N-benzyl-1-H-D-aziridine-2-carboxamide | 1085337-44-5

• 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: N-benzyl-1-H-D-aziridine-2-carboxamide
• 英文别名: (R)-N-benzyl aziridine-2-carboxamide
• CAS: 1085337-44-5
• 化学式: C₁₀H₁₂N₂O
• 分子量: 176.218
• InChiKey: CCPIHWLRHUYGOW-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.27
• 重原子数：
  13.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  51.04
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  N-benzyl-1-H-D-aziridine-2-carboxamide 、 乙酸酐 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以5.7 g的产率得到(R)-N-benzyl 1-acetylaziridine-2-carboxamide
  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
• 作为产物：
  描述：

  脱乙酰基去甲基拉科酰胺 在 DTPP 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以1.83 g的产率得到N-benzyl-1-H-D-aziridine-2-carboxamide
  参考文献：
  名称：

  Lacosamide Isothiocyanate-Based Agents: Novel Agents To Target and Identify Lacosamide Receptors

  摘要：

  (R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique: A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with all appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent Seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2.

  DOI：

  10.1021/jm9012054

文献信息

• Ring-Opening of Aziridine-2-Carboxamides with Carbohydrate C1-<i>O</i>-Nucleophiles. Stereoselective Preparation of α- and β-<i>O</i>-Glycosyl Serine Conjugates
  作者：Daniel A. Ryan、David Y. Gin

  DOI：10.1021/ja804589j

  日期：2008.11.19

  The stereoselective formation of the alpha-GalNAc-Ser linkage via the ring opening of aziridine-2-carboxamides with pyranose C1-O-nucleophiles is described. The process is tolerant to the native C2-NHAc group, can be modulated to provide either the alpha- or beta-glycoside through judicious choice of solvent and metal counterion, and is amenable to other classes of O-glycosyl-Ser constructs such as the B-GlcNAc-Ser and alpha-Man-Ser linkages. This coupling reaction also led to the development of the o-allylbenzyl (ABn) moiety as a new C-terminus carboxyl protective group, which allows for the use of novel methods for N- and C-terminus extension of amino acids following carbohydrate conjugation.