4-(4-甲氧基羰基亚苄基)哌啶-1-羧酸叔丁酯 | 209808-15-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物
• 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: 4-(4-甲氧基羰基亚苄基)哌啶-1-羧酸叔丁酯
• 英文名称: 4-(4-methoxycarbonylbenzylidene)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(4-(methoxycarbonyl)benzylidene)piperidine-1-carboxylate；Methyl 4-[(1-Boc-piperidin-4-ylidene)methyl]benzoate；tert-butyl 4-[(4-methoxycarbonylphenyl)methylidene]piperidine-1-carboxylate
• CAS: 209808-15-1
• 化学式: C₁₉H₂₅NO₄
• 分子量: 331.412
• InChiKey: PKNKIFGUCYQMRH-UHFFFAOYSA-N

物化性质

• 沸点：
  457.6±45.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-甲氧基羰基亚苄基)哌啶-1-羧酸叔丁酯 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以89 %的产率得到4-((1-(tert-butoxycarbonyl)piperidin-4-ylidene)methyl)benzoic acid
  参考文献：
  名称：

  发现具有 II 型抑制剂药效团的有效恶性疟原虫蛋白激酶 6 (PfPK6) 抑制剂

  摘要：

  疟疾是一种毁灭性的疾病，导致全球发病率和死亡率很高。对青蒿素联合疗法耐药性的上升表明有必要开发具有新作用机制的替代抗疟药。我们报告发现Ki8751作为必需激酶 PfPK6 的抑制剂。设计、合成并评估了 79 种衍生物的 PfPK6 抑制和抗疟原虫活性。通过群体效率分析，我们确定了与 II 型抑制剂药效团一致的支架上关键群体的重要性。我们强调了尾部基团上有助于抗疟原虫活性的修饰，最终发现了化合物67 （一种 PfPK6 抑制剂（IC 50 = 13 nM），对恶性疟原虫血液阶段（EC 50 = 160 nM）具有活性）和化合物79 ，一种 PfPK6 抑制剂 (IC 50 < 5 nM)，对恶性疟原虫血液期 (EC 50 = 39 nM) 和伯氏疟原虫肝脏期 (EC 50 = 220 nM) 具有双阶段抗疟原虫活性。

  DOI：

  10.1016/j.ejmech.2022.115043
• 作为产物：
  描述：

  对甲基苯甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 24.0h， 生成 4-(4-甲氧基羰基亚苄基)哌啶-1-羧酸叔丁酯
  参考文献：
  名称：

  Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers

  摘要：

  Opioid receptors, including the mu- and delta-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.

  DOI：

  10.1021/ml300083p

文献信息

• [EN] IMIDAZO [2, 1-F] [1, 2, 4] TRIAZIN-4-AMINE DERIVATIVES AS TLR7 AGONIST<br/>[FR] DÉRIVÉS D'IMIDAZO[2,1-F] [1, 2, 4] TRIAZIN-4-AMINE UTILISÉS EN TANT QU'AGONISTES DE TLR7
  申请人：BEIGENE LTD

  公开号：WO2020160711A1

  公开（公告）日：2020-08-13

  Disclosed herein is an imidazo [2, 1-f] [1, 2, 4] triazin-4-amine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof useful as a TLR7 agonist, and a pharmaceutical composition comprising the same. Also disclosed herein is a method of treating cancer using the imidazo [2, 1-f] [1, 2, 4] triazin-4-amine derivative or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as TLR7 agonist.

  披露的是一种咪唑[2,1-f][1,2,4]三嗪-4-胺衍生物或其立体异构体，或其药用可接受盐，用作TLR7激动剂，以及包含该化合物的药物组合物。还披露了一种使用咪唑[2,1-f][1,2,4]三嗪-4-胺衍生物或其立体异构体，或其药用可接受盐作为TLR7激动剂来治疗癌症的方法。
• Cyclic amine compounds as CCR5 antagonists
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06562978B1

