1-Trifluoroacetyl-1,4,7-triazaheptane | 193143-28-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-Trifluoroacetyl-1,4,7-triazaheptane
• 英文别名: N-[2-(2-aminoethylamino)ethyl]-2,2,2-trifluoroacetamide
• CAS: 193143-28-1
• 化学式: C₆H₁₂F₃N₃O
• 分子量: 199.176
• InChiKey: FPNDPEUYTCQRRC-UHFFFAOYSA-N

物化性质

• 沸点：
  296.9±40.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  67.2
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-Trifluoroacetyl-1,4,7-triazaheptane 在 palladium on activated charcoal 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 、 肼 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 、 叔丁醇 为溶剂， 反应 9.5h， 生成 3,6,9-tris(2-(tert-butoxy)-2-oxoethyl)-13,13-dimethyl-11-oxo-12-oxa-3,6,9-triazatetradecan-1-oic acid
  参考文献：
  名称：

  Reassessment of Diethylenetriaminepentaacetic Acid (DTPA) as a Chelating Agent for Indium-111 Labeling of Polypeptides Using a Newly Synthesized Monoreactive DTPA Derivative

  摘要：

  Previous studies on indium-111 (In-111) labeling of polypeptides and peptides using cyclic diethylenetriaminepentaacetic dianhydride (cDTPA) as a bifunctional chelating agent (BCA) have indicated that DTPA might be a useful BCA for In-111 labeling of polypeptides at high specific activities when DTPA can be incorporated without inducing intra- or intermolecular cross-linking. To investigate this hypothesis, a monoreactive DTPA derivative with a maleimide group as the peptide binding site (MDTPA) was designed and synthesized. A monoclonal antibody (OST7, IgG(1)) was used as a model polypeptide, and conjugation of MDTPA with OST7, In-111 radiolabeling of MDTPA-OST7, and the stability of In-111-MDTPA-OST7 were investigated using cDTPA and benzyl-EDTA derivatives as references. SDS-PAGE analysis demonstrated that while cDTPA induced intramolecular cross-linking, no such undesirable side reactions were observed with MDTPA. MDTPA generated In-111-labeled OST7 with high radiochemical yields at higher specific activities than those produced using cDTPA and benzyl-EDTA derivatives as the BCAs. incubation of each In-111-labeled OST7 in human serum indicated that MDTPA generated In-111-labeled OST7 of much higher and a little lower stability than those derived from cDTPA and benzyl-EDTA derivatives, respectively. These findings indicated that the low in vivo stability of cDTPA-conjugated antibody reported previously is not attributable to low stability of In-111-DTPA but to formation of intramolecular cross-linking during cDTPA conjugation reactions. The present study also indicated that MDTPA and its precursor, the tetra-tert-butyl derivative of DTPA, would be useful BCAs for In-111 radiolabeling of polypeptides that have rapid blood clearance with high specific activities.

  DOI：

  10.1021/jm950949+
• 作为产物：
  描述：

  三氟乙酸乙酯 、 二乙烯三胺 以 甲醇 为溶剂， 反应 3.16h， 生成 1-Trifluoroacetyl-1,4,7-triazaheptane
  参考文献：
  名称：

  取代的9-氨基-4-啶-4-羧酰胺与铂（II）二胺配合物的连接：化学，细胞毒性和DNA序列选择性

  摘要：

  将其中取代的（7-OMe，9-NH 2 ; 7-F，9-NH 2 ;和7-H，9-NH（CH 2）2 OH）9-氨基ac啶-4-羧酰胺的三个铂络合物束缚到合成了铂（II）二胺部分，并在化学和生物学水平上进行了表征。当与亲本7-H，9-NH 2化合物相比时，这些变体显示出通过HeLa细胞中的IC 50值测量的细胞毒性降低。7-F和9-NH（CH 2）2OH取代基引起的细胞毒性下降很小，而7-OMe取代基导致的细胞毒性下降更大。研究了它们与纯化的pUC19质粒DNA的结合，发现添加7-F，9-NH（CH 2）2 OH，尤其是7-OMe取代基导致DNA结合减少。这与IC 50细胞毒性值很好地相关。但是，DNA序列的选择性不受这些部分的添加的影响。

  DOI：

  10.1016/j.jinorgbio.2010.03.011

文献信息

• Rhenium(<scp>v</scp>) oxocomplexes with novel pyrazolyl-based N₄- and N₃S-donor chelators
  作者：Carolina Moura、Rute F. Vítor、Leonor Maria、António Paulo、Isabel C. Santos、Isabel Santos

