5,5'-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraaza-bicyclo[10.2.2]hexadecane) | 871834-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5,5'-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraaza-bicyclo[10.2.2]hexadecane)
• 英文别名: para-xylyl bis(1,5,8,12-tetaazabicyclo[10.2.2]hexadecane)；5-[[4-(1,5,8,12-Tetrazabicyclo[10.2.2]hexadecan-5-ylmethyl)phenyl]methyl]-1,5,8,12-tetrazabicyclo[10.2.2]hexadecane
• CAS: 871834-15-0
• 化学式: C₃₂H₅₈N₈
• 分子量: 554.866
• InChiKey: RIACCWNWDXAFJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  40
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  43.5
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5,5'-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraaza-bicyclo[10.2.2]hexadecane) 在 盐酸 作用下， 以 甲醇 为溶剂， 以65%的产率得到
  参考文献：
  名称：

  [EN] NOVEL ANTIVIRAL MACROCYCLE DERIVATIVES AND METAL COMPLEXES, INCORPORATING BRIDGED MACROCYCLES
  [FR] NOUVEAUX DERIVES DE MACROCYCLES ET COMPLEXES METALLIQUES ANTIVIRAUX COMPRENANT DES MACROCYCLES PONTES

  摘要：

  公开号：

  WO2005121109A3
• 作为产物：
  描述：

  decahydro-3a,5a,8a,10a-tetraazapyrene 在 sodium tetrahydroborate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 25.83h， 生成 5,5'-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraaza-bicyclo[10.2.2]hexadecane)
  参考文献：
  名称：

  [EN] NOVEL ANTIVIRAL MACROCYCLE DERIVATIVES AND METAL COMPLEXES, INCORPORATING BRIDGED MACROCYCLES
  [FR] NOUVEAUX DERIVES DE MACROCYCLES ET COMPLEXES METALLIQUES ANTIVIRAUX COMPRENANT DES MACROCYCLES PONTES

  摘要：

  公开号：

  WO2005121109A3

文献信息

• CXCR4 chemokine receptor antagonists: nickel(ii) complexes of configurationally restricted macrocycles
  作者：Rachel Smith、Dana Huskens、Dirk Daelemans、Ryan E. Mewis、Courtney D. Garcia、Amy N. Cain、TaRynn N. Carder Freeman、Christophe Pannecouque、Erik De Clercq、Dominique Schols、Timothy J. Hubin、Stephen J. Archibald

  DOI：10.1039/c2dt31137b

  日期：——

  Tetraazamacrocyclic complexes of transition metals provide useful units for incorporating multiple coordination interactions into a single protein binding molecule. They can be designed with available sites for protein interactions via donor atom-containing amino acid side chains or labile ligands, such as H2O, allowing facile exchange. Three configurationally restricted nickel(II) cyclam complexes with either

  过渡金属的四氮杂大环配合物为将多个配位相互作用结合到单个蛋白质结合分子中提供了有用的单元。它们可以设计成具有可利用的位点，用于通过含供体原子的氨基酸侧链或不稳定的配体（例如H 2 O）进行蛋白质相互作用，从而实现便捷的交换。合成了三个具有一个或两个大环的结构受限的镍（II）环蛋白复合物，并评估了其消除CXCR4趋化因子受体信号传导过程的能力（IC 50 = 8320、194和14 nM）。通过晶体学表征类似物，以确定作为天冬氨酸的模型的乙酸酯结合的几何参数。活性最高的镍II）化合物在几种抗HIV检测中针对代表性病毒株进行了测试，显示使用病毒对CXCR4的有效EC 50值低至13 nM，没有观察到的细胞毒性（CC 50 > 125μM）。
• Probing key coordination interactions: configurationally restricted metal activated CXCR4 antagonists
  作者：Graeme McRobbie、Gina C. Valks、Christopher J. Empson、Abid Khan、Jon D. Silversides、Christophe Pannecouque、Erik De Clercq、Steven G. Fiddy、Adam J. Bridgeman、Nigel A. Young、Stephen J. Archibald

  DOI：10.1039/b705800d

  日期：——

  The syntheses of configurationally restricted mono- and bis-macrocyclic copper(II) perchlorate complexes (copper(II) 5-benzyl-1,5,8,12-tetraazabicyclo[10.2.2]hexadecane and dicopper(II) 5,5′-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraazabicyclo[10.2.2]hexadecane)) are reported and the X-ray structure of the copper(II) mono-macrocyclic complex has been determined. EXAFS studies on the bis-macrocyclic species in aqueous solution show that the copper coordination spheres are essentially identical to the solid state structure, and do not vary in the presence of 20 equivalents of sodium acetate per metal centre. DFT calculations were carried out at the BP86/TZP level to determine the nature of potential binding interactions with CXCR4 aspartate residues. The alkylated single macrocyclic compound was modelled with an acetate included to represent the aspartate residue, demonstrating that the predicted macrocycle configuration has the lowest energy and the acetate interaction is effectively monodentate giving a distorted trigonal bipyramidal geometry at the copper centre. In vitro anti-HIV infection assays show that the configurationally restricted dicopper(II) complex is more active (average EC50 = 0.026 μM against HIV-1) than the non-constrained dicopper(II) 1,1′-[1,4-phenylenebis(methylene)]-bis(1,4,8,11-tetraazacyclotetradecane) (average EC50 = 0.047 μM against HIV-1) although it is an order of magnitude less active than the configurationally restricted dizinc(II) complex.

