(4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)acetamide | 1301211-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)acetamide
• 英文别名: 2-(5S-methyl-2-oxo-4R-phenylpyrrolidin-1-yl)acetamide；2-[(2S,3R)-2-methyl-5-oxo-3-phenylpyrrolidin-1-yl]acetamide
• CAS: 1301211-78-8
• 化学式: C₁₃H₁₆N₂O₂
• 分子量: 232.282
• InChiKey: ZTGRWYMPQCQTHD-ONGXEEELSA-N

物化性质

• 沸点：
  480.0±45.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：60 mg/ml（258.31 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.4
• 氢给体数：
  1
• 氢受体数：
  2

制备方法与用途

生物活性

E1R 是一种 sigma-1 受体的正变构调节剂 (Sig1R PAM)，具有认知增强效果。

体外研究

仅 E1R 对 sigma 受体有靶向作用，能显著增加非选择性放射配体（[3H]1,3-di(2-对甲基苯基)胍）与 Jurkat 细胞中 sigma 受体的特异性结合，增幅达 38%。在 10 μM 浓度下，E1R 不会置换放射配体，而是增加其结合。

体内研究

E1R 在小鼠模型中显示出对 scopolamine 引起的胆碱能功能障碍的有效性。在训练前 60 分钟通过腹腔注射给予 E1R（剂量分别为 0.1-10 mg/kg），显著以剂量依赖方式改善了认知功能。

动物模型	雄性 ICR 和 Balb/c 小鼠，体重 23-25 g
剂量	0.1, 1 和 10 mg/kg
给药时间	在训练前 60 分钟腹腔注射
结果	相比对照组，剂量为 1 和 10 mg/kg 的治疗分别使保持潜伏期增加了 194% 和 211%。

反应信息

• 作为产物：
  描述：

  (3R)-4-nitro-3-phenylpentanoic acid 在 ammonium hydroxide 、 氯化亚砜 、 sodium hydride 作用下， 以 甲醇 、 乙醇 、 水 、 甲苯 为溶剂， 50.0~120.0 ℃ 、5.07 MPa 条件下， 反应 42.5h， 生成 (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)acetamide
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-(5-methyl-4-phenyl-2-oxopyrrolidin-1-yl)-acetamide stereoisomers as novel positive allosteric modulators of sigma-1 receptor

  摘要：

  Novel positive allosteric modulators of sigma-1 receptor represented by 2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamide enantiomers were synthesised using an asymmetric Michael addition of 2-nitroprop-1-enylbenzene to diethyl malonate. Following the chromatographic separation of the methyl erythro- and threo-4-nitro-3R- and 3S-phenylpentanoate diastereoisomers, target compounds were obtained by their reductive cyclisation into 5-methyl-4-phenylpyrrolidin-2-one enantiomers and the attachment of the acetamide group to the heterocyclic nitrogen. Experiments with electrically stimulated rat vas deference contractions induced by the PRE-084, an agonist of sigma-1 receptor, showed that (4R,5S)- and (4R,5R)-2-(5-methyl-4-phenyl-2-oxopyrrolidin-l-yl)-acetamides with an R-configuration at the C-4 chiral centre in the 2-pyrrolidone ring were more effective positive allosteric modulators of sigma-1 receptor than were their optical antipodes. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.016

文献信息

• [EN] 4R,5S-ENANTIOMER OF 2-(5-METHYL-2-OXO-4-PHENYL-PYRROLIDIN-1-YL)-ACETAMIDE WITH NOOTROPIC ACTIVITY<br/>[FR] ENANTIOMÈRE 4R,5S DE 2-(5-MÉTHYL-2-OXO-4-PHÉNYL-PYRROLIDIN-1-YL)-ACÉTAMIDE AYANT UNE ACTIVITÉ NOOTROPIQUE
  申请人：GRINDEKS JSC

  公开号：WO2011054888A1

  公开（公告）日：2011-05-12

  The invention relates to the 5S,4R-enantiomer of 2-(5-methyl-2-oxo-4-phenyl- pyrrolidin-1-yl)-acetamide with cognition enhancing activity of high pharmacological value and to its preparation method which includes the synthesis of 5S-methyl-4R-phenylpyrrolidin-2-one, its N-alkylation with ethyl haloacetate and the treatment of intermediate ethyl 2-(5S-methyl-2-oxo-4R-phenyl-pyrrolidin-1-yl)-acetate with ammonia.

