5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[4-[[(2R)-2-acetamido-3-[(4-isothiocyanatophenyl)methylamino]-3-oxopropoxy]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl]pentanamide | 1192590-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 生物素及其衍生物
• 英文名称: 5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[4-[[(2R)-2-acetamido-3-[(4-isothiocyanatophenyl)methylamino]-3-oxopropoxy]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl]pentanamide
• CAS: 1192590-46-7
• 化学式: C₃₄H₄₉N₉O₈S₂
• 分子量: 775.951
• InChiKey: WNIMTOUCPIZYIU-GIGUTINRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  53
• 可旋转键数：
  26
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  266
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  N-[2-[2-[2-(2-叠氮乙氧基)乙氧基]乙氧基]乙基]生物素胺 、 (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 15.0h， 以51%的产率得到5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[4-[[(2R)-2-acetamido-3-[(4-isothiocyanatophenyl)methylamino]-3-oxopropoxy]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl]pentanamide
  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