(R)-N-4'-(iodo)benzyl 2-acetamido-3-methoxypropionamide | 1192590-80-9

• 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'-(iodo)benzyl 2-acetamido-3-methoxypropionamide
• 英文别名: (R)-N-(4-iodo)benzyl 2-acetamido-3-methoxypropionamide；(R)-N-4-(iodo)benzyl 2-acetamido-3-methoxypropionamide；(R)-2-acetamido-3-methoxy-N-(4-iodobenzyl)propanamide；(R)-N-4-iodobenzyl 2-acetamido-3-methoxypropionamide；(2R)-2-acetamido-N-[(4-iodophenyl)methyl]-3-methoxypropanamide
• CAS: 1192590-80-9
• 化学式: C₁₃H₁₇IN₂O₃
• 分子量: 376.194
• InChiKey: ULXQVKABLWOAGQ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-N-4'-(iodo)benzyl 2-acetamido-3-methoxypropionamide 在 platinum(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 64.0h， 生成 (R)-N-4-(propyl)benzyl 2-acetamido-3-methoxypropionamide
  参考文献：
  名称：

  [EN] METHODS OF TREATMENT OF NEUROLOGICAL DISORDERS
  [FR] MÉTHODES DE TRAITEMENT D'AFFECTIONS NEUROLOGIQUES

  摘要：

  本发明实施例提供了化合物、药物组合物以及它们在治疗癫痫和神经病痛等神经系统疾病中的使用方法。同时还提供了作为神经保护剂的化合物和药物组合物。

  公开号：

  WO2010148300A1
• 作为产物：
  描述：

  4-碘苄胺盐酸盐 在 N-甲基吗啉 、 盐酸 、 三乙胺 、 silver(l) oxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 72.0h， 生成 (R)-N-4'-(iodo)benzyl 2-acetamido-3-methoxypropionamide
  参考文献：
  名称：

  [EN] NOVEL N-BENZYLAMIDE SUBSTITUTED DERIVATIVES OF 2-(ACYLAMIDO)ACETIC ACID AND 2-(ACYLAMIDO)PROPIONIC ACIDS: POTENT NEUROLOGICAL AGENTS
  [FR] NOUVEAUX DÉRIVÉS SUBSTITUÉS PAR N-BENZYLAMIDE D'ACIDE 2-(ACYLAMIDO)ACÉTIQUES ET ACIDES 2-(ACYLAMIDO)PROPIONIQUES : AGENTS NEUROLOGIQUES PUISSANTS

  摘要：

  公开号：

  WO2009145816A3

文献信息

• Synthesis and Anticonvulsant Activities of (<i>R</i>)-<i>N</i>-(4′-Substituted)benzyl 2-Acetamido-3-methoxypropionamides
  作者：Christophe Salomé、Elise Salomé-Grosjean、Ki Duk Park、Pierre Morieux、Robert Swendiman、Erica DeMarco、James P. Stables、Harold Kohn

  DOI：10.1021/jm901563p

  日期：2010.2.11

  National Institute of Neurological Disorders and Stroke Anticonvulsant Screening Program for seizure protection in the maximal electroshock (MES) and subcutaneous Metrazol models. Comparing activities for two series of substituted aryl regioisomers (2′, 3′, 4′) showed that 4′-modified derivatives had the highest activity. Significantly, structural latitude existed at the 4′-site. The SAR indicated that

  已经探索了临床抗癫痫药 ( R )-拉科酰胺 [( R ) -N-苄基 2-乙酰氨基-3-甲氧基丙酰胺，( R ) -3 ] 中N-苄基的构效关系 (SAR) 。制备了 43 种化合物，然后在国家神经疾病研究所和中风抗惊厥筛查计划中评估其在最大电击 (MES) 和皮下美曲唑模型中的癫痫保护作用。比较两个系列取代的芳基区域异构体（2'、3'、4'）的活性表明，4'-修饰的衍生物具有最高的活性。值得注意的是，结构纬度存在于 4' 位点。SAR 表明非庞大的 4'-取代（R )- 3衍生物表现出极好的活性，与它们的电子特性无关。几种化合物在 MES 测试中的活性与 ( R ) -3的活性相当或超过，并且超过了对传统抗癫痫药苯妥英、苯巴比妥和丙戊酸盐观察到的活性。
• 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：US20120232015A1

  公开（公告）日：2012-09-13

  A first aspect of the invention is a compound (sometimes also referred to herein as an “active agent” or “active compound”) of Formula Ia, or more particularly Formula Ib, 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Ia的化合物（有时也在此处称为“活性剂”或“活性化合物”）或更具体地为公式Ib的化合物，或其药物可接受的盐或前药。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）。
• 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：US08829033B2

  公开（公告）日：2014-09-09

  A first aspect of the invention is a compound (sometimes also referred to herein as an “active agent” or “active compound”) of Formula Ia, or more particularly Formula Ib, 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Ia或更具体地公式Ib的化合物（有时在本文中也称为“活性物质”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）。
• 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.
• Merging the Structural Motifs of Functionalized Amino Acids and α-Aminoamides: Compounds with Significant Anticonvulsant Activities
  作者：Christophe Salomé、Elise Salomé-Grosjean、James P. Stables、Harold Kohn

  DOI：10.1021/jm100185c

  日期：2010.5.13

  Functional amino acids (FAAs) and alpha-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4'-((3 ''-fluoro)benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED50 values of 13, 14, similar to 10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases.