左旋米那普仑盐酸盐 | 175131-60-9

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 左旋米那普仑盐酸盐
• 中文别名: 左旋米那普林盐酸盐；左旋米那普林；(1S-顺式)-盐酸米那普仑；盐酸左旋米那普仑
• 英文名称: (1S,2R)-milnacipran hydrochloride
• 英文别名: levomilnacipran hydrochloride；(1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide hydrochloride；(+)-Milnacipran hydrochloride；(1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide;hydrochloride
• CAS: 175131-60-9
• 化学式: C₁₅H₂₂N₂O*ClH
• 分子量: 282.813
• InChiKey: XNCDYJFPRPDERF-NQQJLSKUSA-N

物化性质

• 溶解度：
  DMSO:57.0(最大浓度 mg/mL);201.55(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  46.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 储存条件：
  室温且干燥

制备方法与用途

生物活性方面，Milnacipran (1S-cis) 氢氯化物是一种5-羟色胺和去甲肾上腺素再摄取抑制剂（SNRI），主要用于研究纤维肌痛。

反应信息

• 作为反应物：
  描述：

  Eosin Y 、 左旋米那普仑盐酸盐 生成
  参考文献：
  名称：

  A new sensitive approach for spectrofluorimetric assay of Milnacipran and Amisulpride in real plasma and pharmaceutical preparations via complexation with Eosin Y dye

  摘要：

  An accurate, economic, rapid, reliable spectrofluorimetric assay was developing for the assay of definite anti-depressant drugs namely Amisulpride and Milnacipran hydrochloride, in those pharmaceutical preparation and biological fluid. The suggested method was established on the detection of quenching process resulting from the action of AMS and MCN to the native fluorescent EosinY. A binary complex between selected medications and Eosin Y was established in acetate buffer (0.2 M) at pH 3.3 & 4.0 for AMS and MCN respectively. The relative fluorescence capacity was determined at lambda ex= 301.8 nm and lambda em= 542.7 nm. The calibration graphs had been linear through extent from 0.02 to 0.3 and 0.1-1 mu g mL(-1), to both dugs respectively. Detection limits have been 0.0047 & 0.0188 mu g mL(-1) while quantitation limits have been 0.0141 & 0.0569 mu g mL(-1) to AMS & MCN respectively. Developed assay has been validated in agreement with ICH recommendations. Due to high sensitivity of the described assay, it allows the quantitation of anti-depressant drugs through biological fluid. (C) 2019 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.saa.2019.02.071
• 作为产物：
  描述：

  (1S5R)-1-苯基-3-氧杂双环[3.1.0]己烷-2-酮（左米那普仑中间体A） 在 盐酸 、 aluminum (III) chloride 、 氯化亚砜 、 C.I.酸性橙108 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 20.0h， 生成 左旋米那普仑盐酸盐
  参考文献：
  名称：

  Enantioselective synthesis of levomilnacipran

  摘要：

  报告采用一种新方法不对称地合成了抗抑郁药物米那西普兰的活性 (1S,2R)-对映体。从苯乙酸开始，依次安装环丙烷环上的两个立体中心。

  DOI：

  10.1039/c2cc33743f

文献信息

• [EN] A NEW PROCESS FOR PREPARING OPTICALLY PURE MILNACIPRAN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS.<br/>[FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE MILNACIPRAN OPTIQUEMENT PUR ET DE SES SELS DE QUALITÉ PHARMACEUTIQUE
  申请人：ARCH PHARMALABS LTD

  公开号：WO2012059933A1

  公开（公告）日：2012-05-10

  The present invention relates to an improved and commercially, viable process for the resolution of racemic cis milnacipran of formula I and its pharmaceutically acceptable salts of formula II. The present invention comprises using racemic cis milnacipran or its pharmaceutically acceptable salts as starting material, a low cost and commercially available resolving agent of formula III and industrially safe and economically low cost material such as water as a solvent. The said process results into optical isomers of racemic cis milnacipran having excellent optical purity without involving multiple crystallization steps. The present invention also comprises the concept of green chemistry as the invention works well with water as a solvent thereby minimizing the use of any other solvent. (Formular I and II should be inserted here) Wherein X is anion selected from Cl, Br, I, HSO4, Phosphate or organic acid(Formular III should be inserted here) *represent asymmetric centre Compound of formula III represent mandelic acid and its derivatives.

