N¹,N⁴,N⁷,N¹⁰,N¹³-pentatosyl-1,4,7,10,13-penta-azacyclopentadecane | 52601-74-8

• 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: N¹,N⁴,N⁷,N¹⁰,N¹³-pentatosyl-1,4,7,10,13-penta-azacyclopentadecane
• 英文别名: 1,4,7,10,13-pentakis(p-toluenesulfonyl)-1,4,7,10,13-pentaazacyclopentadecane；1,4,7,10,13-pentatosyl-1,4,7,10,13-pentaazacyclopentadecane；(penta-N-tosyl)-1,4,7,10,13-pentaazacyclopentadecane；1,4,7,10,13-pentakis-(toluene-4-sulfonyl)-1,4,7,10,13-pentaaza-cyclopentadecane；1,4,7,10,13-penta(p-toluenesulfonyl)-1,4,7,10,13-pentaazacyclopentadecane；1,4,7,10,13-Penta-p-toluenesulfonyl-1,4,7,10,13-pentaazacyclopentadecane；1,4,7,10,13-pentakis-(4-methylphenyl)sulfonyl-1,4,7,10,13-pentazacyclopentadecane
• CAS: 52601-74-8
• 化学式: C₄₅H₅₅N₅O₁₀S₅
• 分子量: 986.289
• InChiKey: PEEVYAVAFWYTMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  65
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  229
• 氢给体数：
  0
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  N¹,N⁴,N⁷,N¹⁰,N¹³-pentatosyl-1,4,7,10,13-penta-azacyclopentadecane 在 硫酸 作用下， 以 水 为溶剂， 反应 0.01h， 以81.7%的产率得到1,4,7,10,13-Pentaaza-cyclopentadecane; compound with sulfuric acid
  参考文献：
  名称：

  Wei; Shi; He, Polish Journal of Chemistry, 2003, vol. 77, # 4, p. 485 - 487

  摘要：

  DOI：
• 作为产物：
  描述：

  三乙烯四胺 在 sodium hydroxide 、 sodium methylate 作用下， 以 乙醚 、 水 为溶剂， 反应 32.0h， 生成 N¹,N⁴,N⁷,N¹⁰,N¹³-pentatosyl-1,4,7,10,13-penta-azacyclopentadecane
  参考文献：
  名称：

  Pilichowski; Borel; Meyniel, European Journal of Medicinal Chemistry, 1984, vol. 19, # 5, p. 425 - 431

  摘要：

  DOI：

文献信息

• Synthetic, kinetic, and stereochemical studies on the copper(II), nickel(II), and cobalt(III) complexes of 1,4,7,10,13-penta-aza-cyclopentadecane
  作者：Robert W. Hay、Ramesh Bembi、W. Thomas Moodie、Paul R. Norman

  DOI：10.1039/dt9820002131

  日期：——

  Acid aquation with kaq= 1.66 × 104 s–1 at 50 °C is quite slow. The CuII and octahedral NiII complexes are labile in acidic solution, unlike the complexes of 1,4,8,11-tetra-azacyclotetradecane. The kinetics of the acid-catalysed dissociation have been studied in detail. For both complexes rate =kH[complex][H +]2, indicating the involvement of two protons in the transition state of the reaction. For

  描述了标题五齿大环配体L的制备。制备并表征了配合物[NiL（OH 2）] [ClO 4 ] 2，[CuL] [ClO 4 ] 2和[CoLCl] [ClO 4 ] 2。由于两个手性氮中心，络合物可以具有三种可能的构型。有两个N-内消旋非对映异构体和一个N-外消旋非对映异构体。碳13 nmr测量表明，Co III配合物是可能的立体异构体的混合物。[COLCl] 2+的碱水解相当迅速，k OH = 2.45×10 4dm 3 mol –1 s –1在30°C且I = 0.1 mol dm –3，可以根据mer -N 3供体组进行合理化。在50°C时，k aq = 1.66×10 4 s –1的酸化过程非常缓慢。与1,4,8,11-四氮杂环十四烷的络合物不同，Cu II和八面体Ni II络合物在酸性溶液中不稳定。已经详细研究了酸催化离解的动力学。对于两个复合物，速率= k H [复合物] [H +
• Expanding and quantifying the crystal chemistry of the flexible ligand <b>15aneN5</b>
  作者：Anthony D. Shircliff、Elisabeth M. A. Allbritton、Dustin J. Davilla、Michael-Joseph Gorbet、Donald G. Jones、David S. Tresp、Michael B. Allen、Alina Shrestha、Gwendolyn E. Burgess、John I. Eze、Andrea T. Fernandez、Daniel Ramirez、Kody J. Shoff、Garet G. Crispin、Sarah B. Crone、Michael Flinn、Tien Tran、Darby S. Bryce、Abbagale L. Bond、Dylan W. Shockey、Allen G. Oliver、Jeanette A. Krause、Timothy J. Prior、Timothy J. Hubin

