4-(4-氟苯基)-3-(4-羟基-3-甲氧基苯氧基甲基)哌啶 | 112058-90-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 4-(4-氟苯基)-3-(4-羟基-3-甲氧基苯氧基甲基)哌啶
• 中文别名: (-)-反式-4-[4-(4'-氟苯基)-3-哌啶基甲基]-2-甲氧基苯酚
• 英文名称: (3S,4R)-4-(4-fluorophenyl)-3-(3-methoxy-4-hydroxyphenoxymethyl)piperidine
• 英文别名: (-)trans 4-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl)piperidine；BRL 36610A；Brl 36610；4-(4-Fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl)piperidine；4-[[(3S,4R)-4-(4-fluorophenyl)piperidin-3-yl]methoxy]-2-methoxyphenol
• CAS: 112058-90-9
• 化学式: C₁₉H₂₂FNO₃
• 分子量: 331.387
• InChiKey: DTXXMQRFTUCBHG-YOEHRIQHSA-N

物化性质

• 熔点：
  189-1920C
• 溶解度：
  氯仿（微溶）、甲醇（微溶、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  50.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  反式-4-(4-氟苯基)-3-羟甲基-1-甲基哌啶 在 palladium on activated charcoal 盐酸 、 氢气 、 三甲胺盐酸盐 、 sodium hydride 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、300.0 kPa 条件下， 反应 18.25h， 生成 4-(4-氟苯基)-3-(4-羟基-3-甲氧基苯氧基甲基)哌啶
  参考文献：
  名称：

  Synthesis of the major metabolites of Paroxetine

  摘要：

  Paroxetine is a well-known antidepressant, used worldwide in therapeutics. In comparison with other selective serotonin reuptake inhibitors, it exhibits the highest activity in serotonin reuptake inhibition. Paroxetine metabolism initially involves its demethylenation to the catechol intermediate, which is then O-methylated at positions C3 or C4. Herein, the chemistry resulting in the syntheses of these metabolites (3S,4R)-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine and (3S,4R)-4-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl) piperidine is described starting from the common intermediate (3S,4R)-4-(4-fluorophenyl)-3hydroxymethyl-1-methylpiperidine. Additionally, the common intermediate was used to synthesize paroxetine, which had the same structure and stereochemistry as commercial paroxetine, thereby confirming our synthetic route. (C) 2003 Elsevier Science (USA). All rights reserved.

  DOI：

  10.1016/s0045-2068(03)00040-3

文献信息

• Novel benzo[D][1,3]-dioxol derivatives
  申请人：Tung Roger

  公开号：US20070191432A1

  公开（公告）日：2007-08-16

  The present invention relates to an isotopologue of Compound 1 substituted with deuterium at the methylene carbon of the benzodioxol ring. The isotopologues of this invention selective serotonin reuptake inhibitors (SSRIs) and possess unique biopharmaceutical and metabolic properties compared to Compound 1. They may also be used to accurately determine the concentration of Compound 1 in biological fluids and to determine metabolic patterns of Compound 1 and its isotopologues. The invention further provides compositions comprising these deuterated isotopologues and methods of treating diseases and conditions that are responsive to increased neuronal serotonin transmission, alone and in combination with additional agents.

  本发明涉及一种在苯并二氧杂环环的亚甲基碳上取代氘的化合物1的同位素。本发明的同位素是选择性血清素再摄取抑制剂(SSRI)，与化合物1相比具有独特的生物制药和代谢特性。它们还可以用于准确确定生物液中化合物1的浓度，并确定化合物1及其同位素的代谢模式。本发明还提供了包含这些氘同位素的组合物以及治疗对增加神经元血清素传递敏感的疾病和病症的方法，单独或与其他药物联合使用。
• Novel benzo[d][1,3]-dioxol derivatives
  申请人：Tung Roger

  公开号：US20080287495A1

  公开（公告）日：2008-11-20

  The present invention relates to an isotopologue of Compound 1 substituted with deuterium at the methylene carbon of the benzodioxol ring. The isotopologues of this invention selective serotonin reuptake inhibitors (SSRIs) and possess unique biopharmaceutical and metabolic properties compared to Compound 1. They may also be used to accurately determine the concentration of Compound 1 in biological fluids and to determine metabolic patterns of Compound 1 and its isotopologues. The invention further provides compositions comprising these deuterated isotopologues and methods of treating diseases and conditions that are responsive to increased neuronal serotonin transmission, alone and in combination with additional agents.

