3-羟基-1-(2-羟基乙基)-2-甲基吡啶-4-酮 | 30652-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 3-羟基-1-(2-羟基乙基)-2-甲基吡啶-4-酮
• 英文名称: CP40
• 英文别名: 3-Hydroxy-1-(2-hydroxyethyl)-2-methylpyridin-4(1h)-one；3-hydroxy-1-(2-hydroxyethyl)-2-methylpyridin-4-one
• CAS: 30652-21-2
• 化学式: C₈H₁₁NO₃
• mdl: MFCD01690788
• 分子量: 169.18
• InChiKey: ZJDRWNJIMXVJQG-UHFFFAOYSA-N

物化性质

• 沸点：
  327.4±42.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.375
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  3-羟基-1-(2-羟基乙基)-2-甲基吡啶-4-酮 生成 3-hydroxy-1-(2-hydroxyethyl)-2-methylpyridin-4-one;trichloroiron
  参考文献：
  名称：

  HIDER, R. C.;KONTOGHIORGHES, G.;SILVER, J.;STOCKHAM, M. A.

  摘要：

  DOI：
• 作为产物：
  描述：

  3-(苄氧基)-2-甲基-4H-吡喃-4-酮 在 palladium on activated charcoal 、 氢气 、 sodium hydroxide 作用下， 生成 3-羟基-1-(2-羟基乙基)-2-甲基吡啶-4-酮
  参考文献：
  名称：

  N-羟烷基取代去铁酮的设计与合成：一种用于帕金森病螯合治疗策略的铁螯合剂

  摘要：

  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

  DOI：

  10.1007/s00775-021-01863-x

文献信息

• 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。
• 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。
• Pharmaceutical compositions
  申请人：National Research Development Corp.

  公开号：US04585780A1

  公开（公告）日：1986-04-29

  Pharmaceutical compositions containing 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, or a salt thereof containing a physiologically acceptable ion or ions, are of value for removing toxic amounts of metals, particularly iron, from the body.

  含有3-羟基吡啶-2-酮或3-羟基吡啶-4-酮的药物组合物，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，并且被脂肪酰基、烷氧基、脂肪胺基、脂肪酰胺基、羧基、脂肪酯基、卤素、羟基和磺酸基中的一个或一个以上的取代基取代，除非是可电离的基团，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基之一取代，或者被烷氧基、脂肪酯基、卤素或羟基取代的脂肪烃基取代，但不包括化合物，其中所述取代氢原子的取代仅由脂肪烃基完成，或者其盐，含有生理上可接受的离子，对于从体内去除有毒金属，特别是铁，具有价值。
• 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，
• Synthesis and characterization of hydrophilic hydroxy-pyridinones and their complexes with molybdenum(VI)
  作者：Noah A. Epstein、Jennifer L. Horton、Christopher M. Vogels、Nicholas J. Taylor、Stephen A. Westcott

  DOI：10.1071/ch00093

  日期：——

  We have prepared four N-substituted hydroxypyridinones containing alcohol and morpholine groups. Complexes of the type cis-MoO2L2, where L represents the hydroxypyridinonato ligands have also been synthesized. The ethanolamine derivative, cis-MoO2(hep)2 (5), has been characterized by an X-ray diffraction study whereby the pyridinone ligands are bound to molybdenum in a cis bidentate fashion via the deprotonated hydroxy groups and the ketone moieties. Crystals of (5) are triclinic, with a 9.1930(7), b 14.2718(8), c 14.6219(9) Å, α 106.816(5), β 95.902(5), γ 96.350(5)°, Z 4, space group P–1.

  我们制备了四种含有醇和吗啉基团的 N-取代羟基吡啶酮 含有醇和吗啉基团。类型的配合物 cis-MoO2L2、 其中 L 代表羟基吡啶配体。 乙醇胺衍生物 顺式-MoO2（hep）2 (5) 的特征已通过 X 射线衍射研究确定。 其中，吡啶酮配体与钼以顺 通过去质子化的羟基和酮基，吡啶酮配体以顺式双齿方式与钼结合。 (5) 晶体为三棱体，a 9.1930(7)、 b 14.2718(8)，c 14.6219(9) 埃，α 106.816(5)，β 95.902(5)，γ 96.350(5)°、 Z 4，空间群 P-1。