1-苄基-4-(苯胺基)哌啶-4-羧酸 | 85098-64-2

• 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 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-苄基-4-(苯胺基)哌啶-4-羧酸
• 中文别名: 1-苄基-4-(苯胺基)-哌啶-4-羧酸
• 英文名称: 1-benzyl-4-(phenylamino)piperidine-4-carboxylic acid
• 英文别名: 1-benzyl-4-phenylaminopiperidine-4-carboxylic acid；4-phenylamino-1-benzyl-4-piperidinecarboxylic acid；1-benzyl-4-phenylamino-4-carboxypiperidine；4-anilino-1-benzyl-piperidine-4-carboxylic acid；4-Anilino-1-benzyl-4-carboxypiperidin；4-Anilino-1-benzylpiperidin-1-ium-4-carboxylate
• CAS: 85098-64-2
• 化学式: C₁₉H₂₂N₂O₂
• mdl: MFCD00023753
• 分子量: 310.396
• InChiKey: YFSCBWDAVTYIMM-UHFFFAOYSA-N

物化性质

• 熔点：
  197-203°C
• 沸点：
  495.6±45.0 °C(Predicted)
• 密度：
  1.234±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶，加热）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.315
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090
• 储存条件：
  室温且干燥

制备方法与用途

1-苄基-4-苯胺基哌啶-4-羧酸是制备3-(4-甲氧羰基-1-哌啶基)-N-(2-苯乙酰氨基)丙酸甲酯的重要中间体。它是一种新型强效镇痛麻醉剂，因其半衰期极短、持续静滴不产生蓄积现象且不良反应较小，成为发达国家近期广泛使用的高效、快速、短时的麻醉性镇痛药。

反应信息

• 作为反应物：
  描述：

  1-苄基-4-(苯胺基)哌啶-4-羧酸 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.0h， 生成 4-(苯基丙酰氨基)哌啶-4-羧酸甲酯
  参考文献：
  名称：

  Syntheses, Biological Evaluation, and Molecular Modeling of ¹⁸F-Labeled 4-Anilidopiperidines as μ-Opioid Receptor Imaging Agents

  摘要：

  The synthesis, evaluation, and molecular modeling of a series of F-18-labeled 4-anilidopiperidines with high affinities for they-opioid receptor (mu-OR) are reported. On the basis of the high brain uptake and selective retention in brain regions that contain a high concentration of they-OR, combined with a good metabolic stability, [F-18]fluoro-pentyl carfentanil ([F-18]4) and 2-(+/-)[F-18]-fluoropropyl-sufentanil ([F-18]6) were selected as the lead compounds for further evaluation. The binding affinity to the human mu-OR was 0.74 and 0.13 nM for [F-18]4 and [F-18]6, respectively. In vitro autoradiography of [F-18]4 and [F-18]6 on rat brain sections produced patterns in accordance with the known distribution of mu-OR expression. Structure-activity relationships of the fluorinated compounds are discussed with respect to the interaction with an activated-state model of the mu-OR. Taken together, the in vivo and in vitro data indicate that [F-18]4 and [F-18]6 hold promise for studying they-opioid receptor in humans by means of positron emission tomography.

  DOI：

  10.1021/jm0507274
• 作为产物：
  描述：

  N-苄基哌啶酮 在 氢氧化钾 、 硫酸 、 溶剂黄146 作用下， 以 乙二醇 为溶剂， 反应 80.0h， 生成 1-苄基-4-(苯胺基)哌啶-4-羧酸
  参考文献：
  名称：

  Syntheses, Biological Evaluation, and Molecular Modeling of ¹⁸F-Labeled 4-Anilidopiperidines as μ-Opioid Receptor Imaging Agents

  摘要：

  The synthesis, evaluation, and molecular modeling of a series of F-18-labeled 4-anilidopiperidines with high affinities for they-opioid receptor (mu-OR) are reported. On the basis of the high brain uptake and selective retention in brain regions that contain a high concentration of they-OR, combined with a good metabolic stability, [F-18]fluoro-pentyl carfentanil ([F-18]4) and 2-(+/-)[F-18]-fluoropropyl-sufentanil ([F-18]6) were selected as the lead compounds for further evaluation. The binding affinity to the human mu-OR was 0.74 and 0.13 nM for [F-18]4 and [F-18]6, respectively. In vitro autoradiography of [F-18]4 and [F-18]6 on rat brain sections produced patterns in accordance with the known distribution of mu-OR expression. Structure-activity relationships of the fluorinated compounds are discussed with respect to the interaction with an activated-state model of the mu-OR. Taken together, the in vivo and in vitro data indicate that [F-18]4 and [F-18]6 hold promise for studying they-opioid receptor in humans by means of positron emission tomography.

