ethyl ((5-chloroquinolin-8-yl)oxy)acetate | 88349-90-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl ((5-chloroquinolin-8-yl)oxy)acetate
• 英文别名: ethyl 2-[(5-chloroquinolin-8-yl)oxy]acetate；ethyl (5-chloro-8-quinolinoxy)acetate；5-chloro-quinoline-8-oxy-acetic acid ethylester；ethyl 5-chloro-quinolin-8-oxy-acetate；ethyl (5-chloro-8-quinolineoxy)acetate；Ethyl [(5-chloroquinolin-8-yl)oxy]acetate；ethyl 2-(5-chloroquinolin-8-yl)oxyacetate
• CAS: 88349-90-0
• 化学式: C₁₃H₁₂ClNO₃
• mdl: MFCD04275530
• 分子量: 265.696
• InChiKey: JEMXUSHXYOXNFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 储存条件：
  -20°C

制备方法与用途

A2793是一种有效的TWIK相关酸敏感K+通道1(TASK-1)的抑制剂，其IC50值为6.8 μM。

反应信息

• 作为反应物：
  描述：

  ethyl ((5-chloroquinolin-8-yl)oxy)acetate 在 一水合肼 作用下， 以 乙醇 为溶剂， 以82%的产率得到2-((2-methylquinolin-8-yl)oxy)acetohydrazide
  参考文献：
  名称：

  新香豆素附加恶二唑的合成、结构分析、DFT 计算和能量框架，通过靶向 VEGF 介导的血管生成来逆转腹水恶性肿瘤

  摘要：

  腹水恶性肿瘤是发病率的常见原因，并且在许多癌症中存在严重的管理问题。血管生成通过血管内皮生长因子 (VEGF) 在腹水肿瘤的预后中起主要作用。抑制VEGF是腹水肿瘤消退的关键策略之一。该研究的目的是合成一类新型 VEGF 抑制剂，用于治疗腹水肿瘤恶性肿瘤。作为一种方法，在多步骤过程中合成了一系列新的 1, 3, 4-恶二唑衍生物，其中包含香豆素-3-取代的芳基和杂芳基部分 ( 7a-l )。这些化合物的结构通过 IR、1 H、13C、核磁共振、质谱和元素分析。新合成的分子通过 MTT 和台盼蓝试验针对 ACHN、A375、SIHA、Skov3 和 EAC 等多种细胞系进行细胞筛选，鉴定出IC 50 -9 µM 的化合物 ( 7k )为铅生物活性分子。此外，VEGF 诱导的非致瘤性 CAM 和 RAT 角膜试验揭示了化合物 ( 7k ) 的血管预防功效。在体外研究中证明了VEGF的表达和相对

  DOI：

  10.1016/j.molstruc.2021.132173
• 作为产物：
  描述：

  ethyl 2-(quinolin-8-yloxy)acetate 在 三氯异氰尿酸 作用下， 以 乙腈 为溶剂， 以75%的产率得到ethyl ((5-chloroquinolin-8-yl)oxy)acetate
  参考文献：
  名称：

  对8取代的喹啉进行无金属，区域选择性，远程C–H卤化的通用方法†

  摘要：

  已经建立了一种操作简单且无金属的方案，用于一系列8取代的喹啉衍生物的几何上C5–H卤化。该反应在室温下在空气中进行，用廉价且原子经济的三卤代异氰尿酸作为卤素源（仅0.36当量）。在喹啉方面观察到异常高的通用性，并且在大多数情况下，反应以完全的区域选择性进行。在8位上具有各种取代基的喹啉仅以良好或优异的收率得到了C5卤代产物。氨基磷酸酯，叔酰胺，ñ -烷基/ Ñ，Ñ喹啉-8-胺，以及烷氧基喹啉的二烷基，和脲衍生物在C5位上被卤代第一次通过远程功能化。该方法为具有优异的官能团耐受性的卤代喹啉提供了一种非常经济的途径，从而为现有的喹啉-8-酰胺衍生物的远程官能化方法提供了很好的补充，并拓宽了远程官能化的领域。通过合成几种具有生物学和药学意义的化合物，进一步展示了该方法的实用性。

  DOI：

  10.1039/c7sc04107a

文献信息

• Biphenyl-Substituted Spirocyclic Ketoenols
  申请人：Bretschneider Thomas

  公开号：US20110306499A1

  公开（公告）日：2011-12-15

  The invention relates to novel compounds of the formula (I) in which W, X, Y, Z and CKE have the meanings given above, to a plurality of processes and intermediates for their preparation and to their use as pesticides and/or herbicides, and also to selective herbicidal compositions comprising, firstly, the compounds of the formula (I) and, secondly, at least one crop plant compatibility-improving compound. The invention further relates to the boosting of the action of crop protection compositions comprising compounds of the formula (I) through the additions of ammonium salts or phosphonium salts and optionally penetrants.

