3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene | 78668-33-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene
• 英文别名: 3,6,9,12,18-pentazabicyclo[12.3.1]octadeca-1(18),14,16-triene
• CAS: 78668-33-4
• 化学式: C₁₃H₂₃N₅
• 分子量: 249.359
• InChiKey: UJPWFBPXKOLBJT-UHFFFAOYSA-N

物化性质

• 熔点：
  280-282 °C (decomp)
• 沸点：
  431.0±40.0 °C(Predicted)
• 密度：
  0.975±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  61
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene 、 zinc(II) chloride 以 乙醇 为溶剂， 以57%的产率得到3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene dichlorozinc(II)
  参考文献：
  名称：

  靶向趋化因子受体CXCR4的吡啶融合大环多胺的金属配合物†

  摘要：

  趋化因子受体CXCR4在HIV感染，多种形式的癌症以及各种其他病理情况（如类风湿性关节炎和哮喘）中起关键细胞表面受体的作用。已知大环多胺及其金属配合物具有抗HIV活性，许多通过与CXCR4特异性结合而充当HIV进入抑制剂。通过锰（II）模板化的三亚乙基四胺与各种二羰基化合物的席夫碱环化反应，合成了三个系列的吡啶opentaazacylopentadecanes，其中吡啶环稠合至零，一个或两个饱和的六元环。通过评估这些大环多胺及其与Mn 2 +，Cu 2 +，Fe 3+和Zn 2+的配合物，我们发现了新颖的CXCR4结合化合物。通过抑制CXCL12与PBMCs的结合，可以证明，新的pentaazacyclopentadecane的MnCl 2复合物具有一个稠合的碳环（11）作为趋化因子受体CXCR4（IC 50：0.014μM）的拮抗剂具有最大的效力。血液单核细胞）。因此，该化合物抑制使用C

  DOI：

  10.1039/c5ob01557j
• 作为产物：
  描述：

  2,6-二氯甲基吡啶 在 盐酸 、 sodium hydroxide 、 四丁基硫酸氢铵 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 4.0h， 生成 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene
  参考文献：
  名称：

  Diethoxyphosphoryl as a Protecting-Activating Group in the Synthesis of Polyazacyclophanes

  摘要：

  The fully diethoxyphosphoryl(Dep)-protected polyamines 1b-3b were prepared from the corresponding polyamines with 'diethyl phosphite' (= diethyl phosphonate) and CCl4 in a solid base/organic liquid two-phase system in the presence of Bu4NBr as phase-transfer catalyst. Subsequent phase-transfer-catalyzed alkylation of phosphoramidates 1b-3b with bis(chloromethyl)arenes 5-8 in the presence of Bu4N(HSO4) followed by deprotection gave good yields of polyazacyclophanes 9a-16a.

  DOI：

  10.1002/(sici)1522-2675(20000412)83:4<793::aid-hlca793>3.0.co;2-3

文献信息

• Pyridine-Containing Macrocycles Display MMP-2/9 Inhibitory Activity and Distinct Effects on Migration and Invasion of 2D and 3D Breast Cancer Models
  作者：Susana Proença、Bernardo Antunes、Rita C. Guedes、Filipa Ramilo-Gomes、M. Fátima Cabral、Judite Costa、Ana S. Fernandes、Matilde Castro、Nuno G. Oliveira、Joana P. Miranda

  DOI：10.3390/ijms20205109

  日期：——

  The role of metalloproteinases (MMPs) on the migration and invasion of cancer cells has been correlated with tumor aggressiveness, namely with the up-regulation of MMP-2 and 9. Herein, two pyridine-containing macrocyclic compounds, [15]pyN5 and [16]pyN5, were synthesized, chemically characterized and evaluated as potential MMP inhibitors for breast cancer therapy using 3D and 2D cellular models. [15]pyN5 and [16]pyN5 (5–20 µM) showed a marked inhibition of MMPs activity (100% at concentrations ≥ 7.5 μM) when compared to ARP-100, a known MMP inhibitor. The inhibitory activity of [15]pyN5 and [16]pyN5 was further supported through in silico docking studies using Goldscore and ChemPLP scoring functions. Moreover, although no significant differences were observed in the invasion studies in the presence of all MMPs inhibitors, cell migration was significantly inhibited by both pyridine-containing macrocycles at concentrations above 5 μM in 2D cells (p < 0.05). In spheroids, the same effect was observed, but only with [16]pyN5 at 20 μM and ARP-100 at 40 μM. Overall, [15]pyN5 and [16]pyN5 led to impaired breast cancer cell migration and revealed to be potential inhibitors of MMPs 2 and 9.

