1,6-bis(3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl)hexane | 117135-43-0

• 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: 1,6-bis(3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl)hexane
• 英文别名: 1,1'-(Hexane-1,6-diyl)bis(3-hydroxy-2-methylpyridin-4(1H)-one)；3-hydroxy-1-[6-(3-hydroxy-2-methyl-4-oxopyridin-1-yl)hexyl]-2-methylpyridin-4-one
• CAS: 117135-43-0
• 化学式: C₁₈H₂₄N₂O₄
• 分子量: 332.4
• InChiKey: QINFICICDYQKSR-UHFFFAOYSA-N

物化性质

• 熔点：
  295-297 °C (decomp)
• 沸点：
  511.9±50.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  [ruthenium(II)(η⁶-biphenyl)(chloride)(μ-chloride)]₂ 、 1,6-bis(3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl)hexane 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以46%的产率得到1,6-bis(chlorido[3-(oxo-κO)-2-methyl-4(1H)-pyridinonato-κO4](η6-biphenyl)ruthenium(II))hexane
  参考文献：
  名称：

  Influence of the Arene Ligand, the Number and Type of Metal Centers, and the Leaving Group on the in Vitro Antitumor Activity of Polynuclear Organometallic Compounds

  摘要：

  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.

  DOI：

  10.1021/om900715j
• 作为产物：
  描述：

  3-(苄氧基)-2-甲基-4H-吡喃-4-酮 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 48.5h， 生成 1,6-bis(3-hydroxy-2-methyl-4(1H)-pyridinon-1-yl)hexane
  参考文献：
  名称：

  Nelson, William O.; Karpishin,Timothy B.; Rettig, Steven J., Canadian Journal of Chemistry, 1988, vol. 66, p. 123 - 131

  摘要：

  DOI：

文献信息

• Transferring the Concept of Multinuclearity to Ruthenium Complexes for Improvement of Anticancer Activity
  作者：Maria G. Mendoza-Ferri、Christian G. Hartinger、Marco A. Mendoza、Michael Groessl、Alexander E. Egger、Rene E. Eichinger、John B. Mangrum、Nicholas P. Farrell、Magdalena Maruszak、Patrick J. Bednarski、Franz Klein、Michael A. Jakupec、Alexey A. Nazarov、Kay Severin、Bernhard K. Keppler

  DOI：10.1021/jm8013234

  日期：2009.2.26

  Multinuclear platinum anticancer complexes are a proven option to overcome resistance of established anticancer compounds. Transferring this concept to ruthenium complexes led to the synthesis of dinuclear Ru(II)−arene compounds containing a bis(pyridinone)alkane ligand linker. A pronounced influence of the spacer length on the in vitro anticancer activity was found, which is correlated to the lipophilicity

  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。
• Anticancer organorhodium and -iridium complexes with low toxicity <i>in vivo</i> but high potency <i>in vitro</i>: DNA damage, reactive oxygen species formation, and haemolytic activity
  作者：Shahida Parveen、Muhammad Hanif、Euphemia Leung、Kelvin K. H. Tong、Annie Yang、Jonathan Astin、Gayan H. De Zoysa、Tasha R. Steel、David Goodman、Sanam Movassaghi、Tilo Söhnel、Vijayalekshmi Sarojini、Stephen M. F. Jamieson、Christian G. Hartinger

  DOI：10.1039/c9cc03822a

  日期：——

  Dinuclear Rh^III(Cp*) and Ir^III(Cp*) complexes demonstrated potent in vitro anticancer activity while exhibiting low toxicity in haemolysis studies and in vivo zebrafish models.

  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。
• Influence of the Spacer Length on the <i>in Vitro</i> Anticancer Activity of Dinuclear Ruthenium−Arene Compounds
  作者：Maria-Grazia Mendoza-Ferri、Christian G. Hartinger、Rene E. Eichinger、Natalya Stolyarova、Kay Severin、Michael A. Jakupec、Alexey A. Nazarov、Bernhard K. Keppler

  DOI：10.1021/om800207t

  日期：2008.6.9

  Water-soluble dinuclear Ru-arene complexes were synthesized and found to exert promising cytotoxic effects in human cancer cells, which could be increased to an IC50 of 0.29 mu M by increasing the spacer length between the metal centers. Cytotoxicity could be correlated with lipophilicity (log P values) and water solubility. The most potent dinuclear compound, 1,12-bischlorido[3-(oxo-kappa O)-2-methyl-4-pyridinonato-kappa O4](eta(6)-p-isopropyltoluene)ruthenium}dodecane, is at least 2-3 orders of magnitude more active than the mononuclear analogue chlorido[3-(oxo-kappa O)-2-methyl-4-pyronato-kappa O4](eta(6)-p-isopropyltoluene)-ruthenium.
• Nelson, William O.; Karpishin,Timothy B.; Rettig, Steven J., Canadian Journal of Chemistry, 1988, vol. 66, p. 123 - 131
  作者：Nelson, William O.、Karpishin,Timothy B.、Rettig, Steven J.、Orvig, Cris

  DOI：——

  日期：——
• 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.