3-(benzyloxy)-1-(2-hydroxyethyl)-2-methylpyridin-4(1H)-one | 95215-50-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(benzyloxy)-1-(2-hydroxyethyl)-2-methylpyridin-4(1H)-one
• 英文别名: 3-benzyloxy-1-(2-hydroxyethyl)-2-methyl-4(1H)-pyridinone；3-Benzyloxy-1-(2-hydroxyethyl)-2-methylpyridin-4-one；1-(2-hydroxyethyl)-2-methyl-3-phenylmethoxypyridin-4-one
• CAS: 95215-50-2
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: YSLBANZJGCOUTB-UHFFFAOYSA-N

物化性质

• 熔点：
  208-210 °C(Solv: ethanol (64-17-5); ethyl ether (60-29-7))
• 沸点：
  451.4±45.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-1-(2-hydroxyethyl)-2-methylpyridin-4(1H)-one 在 palladium on activated charcoal 氢气 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-[2'-(benzoyloxy)ethyl]-2-methyl-3-hydroxy-4(1H)-pyridinone
  参考文献：
  名称：

  Synthesis, physicochemical properties and biological evaluation of ester prodrugs of 3-hydroxypyridin-4-ones: design of orally active chelators with clinical potential

  摘要：

  The synthesis of a range of hydrophobic ester prodrugs of 3-hydroxypyridin-4-ones with potential for oral administration is described. The distribution coefficient values of a range of these ester prodrugs and the corresponding alcohols in 1-octanol and MOPS buffer FH 7.4 are presented together with their rates of hydrolysis at pH 2, pH 7.4, in rat blood and liver homogenate. In vivo iron mobilisation efficacy of the pivaloyl and benzoyl prodrugs has been compared with their parent drugs using a Fe-59-ferritin loaded rat model. Both classes of prodrug enhanced the ability of the parent hydroxypyridinone to facilitate the excretion of Fe-59. The influence of the pivaloyl function was more marked than that of the benzoyl function. The optimal effect was observed with 1-[2'-(pivaloyloxy)ethyl]-2-methyl-3-hydroxy-4(1H)-pyridinone 25. However, not all the prodrugs provide increased efficacy which suggests that lipophilicity is not the only factor which influences the drug efficacy. The metabolism of the compound may have a dominating influence on the overall efficacy. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80097-x
• 作为产物：
  描述：

  麦芽醇 在 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 12.0h， 生成 3-(benzyloxy)-1-(2-hydroxyethyl)-2-methylpyridin-4(1H)-one
  参考文献：
  名称：

  新型双（3-羟基-4-吡啶酮）配体作为铀酰络合的螯合剂的合成。

  摘要：

  这项研究中合成了五种新的双（3-羟基-4-吡啶酮）四齿螯合剂。这些四齿螯合剂的结构通过1 H-NMR，（13）C-NMR，FT-IR，UV-vis和质谱分析来表征。还通过在水介质中的紫外分光光度法测定了这些四齿螯合剂在pH 7.4下对铀酰离子的结合能力。结果表明，这些螯合剂的效率取决于接头的长度。配体4b是最好的螯合剂，适合进一步研究。

  DOI：

  10.3390/molecules21030299

文献信息

• Synthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: orally active iron chelators with clinical potential
  作者：Paul S. Dobbin、Robert C. Hider、Adrian D. Hall、Paul D. Taylor、Patience Sarpong、John B. Porter、Gaoyi Xiao、Dick van der Helm

  DOI：10.1021/jm00069a002

  日期：1993.8

  The synthesis of a range of novel bidentate ligands containing the chelating moiety 3-hydroxy-4(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The crystal structures of one of the ligands and one of the iron(III) complexes are presented. The distribution coefficients of the ligands are reported and are related

  描述了一系列包含螯合部分3-羟基-4（1H）-吡啶酮的新型双齿配体的合成。已经确定了配体的pKa值及其铁（III）配合物的稳定性常数。给出了一种配体和一种铁（III）配合物的晶体结构。报告了配体的分布系数，并且与配体从肝细胞中去除铁的能力有关。描述了3-羟基-4（1H）-吡啶酮对细胞氧化损伤的影响。与目前的铁螯合剂去铁胺-B相比，本研究中描述的许多双齿配体在铁超载小鼠中具有口服活性。
• In vitro studies of lanthanide complexes for the treatment of osteoporosis
  作者：Yasmin Mawani、Jacqueline F. Cawthray、Stanley Chang、Kristina Sachs-Barrable、David M. Weekes、Kishor M. Wasan、Chris Orvig

