1-{2-[bis(2-aminoethyl)amino]ethyl}-3-benzoxy-2-methylpyridin-4(1H)-one | 812653-93-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-{2-[bis(2-aminoethyl)amino]ethyl}-3-benzoxy-2-methylpyridin-4(1H)-one
• 英文别名: 1-[2-[Bis(2-aminoethyl)amino]ethyl]-2-methyl-3-phenylmethoxypyridin-4-one
• CAS: 812653-93-3
• 化学式: C₁₉H₂₈N₄O₂
• 分子量: 344.457
• InChiKey: MFEYLXAEYZNFOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  84.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-{2-[bis(2-aminoethyl)amino]ethyl}-3-benzoxy-2-methylpyridin-4(1H)-one 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 生成 N-(2-{[2-(acetylamino)ethyl][2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl]amino}ethyl)-7-diethylamino-2-oxo-2H-chromene-3-carboxamide hydrochloride
  参考文献：
  名称：

  Design, Synthesis, Physicochemical Properties, and Evaluation of Novel Iron Chelators with Fluorescent Sensors

  摘要：

  The synthesis of a range of novel 3-hydroxypyridin-4-ones and 3-hydroxypyran-4-ones linked with different coumarin substituents is described. These compounds have been developed in order to provide a series of molecular probes for the quantification of intracellular labile iron pools. An evaluation of the effect of iron(III) on fluorescence intensity was undertaken. Chelation of iron(III) causes quenching of fluorescence. The relationship between iron(III) concentration and the extent of fluorescence quenching indicates that the metal is chelated in a complex with a metal-to-ligand stoichiometry of 1:3. The fluorescence of hydroxypyridinone compounds was found to be more efficiently quenched by iron(III) than were the hydroxypyranones. The metal-to-ligand stoichiometry at which maximum quenching is observed was found to depend on the site at which coumarin is attached. The efficiency of fluorescence quenching by iron(III) is markedly influenced by solvent polarity and pH. The permeability of two representative fluorescent chelators across human erythrocyte ghost membranes was investigated. The rate of permeability for a series of probes was found to be related to the corresponding ClogP values.

  DOI：

  10.1021/jm049751s
• 作为产物：
  描述：

  麦芽醇 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 1-{2-[bis(2-aminoethyl)amino]ethyl}-3-benzoxy-2-methylpyridin-4(1H)-one
  参考文献：
  名称：

  Design, Synthesis, Physicochemical Properties, and Evaluation of Novel Iron Chelators with Fluorescent Sensors

  摘要：

  The synthesis of a range of novel 3-hydroxypyridin-4-ones and 3-hydroxypyran-4-ones linked with different coumarin substituents is described. These compounds have been developed in order to provide a series of molecular probes for the quantification of intracellular labile iron pools. An evaluation of the effect of iron(III) on fluorescence intensity was undertaken. Chelation of iron(III) causes quenching of fluorescence. The relationship between iron(III) concentration and the extent of fluorescence quenching indicates that the metal is chelated in a complex with a metal-to-ligand stoichiometry of 1:3. The fluorescence of hydroxypyridinone compounds was found to be more efficiently quenched by iron(III) than were the hydroxypyranones. The metal-to-ligand stoichiometry at which maximum quenching is observed was found to depend on the site at which coumarin is attached. The efficiency of fluorescence quenching by iron(III) is markedly influenced by solvent polarity and pH. The permeability of two representative fluorescent chelators across human erythrocyte ghost membranes was investigated. The rate of permeability for a series of probes was found to be related to the corresponding ClogP values.

  DOI：

  10.1021/jm049751s

文献信息

• COMPOUND
  申请人：Hider Robert

  公开号：US20130157375A1

  公开（公告）日：2013-06-20

  In one aspect, there is provided a fluorescent iron-binding compound bound to a solid phase. Also provided is a method for detecting non-transferrin bound iron in a sample, comprising contacting the sample with a fluorescent iron-binding compound bound to a solid phase and detecting a fluorescent signal derived from the fluorescent iron-binding compound bound to the solid phase, wherein the fluorescent signal is indicative of non-transferrin bound iron levels in the sample. Further provided is use of a fluorescent iron-binding compound bound to a solid phase to detect non-transferrin bound iron in a sample.