  公开（公告）日：2003-05-13

  A compound of formula (I) (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R1 and R2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N+—R5.Y−(R5 is a hydrocarbon group; Y− is a counter anion); R3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G1 is a bond, CO or SO2; G2 is CO, SO2, NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G1 is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  式（I）的化合物（其中R1是氢原子，可能被取代的碳氢基团，可能被取代的非芳香杂环基团，R2是可能被取代的碳氢基团，可能被取代的非芳香杂环基团，或R1和R2可以彼此结合与A一起形成可能被取代的杂环基团；A是N或N+—R5.Y−（R5是碳氢基团；Y−是一个对离子）；R3是可能被取代的环烃基团或可能被取代的杂环基团；n为0或1；R4是氢原子，可能被取代的碳氢基团，可能被取代的杂环基团，可能被取代的烷氧基团，可能被取代的芳基氧基团，或可能被取代的氨基团；E是可能被除氧以外的基团取代的二价脂肪族碳氢基团；G1是键，CO或SO2；G2是CO，SO2，NHCO，CONH或OCO；J是亚甲基或氮原子；Q和R中的每一个是键或可能被取代的二价C1-3脂肪族碳氢基团；条件是当G2为OCO时J为亚甲基，当另一个为键时Q和R中的一个不是键，当G1为键时Q和R中的每一个都不被氧基取代）或其盐具有强大的CCR5拮抗活性，并可优势用于治疗或预防人类体内各种HIV引起的传染病（例如艾滋病）。
• <i>N,N</i>-Diethyl-4-(phenylpiperidin-4-ylidenemethyl)benzamide:  A Novel, Exceptionally Selective, Potent δ Opioid Receptor Agonist with Oral Bioavailability and Its Analogues
  作者：Zhong-Yong Wei、William Brown、Bryan Takasaki、Niklas Plobeck、Daniel Delorme、Fei Zhou、Hua Yang、Paul Jones、Lars Gawell、Helene Gagnon、Ralf Schmidt、Shi-Yi Yue、Chris Walpole、Kemal Payza、Stephane St-Onge、Maryse Labarre、Claude Godbout、Andrea Jakob、Joanne Butterworth、Augustus Kamassah、Pierre-Emmanuel Morin、Denis Projean、Julie Ducharme、Edward Roberts

  DOI：10.1021/jm000229p

  日期：2000.10.1

  and exhibit excellent selectivity for the delta opioid receptor as full agonists. 6a, the simplest structure in the class, exhibited an IC(50) = 0.87 nM for the delta opioid receptors and extremely high selectivity over the mu receptors (mu/delta = 4370) and the kappa receptors (kappa/delta = 8590). Rat liver microsome studies on a selected number of compounds show these olefinic piperidine compounds

  描述了新型δ阿片受体激动剂N，N-二乙基-4-（苯基哌啶丁-4-亚甲基甲基）苯甲酰胺（6a）及其类似物的设计，合成和药理学评价。这些化合物通过用含有环外碳碳双键的哌啶环取代哌嗪环而正式衍生自SNC-80（2），发现它们以高亲和力结合，并且对作为完全激动剂的δ阿片受体表现出优异的选择性。图6a是同类中最简单的结构，其δ阿片受体的IC（50）= 0.87 nM，对mu受体（mu / del = 4370）和kappa受体（kappa / delta = 8590）的选择性极高。对选定数量的化合物进行的大鼠肝微粒体研究显示，这些烯属哌啶化合物（6）比SNC-80稳定得多。这一系列新颖的化合物似乎以与SNC-80类似的方式与δ阿片受体相互作用，因为它们表现出相似的SAR。基于二苯甲基醇的脱水（7）和乙烯基溴的Suzuki偶联反应（8），已经建立了两种合成这些化合物的通用方法，据报道。
• [EN] DIARYLMETHYLIDENE PIPERIDINE DERIVATIVES, PREPARATIONS THEREOF AND USES THEREOF<br/>[FR] DERIVES DE DIARYLMETHYLIDENE PIPERIDINE, LEURS PROCEDES DE PREPARATION ET LEURS UTILISATIONS
  申请人：ASTRAZENECA AB

  公开号：WO2004063157A1

  公开（公告）日：2004-07-29

  Compounds of general formula: wherein R1, R2, R3, R4, and R5 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

  通式化合物：其中R1、R2、R3、R4和R5如规范中定义，以及其盐、对映体以及包括这些化合物的药物组合物已经准备好。它们在治疗中很有用，特别是在疼痛管理方面。
• [EN] DIARYLMETHYLIDENE PIPERIDINE DERIVATIVES, PREPARATIONS THEREOF AND USES THEREOF<br/>[FR] DERIVES DE DIARYLMETHYLIDENE PIPERIDINE, PREPARATIONS A BASE DE CES DERIVES ET PROCEDES DE LEUR UTILISATION
  申请人：ASTRAZENECA AB

  公开号：WO2005066127A1

  公开（公告）日：2005-07-21

  Compounds of formula: wherein R1, R2, and R3 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

  其中R1、R2和R3如规范中定义的化合物，以及其盐、对映体和包括这些化合物的药物组合物已经准备好。它们在治疗中很有用，特别是在疼痛管理中。