  该发明涉及以下式(I)的新化合物： 其中 W、X、Y、Z和CKE具有上述给定的含义，以及它们的制备的多种方法和中间体，以及它们作为杀虫剂和/或除草剂的用途，还涉及包括第一，式(I)的化合物和第二，至少一种作物植物相容性改进化合物的选择性除草组合物。 该发明还涉及通过添加铵盐或磷盐以及可选的渗透剂来增强包含式(I)的化合物的作物保护组合物的作用。
• Chemically Modified Derivatives of the Activator Compound Cloxyquin Exert Inhibitory Effect on TRESK (K_2P18.1) Background Potassium Channel
  作者：Miklós Lengyel、Ferenc Erdélyi、Enikő Pergel、Ágnes Bálint-Polonka、Alice Dobolyi、Péter Bozsaki、Mária Dux、Kornél Király、Tamás Hegedűs、Gábor Czirják、Péter Mátyus、Péter Enyedi

  DOI：10.1124/mol.118.115626

  日期：2019.6

  Cloxyquin has been reported as a specific activator of TRESK [TWIK-related spinal cord K+ channel (also known as K2P18.1)] background potassium channel. In this study, we have synthetized chemically modified analogs of cloxyquin and tested their effects on TRESK and other K2P channels. The currents of murine K2P channels, expressed heterologously in Xenopus oocytes, were measured by two-electrode voltage clamp, whereas the native background K+ conductance of mouse dorsal root ganglion (DRG) neurons was examined by the whole-cell patch-clamp method. Some of the analogs retained the activator character of the parent compound, but, more interestingly, other derivatives inhibited mouse TRESK current. The inhibitor analogs (A2764 and A2793) exerted state-dependent effects. The degree of inhibition by 100 µ M A2764 (77.8% ± 3.5%, n = 6) was larger in the activated state of TRESK (i.e., after calcineurin-dependent stimulation) than in the resting state of the channel (42.8% ± 11.5% inhibition, n = 7). The selectivity of the inhibitor compounds was tested on several K2P channels. A2793 inhibited TWIK-related acid-sensitive K+ channel (TASK)-1 (100 µ M, 53.4% ± 13, 5%, n = 5), while A2764 was more selective for TRESK, it only moderately influenced TREK-1 and TWIK-related alkaline pH-activated K+ channel. The effect of A2764 was also examined on the background K+ currents of DRG neurons. A subpopulation of DRG neurons, prepared from wild-type animals, expressed background K+ currents sensitive to A2764, whereas the inhibitor did not affect the currents in the DRG neurons of TRESK-deficient mice. Accordingly, A2764 may prove to be useful for the identification of TRESK current in native cells, and for the investigation of the role of the channel in nociception and migraine. SIGNIFICANCE STATEMENT TRESK background potassium channel is a potential pharmacological target in migraine and neuropathic pain. In this study, we have identified a selective inhibitor of TRESK, A2764. This compound can inhibit TRESK in native cells, leading to cell depolarization and increased excitability. This new inhibitor may be of use to probe the role of TRESK channel in migraine and nociception.

  有报道称，Cloxyquin是一种特异性激活TRESK[TWIK相关脊髓K⁺通道（也称为K2P18.1）]背景钾通道的物质。在本研究中，我们合成了Cloxyquin的化学修饰类似物，并检测了它们对TRESK和其他K2P通道的影响。通过双电极电压钳技术在爪蟾卵母细胞中异源表达的小鼠K2P通道电流；而通过全细胞膜片钳技术检测小鼠背根神经节（DRG）神经元的内源性背景K⁺电导。部分类似物保持了母体化合物的激活特性，但更有趣的是，其他衍生物抑制了小鼠TRESK电流。抑制剂类似物（A2764和A2793）发挥了状态依赖性效应。100 µ M A2764对TRESK的抑制程度（77.8% ± 3.5%，n = 6）在TRESK激活状态（即环孢菌素依赖性刺激后）大于通道静息状态（42.8% ± 11.5%抑制，n = 7）。对几种K2P通道进行了抑制剂化合物的选择性测试。A2793抑制了TWIK相关酸敏感K⁺通道（TASK）-1（100 µ M，53.4% ± 13.5%，n = 5），而A2764对TRESK更具选择性，仅适度影响TREK-1和TWIK相关碱性pH激活K⁺通道。还检测了A2764对DRG神经元背景K⁺电流的影响。从野生型动物中准备的一组DRG神经元对A2764敏感的背景K⁺电流，而抑制剂不影响TRESK缺陷小鼠的DRG神经元的电流。因此，A2764可能有助于在原代细胞中识别TRESK电流，并研究该通道在痛觉和偏头痛中的作用。**重要声明** TRESK背景钾通道是偏头痛和神经性疼痛的潜在药物靶点。在本研究中，我们鉴定了一种对TRESK具有选择性的抑制剂A2764。该化合物可以抑制原代细胞中的TRESK，导致细胞去极化和兴奋性增加。这种新型抑制剂可能有助于探究TRESK通道在偏头痛和痛觉中的作用。
• Halogen Alkoxy Spirocyclic Tetramic and Tetronic Acid Derivatives
  申请人：Fischer Reiner

