1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride | 67469-78-7

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
• 英文别名: Vanoxerine dihydrochloride；[1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl)piperazine] dihydrochloride；(1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine) dihydrochloride；1-[2-[bis(4-fluorophenyl)methoxy]-ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride；1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride；1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride；Gbr-12909 hydrochloride；1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine;hydrochloride
• CAS: 67469-78-7
• 化学式: C₂₈H₃₂F₂N₂O*2ClH
• 分子量: 523.494
• InChiKey: VAHMWGICKYTGSY-UHFFFAOYSA-N

物化性质

• 熔点：
  221 °C
• 溶解度：
  DMSO: >5 mg/mL 每天新鲜配制的溶液
• 稳定性/保质期：
  远离氧化物。

计算性质

• 辛醇/水分配系数(LogP)：
  5.74
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  15.7
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 储存条件：
  存放在密封容器中，并放置在阴凉、干燥处。储存地点须远离氧化剂。

制备方法与用途

概述

伐诺司林是一种有机化合物，已在哺乳动物中用于治疗可卡因成瘾、急性效应和渴望，并作为多巴胺激动剂用于治疗帕金森综合症、肢端肥大症、高催乳素血症及由多巴胺能系统功能减退引起的相关疾病。研究旨在优化特别适用于人类使用的伐诺司林固体剂型，力求使用最少的赋形剂，并选用便宜且易于获取的药用级材料，以促进大规模生产成本的有效控制。

生物活性

范可素（Vanoxerine，GBR-12909）是一种有效的、选择性的多巴胺摄取抑制剂。

反应信息

• 作为产物：
  描述：

  伐诺司林 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以116.9 g的产率得到1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
  参考文献：
  名称：

  Scale-Up Synthesis of the Dopamine Uptake Inhibitor GBR-12909

  摘要：

  1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR-12909) is a dopamine uptake inhibitor. The development of a robust process for the preparation of this compound in kilogram quantities is described. The primary aims of the development work were to eliminate chromatographic purifications, to minimize the use of environmentally unacceptable reagents, and to improve the overall yield of the three-step convergent process. These objectives were met, with significant improvements obtained in the key coupling reaction of N-(3-phenylpropyl)piperazine dihydrochloride salt with 1-[bis(4-fluorophenyl)methoxy]-2-chloroethane, which was previously low-yielding and lacking in reproducibility.

  DOI：

  10.1021/op020211j

文献信息

• Van Der Zee; Koger; Gootjes, European Journal of Medicinal Chemistry, 1980, vol. 15, # 4, p. 363 - 370
  作者：Van Der Zee、Koger、Gootjes、Hespe

  DOI：——

  日期：——
• PHARMACEUTICAL COMPOSITIONS FOR COMBINATION THERAPY
  申请人：Acesion Pharma ApS

  公开号：EP2861254A2

  公开（公告）日：2015-04-22
• Pharmaceutical Compositions for Combination Therapy
  申请人：Acesion Pharma

  公开号：US20150164871A1

  公开（公告）日：2015-06-18

  This invention relates to the use of pharmaceutical compositions comprising a therapeutically effective amount of a sodium channel inhibitor, in a combination with a small-conductance calcium-activated potassium (SK) channel inhibitor, for the treatment of cardiac arrhythmias.
• PHARMACEUTICAL COMPOSITIONS CONTAINING VANOXERINE AND P450 INHIBITORS AND METHODS OF TERMINATING ACUTE EPISODES OF CARDIAC ARRHYTHMIA, RESTORING NORMAL SINUS RHYTHM, PREVENTING RECURRENCE OF CARDIAC ARRHYTHMIA AND MAINTAINING NORMAL SINUS RYTHYM IN MAMMALS THROUGH ADMINISTRATION OF SAID COMPOSITIONS
  申请人：Laguna Pharmaceuticals, Inc.

  公开号：US20160303114A1

  公开（公告）日：2016-10-20

  Compositions comprising vanoxerine (GBR 12909) and a P450 inhibitor, including compositions of vanoxerine and one or more P450 inhibitors, processes for their preparation thereof, and methods of using the same for treatment of cardiac arrhythmias.
• [EN] PHARMACEUTICAL COMPOSITIONS FOR COMBINATION THERAPY<br/>[FR] COMPOSITIONS PHARMACEUTIQUES POUR POLYTHÉRAPIE
  申请人：ACESION PHARMA

  公开号：WO2013185764A2

  公开（公告）日：2013-12-19

  This invention relates to the use of pharmaceutical compositions comprising a therapeutically effective amount of a sodium channel inhibitor, in a combination with a small-conductance calcium-activated potassium (SK) channel inhibitor, for the treatment of cardiac arrhythmias.