(2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(2-(methylamino)-4-nitrophenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 191352-30-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(2-(methylamino)-4-nitrophenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• 英文别名: methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[2-(methylamino)-4-nitrophenoxy]oxane-2-carboxylate
• CAS: 191352-30-4
• 化学式: C₂₀H₂₄N₂O₁₂
• 分子量: 484.417
• InChiKey: YFFGXDSVCYOLBV-KVIJGQROSA-N

物化性质

• 沸点：
  570.7±50.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  182
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(2-(methylamino)-4-nitrophenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 sodium hydroxide 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 生成 (2S,3S,4S,5R,6S)-6-[2-[[4-[bis(2-chloroethyl)amino]phenoxy]carbonyl-methylamino]-4-nitrophenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
  参考文献：
  名称：

  Glucuronide prodrugs of hydroxy compounds for antibody directed enzyme prodrug therapy (ADEPT) : A phenol nitrogen mustard carbamate

  摘要：

  A prodrug consisting of a beta-D-glucuronic acid linked to a self-immolative spacer (a N-(orthohydroxyphenyl)-N-methylcarbamate) and a phenolic nitrogen mustard was synthesised. As this prodrug was easily cleaved by a beta-glucuronidase enzyme and displayed low cytotoxicity, it must be considered as appropriate for an ADEPT approach. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00157-1
• 作为产物：
  描述：

  N-(2-hydroxy-5-nitrophenyl)formamide 在 盐酸 、 硼烷二甲硫醚络合物 、 potassium carbonate 、 silver(l) oxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 38.0h， 生成 (2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-(2-(methylamino)-4-nitrophenoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  GLUCURONIDE PRODRUGS OF JANUS KINASE INHIBITORS

  摘要：

  本发明涉及具有公式I的糖苷酸前药化合物的Janus激酶（JAK）抑制剂：其中W1、R1和A1如所定义。本发明还涉及包含这些化合物的药物组合物；使用这些化合物治疗胃肠炎性疾病的方法；以及制备这些化合物的过程和中间体。

  公开号：

  US20180339990A1

文献信息

• BENZODICYCLOALKANE DERIVATIVE, PREPARATION METHOD AND USE THEREOF
  申请人：SHANGHAI HAIYAN PHARMACEUTICAL TECHNOLOGY CO., LTD.

  公开号：US20190161468A1

  公开（公告）日：2019-05-30

  It is provided herein a benzobicycloalkane derivative, and a preparation method and use thereof. In particular, it is provided herein a compound of Formula (I), or a pharmaceutically acceptable salt, stereoisomer or solvate thereof, a preparation method, and a use thereof in preparation of drugs for treating pain.

  本文提供了一种苯并螺环烷衍生物，以及其制备方法和用途。具体而言，本文提供了一种式（I）化合物，或其药用可接受的盐、立体异构体或溶剂化合物，以及其制备方法，并用于制备治疗疼痛药物的用途。
• [EN] GLUCURONIDE PRODRUGS OF TOFACITINIB<br/>[FR] PROMÉDICAMENTS À BASE DE GLUCURONIDE DE TOFACITINIB
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2018165250A1

  公开（公告）日：2018-09-13

  The invention relates to glucuronide prodrug compounds of the Janus kinase (JAK) inhibitor tofacitinib having formula (I): (Formula (I)) where A1 and R1 are as defined. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds to treat gastrointestinal inflammatory diseases; and processes and intermediates for preparing such compounds.

  这项发明涉及具有式(I)的Janus激酶（JAK）抑制剂托法替尼的葡萄糖醛酸酯前药化合物：（式(I)）其中A1和R1如所定义。该发明还涉及包含这种化合物的药物组合物；使用这种化合物治疗胃肠道炎症性疾病的方法；以及制备这种化合物的过程和中间体。
• In vitro fluorine-19 nuclear magnetic resonance study of the liberation of antitumor nitrogen mustard from prodrugs
  作者：Frédéric Schmidt、Claude Monneret

  DOI：10.1039/b111549a

  日期：2002.5.10

  The syntheses of two novel glucuronide prodrugs of nitrogen mustard with a fluorine tag are reported. These prodrugs, which differ only by the presence or not of a spacer, were designed for selective activation in the necrotic area of tumors by β-glucuronidase. Kinetics of enzymatic hydrolysis of these prodrugs were determined by 19F-NMR and HPLC in vitro studies. The spacer-containing prodrug was found to be the more stable and more quickly cleaved than the other. Thereby it appeared to be a promising candidate for in vivo studies.

  报道了两种带有氟标签的新型氮芥葡萄糖苷酸前药的合成。这些前药的区别仅在于是否存在间隔基，设计用于通过 β-葡萄糖醛酸酶选择性激活肿瘤坏死区域。通过 19F-NMR 和 HPLC 体外研究确定了这些前药的酶水解动力学。发现含有间隔基的前药比其他药物更稳定且裂解更快。因此，它似乎是体内研究的有希望的候选者。
• Cancer Chemotherapy: A Paclitaxel Prodrug for ADEPT (Antibody‐Directed Enzyme Prodrug Therapy)
  作者：Frédéric Schmidt、Ioana Ungureanu、Romain Duval、Alain Pompon、Claude Monneret

  DOI：10.1002/1099-0690(200106)2001:11<2129::aid-ejoc2129>3.0.co;2-#

  日期：2001.6

  A glucuronide-based prodrug of paclitaxel (taxol®) has been synthesized for use in antibody-directed enzyme prodrug therapy (ADEPT). This three-component prodrug was obtained by coupling a glucuronyl derivative of N-methylamino 4-nitrophenol (10) to the 2′-hydroxy group of the side-chain of paclitaxel through an aromatic carbamate. Once deprotected, prodrug 2 was shown to be relatively stable in human

  已经合成了一种基于葡萄糖醛酸苷的紫杉醇前药 (taxol®)，用于抗体导向酶前药治疗 (ADEPT)。这种三组分前药是通过将 N-甲基氨基 4-硝基苯酚 (10) 的葡萄糖醛酸衍生物通过芳香族氨基甲酸酯偶联到紫杉醇侧链的 2'-羟基上而获得的。一旦脱保护，前药 2 显示在人血清中相对稳定，并且细胞毒性（IC50 分别为 65 μM 和 90 nM）显着低于母体药物。正如预期的那样，化合物 2 在 β-葡萄糖醛酸酶存在下有效地释放紫杉醇。
• Glucuronide prodrugs of tofacitinib
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US10472366B2

  公开（公告）日：2019-11-12

  The invention relates to glucuronide prodrug compounds of the Janus kinase (JAK) inhibitor tofacitinib having formula I: where A1 and R1 are as defined. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds to treat gastrointestinal inflammatory diseases; and processes and intermediates for preparing such compounds.

  本发明涉及具有式 I 的 Janus 激酶（JAK）抑制剂托法替尼的葡糖醛酸原药化合物：其中 A1 和 R1 如所定义。 本发明还涉及包含此类化合物的药物组合物；使用此类化合物治疗胃肠道炎症性疾病的方法；以及制备此类化合物的工艺和中间体。