ethyl [(2-methyl-8-aminoquinolin-6-yloxy)acetate] | 257892-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl [(2-methyl-8-aminoquinolin-6-yloxy)acetate]
• 英文别名: ethyl[(2-methyl-8-aminoquinolin-6-yloxy)acetate]；ethyl[(8-amino-2-methylquinolin-6-yloxy)acetate]；ethyl (2-methyl-8-aminoquinolin-6-yloxy)acetate；ethyl (8-amino-2-methylquinolin-6-yloxy)acetate；ethyl-2-(8-amino-2-methyl-6-quinolyl)acetate；ethyl 2-(8-amino-2-methylquinolin-6-yl)oxyacetate
• CAS: 257892-18-5
• 化学式: C₁₄H₁₆N₂O₃
• 分子量: 260.293
• InChiKey: DFIXRLWRPDMPNB-UHFFFAOYSA-N

物化性质

• 沸点：
  432.2±40.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  74.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl [(2-methyl-8-aminoquinolin-6-yloxy)acetate] 在 吡啶 、 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 (8-Benzenesulfonylamino-2-formyl-quinolin-6-yloxy)-acetic acid ethyl ester
  参考文献：
  名称：

  喹啉基侧臂作为潜在的锌（II）荧光团的氮杂冠醚的合成

  摘要：

  合成了两个新的荧光团12和13，它们由diaza-18-crown-6配体组成，其中含有两个基于喹啉的侧臂，结构上类似于Zn（II）荧光团TSQ（1）和Zinquin（2），作为潜在的Zn（II） ）以三乙酰氧基硼氢化钠（NaBH（OAc）3）为还原剂，通过diaza-18-crown-6与8-zasulfonamido-2-quinoline carboxaldehyde 6和8-phenylsulfonamido-6-quinolyloxyacetate-2-carboxaldehyde 11进行还原胺化反应的荧光团。配体12和13的初步光物理性质结果表明，它们具有有效的Zn 2+化学传感器所必需的特性。还报道了固态结构12。

  DOI：

  10.1016/s0040-4020(02)00451-9
• 作为产物：
  描述：

  8-amino-6-methoxy-2-methylquinoline 在 吡啶 、 三溴化硼 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 12.0h， 生成 ethyl [(2-methyl-8-aminoquinolin-6-yloxy)acetate]
  参考文献：
  名称：

  摘要：

  Zinc(II) specific fluorophores are of substantial importance in the study of intracellular Zn2+. Two such widely used fluorophores are 2-methyl-8-(4-toluenesulfonamido)-6-quinolyloxyacetic acid, Zinquin (1), and its ethyl ester, Zinquin ester (2), which fluoresce strongly when bound by Zn2+. To gain insight into the factors affecting the fluorescence of such fluorophores the closely related 4-methyl-N-(6-methoxy-2-methyl-8-quinolyl)-benzenesulfonamide (3), and nine analogues (4-12), substituted at sulfur by nine different substituents have been prepared and their fluorescing characteristics and those of their Zn2+ complexes have been examined. The nine substituents are: 2,2,2-trifluoroethyl (4), 4-methoxyphenyl (5), 4-acetamidophenyl (6), 4-bromophenyl (7), 4-nitrophenyl (8), 3-trifluoromethylphenyl (9), naphth-1-yl (10), naphth-2-yl (11) and 5-dimethylaminonaphth-1-yl (12). Under neutral conditions in 75/25% v/v ethanol/water solutions, (3)-(7) and (9)-(11) fluoresce weakly in the free state, (8) does not fluoresce and (12) fluoresces strongly. Ultraviolet (UV)- visible spectroscopy shows that (3)-(12) complex to Zn2+, but unlike the remainder, the complexes of (8) and (12) do not fluoresce, with those possessing electron-withdrawing substituents, (4) and (9), being the most fluorescent. On this basis ethyl-2-(2-methyl- quinolyloxy-8-(2,2,2-trifluoroethylsulfonamido)) acetate (19) was prepared and its Zn2+ complex was found to be substantially more fluorescent than that of (2).

  DOI：

  10.1071/ch00134

文献信息

• Direct ratiometric detection of nitric oxide with Cu(<scp>ii</scp>)-based fluorescent probes
  作者：A. Loas、S. J. Lippard

  DOI：10.1039/c7tb02666h

  日期：——

  We report the first Cu(II)-based fluorescent sensors for ratiometric detection of nitric oxide. The two probes operate by energy transfer between hydroxycoumarin and fluorescein chromophores, contain polyproline or piperazine as rigid spacers, and elicit a rapid and selective ratiometric response upon direct reaction with nitric oxide.

  我们报告了第一批基于Cu（II）的荧光传感器，用于一氧化氮的比例检测。这两种探针通过羟基香豆素和荧光素生色团之间的能量转移进行操作，包含聚脯氨酸或哌嗪作为刚性间隔基，并在与一氧化氮直接反应时引起快速和选择性的比例响应。
• Visualization of nitric oxide production in the mouse main olfactory bulb by a cell-trappable copper(II) fluorescent probe
  作者：Lindsey E. McQuade、Jie Ma、Graeme Lowe、Ambarish Ghatpande、Alan Gelperin、Stephen J. Lippard

  DOI：10.1073/pnas.0914794107

  日期：2010.5.11

  We report the visualization of NO production using fluorescence in tissue slices of the mouse main olfactory bulb. This discovery was possible through the use of a novel, cell-trappable probe for intracellular nitric oxide detection based on a symmetric scaffold with two NO-reactive sites. Ester moieties installed onto the fluorescent probe are cleaved by intracellular esterases to yield the corresponding negatively charged, cell-impermeable acids. The trappable probe Cu ₂ (FL2E) and the membrane-impermeable acid derivative Cu ₂ (FL2A) respond rapidly and selectively to NO in buffers that simulate biological conditions, and application of Cu ₂ (FL2E) leads to detection of endogenously produced NO in cell cultures and olfactory bulb brain slices.