  DOI：10.1039/b611034g

  日期：——

  The novel pyrazolyl-based ligands 3,5-Me2pz(CH2)2NH(CH2)2NH(CH2)2NH2 (1) and pz*(CH2)2NH-Gly-CH2STrit (pz* = pz (8), 3,5-Me2pz (9), 4-(EtOOC)CH2-3,5-Me2pz (10)) were synthesized, and their suitability to stabilize Re(V) oxocomplexes was evaluated using different starting materials, namely (NBu4)[ReOCl4], [ReOCl3(PPh3)2] and trans-[ReO2(py)4]Cl. Compound 1 reacts with trans-[ReO2(py)4]Cl yielding the cationic compound [ReO(OMe)3,5-Me2pz(CH2)2N(CH2)2NH(CH2)2NH2}](BPh4) (11) in a low isolated yield. In contrast, the neutral complexes [ReOpz*(CH2)2NH-Gly-CH2S}] (pz* = pz (12), 3,5-Me2pz (13), 4-(EtOOCCH2)-3,5-Me2pz (14)) were synthesized almost quantitatively by reacting [ReOCl3(PPh3)2] or (NBu4)[ReOCl4] with the trityl-protected chelators 8–10. The X-ray diffraction analysis of 11 and 13 confirmed the tetradentate coordination mode of the respective ancillary ligands. In 11 the monoanionic chelator coordinates to the metal through four nitrogen atoms, while in 13 the chelator is trianionic, coordinating to the metal through three nitrogens and one sulfur atom. Solution NMR studies of 12–14, including two-dimensional NMR techniques (1H COSY and 1H/13C HSQC), confirmed that the N3S coordination mode of the chelators is retained in solution. Unlike 11, complexes 12–14 may be considered relevant in the development of radiopharmaceuticals, as further corroborated by the synthesis of the congener [99mTcOpz(CH2)2-NH-Gly-CH2S}] (12a). This radioactive compound was obtained from 99mTcO4− in aqueous medium, in almost quantitative yield and with high specific activity and radiochemical purity.

  合成了新型的以吡唑基为基础的配体3,5-Me2pz(CH2)2NH(CH2)2NH(CH2)2NH2 (1)和pz*(CH2)2NH-Gly-CH2STrit（pz* = pz (8)，3,5-Me2pz (9)，4-(EtOOC)CH2-3,5-Me2pz (10)），并评估了它们稳定Re(V)氧化络合物的适用性，使用的起始材料分别为(NBu4)[ReOCl4]、[ReOCl3(PPh3)2] 和 trans-[ReO2(py)4]Cl。化合物1与trans-[ReO2(py)4]Cl反应，生成阳离子化合物[ReO(OMe)3,5-Me2pz(CH2)2N(CH2)2NH(CH2)2NH2}](BPh4) (11)，其孤立产率较低。相比之下，几乎定量合成了中性复合物[ReOpz*(CH2)2NH-Gly-CH2S}] (pz* = pz (12)，3,5-Me2pz (13)，4-(EtOOCCH2)-3,5-Me2pz (14))，通过将[ReOCl3(PPh3)2]或(NBu4)[ReOCl4]与三苯基保护的螯合剂8–10反应。对11和13的X射线衍射分析确认了各自辅助配体的四齿配位模式。在11中，单阴离子螯合剂通过四个氮原子与金属配位，而在13中，螯合剂是三阴离子，通过三个氮和一个硫原子与金属配位。对12–14的溶液NMR研究，包括二维NMR技术（1H COSY和1H/13C HSQC），确认了螯合剂的N3S配位模式在溶液中的保留。与11不同，复合物12–14被认为在放射药物开发中具有相关性，进一步通过合成同类物[99mTcOpz(CH2)2-NH-Gly-CH2S}] (12a)得到了印证。该放射性化合物在水相中从99mTcO4−获得，几乎定量收率，并具有高特异活性和放射化学纯度。
• A Single Methylene Group in Oligoalkylamine-Based Cationic Polymers and Lipids Promotes Enhanced mRNA Delivery
  作者：Anita Jarzębińska、Tamara Pasewald、Jana Lambrecht、Olga Mykhaylyk、Linda Kümmerling、Philipp Beck、Günther Hasenpusch、Carsten Rudolph、Christian Plank、Christian Dohmen

  DOI：10.1002/anie.201603648

  日期：2016.8.8

  promise as a new class of biologic therapeutics. However, the intracellular delivery and endosomal escape of mRNA encapsulated in nanoparticles has not been systematically investigated. Here, we synthesized a diverse set of cationic polymers and lipids from a series of oligoalkylamines and subsequently characterized their mRNA delivery capability. Notably, a structure with an alternating alkyl chain length

  化学修饰的mRNA的发展作为一种新型的生物疗法具有广阔的前景。然而，尚未系统研究包裹在纳米颗粒中的mRNA的胞内递送和内体逃逸。在这里，我们从一系列的低聚烷基胺合成了各种阳离子聚合物和脂质，随后表征了它们的mRNA传递能力。值得注意的是，胺之间具有交替的烷基链长的结构显示出最高的转染效率，这与在pH 6.2至6.5的窄范围内的高缓冲能力有关。分别施用全身或气雾剂后，仅一个亚甲基的变化导致分别向鼠肝和猪肺的mRNA递送增强。
• Engineering the Binding Kinetics of Synthetic Polymer Nanoparticles for siRNA Delivery
  作者：Hiroyuki Koide、Tatsuya Fukuta、Anna Okishim、Saki Ariizumi、Chiaki Kiyokawa、Hiroki Tsuchida、Masahiko Nakamoto、Keiichi Yoshimatsu、Hidenori Ando、Takehisa Dewa、Tomohiro Asai、Naoto Oku、Yu Hoshino、Kenneth J. Shea