  在一个方面，提供了一种与固相结合的荧光铁结合化合物。还提供了一种检测样品中非转铁蛋白结合铁的方法，包括将样品与与固相结合的荧光铁结合化合物接触，并检测源自与固相结合的荧光铁结合化合物的荧光信号，其中荧光信号表明样品中的非转铁蛋白结合铁水平。进一步提供了使用与固相结合的荧光铁结合化合物来检测样品中的非转铁蛋白结合铁。
• A novel method for non-transferrin-bound iron quantification by chelatable fluorescent beads based on flow cytometry
  作者：Yongmin Ma、Maria Podinovskaia、Patricia J. Evans、Giovanni Emma、Ulrich E. Schaible、John Porter、Robert C. Hider

  DOI：10.1042/bj20140795

  日期：2014.11.1

  The reliable measurement of non-transferrin-bound iron (NTBI) in serum has proved to be difficult and generally time consuming. We have sought a simple and fast method for such a determination. We adopted a fluorescence assay and designed a fluorescent dye with a chelating agent attached to sense iron. To avoid autofluorescence from serum samples, the iron probes were linked to beads and the autofluorescence could be separated and excluded from the measurement by flow cytometry due to the size difference between beads and serum proteins. Fluorescent beads containing both fluorescent and chelating moieties have been synthesized. The nature of the chelating function has been systematically investigated using four different chelators: bidentate hydroxypyranone, bidentate hydroxypyridinone, hexadentate hydroxypyranone and hexadentate hydroxypyridinone, each with different iron affinity constants. Competition studies demonstrate that the hexadentate hydroxypyridinone-based beads are capable of scavenging most of low molecular mass and albumin-bound iron but negligible amounts of iron from transferrin and ferritin. Serum samples from 30 patients with different types of disease and normal volunteers were measured. The concentrations of NTBI fall in the range −0.41 to +6.5 μM. The data have been compared with those obtained from the traditional ‘NTA’ method.

  对血清中的非转铁蛋白结合铁（NTBI）进行可靠的测定已被证明是一件非常困难的事情，而且一般都比较耗时。我们一直在寻找一种简单、快速的测定方法。我们采用了荧光检测法，并设计了一种附有螯合剂的荧光染料来感知铁。为了避免血清样本中的自发荧光，铁探针被连接到珠子上，由于珠子和血清蛋白之间的尺寸差异，自发荧光可以被分离出来，并排除在流式细胞仪的测量之外。我们已经合成了同时含有荧光和螯合分子的荧光珠。我们使用四种不同的螯合剂系统地研究了螯合功能的性质：双叉羟基吡喃酮、双叉羟基吡啶酮、六位羟基吡喃酮和六位羟基吡啶酮，每种螯合剂都具有不同的铁亲和常数。竞争研究表明，基于六齿羟基吡啶酮的珠子能够清除大部分低分子质量和白蛋白结合的铁，但从转铁蛋白和铁蛋白中清除的铁微乎其微。对 30 名不同类型疾病患者和正常志愿者的血清样本进行了测量。NTBI 的浓度范围为 -0.41 至 +6.5 μM。这些数据与传统的 "NTA "方法得出的数据进行了比较。
• Design, Synthesis, Physicochemical Properties, and Evaluation of Novel Iron Chelators with Fluorescent Sensors
  作者：Yongmin Ma、Wei Luo、Peter J. Quinn、Zudong Liu、Robert C. Hider

  DOI：10.1021/jm049751s

  日期：2004.12.1

  The synthesis of a range of novel 3-hydroxypyridin-4-ones and 3-hydroxypyran-4-ones linked with different coumarin substituents is described. These compounds have been developed in order to provide a series of molecular probes for the quantification of intracellular labile iron pools. An evaluation of the effect of iron(III) on fluorescence intensity was undertaken. Chelation of iron(III) causes quenching of fluorescence. The relationship between iron(III) concentration and the extent of fluorescence quenching indicates that the metal is chelated in a complex with a metal-to-ligand stoichiometry of 1:3. The fluorescence of hydroxypyridinone compounds was found to be more efficiently quenched by iron(III) than were the hydroxypyranones. The metal-to-ligand stoichiometry at which maximum quenching is observed was found to depend on the site at which coumarin is attached. The efficiency of fluorescence quenching by iron(III) is markedly influenced by solvent polarity and pH. The permeability of two representative fluorescent chelators across human erythrocyte ghost membranes was investigated. The rate of permeability for a series of probes was found to be related to the corresponding ClogP values.