  DOI：10.1039/c2dt32373g

  日期：——

  Lanthanide ions, Ln(III), are of interest in the treatment of bone density disorders because they are found to accumulate preferentially in bone (in vivo), have a stimulatory effect on bone formation, and exhibit an inhibitory effect on bone degradation (in vitro), altering the homeostasis of the bone cycle. In an effort to develop an orally active lanthanide drug, a series of 3-hydroxy-4-pyridinone ligands were synthesized and eight of these ligands (H1 = 3-hydroxy-2-methyl-1-(2-hydroxyethyl)-4-pyridinone, H2 = 3-hydroxy-2-methyl-1-(3-hydroxypropyl)-4-pyridinone, H3 = 3-hydroxy-2-methyl-1-(4-hydroxybutyl)-4-pyridinone, H4 = 3-hydroxy-2-methyl-1-(2-hydroxypropyl)-4-pyridinone, H5 = 3-hydroxy-2-methyl-1-(1-hydroxy-3-methylbutan-2-yl)-4-pyridinone, H6 = 3-hydroxy-2-methyl-1-(1-hydroxybutan-2-yl)-4-pyridinone, H7 = 1-carboxymethyl-3-hydroxy-2-methyl-4-pyridinone, H8 = 1-carboxyethyl-3-hydroxy-2-methyl-4-pyridinone) were coordinated to Ln3+ (Ln = La, Eu, Gd, Lu) forming stable tris-ligand complexes (LnL3, L = 1−, 2−, 3−, 4−, 5−, 6−, 7− and 8−). The dissociation (pKan) and metal ligand stability constants (log βn) of the 3-hydroxy-4-pyridinones with La3+ and Gd3+ were determined by potentiometric titrations, which demonstrated that the 3-hydroxy-4-pyridinones form stable tris-ligand complexes with the lanthanide ions. One phosphinate-EDTA derivative (H5XT = bis[[bis(carboxymethyl)amino]methyl]phosphinate) was also synthesized and coordinated to Ln3+ (Ln = La, Eu, Lu), forming the potassium salt of [Ln(XT)]2−. Cytotoxicity assays were carried out in MG-63 cells; all the ligands and metal complexes tested were observed to be non-toxic to this cell line. Studies to investigate the toxicity, cellular uptake and apparent permeability (Papp) of the lanthanide ions were conducted in Caco-2 cells where it was observed that [La(XT)]2− had the greatest cell uptake. Binding affinities of free lanthanide ions (Ln = La, Gd and Lu), metal complexes and free 3-hydroxy-4-pyridinones with the bone mineral hydroxyapatite (HAP) are high, as well as moderate to strong for the free ligand with the bone mineral depending on the functional group.

  镧系离子Ln(III)在治疗骨密度紊乱方面具有研究价值，因为它们在体内优先积累于骨组织中，对骨形成有刺激作用，并在体外表现出对骨降解的抑制作用，从而改变骨周期的稳态。为了开发一种口服活性的镧系药物，合成了一系列3-羟基-4-吡啶酮配体，其中的八个配体（H1 = 3-羟基-2-甲基-1-(2-羟基乙基)-4-吡啶酮，H2 = 3-羟基-2-甲基-1-(3-羟基丙基)-4-吡啶酮，H3 = 3-羟基-2-甲基-1-(4-羟基丁基)-4-吡啶酮，H4 = 3-羟基-2-甲基-1-(2-羟基丙基)-4-吡啶酮，H5 = 3-羟基-2-甲基-1-(1-羟基-3-甲基丁烷-2-基)-4-吡啶酮，H6 = 3-羟基-2-甲基-1-(1-羟基丁烷-2-基)-4-吡啶酮，H7 = 1-羧甲基-3-羟基-2-甲基-4-吡啶酮，H8 = 1-羧乙基-3-羟基-2-甲基-4-吡啶酮）与Ln3+（Ln = La, Eu, Gd, Lu）配位，形成了稳定的三配体复合物（LnL3，L = 1−, 2−, 3−, 4−, 5−, 6−, 7− 和 8−）。通过电位滴定法测定了3-羟基-4-吡啶酮与La3+和Gd3+的解离（pKan）和金属配体稳定常数（log βn），结果表明3-羟基-4-吡啶酮与镧系离子形成了稳定的三配体复合物。同时，合成了一种磷酸酯-EDTA衍生物（H5XT = 双[[双(羧甲基)氨基]甲基]磷酸酯），并与Ln3+（Ln = La, Eu, Lu）配位，形成了[Ln(XT)]2−的钾盐。在MG-63细胞中进行了细胞毒性实验，结果显示所有测试的配体和金属复合物对这种细胞系均无毒性。在Caco-2细胞中研究了镧系离子的毒性、细胞摄取和表观渗透性（Papp），观察到[La(XT)]2−具有最大的细胞摄取量。自由镧系离子（Ln = La, Gd 和 Lu）、金属复合物以及自由3-羟基-4-吡啶酮与骨矿物质羟基磷灰石（HAP）的结合亲和力都很高，而自由配体与骨矿物质的结合亲和力则取决于功能团，表现为中等到强。
• Synthesis and Antiviral Evaluation of Cyclic and Acyclic 2-Methyl-3-hydroxy-4-pyridinone Nucleoside Derivatives
  作者：Karine Barral、Jan Balzarini、Johan Neyts、Erik De Clercq、Robert C. Hider、Michel Camplo