  本发明涉及具有高度药理价值的增强认知活性2-(5-甲基-2-氧代-4-苯基吡咯烷-1-基)乙酰胺的5S,4R-对映体及其制备方法，该方法包括合成5S-甲基-4R-苯基吡咯烷-2-酮，将其与乙基卤代乙酸酯进行N-烷基化，以及用氨处理中间体乙基2-(5S-甲基-2-氧代-4R-苯基吡咯烷-1-基)乙酸酯。
• 4R,5S-ENANTIOMER OF 2-(5-METHYL-2-OXO-4-PHENYL-PYRROLIDIN-1-YL)-ACETAMIDE WITH NOOTROPIC ACTIVITY
  申请人：Kalvins Ivars

  公开号：US20120215010A1

  公开（公告）日：2012-08-23

  The invention relates to the 5S,4R-enantiomer of 2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide with cognition enhancing activity of high pharmacological value and to its preparation method which includes the synthesis of 5S-methyl-4R-phenylpyrrolidin-2-one, its N-alkylation with ethyl haloacetate and the treatment of intermediate ethyl 2-(5S-methyl-2-oxo-4R-phenyl-pyrrolidin-1-yl)-acetate with ammonia.

  本发明涉及一种具有高药理学价值的认知增强活性的2-(5-甲基-2-氧代-4-苯基-吡咯烷-1-基)-乙酰胺的5S,4R-对映体及其制备方法，其包括5S-甲基-4R-苯基吡咯烷-2-酮的合成，其与乙酰卤代酸酯的N-烷基化以及中间体乙酰基2-(5S-甲基-2-氧代-4R-苯基-吡咯烷-1-基)-乙酸酯的氨处理。
• USE OF 2-(5S-METHYL-2-OXO-4R-PHENYL-PYRROLIDIN-1-YL)-ACETAMIDE IN THE TREATMENT OF SEIZURES
  申请人：LATVIAN INSTITUTE OF ORGANIC SYNTHESIS

  公开号：EP3127539A1

  公开（公告）日：2017-02-08

  Use of 2-(5S-Methyl-2-oxo-4R-phenyl-pyrrolidin-1-yl)-acetamide or its pharmaceutically acceptable salt in manufacture of a medicament for prophylaxis and treatment of seizure.

  使用 2-(5S-甲基-2-氧代-4R-苯基-吡咯烷-1-基)-乙酰胺或其药学上可接受的盐制造预防和治疗癫痫发作的药物。
• Use of 2-(5S-methyl-2-oxo-4R-phenyl-pyrrolidin-1-yl)-acetamide in the treatment of seizures
  申请人：Latvian Institute of Organic Synthesis

  公开号：US10105348B2

  公开（公告）日：2018-10-23

  Use of 2-(5S-Methyl-2-oxo-4R-phenyl-pyrrolidin-1-yl)-acetamide or its pharmaceutically acceptable salt in manufacture of a medicament for prophylaxis and treatment of seizure.

  使用 2-(5S-甲基-2-氧代-4R-苯基-吡咯烷-1-基)-乙酰胺或其药学上可接受的盐制造预防和治疗癫痫发作的药物。
• Synergistic compositions comprising (R)-dimiracetam (1) and (S)-dimiracetam (2) in a non-racemic ratio
  申请人：Metys Pharmaceuticals AG

  公开号：US10738054B2

  公开（公告）日：2020-08-11

  The present invention relates to a composition of enantiomers of 3,6,7,7a-tetrahydro-1H-pyrrolo[1,5-a]imidazole-2,5-dione and pharmaceutically acceptable solvates or co-crystals thereof in a certain ratio, a pharmaceutical composition comprising said composition, its use as a medicament and the use of the inventive compositions or pharmaceutical compositions in the treatment and/or prevention of a disease or disorder typically and preferably selected from peripheral sensory neuropathy, preferably peripheral neuropathic pain; seizure; depression; or cognitive impairment.

  本发明涉及一种3,6,7,7a-四氢-1H-吡咯并[1,5-a]咪唑-2,5-二酮的对映体及其药学上可接受的溶液或共晶按一定比例组成的组合物，一种包含所述组合物的药物组合物，其作为药物的用途，以及本发明组合物或药物组合物在治疗和/或预防典型和优选选自周围感觉神经病，优选周围神经病理性疼痛的疾病或紊乱中的用途； 癫痫发作；抑郁症；或认知障碍。