1-phenyl-2,5-bis(2-pyridyl)phosphole gold chloride

• 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-phenyl-2,5-bis(2-pyridyl)phosphole gold chloride
• 英文别名: [1-phenyl-2,5-di(2-pyridyl)phosphole]AuCl；Gold(1+);2-(2-phenyl-3-pyridin-2-yl-4,5,6,7-tetrahydroisophosphindol-1-yl)pyridine;chloride
• 化学式: C₂₄H₂₁AuClN₂P
• 分子量: 600.837
• InChiKey: BGMORGNXKXYIFW-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-phenyl-2,5-bis(2-pyridyl)phosphole gold chloride 、 1-硫代-b-D-葡萄糖四乙酸酯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以70%的产率得到gold(1+);2-(2-phenyl-3-pyridin-2-yl-4,5,6,7-tetrahydroisophosphindol-1-yl)pyridine;(2S,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(acetyloxymethyl)oxane-2-thiolate
  参考文献：
  名称：

  Antiglioma activity of GoPI-sugar, a novel gold(I)–phosphole inhibitor: Chemical synthesis, mechanistic studies, and effectiveness in vivo

  摘要：

  Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-beta-D-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC50 of 430 mu M, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC50 4.3 nM) and human glutathione reductase (IC50 88.5 nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. (C) 2014 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbapap.2014.01.006
• 作为产物：
  描述：

  (tetrahydrothiophene)gold(I) chloride 、 C6H8C2P(2-pyridyl)2(phenyl) 以 二氯甲烷 为溶剂， 反应 3.0h， 以70%的产率得到1-phenyl-2,5-bis(2-pyridyl)phosphole gold chloride
  参考文献：
  名称：

  Phosphole Derivatives Complexed with Metals, and Pharmaceutical Uses Thereof

  摘要：

  这项发明涉及包含至少一种一般式（A）化合物作为活性成分的药物组合物，其中：M代表金属原子，并且其用途特别在于预防或治疗与谷胱甘肽还原酶和/或硫氧还蛋白还原酶过度活性相关的病理。

  公开号：

  US20080045465A1

文献信息

• Bimetallic Gold(I) Complexes with Ethynyl‐Helicene and Bis‐Phosphole Ligands: Understanding the Role of Aurophilic Interactions in their Chiroptical Properties
  作者：Mehdi El Sayed Moussa、Hui Chen、Zuoyong Wang、Monika Srebro‐Hooper、Nicolas Vanthuyne、Soizic Chevance、Christian Roussel、J. A. Gareth Williams、Jochen Autschbach、Régis Réau、Zheng Duan、Christophe Lescop、Jeanne Crassous

  DOI：10.1002/chem.201600126

  日期：2016.4.18

  Monometallic gold(I)‐alkynyl‐helicene complexes (1 a,b) and bimetallic gold(I)‐alkynyl‐helicene architectures featuring the presence (2 a,b) or absence (3 a,b) of aurophilic intramolecular interactions were prepared by using different types of phosphole ligands (mono‐phosphole L1 or bis‐phospholes L2,3). The influence of the AuI d10 metal center(s) on the electronic, photophysical, and chiroptical

  单金属金（I） -炔基-螺烯复合物（1，b）和双金属金（I） -炔基-螺烯结构特色的存在（2，b）或不存在（3，b aurophilic的分子内相互作用的）中制备通过使用不同类型的配体磷杂环的（单-磷杂L1或双- phospholes L2，3）。Au I d 10的影响在这些前所未有的磷脂-金（I）-炔基-螺旋烯配合物的电子，光物理和手性性质上研究了金属中心。实验和理论结果强调配体对配体-类型的电荷转移的重要性和Au的存在或不存在的强烈影响我-Au我相互作用2，b。
• Phosphole Derivatives Complexed with Metals, and Pharmaceutical Uses Thereof
  申请人：Davioud-Charvet Elisabeth

  公开号：US20080045465A1

  公开（公告）日：2008-02-21

  The invention concerns pharmaceutical compositions comprising as active compound at least one compound of general formula (A), wherein: M represents a metal atom, and their uses in particular for preventing or treating pathologies associated with an excess activity of glutathion reductase and/or thioredoxin reductase.

  这项发明涉及包含至少一种一般式（A）化合物作为活性成分的药物组合物，其中：M代表金属原子，并且其用途特别在于预防或治疗与谷胱甘肽还原酶和/或硫氧还蛋白还原酶过度活性相关的病理。
• Antiglioma activity of GoPI-sugar, a novel gold(I)–phosphole inhibitor: Chemical synthesis, mechanistic studies, and effectiveness in vivo
  作者：E. Jortzik、M. Farhadi、R. Ahmadi、K. Tóth、J. Lohr、B.M. Helmke、S. Kehr、A. Unterberg、I. Ott、R. Gust、V. Deborde、E. Davioud-Charvet、R. Réau、K. Becker、C. Herold-Mende

  DOI：10.1016/j.bbapap.2014.01.006

  日期：2014.8

  Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-beta-D-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC50 of 430 mu M, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC50 4.3 nM) and human glutathione reductase (IC50 88.5 nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. (C) 2014 Elsevier B.V. All rights reserved.