N-(9-(2-(4-(1-azido-13-oxo-3,6,9-trioxa-12-azahexadecane)piperazine-1-carbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-N-ethylethanaminium | 1204939-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-(9-(2-(4-(1-azido-13-oxo-3,6,9-trioxa-12-azahexadecane)piperazine-1-carbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-N-ethylethanaminium
• 英文别名: [9-[2-[4-[4-[2-[2-[2-(2-Azidoethoxy)ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]piperazine-1-carbonyl]phenyl]-6-(diethylamino)xanthen-3-ylidene]-diethylazanium
• CAS: 1204939-73-0
• 化学式: C₄₄H₅₉N₈O₇
• 分子量: 812.002
• InChiKey: WIYPNFZHNHZCNX-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  59
• 可旋转键数：
  22
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-(9-(2-(4-(1-azido-13-oxo-3,6,9-trioxa-12-azahexadecane)piperazine-1-carbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-N-ethylethanaminium 、 2-[[4-[[4-[[6-amino-2-(2-methoxyethoxy)-8-oxo-7H-purin-9-yl]methyl]phenyl]methylamino]-4-oxobutanoyl]amino]oct-7-ynoic acid 在 3,3,3-膦三基三丙酸 、 copper(II) sulfate 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 甲醇 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 以66%的产率得到[9-[2-[4-[4-[2-[2-[2-[2-[4-[5-[[4-[[4-[[6-amino-2-(2-methoxyethoxy)-8-oxo-7H-purin-9-yl]methyl]phenyl]methylamino]-4-oxobutanoyl]amino]-5-carboxypentyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethylamino]-4-oxobutanoyl]piperazine-1-carbonyl]phenyl]-6-(diethylamino)xanthen-3-ylidene]-diethylazanium
  参考文献：
  名称：

  免疫激动剂靶向化合物的合成及其应用

  摘要：

  本发明发现系列小分子免疫激动剂偶联靶向药物，形成新的具有免疫激活功能的靶向化合物药物，在体外体内产生了有利于提高靶向药的免疫激活效果和抗肿瘤及其它疾病的效果，赋予了所述靶向药双功能(双功能靶向药)，这种提高的效果是由具有免疫抗肿瘤因素(如IFN‑γ)和对致病性靶向位点的抑制二个功能协同作用产生，一种功能合二为一的新型高效靶向药物。

  公开号：

  CN108379591B
• 作为产物：
  描述：

  rhodamine B piperazine amide 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(9-(2-(4-(1-azido-13-oxo-3,6,9-trioxa-12-azahexadecane)piperazine-1-carbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-N-ethylethanaminium
  参考文献：
  名称：

  硫氧还蛋白还原酶激活嘌呤霉素前药克服了其混杂的细胞毒性

  摘要：

  硒蛋白硫氧还蛋白还原酶 (TrxR) 的过度表达已在恶性组织中得到证实，并且对许多类型的肿瘤具有病理学意义。抗生素嘌呤霉素 (Puro) 是一种蛋白质合成抑制剂，会在翻译过程中导致多肽链过早终止。Puro 明确的作用机制使其成为生物医学研究中的有用工具。然而，Puro 的非选择性细胞毒性限制了其治疗应用。我们在此报告了两种 Puro 前药的构建和评估，即具有五元环状二硫键触发的 S1-Puro 和具有线性二硫键触发的 S2-Puro。S1-Puro 被 TrxR 选择性激活并对癌细胞显示出 TrxR 依赖性细胞毒性，而 S2-Puro 很容易被硫醇激活。此外，S1-Puro 在血浆中表现出比 S2-Puro 更高的稳定性。我们期望这种前药策略可以促进 Puro 作为治疗剂的进一步发展。

  DOI：

  10.1021/acs.jmedchem.2c01509

文献信息

• Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities
  作者：Peng-Yu Yang、Kai Liu、Mun Hong Ngai、Martin J. Lear、Markus R. Wenk、Shao Q. Yao

  DOI：10.1021/ja907716f

  日期：2010.1.20

  Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.
• NOVEL SMALL MOLECULE IMMUNE AGONISTS AND IMMUNE TARGETING COMPOUNDS AND APPLICATION THEREOF
  申请人：SHENZHEN UNIVERSITY

  公开号：US20210038605A1

  公开（公告）日：2021-02-11

  Provided is a series of homologous small molecule immune agonists and novel bifunctional immune targeting compounds having targeting and immune activation functions, which are obtained by coupling the small molecule immune agonists to targeting drugs. The resulting immune targeting compounds are beneficial for enhancing immune activation effects, and anti-tumor and other disease fighting effects of the targeting drug. The enhanced effect is produced from a synergy of immunological anti-tumor factors (such as IFN-γ) and inhibition at pathogenic targeting sites.