(2S,3R,4S,5S,6S)-2-(4-(((1H-imidazole-1-carbonyl)oxy)methyl)-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 866611-65-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4S,5S,6S)-2-(4-(((1H-imidazole-1-carbonyl)oxy)methyl)-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• 英文别名: [3-nitro-4-[(2S,3R,4S,5S,6S)-3,4,5-triacetyloxy-6-methoxycarbonyloxan-2-yl]oxyphenyl]methyl imidazole-1-carboxylate
• CAS: 866611-65-6
• 化学式: C₂₄H₂₅N₃O₁₄
• 分子量: 579.474
• InChiKey: XQRUBAFUEYRFDP-YKZCJQPKSA-N

物化性质

• 沸点：
  697.2±65.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  214
• 氢给体数：
  0
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5S,6S)-2-(4-(((1H-imidazole-1-carbonyl)oxy)methyl)-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 (2S,3R,4S,5S,6S)-2-(4-((((2-(4-(3-amino-1-(3-(cyanomethyl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinyl)piperidin-4-yl)azetidin-3-yl)-1H-pyrazol-4-yl)-N-methyl-7H-pyrrolo[2,3-d]pyrimidine-7-carboxamido)ethyl)(methyl)carbamoyl)oxy)methyl)-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  一种JAK抑制剂的化合物前药及其制备与应用

  摘要：

  本申请公开了一种JAK抑制剂的化合物前药及其制备与应用，所述JAK抑制剂的化合物前药如式1所示。

  公开号：

  CN115073543A
• 作为产物：
  描述：

  (2R,3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 sodium tetrahydroborate 、 异丙醇 、 silver(l) oxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 (2S,3R,4S,5S,6S)-2-(4-(((1H-imidazole-1-carbonyl)oxy)methyl)-2-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  一种JAK抑制剂的化合物前药及其制备与应用

  摘要：

  本申请公开了一种JAK抑制剂的化合物前药及其制备与应用，所述JAK抑制剂的化合物前药如式1所示。

  公开号：

  CN115073543A

文献信息

• Prodrugs of a JAK Inhibitor Compound for Treatment of Gastrointestinal Inflammatory Disease
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20170145044A1

  公开（公告）日：2017-05-25

  The invention provides compounds which are prodrugs of a JAK inhibitor agent for the targeted delivery of the JAK inhibitor to the gastrointestinal tract of a mammal. The invention also provides pharmaceutical compositions comprising the compounds, methods of using the compounds to treat gastrointestinal inflammatory diseases, and processes and intermediates useful for preparing the compounds.

  本发明提供了一种前药化合物，它是针对哺乳动物胃肠道靶向输送JAK抑制剂的前药。本发明还提供了包含该化合物的药物组合物，使用该化合物治疗胃肠道炎症性疾病的方法，以及用于制备该化合物的过程和中间体。
• A Gadolinium Chelate for Detection of β-Glucuronidase:  A Self-Immolative Approach
  作者：Joseph A. Duimstra、Frank J. Femia、Thomas J. Meade

  DOI：10.1021/ja042162r

  日期：2005.9.1

  New classes of physiologically responsive magnetic resonance (MR) contrast agents are being developed that are activated by enzymes, secondary messengers, pH, and temperature. To this end, we have prepared a new class of enzyme-activated MR contrast agents using a self-immolative mechanism and investigated the properties of these agents using novel in vitro assays. We have synthesized in nine steps

  正在开发新类别的生理反应性磁共振 (MR) 造影剂，它们可被酶、二级信使、pH 值和温度激活。为此，我们使用自焚机制制备了一类新的酶激活 MR 造影剂，并使用新的体外试验研究了这些试剂的特性。我们已经在九个步骤中合成了 Gd(III) 试剂 1，它被具有肿瘤学意义的 β-葡萄糖醛酸酶激活。图 1 由 Gd(III)DO3A（DO3A = 1,4,7-三羧基亚甲基-1,4,7,10-四氮杂环十二烷）组成，带有一个侧链 β-葡糖醛酸部分，通过自燃接头连接到大环。LC-MS 分析显示 1 经酶处理，如牛肝 β-葡萄糖醛酸酶预测的那样，生成 2-氨基乙基 GdDO3A, 2。化合物 2 是通过四步合成程序独立制备的。用碳酸氢根阴离子滴定时，配合物 1 显示弛豫度降低。当 1 转换为 t 时，弛豫度增加...
• Self-immolative magnetic resonance imaging contrast agents sensitive to beta-glucuronidase
  申请人：Duimstra A. Joseph