  合成了构型受限的单高氯酸铜(II)和双高氯酸铜(II)高环配合物（5-苄基-1,5,8,12-四氮杂双环[10.2.2]十六烷和 5,5′-[1,4-亚苯基双(亚甲基)]-双(1,5,8,12-四氮杂双环[10.2.2]十六烷)二氯化铜(II)，并确定了铜(II)单高环配合物的 X 射线结构。对水溶液中的双大环物种进行的 EXAFS 研究表明，铜配位球与固态结构基本相同，并且在每个金属中心存在 20 个等量的醋酸钠时也不会发生变化。我们在 BP86/TZP 水平上进行了 DFT 计算，以确定与 CXCR4 天门冬氨酸残基的潜在结合相互作用的性质。对烷基化的单一大环化合物进行了建模，并加入了代表天冬氨酸残基的醋酸盐，结果表明预测的大环构型具有最低的能量，醋酸盐的相互作用实际上是单价的，从而在铜中心形成了扭曲的三叉双锥几何形状。体外抗艾滋病毒感染试验表明，构型受限的二氯化铜（II）复合物活性更高（平均 EC50 = 0.0.047 μM），但其活性比构型受限的二锌(II)复合物低一个数量级。
• Compositions comprising macrocycle derivatives incorporating bridged macrocycles and methods of producing and using same
  申请人：Southwestern Oklahoma State University

  公开号：US10927108B2

  公开（公告）日：2021-02-23

  Compositions are disclosed herein that include macrocycle derivatives incorporating bridged macrocycles. Also disclosed are methods of producing and using the compositions.

  本文公开了包括桥接大环在内的大环衍生物的组合物。还公开了生产和使用这些组合物的方法。
• <i>trans</i>-IV restriction: a new configuration for metal bis-cyclam complexes as potent CXCR4 inhibitors
  作者：Seraj O. Alzahrani、Graeme McRobbie、Abid Khan、Thomas D'huys、Tom Van Loy、Ashlie N. Walker、Isaline Renard、Timothy J. Hubin、Dominique Schols、Benjamin P. Burke、Stephen J. Archibald

  DOI：10.1039/d3dt01729j

  日期：2024.3.19

  been shown to be effective in cancer treatment as an individual agent. Configurational restriction and transition metal complex formation increases receptor binding affinity and residence time. In the present study, we have synthesized novel trans-IV locked cyclam-based CXCR4 inhibitors, a previously unexploited configuration, and demonstrated their higher affinity for CXCR4 binding and CXCL12-mediated

  趋化因子受体 CXCR4 与多种疾病有关，包括炎症性疾病、癌症生长和转移以及 HIV/AIDS。 CXCR4 靶向治疗已在治疗癌症转移和治疗耐药方面进行了评估。仙客来衍生物，尤其是 AMD3100 (Plerixafor™)，是小分子 CXCR4 拮抗剂中的常见基序。然而，AMD3100 尚未被证明作为单独药物在癌症治疗中有效。构型限制和过渡金属络合物的形成增加了受体结合亲和力和停留时间。在本研究中，我们合成了新型反式IV锁定的cyclam基CXCR4抑制剂，这是一种以前未开发的配置，并证明了与AMD3100相比，它们对CXCR4结合和CXCL12介导的信号抑制具有更高的亲和力。这些结果为更有效的 CXCR4 抑制剂铺平了道路，这些抑制剂可能在癌症治疗中提供显着的疗效。
• Configurationally Restricted Bismacrocyclic CXCR4 Receptor Antagonists
  作者：Gina C. Valks、Graeme McRobbie、Elizabeth A. Lewis、Timothy J. Hubin、Tina M. Hunter、Peter J. Sadler、Christophe Pannecouque、Erik De Clercq、Stephen J. Archibald

  DOI：10.1021/jm0607810

  日期：2006.10.1

  A zinc(II) containing configurationally restricted analogue of bismacrocyclic cyclam-type CXCR4 chemokine receptor antagonists has been synthesized and shown to adopt only one configuration in solution. The single crystal X-ray structure reveals favorable binding to acetate via a bidentate chelation that can be related to the proposed interaction with aspartate on the receptor protein surface. The zinc(II) complex is highly active against HIV infection in vitro.