N-去甲基佐匹克隆 | 59878-63-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡嗪类
• 中文名称: N-去甲基佐匹克隆
• 中文别名: N-去甲佐匹克隆；N-去甲佐匹克隆-D8
• 英文名称: N-Desmethylzopiclone
• 英文别名: N-desmethyl-zopiclone；piperazine-1-carboxylic acid 6-(5-chloro-pyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl ester；[6-(5-chloropyridin-2-yl)-5-oxo-7H-pyrrolo[3,4-b]pyrazin-7-yl] piperazine-1-carboxylate
• CAS: 59878-63-6
• 化学式: C₁₆H₁₅ClN₆O₃
• 分子量: 374.786
• InChiKey: CGSFZSTXVVJLIX-UHFFFAOYSA-N

物化性质

• 熔点：
  226-2280C
• 沸点：
  599.0±50.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)
• 闪点：
  2°C
• 溶解度：
  DMSO（少许）、甲醇（少许）、水（少许）
• 保留指数：
  3089

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

代谢

N-去甲基佐匹克隆是eszopiclone（艾司佐匹克隆）的人体已知代谢物。

N-desmethyl-zopiclone is a known human metabolite of eszopiclone.

来源:NORMAN Suspect List Exchange

制备方法与用途

诺扎匹隆是佐匹克隆的无活性代谢物。虽然它不具备催眠效果，却有一定的抗焦虑作用。

反应信息

• 作为反应物：
  描述：

  1-[3-[4-羟基-3-(碘-125I)苯基]-1-氧代丙氧基]-2,5-吡咯烷二酮 、 N-去甲基佐匹克隆 以 1,4-二氧六环 、 苯 为溶剂， 生成 desmethylzopiclone-N-<3-(4-hydroxy-3-<¹²⁵I>iodophenyl)-propionamide>
  参考文献：
  名称：

  Synthesis and purification of desmethylzopiclone-N-{3-(4-hydroxy-3-[125I]-iodophenyl) propionamide}, a prosthetic derivative of zopiclone for use in immunoassay

  摘要：

  将[125I]-Bolton/Hunter试剂与N-去甲基佐匹克隆缩合，得到了标题化合物，并通过正相高效液相色谱法和伽马计数检测分离和纯化了该化合物。通过 L-SIMS 验证了在示踪剂前体中引入了人工基团。

  DOI：

  10.1002/jlcr.2580340311
• 作为产物：
  描述：

  佐匹克隆 以 乙腈 为溶剂， 反应 0.5h， 生成 N-去甲基佐匹克隆
  参考文献：
  名称：

  Electrochemical oxidation of zopiclone

  摘要：

  Electrochemical behaviour of zopiclone was investigated on glassy carbon electrode in static and rotation disc arrangement. Strong influence of kinetics and adsorption phenomena on the electrode processes was proved by voltammetric techniques. Controlled potential electrolysis in off-line and on-line combination with tandem mass spectrometry was employed for investigation of the products of electrochemical oxidation. N-Desmethyl zopiclone was identified and three other oxidation products formed by an introduction of one or two oxygen atom(s) to the molecule of zopiclone (including zopiclone N-oxide) were characterized. Based on mass spectrometric investigation of those products, piperazine moiety was proved as a target of electrochemical oxidation of zopiclone. Since N-desmethyl zopiclone and zopiclone N-oxide have been reported as products of enzymatic metabolism of the drug, the combination of electrochemistry with mass spectrometry may be considered as a reliable tool for simulation of some metabolic transformations.[GRAPHICS].

  DOI：

  10.1007/s00706-015-1602-9

文献信息

• Process for Preparation of Dextrorotatory Isomer of 6-(5- chloro-pyrid-2-yl)-5-[(4-methyl -1-piperazinyl) carbonyloxy] -7-oxo-6,7-dihydro-5H-pyrrolo [3,4-b] pyrazine (Eszopiclone)
  申请人：SATHE Dhananjay Govind

  公开号：US20090198058A1

  公开（公告）日：2009-08-06

  Disclosed herein is the process for preparation of 6-(5-chloro-pyrid-2-yl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (Zopiclone), its resolution to get the dextrorotatory isomer of formula (I) substantially free of R(−) enantiomer and recovery of key raw material i.e. 6-(5-chloro pyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydropyrrolo[3,4-b]pyrazine from the R-isomer of Zopiclone followed by conversion of the recovered compound to get pure Eszopiclone (I) in high yield and high purity.

