erythro-(4R,5S)-5-methyl-4-phenylpyrrolidin-2-one

• 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: erythro-(4R,5S)-5-methyl-4-phenylpyrrolidin-2-one
• 英文别名: (4S,5R)-4-methyl-5-phenyl-1,3-oxazolidin-2-one；cis-5-Methyl-4-phenyl-2-pyrrolidinon；(5S)-methyl-(4R)-phenylpyrrolidin-2-one；(4r,5s)-5-Methyl-4-phenylpyrrolidin-2-one
• 化学式: C₁₁H₁₃NO
• 分子量: 175.23
• InChiKey: ZIZRQVWVGIHEIC-WPRPVWTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  erythro-(4R,5S)-5-methyl-4-phenylpyrrolidin-2-one 在 氨 、 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 11.5h， 生成 (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)acetamide
  参考文献：
  名称：

  [EN] 4R,5S-ENANTIOMER OF 2-(5-METHYL-2-OXO-4-PHENYL-PYRROLIDIN-1-YL)-ACETAMIDE WITH NOOTROPIC ACTIVITY
  [FR] ENANTIOMÈRE 4R,5S DE 2-(5-MÉTHYL-2-OXO-4-PHÉNYL-PYRROLIDIN-1-YL)-ACÉTAMIDE AYANT UNE ACTIVITÉ NOOTROPIQUE

  摘要：

  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。

  公开号：

  WO2011054888A1
• 作为产物：
  描述：

  (3R)-4-nitro-3-phenylpentanoic acid 在 氯化亚砜 作用下， 以 乙醇 、 水 为溶剂， 50.0 ℃ 、5.07 MPa 条件下， 反应 24.0h， 生成 erythro-(4R,5S)-5-methyl-4-phenylpyrrolidin-2-one
  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] PYRAZOLOPYRIDINAMINES AS MKNK1 AND MKNK2 INHIBITORS<br/>[FR] PYRAZOLOPYRIDINAMINES UTILISÉES COMME INHIBITEURS DE MKNK1 ET DE MKNK2
  申请人：BAYER PHARMA AG

  公开号：WO2016096721A1

  公开（公告）日：2016-06-23

  The present invention relates to substituted pyrazolopyridinamine compounds of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyperproliferative and/or angiogenesis disorder, inflammatory disease and disease associated with inflammatory pain, as a sole agent or in combination with other active ingredients.

  本发明涉及通式（I）所述的取代吡唑吡啶胺化合物，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和配方，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是治疗或预防过度增殖和/或血管生成紊乱、炎症性疾病和与炎症性疼痛相关的疾病的单一药剂或与其他活性成分组合使用。
• 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。
• US8791273B2
  申请人：——

  公开号：US8791273B2

  公开（公告）日：2014-07-29
• [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。
• 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
  作者：Grigory Veinberg、Maxim Vorona、Liga Zvejniece、Reinis Vilskersts、Edijs Vavers、Edvards Liepinsh、Helena Kazoka、Sergey Belyakov、Anatoly Mishnev、Jevgenijs Kuznecovs、Sergejs Vikainis、Natalja Orlova、Anton Lebedev、Yuri Ponomaryov、Maija Dambrova

  DOI：10.1016/j.bmc.2013.03.016

  日期：2013.5

  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.