4-methyl-piperazine-1-carboxylic acid 2-(5-chloro-pyridin-2-yl)-3-oxo-1,3-dihydro-isoindol-1-yl ester | 36935-86-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 英文名称: 4-methyl-piperazine-1-carboxylic acid 2-(5-chloro-pyridin-2-yl)-3-oxo-1,3-dihydro-isoindol-1-yl ester
• 英文别名: [2-(5-chloropyridin-2-yl)-3-oxo-1H-isoindol-1-yl] 4-methylpiperazine-1-carboxylate
• CAS: 36935-86-1
• 化学式: C₁₉H₁₉ClN₄O₃
• 分子量: 386.838
• InChiKey: CROUDGNPJLQKNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  66
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methyl-piperazine-1-carboxylic acid 2-(5-chloro-pyridin-2-yl)-3-oxo-1,3-dihydro-isoindol-1-yl ester 在 盐酸 作用下， 以80%的产率得到2-(5-chloro-pyridin-2-yl)-3-hydroxy-2,3-dihydro-isoindol-1-one
  参考文献：
  名称：

  酸催化水解一系列佐匹克隆类似物

  摘要：

  佐匹克隆和类似物的质子化涉及的酸碱平衡的pKa值通过紫外可见吸收光谱法和pH值测定法确定。氨基甲酸酯水解证明存在氢离子催化作用。

  DOI：

  10.1002/jps.2600780805

文献信息

• Preparation Of Zopiclone And Its Enantiomerically Enriched Isomer
  申请人：Tyagi Om Dutt

  公开号：US20100056785A1

  公开（公告）日：2010-03-04

  Present invention relates to an improved process for the preparation of Zopiclone and its enantiomerically enriched isomer (Eszopiclone). 6-(5-Chloropyridin-2-yl)-5-hydroxy-7-oxo-5,6-dihydropyrrolo[3,4-b]pyrazine is reacted with 1-chloro-carbonyl-4-methylpiperazine in the presence of alkali earth metal carbonates, hydroxides or oxides in a solvent medium to give Zopiclone. It is reacted with optically active acid in a mixture of water and water miscible organic solvent followed by work up to give Eszopiclone. The present invention also relates to process for the conversion of (R) or (S) Zopiclone to 6-(5-chloropyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydro-pyrrolo-[3,4-b]-pyrazine of the intermediate which can be converted to racemic Zopiclone.

  本发明涉及一种改进的制备Zopiclone及其对映富集异构体（Eszopiclone）的过程。将6-(5-氯吡啶-2-基)-5-羟基-7-氧代-5,6-二氢吡咯并[3,4-b]吡嗪与1-氯甲酰-4-甲基哌嗪在碱土金属碳酸盐、氢氧化物或氧化物的溶剂介质中反应，得到Zopiclone。它与光学活性酸在水和水亲和性有机溶剂的混合物中反应，然后进行后处理，得到Eszopiclone。本发明还涉及将（R）或（S）Zopiclone转化为中间体6-(5-氯吡啶-2-基)-5-羟基-7-氧代-5,6-二氢吡咯并[3,4-b]吡嗪的过程，该中间体可以转化为外消旋Zopiclone。
• Combination of a sedative and a neurotransmitter modulator, and methods for improving sleep quality and treating depression
  申请人：Sepracor Inc.

  公开号：EP2343073A2

  公开（公告）日：2011-07-13

  One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., insomnia and/or depression. The first component of the pharmaceutical composition is a GABA receptor modulating compound. The second component of the pharmaceutical composition is a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, a 5-HT2A modulator, or dopamine reuptake inhibitor. In certain embodiments, the pharmaceutical composition comprises eszopiclone. In a preferred embodiment, the pharmaceutical composition comprises eszopiclone and fluoxetine. The present invention also relates to a method of treating a sleep abnormality, treating insomnia, treating depression, augmenting antidepressant therapy, eliciting a dose-sparing effect, reducing depression relapse, improving the efficacy of antidepressant therapy or improving the tolerability of antidepressant therapy, comprising co-administering to a patient in need thereof a GABA-receptor-modulating compound; and a SRI, NRI, 5-HT2A modulator or DRI.

  本发明的一个方面涉及含有两种或两种以上活性剂的药物组合物，这些活性剂一起服用时可用于治疗失眠和/或抑郁症等。药物组合物的第一种成分是 GABA 受体调节化合物。药物组合物的第二种成分是血清素再摄取抑制剂、去甲肾上腺素再摄取抑制剂、5-HT2A调节剂或多巴胺再摄取抑制剂。在某些实施方案中，药物组合物包含艾佐匹克隆。在一个优选的实施方案中，药物组合物包括艾司佐匹克隆和氟西汀。本发明还涉及一种治疗睡眠异常、治疗失眠、治疗抑郁症、增强抗抑郁治疗、引起剂量节省效应、减少抑郁症复发、改善抗抑郁治疗的疗效或改善抗抑郁治疗的耐受性的方法，包括向有需要的患者联合施用GABA受体调节化合物；和SRI、NRI、5-HT2A调节剂或DRI。
• COMBINATION OF A SEDATIVE AND A NEUROTRANSMITTER MODULATOR, AND METHODS FOR IMPROVING SLEEP QUALITY AND TREATING DEPRESSION
  申请人：Sunovion Pharmaceuticals Inc.

  公开号：EP1691811B1

  公开（公告）日：2014-07-23
• DOPAMINE-AGONIST COMBINATION THERAPY WITH SEDATIVES FOR IMPROVING SLEEP QUALITY
  申请人：SEPRACOR, INC.

  公开号：EP1742624B1

  公开（公告）日：2010-01-06
• Dopamine-Agonist Combination Therapy For Improving Sleep Quality
  申请人：Barberich Timothy J.

  公开号：US20100004251A1

  公开（公告）日：2010-01-07

  The present invention generally relates to pharmaceutical compositions comprising a dopamine agonist and sedative agent. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine. In a preferred embodiment, the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine; and the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone. The pharmaceutical compositions of the invention are useful in the treatment of restless-leg syndrome and periodic-limb-movement disorder, as well as various sleep disorders. In addition, the present invention relates to a method of treating a patient suffering from restless-leg syndrome, periodic-limb-movement disorder, a sleep abnormality, or insomnia, comprising coadministering a therapeutically effective amount of a dopamine agonist and a therapeutically effective amount of a sedative agent. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine. In a preferred embodiment, the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone. In a preferred embodiment, the dopamine agonist is optically pure (S)-didesmethylsibutramine; and the sedative agent is optically pure (S)-zopiclone or optically pure (S)—N-desmethylzopiclone.