3-(benzyloxy)-2-ethyl-1-(2-hydroxyethyl)pyridin-4(1H)-one | 210244-51-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(benzyloxy)-2-ethyl-1-(2-hydroxyethyl)pyridin-4(1H)-one
• 英文别名: 3-Benzyloxy-2-ethyl-1-(2-hydroxyethyl)pyridin-4-one；2-ethyl-1-(2-hydroxyethyl)-3-phenylmethoxypyridin-4-one
• CAS: 210244-51-2
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: PDXOIPHDAYJEKC-UHFFFAOYSA-N

物化性质

• 沸点：
  461.3±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 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)-2-ethyl-1-(2-hydroxyethyl)pyridin-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， 反应 42.0h， 生成 1-[2'-(benzoyloxy)ethyl]-2-ethyl-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：

  乙基麦芽酚 在 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 6.0h， 生成 3-(benzyloxy)-2-ethyl-1-(2-hydroxyethyl)pyridin-4(1H)-one
  参考文献：
  名称：

  Synthesis, Physicochemical Properties and Biological Evaluation of Aromatic Ester Prodrugs of 1-(2‘-Hydroxyethyl)-2-ethyl-3-hydroxypyridin-4-one (CP102): Orally Active Iron Chelators with Clinical Potential

  摘要：

  摘要：描述了合成7种芳香酯衍生物的方法，这些衍生物是1-(2′-羟乙基)-2-乙基-3-羟基吡啶-4-酮的酯前药。这些酯前药的设计旨在将铁螯合剂靶向肝脏，这是主要的铁贮存器官。原则上，这应该提高螯合效果并最小化毒性。这些酯前药在1-辛醇和MOPS缓冲液pH 7·4之间的分配系数被测量，以及它们在pH 2和pH 7·4下在大鼠血液和肝组织匀浆中的水解速率。发现含杂环芳酸基团的酯比苯甲酰类似物不稳定。使用59Fe-铁蛋白负载大鼠模型比较了这些酯前药的体内铁动员效果与母药的效果。发现许多酯前药能增强母羟基吡啶酮促进59Fe排泄的能力。然而，并非所有酯前药都提供了增加的效果，表明亲脂性并非是影响药物效果的唯一因素。此外，并未发现效果与水解易感性之间的明确相关性。吡啶甲酸和烟酸酯衍生物似乎具有最佳的前药潜力，因为它们具有相对较低的LogP值，但能提高母羟基吡啶酮的效果。

  DOI：

  10.1211/0022357991772655

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。
• 5-氨基酮戊酸/3-羟基吡啶酮缀合物及其制备 法和用途
  申请人：浙江工商大学

  公开号：CN106478493B

  公开（公告）日：2018-12-11

  本发明公开了5‑氨基酮戊酸与3‑羟基吡啶‑4‑酮的缀合物，该缀合物是5‑氨基酮戊酸与铁螯合剂3‑羟基吡啶‑4‑酮的缀合物，分别为ALA‑HPO缀合物1‑4。本发明还同时公开了上述5‑氨基酮戊酸与3‑羟基吡啶‑4‑酮的缀合物的制备方法及其用途，其能用作制备光动力学治疗药物，也能用于制备治疗皮肤癌、肺癌或尖锐湿疣的药物。
• CN128: A New Orally Active Hydroxypyridinone Iron Chelator
  作者：Wenteng Chen、Xin Yuan、Zhi Li、Zidong Lu、Sisi Kong、Huidi Jiang、Houbing Du、Xiuhong Pan、Manasi Nandi、Xiaole Kong、Kathryn Brown、Zudong Liu、Guolin Zhang、Robert C. Hider、Yongping Yu

  DOI：10.1021/acs.jmedchem.0c00137

  日期：2020.4.23

  Deferoxamine, deferiprone, and deferasirox are used for the treatment of systemic iron overload, although they possess limitations due to lack of oral activity, lower efficacy, and side effects. These limitations led to a search for an orally active iron chelator with an improved therapeutic index. The lower efficacy of deferiprone is due to rapid glucuronidation, leading to the formation of a nonchelating

  去铁胺，去铁酮和地拉罗司用于治疗全身性铁超负荷，尽管由于缺乏口服活性，疗效较低和副作用而存在局限性。这些限制导致寻找具有改善的治疗指数的口服活性铁螯合剂。去铁酮的功效较低是由于快速的葡萄糖醛酸化作用，导致形成非螯合的代谢产物。在这里，我们证明可以通过引入牺牲部位进行葡萄糖醛酸化来减少新陈代谢的影响。在对数P指导下对20个羟基吡啶并酮的研究导致CN128的鉴定。CN128的Fe（III）亲和力和金属选择性与去铁酮相似，log P值更具亲脂性，并且其铁清除能力优越。总体，
• 3-hydroxypyridin-4-one derivatives as chelating agents
  申请人：British Technology Group Limited

  公开号：US05480894A1

  公开（公告）日：1996-01-02

  3-Hydroxypyridin-4-ones of formula (I) ##STR1## in which R.sub.1 is a methyl, ethyl, 2-(.alpha.-methylpropionyloxy)ethyl or 2-pivoloyloxyethyl group and R.sub.2, R.sub.3 and R.sub.4 are each separately selected from hydrogen and methyl, ethyl, 2-(.alpha.-methylpropionyloxy)ethyl and 2-pivaloyloxyethyl groups with the provisos that (a) one only of R.sub.1 to R.sub.4 is either a 2-(.alpha.-methylpropionyloxy)ethyl group or a 2-pivaloyloxyethyl group, (b) at least one of R.sub.2 and R.sub.3 is other than hydrogen and (c) the total number of carbon atoms in R.sub.1 to R.sub.4 is no more than eleven, and physiologically acceptable salts thereof are of use in therapy, particularly in the treatment of conditions in which there is a toxic concentration of a metal, for example iron, in the body.

  化学式(I)中的3-羟基吡啶-4-酮，其中R.sub.1是甲基、乙基、2-(α-甲基丙酰氧基)乙基或2-戊酰氧基乙基基团，R.sub.2、R.sub.3和R.sub.4分别选择自氢和甲基、乙基、2-(α-甲基丙酰氧基)乙基和2-戊酰氧基乙基基团，但要注意的是(a)只有R.sub.1到R.sub.4中的一个是2-(α-甲基丙酰氧基)乙基基团或2-戊酰氧基乙基基团，(b)至少有一个R.sub.2和R.sub.3不是氢，(c)R.sub.1到R.sub.4中碳原子的总数不超过十一，以及其生理上可接受的盐在治疗中有用，特别是在治疗体内存在有毒金属浓度的疾病，例如铁中毒。
• PYRIDINONE COMPOUNDS FOR USE IN PHOTODYNAMIC THERAPY
  申请人：UNIVERSITY OF EXETER

  公开号：US20150210642A1

  公开（公告）日：2015-07-30

  A compound which is a compound of formula (I) or any salt thereof: wherein R1 is a Ci-C6 alkyl group, R2 is H or a Ci-C6 alkyl group, R3 is H or a Ci-C6 alkyl group, and n is an integer from 0 to 5.

  一种化合物，其化学式为（I）或其任何盐：其中R1为Ci-C6烷基基团，R2为H或Ci-C6烷基基团，R3为H或Ci-C6烷基基团，n为0至5之间的整数。