(2-(aminomethyl)-3-(benzyloxy)-6-methyl-4H-pyran-4-one) | 812653-99-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: (2-(aminomethyl)-3-(benzyloxy)-6-methyl-4H-pyran-4-one)
• 英文别名: 2-(Aminomethyl)-3-(benzyloxy)-6-methyl-4H-pyran-4-one；2-(aminomethyl)-6-methyl-3-phenylmethoxypyran-4-one
• CAS: 812653-99-9
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: KESMMQFLKNRPFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-(aminomethyl)-3-(benzyloxy)-6-methyl-4H-pyran-4-one) 在 palladium on activated charcoal 氢气 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[(3-hydroxy-6-methyl-4-oxopyran-2-yl)methyl]-2-(7-methoxy-2-oxochromen-4-yl)acetamide
  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：

  曲酸 在 盐酸 、 sodium hydroxide 、 氯化亚砜 、 一水合肼 、 三苯基膦 、 锌 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 15.08h， 生成 (2-(aminomethyl)-3-(benzyloxy)-6-methyl-4H-pyran-4-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

• Synthesis and iron chelating properties of hydroxypyridinone and hydroxypyranone hexadentate ligands
  作者：Tao Zhou、Xiao-Le Kong、Robert C Hider

  DOI：10.1039/c8dt05014g

  日期：——

  chelators, four hexadentate ligands were synthesized by conjugating the corresponding bidentate ligands (3-hydroxypyridin-4-one (3,4-HOPO), 3-hydroxypyridin-2-one (3,2-HOPO), 1-hydroxypyridin-2-one (1,2-HOPO), and 3-hydroxypyran-4-one) each with a free amino group to a tripodal acid. Their pKa values and affinities for iron(III) were investigated. The pFe3+ values of the hexadentate pyridinones 1 (3

  螯合疗法已成为治疗某些疾病的重要方法。为了确定临床上有用的螯合剂，通过缀合相应的二齿配体（3-羟基吡啶-4-酮（3,4-HOPO），3-羟基吡啶-2-酮（3,2-HOPO）， 1-羟基吡啶-2-酮（1,2-HOPO）和3-羟基吡喃-4-酮）各自具有与三脚架酸形成的游离氨基。研究了它们对铁（III）的p K a值和亲和力。该PFE 3+的六齿吡啶酮的值1（3,4- HOPO），3（3,2-HOPO）和4（1,2- HOPO）和吡喃酮2被发现跟随序列1 >4 » 3 > 2，这是对PFE不同3+的相应的二齿形式（3,4- HOPO»3,2-HOPO> 1,2- HOPO> 3- hydroxypyranone）值序列。六齿的3,4-HOPO和1,2-HOPO具有最大的除铁剂潜力。
• 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。
• Tuning the properties of tris(hydroxypyridinone) ligands: efficient ⁶⁸Ga chelators for PET imaging
  作者：Cinzia Imberti、Yu-Lin Chen、Calum A. Foley、Michelle T. Ma、Brett M. Paterson、Yifu Wang、Jennifer D. Young、Robert C. Hider、Philip J. Blower

  DOI：10.1039/c8dt04454f

  日期：——

  replacing the 1,6-dimethyl-3-hydroxypyridin-4-one N1–CH3 group of THPMe with O (tris(6-methyl-3-hydroxypyran-4-one, THPO) and N1–H (tris(6-methyl-3-hydroxypyridin-4-one), THPH) groups. The effect of these structural modifications on lipophilicity, gallium binding and metal ion selectivity was investigated. THPH was able to bind 68Ga in extremely mild conditions (5 min, room temperature, pH 6, 1 μM ligand

  用于镓 68 的原型 tris(1,6-dimethyl-3-hydroxypyridin-4-one) 螯合剂 THP Me已显示出对 PET 放射性药物快速有效的基于试剂盒的68 Ga 标记的巨大希望。THP Me的肽衍生物已用于在临床前和临床研究中对其靶受体的体内表达进行成像。在此，我们描述了THP平台的新合成路线，包括用O （ tris (6-methyl- 3 -hydroxypyran-4-一, THPO) 和 N 1 –H (tris(6-methyl-3-hydroxypyridin-4-one), THP H) 组。研究了这些结构修饰对亲脂性、镓结合和金属离子选择性的影响。THP H能够在极其温和的条件下（5 分钟，室温，pH 6，1 μM 配体浓度）结合68 Ga，尤其是在体内，当对先前注射了68 Ga 醋酸盐的小鼠给药时。67 Ga 放射性标记的复合物在血清中稳定超过
• The selective quantification of iron by hexadentate fluorescent probes
  作者：Yong Min Ma、Robert C. Hider

  DOI：10.1016/j.bmc.2009.09.052

  日期：2009.12

  The synthesis of four hexadentate fluorescent probes is described, where the fluorescent moiety is based on either coumarin or fluorescein and the chelating moiety is based on either 3-hydroxypyridin-4-one or 3-hydroxypyran-4-one. The fluorescence is quenched when the probe chelating moieties bind iron. The probes were found to be selective for iron over other metals such as Cu, Zn, Ni, Mn and Co. The effect of Cu on fluorescence quenching can be eliminated in the presence of N, N, N', N'-tetrakis(2-pyridylmethyl)-ethylenediamine. Competition studies demonstrate that the exchange of iron between pyridinone-based probes and apotransferrin is very slow. The ability to scavenge iron from oligomeric iron(III) citrate complexes demonstrate that the pyridinone probes scavenges iron faster than deferiprone and desferrioxamine. The fluorescence intensity of the fluorescein-based probe is quantitatively related to the iron concentration with the limit of detection being 10(8) M. (C) 2009 Elsevier Ltd. All rights reserved.