(3S,4R)-4-nitrophenyl 3-((benzo[d][1,3]dioxol-(2,2-d2)-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate | 1005412-34-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S,4R)-4-nitrophenyl 3-((benzo[d][1,3]dioxol-(2,2-d2)-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate
• 英文别名: (3S,4R)-4-nitrophenyl 3-((2,2-d2-benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate；4-nitrophenyl (3S,4R)-3-(((benzo[d][1,3]dioxol-5-yl-2,2-d2)oxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate；(4-nitrophenyl) (3S,4R)-3-[(2,2-dideuterio-1,3-benzodioxol-5-yl)oxymethyl]-4-(4-fluorophenyl)piperidine-1-carboxylate
• CAS: 1005412-34-9
• 化学式: C₂₆H₂₃FN₂O₇
• 分子量: 496.46
• InChiKey: NODNWVRWWBITOS-YPGRDDPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  103
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-nitrophenyl 3-((benzo[d][1,3]dioxol-(2,2-d2)-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate 生成 (3S,4R)-3-((2,2-d2-benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine
  参考文献：
  名称：

  [EN] SYNTHESIS OF DEUTERATED CATECHOLS AND BENZO[D][1,3] DIOXOLES AND DERIVATIVES THEREOF
  [FR] SYNTHÈSE DE BENZO[D][1,3]DIOXOLES ET DE CATÉCHOLS DEUTÉRIÉS, AINSI QUE DE LEURS DÉRIVÉS

  摘要：

  本发明提供了一种方便高效的合成d2-苯并[d][1,3]二氧杂环的方法。

  公开号：

  WO2009035652A1
• 作为产物：
  描述：

  ((3S,4R)-4-(4-fluorophenyl)-1-methylpiperidin-3-yl)methylmethanesulfonate hydrochloride 在 四丁基溴化铵 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 10.0h， 生成 (3S,4R)-4-nitrophenyl 3-((benzo[d][1,3]dioxol-(2,2-d2)-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Altering Metabolic Profiles of Drugs by Precision Deuteration: Reducing Mechanism-Based Inhibition of CYP2D6 by Paroxetine

  摘要：

  本研究展示了选择性氘代替作为改善临床相关药物代谢动力学相互作用的一种手段。碳-氘键比对应的碳-氢键更稳定。利用精确氘代平台，帕罗西汀的亚甲基二氧碳上的两个氢原子被氘替代。新化合物CTP-347 \[(3 S ,4 R )-3-((2,2-二氘苯并[ d \]1,3-二氧ol-5-yloxy)甲基)-4-(4-氟苯基)哌啶\]展示了与未修饰的帕罗西汀类似的对血清素受体的选择性，以及在体外大鼠突触体模型中相似的神经递质摄取抑制。然而，人体肝微粒体对CTP-347的清除速度比帕罗西汀更快，原因是对CYP2D6的失活减少。在一期临床研究中，CTP-347在人体内代谢更快，并表现出比帕罗西汀更低的药代动力学蓄积指数。这些代谢特征的改变导致CTP-347与两种其他CYP2D6代谢药物（他莫昔芬（体外）和右美沙芬（人体））之间的药物-药物相互作用显著减少。我们的结果表明，精确氘代可以改善现有药物疗法的代谢特征，而不影响其内在药理作用。

  DOI：

  10.1124/jpet.115.223768

文献信息

• NOVEL BENZO[D][1,3]-DIOXOL DERIVATIVES
  申请人：Tung Roger

  公开号：US20080033011A1

  公开（公告）日：2008-02-07

  The present invention relates to an isotopologue of paroxetine 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 paroxetine. They may also be used to accurately determine the concentration of paroxetine in biological fluids and to determine metabolic patterns of paroxetine 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.

  本发明涉及一种取代苯并二氧戊环环上亚甲基碳上的氘代帕罗西汀同位素。本发明的同位素是选择性血清素再摄取抑制剂(SSRIs)，与帕罗西汀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液体中帕罗西汀的浓度以及确定帕罗西汀及其同位素的代谢模式。本发明还提供了包含这些氘代同位素的组合物和治疗对增加神经元血清素传递敏感的疾病和状况的方法，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：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。
• 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。
• Synthesis of deuterated catechols and benzo[D][1,3]dioxoles and derivatives thereof
  申请人：Jones Andrew D.

  公开号：US20090143432A1

  公开（公告）日：2009-06-04

  The present invention provides a convenient and efficient process for the synthesis of d 2 -benzo[d][1,3]dioxoles.