  金属蛋白酶（MMPs）在癌细胞的迁移和侵袭中的作用与肿瘤的侵略性有关，即与MMP-2和9的上调有关。本研究合成了两种含吡啶的大环化合物[15]pyN5和[16]pyN5，并在3D和2D细胞模型中评估其作为乳腺癌治疗的潜在MMP抑制剂。[15]pyN5和[16]pyN5（5-20 µM）与已知的MMP抑制剂ARP-100相比，显示出明显的MMP活性抑制作用（在浓度≥7.5 μM时为100%）。通过使用Goldscore和ChemPLP评分函数的计算机模拟对接研究，进一步支持了[15]pyN5和[16]pyN5的抑制活性。此外，尽管在所有MMP抑制剂存在的情况下侵袭研究中没有显着差异，但在2D细胞中，仅在浓度高于5 μM时，这两种含吡啶的大环化合物显着抑制了细胞迁移（p<0.05）。在球体中，只有[16]pyN5在20 μM和ARP-100在40 μM时才观察到相同的效果。总的来说，[15]pyN5和[16]pyN5导致了乳腺癌细胞迁移的受损，并显示出成为MMP-2和9的潜在抑制剂的可能性。
• METHODS AND COMPOUNDS FOR ENHANCING CONTRAST IN MAGNETIC RESONANCE IMAGING (MRI)
  申请人：Brock University

  公开号：US20160362434A1

  公开（公告）日：2016-12-15

  The present application relates to methods and compounds for enhancing contrast in magnetic resonance imaging. The methods comprise administering compounds of Formula I(a) or I(b) to a subject and obtaining a magnetic resonance image of the subject. The present application also relates to methods of preparing compounds of the Formula I(a) as well as intermediate compounds used in such a method of preparation.

  本申请涉及增强磁共振成像对比度的方法和化合物。该方法包括向受试者注射I(a)或I(b)公式的化合物，并获取受试者的磁共振图像。本申请还涉及制备I(a)公式化合物的方法，以及用于此类制备方法的中间化合物。
• Mn²⁺Complexes with Pyridine-Containing 15-Membered Macrocycles: Thermodynamic, Kinetic, Crystallographic, and¹H/¹⁷O Relaxation Studies
  作者：Bohuslav Drahoš、Jan Kotek、Petr Hermann、Ivan Lukeš、Éva Tóth

  DOI：10.1021/ic9020756

  日期：2010.4.5

  long electronic relaxation time, and fast water exchange, Mn2+ is a potential candidate for contrast agent application in medical magnetic resonance imaging. Nevertheless, the design of chelators that ensure stable Mn2+ complexation and optimal relaxation properties remains a coordination chemistry challenge. Here, we report the synthesis of two pyridine-containing ligands L1 and L2, with 15-membered triaza-dioxa-crown

  鉴于其五个不成对的d电子，长的电子弛豫时间和快速的水交换，Mn 2+是在医学磁共振成像中应用造影剂的潜在候选者。然而，确保稳定的Mn 2+络合和最佳弛豫性能的螯合剂设计仍然是配位化学挑战。在这里，我们报告两个含吡啶的配体L1和L2的合成，分别具有15元的三氮杂-二恶英-冠和五氮杂-冠醚大环，以及其Mn 2+的表征复合体。配位体的质子化常数和各种金属配合物的稳定性常数通过电位法测定。大环上吡啶的存在引起配合物的刚性，这导致相对于非吡啶类似物更大的热力学稳定性。锰的固态结构L1和Mn L2确认锰七协调2+有Cl -和H 2 ö中的轴向位置。Zn 2+存在下Mn L2的解离动力学然后进行弛豫测量。他们证明了质子辅助解离的首要重要性，而锌（II）辅助途径在生理pH下并不重要。对于锰L1，解离太快通过常规弛豫测量在pH 6进行研究的组合17 öNMR和1个上的MnħNMRD研究L1和Mn L2产生控
• Super-oxide dismutase mimetics
  申请人：Galera Labs, LLC

  公开号：US10350193B2

  公开（公告）日：2019-07-16

  The present invention relates to compounds which are effective as catalysts for dismutating superoxide and, more particularly, the manganese or iron complexes of substituted, unsaturated heterocyclic 16-membered macrocyclic complexes that catalytically dismutate superoxide. It also relates to methods of using these complexes to reduce the concentration or the effects of superoxide, pharmaceutical compositions comprising these compounds or their metal complexes, and methods of treating conditions associated with excessive superoxide activity.

  本发明涉及可有效作为催化剂分解超氧化物的化合物，特别是可催化分解超氧化物的取代的不饱和杂环16元大环络合物的锰或铁络合物。它还涉及使用这些络合物降低超氧化物浓度或影响的方法、包含这些化合物或其金属络合物的药物组合物，以及治疗与过量超氧化物活性相关的病症的方法。
• Methods and compounds for enhancing contrast in magnetic resonance imaging (MRI)
  申请人：Brock University

  公开号：US10377783B2

  公开（公告）日：2019-08-13

  The present application relates to methods and compounds for enhancing contrast in magnetic resonance imaging. The methods comprise administering compounds of Formula I(a) or I(b) to a subject and obtaining a magnetic resonance image of the subject. The present application also relates to methods of preparing compounds of the Formula I(a) as well as intermediate compounds used in such a method of preparation.

  本申请涉及增强磁共振成像对比度的方法和化合物。这些方法包括向受试者施用式 I(a)或 I(b)化合物并获得受试者的磁共振图像。本申请还涉及制备式 I(a)化合物的方法以及用于这种制备方法的中间化合物。