  DOI：

  10.1021/jm0507274

文献信息

• INTERMEDIATES FOR THE PREPARATION OF REMIFENTANIL HYDROCHLORIDE
  申请人：Hameln Pharma Plus GmbH

  公开号：US20200131127A1

  公开（公告）日：2020-04-30

  A new intermediate for synthesizing 1-substituted-4-[phenyl(propanoyl)amino]piperidine-4-carbonitrile derivatives is laid open. Specifically set out is a method for use of this intermediate in the preparation of remifentanil. The enclosed shorter process offers a greater yield of products with higher purity as compared to methods reported in the prior art.

  一种用于合成1-取代-4-[苯基(丙酰基)氨基]哌啶-4-羧腈衍生物的新中间体被揭示。具体提出了一种利用该中间体在制备雷米芬太尼中的方法。这种包含的较短过程相比先前报道的方法，提供了更高纯度的产物更高的产量。
• SUBSTITUTED 4-AMINO-PIPERIDINES
  申请人：Gant Thomas G.

  公开号：US20100016365A1

  公开（公告）日：2010-01-21

  The present invention relates to new substituted 4-amino-piperidine opioid receptor modulators, pharmaceutical compositions thereof, and methods of use thereof.

  本发明涉及新的取代4-氨基哌啶类阿片受体调节剂，其药物组成物以及使用方法。
• Process for preparing remifentanil, intermediates thereof, use of said intermediates and processes for their preparation
  申请人：KERN PHARMA, S.L.

  公开号：EP1867635A1

  公开（公告）日：2007-12-19

  A process for preparing remifentanil by conversion of the nitrile group of a cyanopiperidinyl propanoate derivative to an ester group. Advantageously, with this process the number of steps for preparing remifentanil from commercial products is significantly reduced, compared to the processes known in the art.

  通过将氰基哌啶丙酸酯衍生物的腈基转化为酯基来制备雷米芬太尼的方法。优点是，与已知的工艺相比，使用这种方法从商业产品制备雷米芬太尼的步骤数量大大减少。
• [EN] SUBSTITUTED N-(2-(AMINO)-2-OXOETHYL)BENZAMIDE INHIBITORS OF AUTOTAXIN AND THEIR PREPARATION AND USE IN THE TREATMENT OF LPA-DEPENDENT OR LPA-MEDIATED DISEASES<br/>[FR] N-(2-AMINO)-2-OXOÉTRIYLBENZAMIDES SUBSTITUÉS EN TANT QU'INHIBITEURS D'AUTOTAXINE
  申请人：X RX DISCOVERY INC

  公开号：WO2015175171A1

  公开（公告）日：2015-11-19

  The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancer, lymphocyte homing, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis, and cholestatic pruritus, mediated at least in part by ATX.

  本发明涉及符合式I的化合物及药用盐，以及与之相关的合成、中间体、配方和用于治疗疾病的方法，包括癌症、淋巴细胞归巢、慢性炎症、神经病痛、纤维化疾病、血栓形成和胆汁淤积性瘙痒，至少部分由ATX介导。
• Synthesis and pharmacological evaluation of 4,4-disubstituted piperidines
  作者：John A. Colapret、George Diamantidis、H. Kenneth Spencer、Ted C. Spaulding、Frieda G. Rudo

  DOI：10.1021/jm00125a008

  日期：1989.5

  new class of piperidine derivatives is added to the increasing family of compounds related to fentanyl and carfentanil. Herein, we describe the synthesis and pharmacology of a number of 1-(arylethyl)-4-(acylamino)-4-[(acyloxy)-methyl]piperidines such as 9, 15, and 23. As expected, many of these congeners of fentanyl are extremely potent narcotic agonists. The aim of the study was to identify short-acting

  一类新的哌啶衍生物被添加到与芬太尼和卡芬太尼有关的化合物家族中。在这里，我们描述了许多1-（芳基乙基）-4-（酰基氨基）-4-[（酰氧基）-甲基]哌啶的合成和药理作用，例如9、15和23。芬太尼是非常有效的麻醉激动剂。该研究的目的是确定短效镇痛药（即，在小鼠热板试验中少于6分钟），以便在手术室中使用。许多药物被证明是中度和长期持续时间（即分别为6-15分钟和大于15分钟）。除了止痛活性外，许多化合物还表现出麻醉特性。提出并讨论了这些实体的构效关系。