(R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide | 1192590-38-7

• 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)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide
• 英文别名: (R)-N-(4-isothiocyanato)benzyl-2-acetamido-3-(prop-2-ynyloxy)propionamide；(R)-N-(4-isothiocyanatobenzyl)-2-acetamido-3-(prop-2-ynyloxy)propanamide；(2R)-2-acetamido-N-[(4-isothiocyanatophenyl)methyl]-3-prop-2-ynoxypropanamide
• CAS: 1192590-38-7
• 化学式: C₁₆H₁₇N₃O₃S
• 分子量: 331.395
• InChiKey: MVTYKCOOBXZMAH-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (R)-N-(4-amino)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide 、 二吡啶硫碳酸酯 以 四氢呋喃 为溶剂， 以77%的产率得到(R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide
  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

• Novel N-Benzylamide Substituted Derivatives of 2-(Acylamido)acetic Acid and 2-(Acylamido)propionic Acids: Potent Neurological Agents
  申请人：Kohn Harold L.

  公开号：US20110021482A1

  公开（公告）日：2011-01-27

  A first aspect of the invention is a compound (sometimes also referred to herein as an “active agent” or “active compound”) of Formula I or Ia: or a pharmaceutically acceptable salt or prodrug thereof. Compositions thereof and methods of using the same (e.g. for the treatment of a neurological disease) are also described.

  本发明的第一个方面是公式I或Ia的化合物（有时也在此处称为“活性剂”或“活性化合物”）：或其药学上可接受的盐或前药。还描述了其组成物和使用方法（例如用于治疗神经系统疾病）。
• NOVEL N-BENZYLAMIDE SUBSTITUTED DERIVATIVES OF 2-(ACYLAMIDO)ACETIC ACID AND 2-(ACYLAMIDO)PROPIONIC ACIDS: POTENT NEUROLOGICAL AGENTS
  申请人：The University of North Carolina At Chapel Hill

  公开号：EP2262764B1

  公开（公告）日：2014-11-12
• US8933065B2
  申请人：——

  公开号：US8933065B2

  公开（公告）日：2015-01-13
• Lacosamide Isothiocyanate-Based Agents: Novel Agents To Target and Identify Lacosamide Receptors
  作者：Ki Duk Park、Pierre Morieux、Christophe Salomé、Steven W. Cotten、Onrapak Reamtong、Claire Eyers、Simon J. Gaskell、James P. Stables、Rihe Liu、Harold Kohn

  DOI：10.1021/jm9012054

  日期：2009.11.12

  (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.