  本发明涉及一种在苯二氧杂环环的亚甲基碳上用氘取代的化合物1的同位素。本发明的同位素选择性地抑制5-羟色胺再摄取，具有与化合物1相比独特的生物制药和代谢特性。它们还可用于准确测定生物液体中化合物1的浓度，并确定化合物1及其同位素的代谢模式。本发明还提供了包含这些氘同位素的组合物和治疗对增加神经元5-羟色胺传递敏感的疾病和病症的方法，单独或与其他药物联合使用。
• DEUTERATED BENZO[D][1,3]-DIOXOL DERIVATIVES
  申请人：Tung Roger

  公开号：US20100222589A1

  公开（公告）日：2010-09-02

  The present invention relates to an isotopologue of Compound 1 substituted with deuterium at the methylene carbon of the benzodioxol ring. The isotopologues of this invention selective serotonin reuptake inhibitors (SSRIs) and possess unique biopharmaceutical and metabolic properties compared to Compound 1. They may also be used to accurately determine the concentration of Compound 1 in biological fluids and to determine metabolic patterns of Compound 1 and its isotopologues. The invention further provides compositions comprising these deuterated isotopologues and methods of treating diseases and conditions that are responsive to increased neuronal serotonin transmission, alone and in combination with additional agents.

  本发明涉及一种在苯并二氧杂环环的亚甲基碳上用氘取代的化合物1的同位素。本发明的同位素选择性地抑制5-羟色胺再摄取抑制剂（SSRI），并且与化合物1相比具有独特的生物制药和代谢特性。它们还可以用于准确测定生物体液中化合物1的浓度，并确定化合物1及其同位素的代谢模式。本发明还提供了包含这些氘同位素的组合物和治疗对增加神经元5-羟色胺传递敏感的疾病和病症的方法，单独或与其他药物联合使用。
• NOVEL BENZO[d][1,3]-DIOXOL DERIVATIVES
  申请人：Tung Roger D.

  公开号：US20150196544A1

  公开（公告）日：2015-07-16

  The present invention relates to an isotopologue of Compound 1 substituted with deuterium at the methylene carbon of the benzodioxol ring. The isotopologues of this invention selective serotonin reuptake inhibitors (SSRIs) and possess unique biopharmaceutical and metabolic properties compared to Compound 1. They may also be used to accurately determine the concentration of Compound 1 in biological fluids and to determine metabolic patterns of Compound 1 and its isotopologues. The invention further provides compositions comprising these deuterated isotopologues and methods of treating diseases and conditions that are responsive to increased neuronal serotonin transmission, alone and in combination with additional agents.

  本发明涉及化合物1的同位素拓扑异构体，在苯并二氧杂环环的亚甲基碳上用氘取代。本发明的同位素拓扑异构体是选择性血清素再摄取抑制剂（SSRI），与化合物1相比具有独特的生物制药和代谢特性。它们还可以用于准确测定生物流体中化合物1的浓度，并确定化合物1及其同位素拓扑异构体的代谢模式。本发明还提供了包含这些氘化同位素拓扑异构体的组合物及其治疗对增加神经元血清素传递响应的疾病和病状的方法，单独使用或与其他药物联合使用。
• USE OF KNOWN COMPOUNDS AS D-AMINO ACID OXIDASE INHIBITORS
  申请人：TSENG Yufeng Jane

  公开号：US20170037448A1

  公开（公告）日：2017-02-09

  The invention utilizes virtual screening strategy to seek for current market drugs as anti-schizophrenia therapy drug repurposing. Drug repurposing strategy finds new uses other than the original medical indications of existing drugs. Finding new indications for such drugs will benefit patients who are in needs for a potential new therapy sooner since known drugs are usually with acceptable safety and pharmacokinetic profiles. In this study, repurposing marketed drugs for DAAO inhibitor as new schizophrenia therapy was performed with virtual screening on marketed drugs and its metabolites. The identified and available drugs and compounds were further confirmed with in vitro DAAO enzymatic inhibitory assay.