  本发明涉及一种改进的商业可行的过程，用于分离式异构体顺式米纳西普兰（化学式I）及其药用可接受盐（化学式II）。本发明包括使用顺式米纳西普兰的异构体或其药用可接受盐作为起始物质，以及具有低成本且商业上可获得的分离剂（化学式III）和工业安全以及经济低成本材料（如水）作为溶剂。该过程导致顺式米纳西普兰的光学异构体具有优异的光学纯度，而无需进行多次结晶步骤。本发明还包括绿色化学概念，因为该发明与水作为溶剂良好配合，从而最小化了对任何其他溶剂的使用。 （化学式I和II应在此处插入） 其中X是从Cl、Br、I、HSO4、磷酸盐或有机酸中选择的阴离子 （化学式III应在此处插入） *代表不对称中心，化合物的化学式III代表苯乙酸及其衍生物。
• PROCESS FOR PREPARING OPTICALLY PURE MILNACIPRAN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS
  申请人：Pai Ganesh Gurpur

  公开号：US20120289744A1

  公开（公告）日：2012-11-15

  The present invention relates to an improved and commercially, viable process for the resolution of racemic cis milnacipran of formula I and its pharmaceutically acceptable salts of formula II. The present invention comprises using racemic cis milnacipran or its pharmaceutically acceptable salts as starting material, a low cost and commercially available resolving agent of formula III and industrially safe and economically low cost material such as water as a solvent. The said process results into optical isomers of racemic cis milnacipran having excellent optical purity without involving multiple crystallization steps. The present invention also comprises the concept of green chemistry as the invention works well with water as a solvent thereby minimizing the use of any other solvent. (Formular I and II should be inserted here) Wherein X is anion selected from Cl, Br, I, HSO 4 , Phosphate or organic acid (Formular III should be inserted here) *represent asymmetric centre Compound of formula III represent mandelic acid and its derivatives.

  本发明涉及一种改进的商业化可行的过程，用于分离式解决式I的顺式米纳西普兰的外消旋体和其药用可接受盐II。本发明包括使用外消旋式顺式米纳西普兰或其药用可接受盐作为起始物质，采用具有低成本和商业化可用性的分离剂III的工业安全和经济低成本材料，例如水作为溶剂。所述过程导致具有优异光学纯度的外消旋式顺式米纳西普兰的光学异构体，而无需进行多次结晶步骤。本发明还包括绿色化学的概念，因为该发明在水作为溶剂的情况下运作良好，从而最大限度地减少了对任何其他溶剂的使用。其中X是从Cl、Br、I、HSO4、磷酸盐或有机酸中选择的阴离子。III的化学式应插入此处，*代表不对称中心，化合物III的化学式代表苹果酸及其衍生物。
• PROCESS FOR THE PREPARATION OF PHARMACEUTICALLY ACCEPTABLE SALTS OF RACEMIC MILNACIPRAN AND ITS OPTICAL ENANTIOMERS THEREOF
  申请人：Jagtap Vikram Sarjerao

  公开号：US20120184774A1

  公开（公告）日：2012-07-19

  The present invention relates to an improved process for the preparation of pharmaceutically acceptable salts of milnacipran by mutual acid radical exchange.

  本发明涉及一种通过酸基交换改进的制备米氮西普兰药用可接受盐的方法。
• [EN] PROCESS FOR THE PREPARATION OF (1S,2R)-MILNACIPRAN<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE (1S,2R)-MILNACIPRAN
  申请人：SINT QUIMICA SA

  公开号：WO2016071303A1

  公开（公告）日：2016-05-12

  The invention relates to a process for the preparation of Levomilnacipran, a compound useful in the treatment of depression, comprising the following steps: a) directly converting the enantiomerically enriched form of alcohol (D) into the enantiomerically enriched form of the phthalimido derivative (C) by treatment with phthalimide in the presence of a trialkyl or triarylphosphine and of a dialkyl azodicarboxylate, formula (I) wherein the amount of phthalimide is comprised between 1 and 1.3 equivalents with respect to the molar amount of alcohol (D) used, and the amounts of both the phosphine and the azodicarboxylate are comprised, independently from each other, between 1 and 1.5 equivalents with respect to the molar amount of alcohol (D) used; b) deblocking the enantiomerically enriched form of the phthalimido derivative (C) to obtain Levomilnacipran, formula (II).

  该发明涉及一种用于制备左旋米氮平的过程，左旋米氮平是一种用于治疗抑郁症的化合物，包括以下步骤：a)将对映选择性富集的醇（D）直接转化为对映选择性富集的邻苯二甲酰亚胺衍生物（C），方法是在三烷基或三芳基膦和二烷基双氮基二羧酸酯的存在下，用邻苯二甲酰亚胺处理，式（I）中邻苯二甲酰亚胺的量在摩尔量方面相对于使用的醇（D）之间为1至1.3当量之间，磷和双氧基二羧酸酯的量分别独立于彼此，相对于使用的醇（D）的摩尔量在1至1.5当量之间；b)去保护对映选择性富集的邻苯二甲酰亚胺衍生物（C）以获得左旋米氮平，式（II）。
• [EN] PROCESS FOR PREPARING LEVOMILNACIPRAN<br/>[FR] PROCÉDÉ DE PRÉPARATION DE LEVOMILNACIPRAN
  申请人：LABORATORIO CHIMICO INT SPA

  公开号：WO2015092502A1

  公开（公告）日：2015-06-25

  The present invention refers to a new process for preparing levomilnacipran, in particular to a process for the resolution of racemic tw-milnacipran with a derivative of optically active phenylglycine.

  本发明涉及一种制备左美沙芬的新工艺，具体涉及一种用光学活性苯基甘氨酸衍生物对混合型双克美沙芬进行拆分的工艺。