  我们报告了使用荧光技术在小鼠主嗅球组织切片中观察NO产生的结果。这项发现是通过使用一种基于对称支架的新型细胞可捕获探针来检测细胞内一氧化氮而实现的。将酯基安装到荧光探针上，细胞内酯酶将其裂解为相应的带负电、不可渗透的酸。可捕获的探针Cu ₂ (FL2E)和膜不可渗透的酸衍生物Cu ₂ (FL2A)在模拟生物条件的缓冲液中对NO做出快速、选择性的反应，应用Cu ₂ (FL2E)可检测到细胞培养和嗅球脑片中内源性产生的NO。
• Seminaphthofluorescein-Based Fluorescent Probes for Imaging Nitric Oxide in Live Cells
  作者：Michael D. Pluth、Maria R. Chan、Lindsey E. McQuade、Stephen J. Lippard

  DOI：10.1021/ic200986v

  日期：2011.10.3

  Fluorescent turn-on probes for nitric oxide based on seminaphthofluorescein scaffolds were prepared and spectroscopically characterized. The Cu(II) complexes of these fluorescent probes react with NO under anaerobic conditions to yield a 20-45-fold increase in integrated emission. The seminaphthofluorescein-based probes emit at longer wavelengths than the parent FL1 and FL2 fluorescein-based generations of NO probes, maintaining emission maxima between 550 and 625 nm. The emission profiles depend on the excitation wavelength; maximum fluorescence turn-on is achieved at excitations between 535 and 575 nm. The probes are highly selective for NO over other biologically relevant reactive nitrogen and oxygen species including NO3-, NO2-, HNO, ONOO-, NO2, OCl-, and H2O2. The seminaphthofluorescein-based probes can be used to visualize endogenously produced NO in live cells, as demonstrated using Raw 264.7 macrophages.
• Fluorescence-Based Nitric Oxide Sensing by Cu(II) Complexes That Can Be Trapped in Living Cells
  作者：Lindsey E. McQuade、Stephen J. Lippard

  DOI：10.1021/ic100802q

  日期：2010.8.16

  A series of symmetrical, fluorescein-derived ligands appended with two derivatized 2-methyl-8-aminoquinolines were prepared and spectroscopically characterized. The ligands FL2, FL2E, and FL2A were designed to improve the dynamic range of previously described asymmetric systems, and the copper complex Cu-2(FL2E) was constructed as a trappable NO probe that is hydrolyzed intracellularly to form Cu-2(FL2A). The ligands themselves are only weakly emissive, and the completely quenched Cu(II) complexes, generated in situ by combining each ligand with 2 equiv of CuCl2, were investigated as fluorescent probes for nitric oxide. Upon introduction of excess NO under anaerobic conditions to buffered solutions of Cu-2(FL2), Cu-2(FL2E), and Cu-2(FL2A), the fluorescence increased by factors of 23 +/- 3, 17 +/- 2, and 27 +/- 3, respectively. The corresponding rate constants for fluorescence turn-on were determined to be 0.4 +/- 0, 0.35 +/- 0.05, and 0.6 +/- 0.1 min(-1). The probes are highly specific for NO over other biologically relevant reactive oxygen and nitrogen species, as well as Zn(II), the metal ion for which similar probes were designed to detect.
• Aqueous Coordination Chemistry of Quinoline-Based Fluorescence Probes for the Biological Chemistry of Zinc
  作者：Christoph J. Fahrni、Thomas V. O'Halloran

  DOI：10.1021/ja992709f

  日期：1999.12.1

  Metal-specific fluorescence probes are of increasing importance in understanding the neurobiology and general cell biology of zinc. Several quinoline-based compounds such as TSQ and zinquin have been employed to detect zinc in fluorescence microscopy experiments in vivo; however, the aqueous solution chemistry remains equivocal. In some cases, this family of probes is said to reveal labile pools of Zn(II) inside the cell, yet in other cases, these probes ate suggested to remove Zn(II) from tightly bound sites in proteins. Since the binding modes, coordination numbers, and thermodynamics of zinc-zinquin interactions in aqueous solution have not been established, these proposals are difficult to distinguish. Here we show that, under physiological conditions, the various forms of zinquin bind Zn(II) with a high degree of cooperativity forming 2:1 complexes. Potentiometric, UV-visible, and fluorescence methods all yield an overall binding constant of log K = 13.5 under physiological conditions. To put this number in perspective with other Zn chelators and biological ligands, we compare the calculated so-called pM values (-log[Zn(II)](free)) for a series of compounds with different stoichiometries under a typical condition. The pZn value for zinquin (9.3) is similar to that of EGTA. (9.5) but much smaller than the value for carbonic anhydrase (12.4) or EDTA (14.3) and, thus, serves as a useful gauge for comparing zinc affinities. With respect to in vivo applications of zinquin, such as intracellular fluorescence microscopy studies, we End that the typical detection limit for free Zn(II) in aqueous solution is 4 phl, or 0.3 parts per trillion, at pH 7.2. These results have implications for the availability of zinc in various intracellular compartments.