1,8-bis[3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl]octane | 99110-53-9

• 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
• 英文名称: 1,8-bis[3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl]octane
• 英文别名: 1,8-di-(3-hydroxy-2-methyl-4-oxopyrid-1-yl)octane；3-hydroxy-1-[8-(3-hydroxy-2-methyl-4-oxopyridin-1-yl)octyl]-2-methylpyridin-4-one
• CAS: 99110-53-9
• 化学式: C₂₀H₂₈N₂O₄
• 分子量: 360.453
• InChiKey: FUTWXOBEAYKVDA-UHFFFAOYSA-N

物化性质

• 熔点：
  261-263 °C (decomp)
• 沸点：
  531.6±50.0 °C(Predicted)
• 密度：
  1.202±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] 、 1,8-bis[3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl]octane 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以68%的产率得到1,8-bis{chlorido[3-(oxo-κO)-2-methyl-4(1H)-pyridinonato-κO4](η5-pentamethylcyclopentadienyl)iridium(III)}octane
  参考文献：
  名称：

  Anticancer organorhodium and -iridium complexes with low toxicity in vivo but high potency in vitro: DNA damage, reactive oxygen species formation, and haemolytic activity

  摘要：

  双核Rh（III）（Cp*）和Ir（III）（Cp*）配合物展示了强大的体外抗癌活性，同时在溶血研究和体内斑马鱼模型中表现出低毒性。

  DOI：

  10.1039/c9cc03822a
• 作为产物：
  描述：

  1,8-bis[3-benzyloxy-2-methyl-4(1H)-pyridinon-1-yl]octane 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以68%的产率得到1,8-bis[3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl]octane
  参考文献：
  名称：

  将多核概念转移到钌配合物以提高抗癌活性

  摘要：

  多核铂抗癌复合物是克服已建立的抗癌化合物耐药性的一种行之有效的选择。将此概念转移到钌配合物导致合成含有双（吡啶酮）烷烃配体接头的双核 Ru(II)-芳烃化合物。发现间隔长度对体外抗癌活性的显着影响，这与复合物的亲脂性相关。集成电路50在人类肿瘤细胞系中发现了与已建立的铂类药物相同维度的值。对于三种耐药细胞系中活性最高的复合物，未观察到对顺铂前药奥索铂的交叉耐药性；事实上，在两个耐奥索铂品系中发现了 10 倍的敏感性逆转。代表性实例的（生物）分析表征表明，钌络合物快速水解，主要形成对转铁蛋白和 DNA 表现出亲和力的 diaqua 物种，表明蛋白质和核碱基都是潜在的目标。

  DOI：

  10.1021/jm8013234

文献信息

• Pharmaceutical compositions of hydroxypyridones
  申请人：National Research Development Corporation

  公开号：US04666927A1

  公开（公告）日：1987-05-19

  Compounds in which two or more rings, being a 3-hydroxypypyrid-2-one, 3-hydroxypyrid-4-one or 1-hydroxpyrid-2-one, are linked are of value in the treatment of patients having a toxic concentration of a metal, particularly iron, in the body while the iron complexes of such compounds are of value in the treatment of iron deficiency anaemia.

  含有两个或更多环的化合物，其中一个是3-羟基吡啶-2-酮，3-羟基吡啶-4-酮或1-羟基吡啶-2-酮，它们被用于治疗体内有毒金属，尤其是铁，浓度过高的患者，而这些化合物的铁配合物在治疗缺铁性贫血方面也具有价值。
• Pharmaceutical compositions
  申请人：National Research Development Corporation

  公开号：US04912118A1

  公开（公告）日：1990-03-27

  Compounds in which two or more rings, being a 3-hydroxpypyrid-2-one, 3-hydroypyrid-4-one or 1-hydropyrid-2-one, are linked are of value in the treatment of patients having a toxic concentration of a metal, particularly iron, in the body while the iron complexes of such compounds are of value in the treatment of iron deficien

  含有两个或更多环的化合物，其中一个是3-羟基吡啶-2-酮，3-羟基吡啶-4-酮或1-羟基吡啶-2-酮，这些化合物在治疗身体内含有毒性浓度的金属，特别是铁的患者方面具有价值，而这些化合物的铁络合物在治疗缺铁的情况下也具有价值。
• Iron complexes of hydroxypyridones useful for treating iron overload
  申请人：National Research Development Corporation

  公开号：US05104865A1

  公开（公告）日：1992-04-14

  Compounds in which two or more rings, being a 3-hydroxpypyrid-2-one, 3-hydroxypyrid-4-one or 1-hydroxpyrid-2-one, are linked are of value in the treatment of patients having a toxic concentration of a metal, particularly iron, in the body while the iron complexes of such compounds are of value in the treatment of iron deficiency anaemia.

  含有两个或多个环的化合物，其中一个环是3-羟基吡啶-2-酮，3-羟基吡啶-4-酮或1-羟基吡啶-2-酮，这些化合物在治疗体内具有毒性浓度的金属，特别是铁，的患者方面具有价值，而这些化合物的铁络合物在治疗缺铁性贫血方面具有价值。
• Hydroxypyridone derivatives and pharmaceutical compositions containing them
  申请人：NATIONAL RESEARCH DEVELOPMENT CORPORATION

  公开号：EP0138421A2

  公开（公告）日：1985-04-24

  Compounds in which two or more rings, being a 3-hydroxpy- pyrid-2-one, 3-hydroxypyrid-4-one or 1-hydroxpyrid-2-one, are linked are of value in the treatment of patients having a toxic concentration of a metal, particularly iron, in the body whilst the iron complexes of such compounds are of value in the treatment of iron deficiency anaemia.

  两个或两个以上环（3-羟基吡啶-2-酮、3-羟基吡啶-4-酮或 1-羟基吡啶-2-酮）相连的化合物对治疗体内金属（尤其是铁）浓度过高的病人很有价值，而此类化合物的铁络合物对治疗缺铁性贫血症很有价值。
• Influence of the Arene Ligand, the Number and Type of Metal Centers, and the Leaving Group on the <i>in Vitro</i> Antitumor Activity of Polynuclear Organometallic Compounds
  作者：Maria G. Mendoza-Ferri、Christian G. Hartinger、Alexey A. Nazarov、Rene E. Eichinger、Michael A. Jakupec、Kay Severin、Bernhard K. Keppler

  DOI：10.1021/om900715j

  日期：2009.11.9

  Dinuclear ruthenium complexes were shown to exhibit strong antiproliferative properties in human tumor cell lines. In order to extend the structure-activity relationships (SARs), a series of new Ru-II(arene)X complexes (X = Cl, Br, I) linked by pyridinone-based spacers were synthesized and assayed for their in vitro antineoplastic effect. The SARs were established in terms of the arene ligand. the leaving group (the halide ligand), and the nature and number of the metal centers. It was demonstrated that, besides the previously shown effect or the spacer length, the nature of the metal center has the biggest influence on the in vitro anticancer activity. The halide ligand had no effect on the cytotoxicity, due to rapid formation of the same aquation product for all evaluated compounds. Furthermore, nearly identical activity was observed when varying the arene ligand from p-cymene to biphenyl. However, the number of metal centers was found to be important, with the dinuclear compound being more active than the analogous mono- and trinuclear species.