fluphenazine dihydrochloride | 146-56-5

• 物质功能分类: 原料药 - 神经系统用药 - 抗精神病药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: fluphenazine dihydrochloride
• 英文别名: Fluphenazindihydrochlorid；fluphenazine hydrochloride；2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;hydrochloride
• CAS: 146-56-5
• 化学式: C₂₂H₂₆F₃N₃OS*2ClH
• 分子量: 510.451
• InChiKey: CUXQPMGPJPHNFO-UHFFFAOYSA-N

物化性质

• 熔点：
  200-2020C
• 溶解度：
  溶于二甲基亚砜和甲醇。
• 稳定性/保质期：

  常温常压下稳定。

  禁配物：强氧化剂

计算性质

• 辛醇/水分配系数(LogP)：
  4.73
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  55.2
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• 危险等级：
  6.1
• 危险品标志：
  Xn
• 安全说明：
  S26,S36,S36/37/39
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  3003909090
• 危险品运输编号：
  UN2811
• RTECS号：
  TL9800000
• 包装等级：
  III
• 危险类别：
  6.1
• 储存条件：
  密封于干燥阴凉处保存。

制备方法与用途

作用

药理作用及机制与氯丙嗪及奋乃静相似。氟奋乃静的抗精神病作用比奋乃静强4倍，比氯丙嗪强20～40倍，且作用迅速而持久，镇吐作用较强，但降压及催眠作用较弱。临床主要用于治疗精神分裂症，能够改善慢性患者的振奋情绪。氟奋乃静癸酸酯为氟奋乃静的长效酯类化合物，其作用时间比氟奋乃静长9～20倍。

适应症

适用于维持治疗和慢性精神分裂症，尤其对拒药或藏药患者，可作为首选药物。

制备

盐酸氟奋乃静由两步反应制得。第一步以羟乙基哌嗪及1,3-溴氯丙烷为起始物料制备1-(3-氯丙基)-4-(2-羟乙基)哌嗪，不经后处理直接与三氟甲基吩噻嗪在碱性条件下反应得到盐酸氟奋乃静。合成反应式如下：

生物活性

Fluphenazine dihydrochloride (Prolixin)是吩噻嗪类的D1DR和D2DR抑制剂，能够抑制组胺H1受体。

化学性质

盐酸氟奋乃静为白色或类白色的结晶性粉末，熔点在226-233℃（分解）。易溶于水，略溶于乙醇，极微溶于丙酮，不溶于苯、乙醚，无臭且味微苦。遇光易变色。

氟奋乃静碱为暗褐色油状液体，沸点在268-274℃（66.5）。

用途

盐酸氟奋乃静是强安定药，用于治疗急慢性精神分裂症、躁狂症及神经官能症，并可用于缓解呕吐等症状。

反应信息

• 作为反应物：
  描述：

  fluphenazine dihydrochloride 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 0.03h， 以70%的产率得到fluphenazine-sulfoxide
  参考文献：
  名称：

  Enrichment of Relevant Oxidative Degradation Products in Pharmaceuticals With Targeted Chemoselective Oxidation

  摘要：

  The ability to produce and isolate relatively pure amounts of relevant degradation products is key to several aspects of drug product development: (a) aid in the unambiguous structural identification of such degradation products, fulfilling regulatory requirements to develop safe formulations (International Conference on Harmonization Q3B and M7); (b) pursue as appropriate safety evaluations with such material, such as chronic toxicology or Ames testing; (c) for a specified degradation product in a late-stage regulatory filing, use pure and well-characterized material as the analytical standard. Producing such materials is often a resource-and time-intensive activity, either relying on the isolation of slowly formed degradation products from stressed drug product or by re-purposing the drug substance synthetic route. This problem is exacerbated if the material of interest is an oxidative degradation product, because typical oxidative stressing (H2O2 and radical initiators) tends to produce a myriad of irrelevant species beyond a certain stress threshold, greatly complicating attempts for isolating the relevant degradation product. In this article, we present reagents and methods that may allow the rapid and selective enrichment of active pharmaceutical ingredient with the desired oxidative degradation product, which can then be isolated and used for purposes described above. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.xphs.2018.10.059

文献信息

• HETEROBICYCLIC COMPOUNDS
  申请人：Amgen Inc.

  公开号：US20130225552A1

  公开（公告）日：2013-08-29

  Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

  Formula (I)的杂环化合物： 或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
• [EN] PHENOTHIAZINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE PHÉNOTHIAZINE ET LEURS UTILISATIONS
  申请人：CAMP4 THERAPEUTICS CORP

  公开号：WO2019195789A1

  公开（公告）日：2019-10-10

  The present invention provides phenothiazine compounds, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment of various diseases or conditions, for example ribosomal disorders and ribosomopathies, e.g. Diamond Blackfan anemia (DBA).

  本发明提供了吩噻嗪化合物，其制备方法，包含该化合物的药物组合物，以及在治疗各种疾病或症状中使用该化合物或组合物，例如核糖体紊乱和核糖体病，例如钻石-布莱克范贫血（DBA）。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE LA QUINOLIZIDINONE
  申请人：MERCK & CO INC

  公开号：WO2009051715A1

  公开（公告）日：2009-04-23

  The present invention is directed to spiropiperidine compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的螺环哌啶化合物，这些化合物是M1受体阳性变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍方面有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。