  本发明涉及制备6-（5-氯吡啶-2-基）-5-[(4-甲基-1-哌嗪基)羰氧基]-7-氧代-6,7-二氢-5H-吡咯并[3,4-b]吡嗪（Zopiclone）的过程，其分离获得公式（I）右旋异构体，基本上不含R（-）对映体，以及从Zopiclone的R-异构体中恢复关键原料，即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，随后将恢复的化合物转化为高产率和高纯度的纯Eszopiclone（I）。
• Heterocyclic compounds
  申请人：Rhone-Poulenc Industries

  公开号：US04220646A1

  公开（公告）日：1980-09-02

  Heterocyclic compounds of the formula: ##STR1## wherein the pyrroline ring and the symbols R.sub.1 and R.sub.2 together form an isoindoline, 6,7-dihydro-5H-pyrrolo-[3,4-b]pyrazine, 2,3,6,7-tetrahydro-5H-1,4-oxathiino-[2,3-c]pyrrole or 2,3,6,7-tetrahydro-5H-1,4-dithiino-[2,3-c]pyrrole nucleus, Het represents an optionally substituted pyrid-2-yl, quinol-2-yl or 1,8-naphthyridin-2-yl radical, Z represents oxygen or sulphur and R represents hydrogen, alkyl or halo-substituted alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, optionally substituted phenyl, phenylalkyl, the phenyl ring of which may optionally be substituted, phenylalkenyl, the phenyl ring of which may optionally be substituted, or R represents a 5- or 6-membered heterocyclic radical containing one or two hetero-atoms selected from nitrogen, oxygen and sulphur, and, when the pyrroline ring and the symbols R.sub.1 and R.sub.2 together form an isoindoline nucleus, the residue of the isoindoline nucleus represented by R.sub.1 and R.sub.2 may optionally be substituted, possess pharmacological properties, and are especially useful as tranquillizers, anti-convulsant agents, decontracturants and agents to produce hypnosis.

  式为：##STR1## 的杂环化合物，其中吡咯烃环和符号R.sub.1和R.sub.2共同形成异吲哚啉、6,7-二氢-5H-吡咯并[3,4-b]吡嗪、2,3,6,7-四氢-5H-1,4-噁嗪并[2,3-c]吡咯或2,3,6,7-四氢-5H-1,4-二噻吩并[2,3-c]吡咯核，Het代表可选取代的吡啶-2-基、喹啉-2-基或1,8-萘啉-2-基基团，Z代表氧或硫，R代表氢、烷基或卤代烷基、烯基、炔基、环烷基、烷氧基、可选取代的苯基、苯基烷基，其中苯环可选取代，苯基烯基，其中苯环可选取代，或R代表含有一或两个来自氮、氧和硫的杂原子的5-或6-成员杂环基，当吡咯烃环和符号R.sub.1和R.sub.2共同形成异吲哚啉核时，由R.sub.1和R.sub.2表示的异吲哚啉核残基可选取代，具有药理学特性，特别是作为镇静剂、抗惊厥剂、解痉剂和催眠剂非常有用。
• Compositions comprising zopiclone derivatives and methods of making and using the same
  申请人：Jerussi P. Thomas

  公开号：US20070049590A1

  公开（公告）日：2007-03-01

  The invention is directed to racemic and stereomerically pure compounds of Formula 3: and to pharmaceutical compositions comprising them, methods of their use, and methods of their preparation.

  该发明涉及公式3的外消旋和立体异构纯化化合物，以及包含它们的制药组合物、使用方法和制备方法。
• COMBINATION PRODUCT FOR THE INDUCTION AND/OR MAINTENANCE OF GENERAL ANESTHESIA
  申请人：BLUMENTECH, S.L.

  公开号：US20210186927A1

  公开（公告）日：2021-06-24

  The state of general anesthesia (GA) is essential to many surgical and medical procedures. This state is characterized by loss of consciousness, deep analgesia and suppression of movements. GA is rarely achieved with a single drug, usually requiring the combination of various pharmacological agents. Each drug can interact with one or more molecular targets affecting neuronal excitability and synaptic transmission in multiple regions of the CNS. Agonists of the μ-opioid receptor are commonly used in GA to cause analgesia, but not to induce or maintain loss of consciousness or movement suppression. Additionally, agonists of the μ-opioid receptor can cause serious unwanted side effects, e.g. respiratory depression. The present invention provides alternative combination products based on K-opioid receptor agonists. These combination products unexpectedly induced loss of consciousness, and were able to achieve and maintain GA. Furthermore, the combination products suppressed pain perception without the need of a μ-opioid receptor agonist. The combination of Salvinorin A, a selective κ-opioid receptor agonist, with Diazepam or Medetomidine surprisingly led to rapid consciousness, deep analgesia and movement suppression. This combination was found to effectively induce and maintain a state of general anesthesia.
• US4220646A
  申请人：——

  公开号：US4220646A

  公开（公告）日：1980-09-02