  DOI：10.1021/acs.biomac.9b00611

  日期：2019.10.14

  synthetic polymer nanoparticle (NP) to a target biomacromolecule is determined by the association and dissociation rate constants (kon, koff) of the interaction. The individual rates and their sensitivity to local environmental influences are important factors for the on-demand capture and release a target biomacromolecule. Positively charged NPs for small interfering RNA (siRNA) delivery is a case

  合成聚合物纳米粒子（NP）对目标生物大分子的亲和力由相互作用的缔合和解离速率常数（k on，k off）决定。个体速率及其对当地环境影响的敏感性是按需捕获和释放目标生物大分子的重要因素。带小电荷干扰RNA（siRNA）的带正电荷的NP就是一个很好的例子。siRNA的敲低功效会受到与NP的结合动力学的强烈影响。在这里，我们显示可通过调节NP的化学结构和组成来分别设计siRNA与NP的k on和k off。ñ使用了以疏水和胺单体官能化的基于异丙基丙烯酰胺的NP。k off通过增加NP中胺基的数量而降低，而k on不变。重要的是，当将NP / siRNA复合物包装在脂质纳米颗粒中时，在pH 5.5时k off值低而在pH 7.4时k off值高的NPs表现出较高的敲低效率。这些结果为直接的证据提供了前提，即siRNA传递载体的功效与内体中对siRNA的强亲和力和细胞质中的低亲和力有关。
• Substituted 9-aminoacridine-4-carboxamides tethered to platinum(II)diamine complexes: Chemistry, cytotoxicity and DNA sequence selectivity
  作者：Michael Carland、Martin J. Grannas、Murray J. Cairns、Vanessa J. Roknic、William A. Denny、W. David McFadyen、Vincent Murray

  DOI：10.1016/j.jinorgbio.2010.03.011

  日期：2010.8

  Three platinum complexes in which substituted (7-OMe, 9-NH2; 7-F, 9-NH2; and 7-H, 9-NH(CH2)2OH) 9-aminoacridine-4-carboxamides were tethered to a platinum(II)diamine moiety were synthesised and characterised at the chemical and biological level. These variants showed a decrease in cytotoxicity, as measured by IC50 values in HeLa cells, when compared with the parent 7-H, 9-NH2 compound. The 7-F and

  将其中取代的（7-OMe，9-NH 2 ; 7-F，9-NH 2 ;和7-H，9-NH（CH 2）2 OH）9-氨基ac啶-4-羧酰胺的三个铂络合物束缚到合成了铂（II）二胺部分，并在化学和生物学水平上进行了表征。当与亲本7-H，9-NH 2化合物相比时，这些变体显示出通过HeLa细胞中的IC 50值测量的细胞毒性降低。7-F和9-NH（CH 2）2OH取代基引起的细胞毒性下降很小，而7-OMe取代基导致的细胞毒性下降更大。研究了它们与纯化的pUC19质粒DNA的结合，发现添加7-F，9-NH（CH 2）2 OH，尤其是7-OMe取代基导致DNA结合减少。这与IC 50细胞毒性值很好地相关。但是，DNA序列的选择性不受这些部分的添加的影响。
• [DE] NEUE MONOFUNKTIONALISIERTE EDTA-, DTPA- UND TTHA-DERIVATE UND DEREN VERWENDUNG IN DER MEDIZINISCHEN DIAGNOSTIK UND THERAPIE<br/>[EN] NOVEL MONOFUNCTIONALISED EDTA, DTPA AND TTHA DERIVATIVES AND THEIR USE IN MEDICAL DIAGNOSIS AND THERAPY<br/>[FR] NOUVEAUX DERIVES D'EDTA, DE DTPA ET DE TTHA MONOFONCTIONNALISES ET LEUR UTILISATION EN MEDECINE POUR LA THERAPIE ET LE DIAGNOSTIC
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：WO1997025305A1

  公开（公告）日：1997-07-17

  (DE) Die Erfindung betrifft neue monofunktionalisierte Ethylendiamintetraessigsäure-, Diethylentriaminpentaessigsäure- und Triethylentetraaminhexaessigsäure-Derivate, deren Herstellung und deren Verwendung zur Herstellung pharmazeutischer Mittel.(EN) The invention relates to novel monofunctionalised ethylene diamine tetracetic acid, diethylene triamine pentacetic acid and triethylene tetramine hexacetic acid derivatives, their production and their use in the production of pharmaceutical agents.(FR) L'invention concerne de nouveaux dérivés monofonctionnalisés d'acide tétracétique d'éthylènediamine, d'acide pentacétique de diéthylènetriamine et d'acide hexacétique de triétylènetétramine, leur préparation et leur utilisation pour produire des agents pharmaceutiques.

  该发明涉及新的单官能化的 ethylene diamine tetradecetic 酸、diethylene triamine pentadecetic 酸和 triethylene tetramine hexadecetic 酸的衍生物，它们的合成及其在医药产品的生产中的应用。