  DOI：10.1021/jm0504306

  日期：2006.1.1

  A series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the Vorbruggen reaction. Iron chelation studies, and antiviral evaluation against a broad panel of viruses, were performed. The pK(a) value of ligand 25 and the stability constant of the corresponding iron(III) complex were compared to those of deferiprone. The pFe(3+) values were found to

  使用Vorbruggen反应合成了一系列衍生自3-羟基-4-吡啶酮的环状和无环核苷类似物。进行了铁螯合研究和针对多种病毒的抗病毒评估。将配体25的pK（a）值和相应的铁（III）配合物的稳定性常数与去铁酮进行了比较。发现pFe（3+）值相似。一些化合物对野生型HSV-1和HSV-2以及对胸腺嘧啶激酶缺陷的HSV-1菌株均显示中等活性。这些结果表明该组核苷类似物的新型作用方式。
• Design and synthesis of N-hydroxyalkyl substituted deferiprone: a kind of iron chelating agents for Parkinson's disease chelation therapy strategy
  作者：Qingchun Zhang、Shufan Feng、Yulian Zhao、Bo Jin、Rufang Peng

  DOI：10.1007/s00775-021-01863-x

  日期：2021.6

  drazyl radical scavenging assays indicated that the N-hydroxyalkyl substituted deferiprone also possesses similar radical scavenging ability in comparison to deferiprone. Meanwhile, the Cell Counting Kit-8 assays of neuron-like rat pheochromocytoma cell-line demonstrated that the N-hydroxyalkyl substituted deferiprone exhibits extremely low cytotoxicity and excellent H2O2-induced oxidative stress protection

  分子的血脑屏障（BBB）通透性需要满足利平斯基规则的严格要求，这给合理设计用于帕金森病螯合治疗的高效螯合剂带来了困难。因此，本工作合理设计了使用去铁酮的N-脂肪醇修饰的铁螯合剂。螯合剂不仅满足利平斯基对血脑屏障通透性的规则，而且保证了铁的亲和力。溶液热力学结果表明，N-羟烷基取代去铁酮的pFe 3+值在19.20～19.36之间，与临床去铁酮相当。2,2-diphenyl-1-picrylhydrazyl 自由基清除实验结果表明，N与去铁酮相比，-羟烷基取代的去铁酮还具有类似的自由基清除能力。同时，神经元样大鼠嗜铬细胞瘤细胞系的Cell Counting Kit-8分析表明，N-羟烷基取代的去铁酮表现出极低的细胞毒性和优异的H 2 O 2诱导的氧化应激保护作用。这些结果表明，N-羟烷基取代的去铁酮作为帕金森病螯合治疗策略的螯合剂具有潜在的应用前景。 图形摘要
• Iron-pyridone complexes for anemia
  申请人：National Research Development Corporation

  公开号：US04650793A1

  公开（公告）日：1987-03-17

  Pharmaceutical compositions containing an iron complex of a 3-hydroxypyrid-2-one or 3-hydroxypyrid-4-one in which the hydrogen atom attached to the nitrogen atom is replaced by an aliphatic acyl group, by an aliphatic hydrocarbon group, or by an aliphatic hydrocarbon group substituted by one or, except in the case of ionizable groups, more than one substituent selected from aliphatic acyl, alkoxy, aliphatic amine, aliphatic amide, carboxy, aliphatic ester, halogen, hydroxy and sulpho groups and, optionally, in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by one of said substituents, by an aliphatic hydrocarbon group, or by an aliphatic hydrocarbon group substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms in the compound is effected only by aliphatic hydrocarbon groups, are of value for the treatment of iron deficiency anemia.

  含有3-羟基吡啶-2-酮或3-羟基吡啶-4-酮的铁配合物的制药组合物，其中连接到氮原子的氢原子被脂肪酰基、脂肪烃基或被脂肪烃基取代，或者被脂肪烃基取代，该脂肪烃基被选自脂肪酰基、烷氧基、脂肪胺基、脂肪酰胺基、羧基、脂肪酯基、卤素、羟基和磺酸基，并且可选地，其中连接到环碳原子的一个或多个氢原子被上述取代物之一取代，被烷氧基、脂肪酯基、卤素或羟基取代的脂肪烃基取代，但不包括只通过脂肪烃基进行氢原子取代的化合物，对于治疗缺铁性贫血具有价值。