N-Boc-4-(4-氯苄基)哌啶-4-羧酸乙酯 | 174605-91-5

• 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: N-Boc-4-(4-氯苄基)哌啶-4-羧酸乙酯
• 英文名称: 1-tert-butyl 4-ethyl 4-(4-chlorobenzyl)piperidine-1,4-dicarboxylate
• 英文别名: Ethyl N-Boc-4-(4-chlorobenzyl)piperidine-4-carboxylate；1-O-tert-butyl 4-O-ethyl 4-[(4-chlorophenyl)methyl]piperidine-1,4-dicarboxylate
• CAS: 174605-91-5
• 化学式: C₂₀H₂₈ClNO₄
• 分子量: 381.9
• InChiKey: QTVIWIWJGWSTDC-UHFFFAOYSA-N

物化性质

• 熔点：
  69-73 °C
• 沸点：
  455.1±35.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• WGK Germany：
  3
• 危险品标志：
  T,N
• 危险品运输编号：
  UN 2811 6.1/PG 3

反应信息

• 作为反应物：
  描述：

  N-Boc-4-(4-氯苄基)哌啶-4-羧酸乙酯 在 sodium hexamethyldisilazane 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 145.5h， 生成 tert-butyl (Z)-5-(4-(4-(tert-butoxy)-3-hydroxy-4-oxobut-2-enoyl)-4-(4-chlorobenzyl)- piperidine-1-carbonyl)-2-((2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azahexadecan-16-yl)oxy)benzoate
  参考文献：
  名称：

  Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors

  摘要：

  The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC₅₀ of 72 ± 2 nM and its 8-C-glucoside orientin with an IC₅₀ of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 Å resolution and quambalarine B at 2.5 Å resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.

  DOI：

  10.1016/j.ejmech.2020.112754
• 作为产物：
  描述：

  哌啶-4-甲酸乙酯 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.67h， 生成 N-Boc-4-(4-氯苄基)哌啶-4-羧酸乙酯
  参考文献：
  名称：

  发现，合成，生物学评估和基于哌啶衍生物作为乙酰胆碱结合蛋白配体的基于结构的优化。

  摘要：

  同源的α7烟碱受体（α7nAChR）在人脑中广泛表达，可以被激活以抑制神经炎症，氧化应激和神经性疼痛。因此，许多α7nAChR激动剂已作为抗阿尔茨海默氏病或​​抗精神病疗法进入临床试验。但是，到目前为止，还没有全长α7受体的高分辨率晶体结构。由于来自阔叶林的乙酰胆碱结合蛋白（AChBP）与nAChRs的α-亚基关系最密切，因此已将其用作nAChR的α-亚基的N末端结构域的模板，以研究nAChR的分子识别过程-配体相互作用，并鉴定具有潜在nAChR样活性的配体。在此，我们报告了通过筛选发现和优化新型乙酰胆碱结合蛋白配体的方法，结构-活动关系和基于结构的设计。我们在体外手动筛选了偏重于CNS的内部化合物库，并将化合物1（哌啶衍生物）鉴定为对AChBP具有中等结合亲和力的初始化合物（在100 nmol / L下抑制率为17.2％）。在第一轮优化过程中，以化合物2（在100 nmol / L处抑制率为21

  DOI：

  10.1038/aps.2016.124

文献信息

• Dioxobutanoic acid derivatives as inhibitors of influenza endonuclease
  申请人：Merck & Co., Inc.

  公开号：US05475109A1

  公开（公告）日：1995-12-12

  Dioxobutanoic acids substituted with piperidine or similar N-substituted saturated cycloalkyls are found to inhibit the cap-dependent endonuclease of influenza virus. These compounds are useful in the prevention or treatment of infection by influenza virus and the treatment of influenza, either as compound, pharmaceutically acceptable salts,. pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating influenza and methods of preventing or treating infection by influenza virus are also described.

  用哌啶或类似N-取代饱和环烷基取代的二酮丁酸被发现能抑制流感病毒的依赖帽端核酸酶。这些化合物在预防或治疗流感病毒感染以及治疗流感方面是有用的，无论是作为化合物、药学上可接受的盐、药用组合成分，无论是否与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合在一起。还描述了治疗流感的方法以及预防或治疗流感病毒感染的方法。
• THERAPEUTIC COMPOUNDS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20130324576A1

  公开（公告）日：2013-12-05

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof in which m, n, W, X, Y, Z, R, R 1 , R 2 , R 3 and R 4 are as defined in the specification, for use in therapy.

  本发明提供了式(I)的化合物及其药学上可接受的盐，其中m、n、W、X、Y、Z、R、R1、R2、R3和R4如规范中定义，用于治疗。
• [EN] SULFONYL PIPERIDINE DERIVATIVES AND THEIR USE FOR TREATING PROKINETICIN MEDIATED DISEASES<br/>[FR] DÉRIVÉS DE SULFONYLPIPÉRIDINE ET LEUR UTILISATION POUR LE TRAITEMENT DE MALADIES MÉDIÉES PAR UNE PROKINÉTICINE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013179024A1

  公开（公告）日：2013-12-05

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof : (I) in which m, n, W, X, Y, Z, R1, R2, R3 and R4 are as defined in the specification, for use in the treatment or prevention of a diseases o conition mediated by a prokineticin, such as psychiatric and neurological conitions.

  本发明提供了以下式（I）的化合物及其药学上可接受的盐：（I）其中m、n、W、X、Y、Z、R1、R2、R3和R4如规范中定义，用于治疗或预防由前动力素介导的疾病或状况，如精神疾病和神经病状。
• SULFONYL PIPERIDINE DERIVATIVES AND THEIR USE FOR TREATING PROKINETICIN MEDIATED DISEASES
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20150111922A1

  公开（公告）日：2015-04-23

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof: (I) in which m, n, W, X, Y, Z, R 1 , R 2 , R 3 and R 4 are as defined in the specification, for use in the treatment or prevention of a diseases o conition mediated by a prokineticin, such as psychiatric and neurological conditions.

  本发明提供了公式（I）的化合物及其药学上可接受的盐：（I）其中m、n、W、X、Y、Z、R1、R2、R3和R4如规范中所定义，用于治疗或预防由前动力素介导的疾病或情况，例如精神和神经疾病。
• US5475109A
  申请人：——

  公开号：US5475109A

  公开（公告）日：1995-12-12