去氨基氯(S)-氟西汀 | 114446-51-4

• 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: 去氨基氯(S)-氟西汀
• 英文名称: -(-)-1-chloro-3-phenyl-3-<4-(trifluoromethyl)phenoxy>propane
• 英文别名: (S)-1-chloro-3-(4-trifluormethyl-phenoxy)-3-phenyl-propane；(S)-4-(3-Cloro-1-phenylpropoxy)-1-trifluoromethylbenzene；[S]-(-)-1-Chloro-3-phenyl-3-(4-trifluoromethylphenoxy)propane；[S]-(-)-1-chloro-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propane；Desamino Chloro (S)-Fluoxetine；1-[(1S)-3-chloro-1-phenylpropoxy]-4-(trifluoromethyl)benzene
• CAS: 114446-51-4
• 化学式: C₁₆H₁₄ClF₃O
• 分子量: 314.735
• InChiKey: VOPIMWRKIKTDPS-HNNXBMFYSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  去氨基氯(S)-氟西汀 在 sodium hydride 、 一水合肼 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.33h， 生成 4-(3,4-dimethoxyphenyl)-2-(5-((S)-3-phenyl-3-(4-(trifluoromethyl)phenoxy)propylamino)pentyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
  参考文献：
  名称：

  Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression

  摘要：

  Multi-target compounds where more than one functional activity is incorporated into the same molecule may have advantages in treating disease states. Selective serotonin re-uptake inhibitors (SSRIs)(a) (i.e., (R)- and (S)-norfluoxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual PDE4 inhibitor/SSRIs (i.e., (R)-8 and (S)-8) showed moderately potent but highly selective serotonin re-uptake inhibition (IC50 values of 173 and 42 nM, respectively) in vitro. The dual PDE4 inhibitor/SSRIs (R)-8 and (S)-8 also inhibited PDE4D2 (i.e., K-i values of 106 and 253 nM, respectively). Due to the synergistic functional activity, PDE4 inhibitor/SSRIs may be effective in treating diseases such as depression. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.10.065
• 作为产物：
  描述：

  3-氯-1-苯基丙醇 在 吡啶 、 buffer pH 7 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 为溶剂， 生成 去氨基氯(S)-氟西汀
  参考文献：
  名称：

  An efficient route to enantiomerically pure antidepressants: tomoxetine, nisoxetine and fluoxetine

  摘要：

  Both enantiomers (R)- and (S)- 3-chloro- 1-phenyl- 1-propanol can be obtained conveniently by an efficient enzymatic resolution process. They can be converted via enantioconvergent routes into all enantiomers of the important antidepressants (R)- and (S)- Tomoxetine, Fluoxetine and Nisoxetine.

  DOI：

  10.1016/s0957-4166(00)80257-8

文献信息

• Chemoenzymatic synthesis of the non-tricyclic antidepressants Fluoxetine, Tomoxetine and Nisoxetine
  作者：Hui-Ling Liu、Bård Helge Hoff、Thorleif Anthonsen

  DOI：10.1039/b000846j

  日期：——

  3-Chloro-1-phenylpropan-1-ol and the corresponding butanoate, 3-chloro-1-phenyl-1-propyl butanoate, were kinetically resolved using lipase B from Candida antarctica catalysis by transesterification and hydrolysis respectively. The resulting chiral building blocks (S)- and (R)-3-chloro-1-phenylpropanol were converted into both enantiomers of the antidepressant drugs, Fluoxetine, Tomoxetine and Nisoxetine.

  使用来自南极念珠菌的脂肪酶B，通过酯交换和水解分别对3-氯-1-苯基丙醇及其相应的丁酸酯——3-氯-1-苯基-1-丙基丁酸酯进行了动力学拆分。得到的立体构建单元（S）-和（R）-3-氯-1-苯基丙醇被转化为抗抑郁药物氟西汀、托莫西汀和尼索西汀的两种对映体。
• Novel process of producing phenyl or substituted phenylalkylamine
  申请人：Aldrich-Boranes, Inc.

  公开号：US04868344A1

  公开（公告）日：1989-09-19

  A process for producing the optically pure (+)- or (-) isomer of a phenyl- or substituted- phenylalkanolamine compounds having pharmacologic activity without the need for resoltuion processes ad novel intermediates useful in the process including optically pure haloalcohols are provided.

  提供一种生产具有药理活性的光学纯（+）或（-）苯基或取代苯基醇胺化合物的方法，无需分离过程，包括在该过程中有用的新型中间体，其中包括光学纯卤代醇。
• Modulators of Central Nervous System Neurotransmitters
  申请人：Cashman John

  公开号：US20080261967A1

  公开（公告）日：2008-10-23

  Disclosed are agents having pharmacological activity against cellular receptors and intracellular signaling, particularly receptors and signaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.

  本发明涉及具有药理活性的药物，特别是针对细胞受体和细胞内信号传导的药物，尤其是中枢神经系统（CNS）神经递质的受体和信号通路。本发明还涉及使用这些药物的相关方法和组合物，用于治疗或预防疾病或障碍。
• MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS
  申请人：CASHMAN John

  公开号：US20130123253A1

  公开（公告）日：2013-05-16

  Disclosed are agents having pharmacological activity against cellular receptors and intracellular signaling, particularly receptors and signaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.

  本发明涉及一种对细胞受体和细胞内信号传导具有药理活性的药剂，特别是针对中枢神经系统（CNS）神经递质的受体和信号通路。本发明还涉及使用这些药剂的相关方法和组合物，用于治疗或预防疾病或障碍。
• Chiral synthesis via organoboranes. 18. Selective reductions. 43. Diisopinocampheylchloroborane as an excellent chiral reducing reagent for the synthesis of halo alcohols of high enantiomeric purity. A highly enantioselective synthesis of both optical isomers of Tomoxetine, Fluoxetine, and Nisoxetine
  作者：Morris Srebnik、P. V. Ramachandran、Herbert C. Brown

  DOI：10.1021/jo00248a005

  日期：1988.6