以 D-丝氨酸甲酯开头的 N-苄基 (2R)-2-乙酰氨基-3-氧取代丙酰胺类似物的权宜五步立体定向合成。该程序在该位置并入烷基（例如甲基、伯、仲和叔）和芳基。3-氧位点的 SAR 在小 3-烷氧基取代基的动物癫痫模型中显示出最大的活性。