  DOI：10.1039/d1ce01534f

  日期：——

  made using typical complexation methods. X-ray crystallography of multiple novel complexes yielded insight into the flexibility in coordination geometry of this interesting macrocycle as well as the first crystal structures of 15aneN5 with Cr3+, Mn3+, Fe3+, Co3+, Cu2+, and Ru2+. A parameter to quantify the coordination geometry adopted by the ligand was devised and applied to all known crystal structures

  四氮杂大环已被广泛用作过渡金属配体，用于多种用途，包括催化、医学成像、药物等。然而，五氮杂大环由于可用性差、合成困难和较少用于类似目的而不太常用。众所周知的金属配位特性。1,4,7,10,13-五氮杂环戊烷（15aneN5) 最初是通过已公布的合成路线合成的，我们将其简化和缩短，产量下降最小。使用典型的络合方法制备了八种不同的过渡金属络合物。多种新型配合物的 X 射线晶体学深入了解了这种有趣的大环的配位几何形状的灵活性以及15aneN5与 Cr 3+、Mn 3+、Fe 3+、Co 3+、Cu 2+、和Ru 2+。设计了一个量化配体所采用的配位几何的参数，并将其应用于其金属配合物的所有已知晶体结构。最后氧化15aneN5在与钌络合的过程中观察到一个新的二亚胺大环。
• Methods of preparing manganese complexes of nitrogen-containing
  申请人：Monsanto Company

  公开号：US05610293A1

  公开（公告）日：1997-03-11

  The present invention is directed to low molecular weight mimics of superoxide dismutase (SOD) represented by the formula: ##STR1## wherein R, R', R.sub.1, R'.sub.1, R.sub.2, R'.sub.2, R.sub.3, R'.sub.3, R.sub.4, R'.sub.4, R.sub.5, R'.sub.5, R.sub.6, R'.sub.6, R.sub.7, R'.sub.7, R.sub.8, R'.sub.8, R.sub.9, and R'.sub.9 and X, Y, Z and n are as defined herein, useful as therapeutic agents for inflammatory disease states and disorders, ischemic/reperfusion injury, stroke, atherosclerosis, hypertension and all other conditions of oxidant-induced tissue damage or injury.

  本发明涉及超氧化物歧化酶（SOD）的低分子量模拟物，其表示为以下式子：##STR1## 其中R，R'，R1，R'1，R2，R'2，R3，R'3，R4，R'4，R5，R'5，R6，R'6，R7，R'7，R8，R'8，R9和R'9以及X，Y，Z和n如本文所定义，可用作治疗炎症性疾病状态和障碍，缺血/再灌注损伤，中风，动脉硬化，高血压以及所有其他氧化剂引起的组织损伤或损伤的治疗剂。
• Manganese complexes of nitrogen-containing macrocyclic ligands effective
  申请人：——

  公开号：US05637578A1

  公开（公告）日：1997-06-10

  The present invention is directed to low molecular weight mimics of superoxide dismutase (SOD) represented by the formula: ##STR1## wherein R, R', R.sub.1, R'.sub.1, R.sub.2, R'.sub.2, R.sub.3, R'.sub.3, R.sub.4, R'.sub.4, R.sub.5, R'.sub.5, R.sub.6, R'.sub.6, R.sub.7, R'.sub.7, R.sub.8, R'.sub.8, R.sub.9, and R'.sub.9 and X, Y, Z and n are as defined herein, useful as therapeutic agents for inflammatory disease states and disorders, ischemic/reperfusion injury, stroke, atherosclerosis, hypertension and all other conditions of oxidant-induced tissue damage or injury.

