KP1019 | 142388-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: KP1019
• 英文别名: indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]；1H-indazole;ruthenium(3+);trichloride;hydrochloride
• CAS: 142388-45-2
• 化学式: C₇H₆N₂*C₁₄H₁₂Cl₄N₄Ru*H
• 分子量: 598.304
• InChiKey: PJXASRBEMZORRI-UHFFFAOYSA-K

计算性质

• 辛醇/水分配系数(LogP)：
  -7.88
• 重原子数：
  32
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.3
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  KP1019 在 sodium dihydrogenphosphate dihydrate 作用下， 以 水 、 丙酮 为溶剂， 以41%的产率得到sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]
  参考文献：
  名称：

  WO2008/154553

  摘要：

  公开号：
• 作为产物：
  描述：

  吲唑 、 盐酸 、 ruthenium trichloride 以 水 为溶剂， 生成 KP1019
  参考文献：
  名称：

  含唑杂环的钌羰基配合物 - 合成、X 射线衍射结构、DFT 计算、溶液行为和抗增殖活性

  摘要：

  (H2azole)[trans-RuCl4(Hazole)2] [Hazole = 1H-pyrazole (Hpz), 1H-indazole (Hind), 1-methylindazole (1-Me-ind), or 1H-benzimidazole (Hbzim) 的反应] 与 12 M HCl 和甲酸的 1:1 混合物形成反式-[RuCl4(CO)(Hazole)]– 复合物，通过 X 射线衍射将其分离并鉴定为 nBu4N[trans-RuCl4(CO) )(Hpz)] (1a), nBu4N[trans-RuCl4(CO)(Hind)] (2a), [(Hind)2H][trans-RuCl4(CO)(Hind)] (2b), nBu4N[trans- RuCl4(CO)(1-Me-ind)] (3a) 和 nBu4N[trans-RuCl4(CO)(Hbzim)] (6a)，而与

  DOI：

  10.1002/ejic.201501393

文献信息

• Tuning of Redox Potentials for the Design of Ruthenium Anticancer Drugs − an Electrochemical Study of [<i>trans</i>-RuCl₄L(DM<i>S</i>O)]^- and [<i>trans</i>-RuCl₄L₂]^- Complexes, where L = Imidazole, 1,2,4-Triazole, Indazole
  作者：Erwin Reisner、Vladimir B. Arion、M. Fátima C. Guedes da Silva、Roman Lichtenecker、Anna Eichinger、Bernhard K. Keppler、Vadim Yu. Kukushkin、Armando J. L. Pombeiro

  DOI：10.1021/ic049479c

  日期：2004.11.1

  electrochemical behavior of [trans-RuCl(4)L(DMSO)](-) (A) and [trans-RuCl(4)L(2)](-) (B) [L = imidazole (Him), 1,2,4-triazole (Htrz), and indazole (Hind)] complexes has been studied in DMF, DMSO, and aqueous media by cyclic voltammetry and controlled potential electrolysis. They exhibit one single-electron Ru(III)/Ru(II) reduction involving, at a sufficiently long time scale, metal dechlorination on solvolysis,

  [反式-RuCl（4）L（DMSO）]（-）（A）和[反式-RuCl（4）L（2）]（-）（B）的电化学行为[L =咪唑（Him），1 1,2,4-三唑（Htrz）和吲唑（Hind）]配合物已在DMF，DMSO和水性介质中通过循环伏安法和可控电位电解进行了研究。它们表现出一种单电子Ru（III）/ Ru（II）还原，包括在足够长的时间范围内进行溶剂分解时的金属脱氯，以及在有机介质中一种单电子可逆Ru（III）/ Ru（ IV）氧化。氧化还原电位值是根据Lever的参数化方法进行解释的，并且首次提出了此线性表达式的特定形式（将氧化还原电位与配体E（L）参数相关联），用于在磷酸盐缓冲液（pH 7）介质中与Ru（III / II）氧化还原对中心带负电荷的（1-）配合物，以及在有机介质中与Ru（III / IV）耦合对的配合物。对吲唑的E（L）参数进行了估计，表明该配体的行为比咪唑或三唑的净电子给
• MANUFACTURE OF TRANS-[TETRACHLOROBIS(1H-INDAZOLE)RUTHENATE (III)] AND COMPOSITIONS THEREOF
  申请人：INTEZYNE TECHNOLOGIES, INC.