  公开号：US20060088475A1

  公开（公告）日：2006-04-27

  The present invention relates to magnetic resonance imaging (MRI) contrast agent. In particular, the present invention provides MRI contrast agents that are sensitive to the enzyme beta-glucoronidase. The MRI contrast agents provide compositions and methods for non-invasive diagnostic imaging of tissues, including necrotic tumors.

  本发明涉及磁共振成像（MRI）造影剂。具体而言，本发明提供对酶β-葡萄糖醛酸酶敏感的MRI造影剂。MRI造影剂提供了用于非侵入性诊断组织，包括坏死肿瘤的成分和方法。
• Synthesis and Evaluation of [¹⁸F]-FEAnGA as a PET Tracer for β-Glucuronidase Activity
  作者：Inês F. Antunes、Hidde J. Haisma、Philip H. Elsinga、Rudi A. Dierckx、Erik F. J. de Vries

  DOI：10.1021/bc9004602

  日期：2010.5.19

  To increase the therapeutic index of chemotherapeutic drugs, prodrugs have been investigated as anticancer agents, as they may present fewer eytotoxic side effects than conventional cytotoxic drugs, while therapeutic efficacy is maintained or even increased. Extracellular beta-glucuronidase (beta-GUS) in the tumors has been investigated as a target enzyme for prodrug therapy, as it can convert nontoxic prodrugs into cytostatic drugs. To optimize beta-GUS-based prodrug therapies, PET imaging could be a useful tool by providing information regarding the localization and quantification of beta-GUS. Here, we describe our first PET tracer for extracellular beta-GUS, [F-18]-FEAnGA, which consists of a 2-[F-18]fluorocthylamine ([F-18]-FEA) group bound to a glucuronic acid via a self-immolative nitrophenyl spacer. [F-18]-FEAnGA was synthesized by alkylation of its imidazole carbamate precursor with [F-18]-FEA, followed by deprotection of the sugar moiety with NaOH in 10-20% overall radiochemical yield. [F-18]-FEAnGA is about 10-fold more hydrophilic than the cleavage product [F-18]-FEA, and it is stable in PBS and rat plasma for at least 3 h. In the presence of either Escherichia coli beta-GUS or bovine liver beta-GUS, in vitro cleavage of [F-18]-FEAnGA with complete release of [F-18]-FEA was observed within 30 mm. C6 glioma cells incubated with the tracer and Escherichia coli beta-GUS or bovine liver beta-GUS showed a 4- and 1.5-fold higher uptake of radioactivity, respectively, as compared to control C6 cells without beta-GUS. Incubation of CT26 murine colon adenocarcinoma cells or the genetically engineered CT26m beta GUS cells, which expressed membrane-anchored GUS on the outer cell membrane, with the tracer, resulted in a 3-fold higher uptake into GUS-expressing cells as compared to control cells. In a preliminary microPET study in mice bearing both CT26 and CT26m beta GUS tumors, [F-18]-FEAnGA exhibited a 2-fold higher retention of radioactivity in the tumor expressing beta-GUS than in the control tumor. [F-18]-FEA did not show any difference in tracer uptake between tumors. These results suggest that [F-18]-FEAnGA may be a suitable PET tracer for evaluation of beta-GUS activity, since it is specifically cleaved by beta-GUS and the released [F-18]-FEA remains attached to targeted cells.
• PRODRUGS OF A JAK INHIBITOR COMPOUND FOR TREATMENT OF GASTROINTESTINAL INFLAMMATORY DISEASE
  申请人：Theravance Biopharma R&D IP, LLC

  公开号：EP3380486B1

  公开（公告）日：2020-02-19