4-methyl-11-[4-(4-methyl-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadec-11-ylmethyl)-benzyl]-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadecane

• 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: 4-methyl-11-[4-(4-methyl-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadec-11-ylmethyl)-benzyl]-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadecane
• 英文别名: 1,4-bis((11-methyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecan-4-yl)methyl)benzene；para-xylyl bis(1-methyl-1,5,8,12-tetraazabicyclo[6.6.2]hexadecane)；11-Methyl-4-[[4-[(11-methyl-1,4,8,11-tetrazabicyclo[6.6.2]hexadecan-4-yl)methyl]phenyl]methyl]-1,4,8,11-tetrazabicyclo[6.6.2]hexadecane；4-methyl-11-[[4-[(11-methyl-1,4,8,11-tetrazabicyclo[6.6.2]hexadecan-4-yl)methyl]phenyl]methyl]-1,4,8,11-tetrazabicyclo[6.6.2]hexadecane
• 化学式: C₃₄H₆₂N₈
• 分子量: 582.92
• InChiKey: DGGMQRFSISVZAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  42
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  25.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-methyl-11-[4-(4-methyl-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadec-11-ylmethyl)-benzyl]-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadecane 在 copper dichloride 作用下， 以 甲醇 为溶剂， 反应 50.0h， 生成
  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：

  3a-[4-(8a-methyl-cis-decahydro-{5a,10a-diaza-3a,8a-azonia}pyren-3a-ylmethyl)benzyl]-8a-methyl-cis-decahydro{5a,10a-diaza-3a,8a-azonia}pyrene tetraiodide 在 sodium tetrahydroborate 、 乙醇 作用下， 反应 120.0h， 以71%的产率得到4-methyl-11-[4-(4-methyl-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadec-11-ylmethyl)-benzyl]-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadecane
  参考文献：
  名称：

  [EN] COMPOSITIONS COMPRISING MACROCYCLE DERIVATIVES INCORPORATING BRIDGED MACROCYCLES AND METHODS OF PRODUCING AND USING SAME
  [FR] COMPOSITIONS COMPRENANT DES DÉRIVÉS DE MACROCYCLES CONTENANT DES MACROCYCLES PONTÉS ET PROCÉDÉS DE PRODUCTION ET D'UTILISATION DE CELLES-CI

  摘要：

  本文披露了包含桥接大环的大环衍生物的组合物。还披露了生产和使用这些组合物的方法。

  公开号：

  WO2017030728A1

文献信息

• Acetate as a model for aspartate-based CXCR4 chemokine receptor binding of cobalt and nickel complexes of cross-bridged tetraazamacrocycles
  作者：Amy N. Cain、TaRynn N. Carder Freeman、Kimberly D. Roewe、David L. Cockriel、Travis R. Hasley、Randall D. Maples、Elisabeth M. A. Allbritton、Thomas D'Huys、Tom van Loy、Benjamin P. Burke、Timothy J. Prior、Dominique Schols、Stephen J. Archibald、Timothy J. Hubin

  DOI：10.1039/c8dt04728f

  日期：——

  linked to the chemokine receptor CXCR4. High-affinity CXCR4 antagonist transition metal complexes of configurationally restricted bis-tetraazamacrocyclic ligands have been identified in previous studies. Recently synthesised and structurally characterised Co2+/Co3+ and Ni2+ acetate complexes of mono-macrocycle cross-bridged ligands have been used to mimic their known coordination interaction with the

  多种疾病包括WHIM综合征，HIV感染和癌症与趋化因子受体CXCR4相关。在先前的研究中已经确定了构象受限的双-四氮杂大环配体的高亲和力CXCR4拮抗剂过渡金属络合物。最近合成和结构表征的单宏环交桥配体的Co2 + / Co3 +和Ni2 +乙酸酯络合物已被用来模拟它们与CXCR4结合时与天冬氨酸侧链的已知配位相互作用。在这里，提出了三个Co2 + / Co3 +乙酸盐配合物和五个Ni2 +乙酸盐配合物的X射线晶体结构，并证明了在与乙酸盐配体结合的模式中具有灵活性，同时具有必需的顺式-V-构型的交叉桥联四氮杂丙烯醛。较小的Co3 +金属离子的络合物通过螯合乙酸盐的两个氧而完全结合乙酸盐。跨桥四氮杂大环化合物中较大的Co2 +和Ni2 +金属离子显示出明显趋势，即单齿形式的乙酸盐与完整的八面体配位球的配位水分子配位。然而，在文献中报道的未桥连的四氮杂大环乙酸酯结构中，配位偏爱是螯合两个乙酸氧
• Discovery of Antischistosomal Drug Leads Based on Tetraazamacrocyclic Derivatives and Their Metal Complexes
  作者：M. O. Faruk Khan、Jennifer Keiser、P. N. A. Amoyaw、Mohammad F. Hossain、Mireille Vargas、Justin G. Le、Natalie C. Simpson、Kimberly D. Roewe、TaRynn N. Carder Freeman、Travis R. Hasley、Randall D. Maples、Stephen J. Archibald、Timothy J. Hubin

  DOI：10.1128/aac.00778-16

  日期：2016.9

  schistosomiasis, and since its large-scale use might be associated with the onset of resistance, new antischistosomal drugs should be developed. A series of 26 synthetic tetraazamacrocyclic derivatives and their metal complexes were synthesized, characterized, and screened for antischistosomal activity by application of a phased screening program. The compounds were first screened against newly transformed

  吡喹酮（PZQ）是唯一可用于治疗血吸虫病的药物，由于其大规模使用可能与耐药性的发生有关，因此应开发新的抗血吸虫药物。通过应用分阶段筛选程序，合成、表征和筛选了一系列 26 种合成四氮杂大环衍生物及其金属配合物的抗血吸虫活性。这些化合物首先针对收获的曼氏血吸虫尾蚴的新转化血吸虫 (NTS) 进行筛选，然后针对成虫进行筛选，最后在体内使用曼氏血吸虫感染的小鼠模型进行筛选。在 33 μM 浓度下，与总共 12 种化合物一起孵育导致 NTS 的死亡率在 62% 至 100% 的水平。其中五个在 10 μM 时显示 100% 抑制 NTS 的活力，被选择用于进一步筛选以确定针对 NTS 和成虫的 50 种抑制浓度 (IC50)。针对 NTS，所有 5 种化合物的 IC50 与标准药物 PZQ 的 IC50 相当（5 种化合物为 0.87 至 9.65 μM，而 PZQ 为 2.20 μM）。其中三种
• 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。
• Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands
  作者：Timothy J. Hubin、Prince N.-A. Amoyaw、Kimberly D. Roewe、Natalie C. Simpson、Randall D. Maples、TaRynn N. Carder Freeman、Amy N. Cain、Justin G. Le、Stephen J. Archibald、Shabana I. Khan、Babu L. Tekwani、M.O. Faruk Khan

  DOI：10.1016/j.bmc.2014.05.003

  日期：2014.7

  Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn2+ complex of this ligand was the most potent with IC(50)s of 0.127 and 0.157 mu M against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn2+. Few of the Cu2+ and Fe2+ complexes also showed improvement in activity but Ni2+, Co2+ and Zn2+ complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development. Published by Elsevier Ltd.
• COMPOSITIONS COMPRISING MACROCYCLE DERIVATIVES INCORPORATING BRIDGED MACROCYCLES AND METHODS OF PRODUCING AND USING SAME
  申请人：Southwestern Oklahoma State University

  公开号：EP3337519B1

  公开（公告）日：2021-12-01