  公开号：US20180327435A1

  公开（公告）日：2018-11-15

  The present invention relates to the preparation of compositions comprising sodium trans-[tetrachlorobis(1H-indazole)ruthenate (III)]. Synthesis and formulation preparation is detailed. Impurity profiles are also discussed. Compositions herein are useful for anti-cancer applications.

  本发明涉及制备含有氯化铑(III)的钠对映体-[四氯二(1H-吲唑)合铑]的组合物。合成和配方制备已详细描述。还讨论了杂质的特征。本组合物对抗癌应用具有用途。
• Synthesis of Tumor-Inhibiting Complex Salts Containing the Aniontrans-Tetrachlorobis(indazole)ruthenate(III) and Crystal Structure of the Tetraphenylphosphonium Salt
  作者：Wolfgang Peti、Thomas Pieper、Martina Sommer、Bernhard K. Keppler、Gerald Giester

  DOI：10.1002/(sici)1099-0682(199909)1999:9<1551::aid-ejic1551>3.0.co;2-7

  日期：1999.9

  (indazole)ruthenate(III) exhibits excellent results against different tumor models in vitro and in vivo. To improve the water solubility necessary for the introduction of this tumor-inhibiting compound into clinical trials, we synthesized the corresponding sodium salt in a two-step ion exchange via the tetramethylammonium salt. The sodium salt shows a 35-fold higher solubility in water relative to

  Indazolium trans-tetrachlorobis(indazole)ruthenate (III) 在体外和体内针对不同肿瘤模型表现出优异的结果。为了提高将这种肿瘤抑制化合物引入临床试验所需的水溶性，我们通过四甲基铵盐在两步离子交换中合成了相应的钠盐。钠盐在水中的溶解度比吲唑盐高 35 倍。我们还合成了正丁基铵、正辛基铵和四苯基鏻盐，所有这些盐都在有机溶剂中显示出改善的溶解度。可以解析后者的 X 射线晶体结构，证明复合阴离子的反式构型。
• Pieper, Thomas; Sommer, Martina; Galanski, Markus, Zeitschrift fur Anorganische und Allgemeine Chemie, 2001, vol. 627, # 2, p. 261 - 265
  作者：Pieper, Thomas、Sommer, Martina、Galanski, Markus、Keppler, Bernhard K.、Giester, Gerald

  DOI：——

  日期：——
• Anti-cancer drug KP1019 induces Hog1 phosphorylation and protein ubiquitylation in Saccharomyces cerevisiae
  作者：Vikash Singh、Gajendra Kumar Azad、Amarendar Reddy M.、Shivani Baranwal、Raghuvir S. Tomar

  DOI：10.1016/j.ejphar.2014.04.032

  日期：2014.8

  Ruthenium-based anti-cancer drugs have attracted increasing interest in the last 20 years. KP1019 is one of the ruthenium-containing compounds that has demonstrated anti-tumor activity against various cancers, and has been tested in several clinical trials. Despite its success, the mode of action of KP1019 is not well described. In the present study, we have used budding yeast Saccharomyces cerevisiae to elucidate the action of KP1019. We have found that KP1019 causes dose-dependent cell arrest in the S-phase of cell cycle. Furthermore, we have demonstrated for the first time that the yeast mitogen-activated protein (MAP) kinase Hog1 is essential for the cells in response to KP1019. Hog1 is rapidly phosphorylated upon treatment with KP1019, and the deletion of the HOG1 gene potentiates the growth inhibition effect of KP1019. Moreover, we also observed the up-regulation of glycerol-3-phosphate dehydrogenase I (GPD1) mRNA in response to KP1019 treatment, a factor that is essential for the hyperosmotic stress response. Our results also reveal that membrane-bound sensor proteins of high osmolarity glycerol (HOG) pathway are crucial for Hog1 phosphorylation in response to KP1019-induced stress. Furthermore, KP1019 has also been found to increase the accumulation of ubiquitinated proteins and deletion of several members of ubiquitination pathways conferred sensitivity for KP1019. The findings presented here strongly suggest the ability of KP1019 to activate Hog1 MAP kinase and induce protein ubiquitination, which may underlie the therapeutic potential of this compound. In summary, we have disclosed a novel mechanism of KP1019 activity. (C) 2014 Elsevier B.V. All rights reserved.