  本发明涉及超氧化物歧化酶（SOD）的低分子量模拟物，其化学式为：##STR1## 其中R、R'、R1、R'1、R2、R'2、R3、R'3、R4、R'4、R5、R'5、R6、R'6、R7、R'7、R8、R'8、R9和R'9以及X、Y、Z和n的定义如本文所述，作为治疗炎症性疾病状态和紊乱、缺血/再灌注损伤、中风、动脉粥样硬化、高血压以及其他氧化剂引起的组织损伤或损伤的治疗剂使用。
• Synthesis and In Vitro Comparison of DOTA, NODAGA and 15-5 Macrocycles as Chelators for the 64Cu-Labelling of Immunoconjugates
  作者：Aurélie Maisonial-Besset、Tiffany Witkowski、Mercedes Quintana、Sophie Besse、Vincent Gaumet、Axel Cordonnier、Cyrille Alliot、Aurélien Vidal、Caroline Denevault-Sabourin、Sébastien Tarrit、Sophie Levesque、Elisabeth Miot-Noirault、Jean-Michel Chezal

  DOI：10.3390/molecules28010075

  日期：——

  The development of 64Cu-based immuno-PET radiotracers requires the use of copper-specific bifunctional chelators (BFCs) that contain functional groups allowing both convenient bioconjugation and stable copper complexes to limit in vivo bioreduction, transmetallation and/or transchelation. The excellent in vivo kinetic inertness of the pentaazamacrocyclic [64Cu]Cu-15-5 complex prompted us to investigate its potential for the 64Cu-labelling of monoclonal antibodies (mAbs), compared with the well-known NODAGA and DOTA chelators. To this end, three NODAGA, DOTA and 15-5-derived BFCs, containing a pendant azadibenzocyclooctyne moiety, were synthesised and a robust methodology was determined to form covalent bonds between them and azide-functionalised trastuzumab, an anti-HER2 mAb, using strain-promoted azide-alkyne cycloaddition. Unlike the DOTA derivative, the NODAGA- and 15-5-mAb conjugates were radiolabelled with 64Cu, obtaining excellent radiochemical yields, under mild conditions. Although all the radioimmunoconjugates showed excellent stability in PBS or mouse serum, [64Cu]Cu-15-5- and [64Cu]Cu-NODAGA-trastuzumab presented higher resistance to transchelation when challenged by EDTA. Finally, the immunoreactive fraction of the radioimmunoconjugates (88–94%) was determined in HER-2 positive BT474 human breast cancer cells, confirming that the bioconjugation and radiolabelling processes implemented had no significant impact on antigen recognition.

  64Cu基免疫PET放射性示踪剂的开发需要使用含有功能基团的铜特异性双功能螯合剂（BFCs），以便进行方便的生物偶联并形成稳定的铜配合物，以限制体内生物还原、金属转移和/或转螯合。五胺大环[64Cu]Cu-15-5配合物的出色体内动力学惰性促使我们研究其与著名的NODAGA和DOTA螯合剂相比，用于标记单克隆抗体（mAbs）的64Cu。为此，合成了三种含有嵌二氮苯并环辛炔基的NODAGA、DOTA和15-5衍生的BFCs，并确定了一种强大的方法，通过应变促进的偶联反应，在其中与带有偶氮基的Trastuzumab进行共价键的形成，这是一种针对HER2的抗体。与DOTA衍生物不同，NODAGA-和15-5-mAb偶联物在温和条件下用64Cu标记，获得了优异的放射化学收率。虽然所有的放射免疫偶联物在PBS或小鼠血清中均表现出良好的稳定性，但当受到EDTA挑战时，[64Cu]Cu-15-5-和[64Cu]Cu-NODAGA-trastuzumab表现出更高的抗转螯合能力。最后，在HER-2阳性BT474人类乳腺癌细胞中确定了放射免疫偶联物的免疫反应性分数（88-94%），确认实施的生物偶联和放射标记过程对抗原识别没有显著影响。