(R)-ethyl 2-acetamido-3-(2-cyclopropylethoxy)propionate | 1239017-26-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-ethyl 2-acetamido-3-(2-cyclopropylethoxy)propionate
• 英文别名: ethyl (2R)-2-acetamido-3-(2-cyclopropylethoxy)propanoate
• CAS: 1239017-26-5
• 化学式: C₁₂H₂₁NO₄
• 分子量: 243.303
• InChiKey: GNOBVOVCOQGSFJ-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-环丙基乙醇 、 diethoxyltriphenylphosphorane 、 乙酸酐 、 D-丝氨酸甲酯盐酸盐 在 三乙胺 作用下， 生成 (R)-methyl 2-acetamido-3-(2-cyclopropylethoxy)propionate 、 (R)-ethyl 2-acetamido-3-(2-cyclopropylethoxy)propionate
  参考文献：
  名称：

  The Structure−Activity Relationship of the 3-Oxy Site in the Anticonvulsant (R)-N-Benzyl 2-Acetamido-3-methoxypropionamide

  摘要：

  Lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-1) is a low molecular weight anticonvulsant recently introduced in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. In this study, we define the structure-activity relationship (SAR) for the compound's 3-oxy site, Placement of small nonpolar, nonbulky substituents at the 3-oxy site provided compounds with pronounced seizure protection in the maximal electroshock (MES) seizure test with activities similar to (R)-1. The anticonvulsant activity loss that accompanied introduction of larger moieties at the 3-oxy site in (R)-1 was offset, in part, by including unsaturated groups at this position. Our findings were similar to a recently reported SAR study of the 4'-benzylamide site in (R)-1 (J. Med. Chem. 2010, 53, 1288-1305). Together, these results indicate that both the 3-oxy and 4'-benzylamide positions in (R)-1 can accommodate nonbulky, hydrophobic groups and still retain pronounced anticonvulsant activities in rodents in the MES seizure model.

  DOI：

  10.1021/jm100508m

文献信息

• The Structure−Activity Relationship of the 3-Oxy Site in the Anticonvulsant (<i>R</i>)-<i>N</i>-Benzyl 2-Acetamido-3-methoxypropionamide
  作者：Pierre Morieux、Christophe Salomé、Ki Duk Park、James P. Stables、Harold Kohn

  DOI：10.1021/jm100508m

  日期：2010.8.12

  Lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-1) is a low molecular weight anticonvulsant recently introduced in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. In this study, we define the structure-activity relationship (SAR) for the compound's 3-oxy site, Placement of small nonpolar, nonbulky substituents at the 3-oxy site provided compounds with pronounced seizure protection in the maximal electroshock (MES) seizure test with activities similar to (R)-1. The anticonvulsant activity loss that accompanied introduction of larger moieties at the 3-oxy site in (R)-1 was offset, in part, by including unsaturated groups at this position. Our findings were similar to a recently reported SAR study of the 4'-benzylamide site in (R)-1 (J. Med. Chem. 2010, 53, 1288-1305). Together, these results indicate that both the 3-oxy and 4'-benzylamide positions in (R)-1 can accommodate nonbulky, hydrophobic groups and still retain pronounced anticonvulsant activities in rodents in the MES seizure model.