  公开号：US20100279873A1

  公开（公告）日：2010-11-04

  The invention relates to novel haloalkoxyspirocyclic tetramic and tetronic acid derivatives of the formula (I) in which W, X, Y, Z, A, D, Q 1 , Q 2 , m and G have the meanings given above, to a plurality of processes and intermediates for their preparation, and to their use as pesticides and/or herbicides. Moreover, the invention provides selective herbicidal compositions comprising, firstly, haloalkoxyspirocyclic tetramic and tetronic acid derivatives and, secondly, a crop plant compatibility-improving compound. The invention furthermore relates to increasing the action of crop protection compositions comprising compounds of the formula (I) through the addition of ammonium salts or phosphonium salts and optionally penetrants.

  该发明涉及公式（I）的新型卤代烷氧螺环四酮和四酸衍生物， 其中W、X、Y、Z、A、D、Q1、Q2、m和G具有上述给定的含义， 以及用于它们的制备的多种过程和中间体，以及它们作为杀虫剂和/或除草剂的用途。 此外，该发明提供了包括首先卤代烷氧螺环四酮和四酸衍生物，其次是一种改善作物植物相容性的化合物的选择性除草剂组合物。 该发明还涉及通过添加铵盐或磷盐以及可选的渗透剂来增强包含公式（I）化合物的作物保护组合物的作用。
• Facile Synthesis of Tricyclic Oxazino- or Oxazepino-Fused Tetrahydroquinolines via Intramolecular Reductive Amidation
  作者：Nirup Mondal、Shyamal Mondal、Arindam Maity、Subhendu Naskar、Rupankar Paira、Abhijit Hazra、Krishnendu Sahu、Pritam Saha、Saktipada Das、Sukdeb Banerjee

  DOI：10.1055/s-0030-1260056

  日期：2011.7

  Reductive cyclization of ω-(8-quinolyloxy)alkyl esters by zinc in acetic acid is shown to constitute a convenient methodology for the synthesis of oxazino- or oxazepino-fused tetrahydroquinolines. It is operationally simple, requires a short reaction time, and provides excellent yields.

  乙酸中锌促进的（8-喹啉氧基）烷基酯还原环化反应被证明是一种便捷的方法，用于合成含氧杂环或氧杂环并环的氢化喹啉类化合物。该方法操作简单，反应时间短，并能提供优异的产率。
• Alkoxyalkyl-Substituted Cyclic Keto-Enols
  申请人：Fischer Reiner

  公开号：US20090298828A1

  公开（公告）日：2009-12-03

  The invention relates to new alkoxyalkyl-substituted cyclic ketoenols of the formula (I) in which A, B, D, G, W, X, Y and Z have the definitions indicated above, to a number of processes and intermediates for their preparation, and to their use as pesticides and/or herbicides and/or microbicides. The invention further provides selectively herbicidal, compositions which comprise alkoxyalkyl-substituted cyclic ketoenols on the one hand and a crop plant tolerance promoter compound on the other. The invention further relates to the boosting of the action of crop protection compositions comprising compounds of the formula (I) through the additions of ammonium salts or phosphonium salts and optionally penetration promoters.

  该发明涉及公式（I）中A、B、D、G、W、X、Y和Z具有上述定义的新烷氧基烷基取代的环烯醇化合物，以及它们的制备过程和中间体，以及它们作为杀虫剂和/或除草剂和/或微生物杀灭剂的用途。该发明还提供了一种选择性除草剂，其中一方包括烷氧基烷基取代的环烯醇化合物，另一方包括作物植物耐受促进剂化合物的组合物。该发明还涉及通过添加铵盐或磷盐以及可选的渗透促进剂来增强包含公式（I）化合物的作物保护组合物的作用。