(2S,3R,4S,5S,6S)-2-(2-((tert-butoxycarbonyl)(methyl)amino)-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 191352-29-1

• 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-(2-((tert-butoxycarbonyl)(methyl)amino)-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• 英文别名: methyl (2S,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-4-nitrophenoxy]oxane-2-carboxylate
• CAS: 191352-29-1
• 化学式: C₂₅H₃₂N₂O₁₄
• 分子量: 584.534
• InChiKey: ULNUYZKKDSUSMY-YKZCJQPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  199
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5S,6S)-2-(2-((tert-butoxycarbonyl)(methyl)amino)-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 盐酸 、 sodium hydroxide 、 sodium methylate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 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 dimethyl sulfide borane 、 potassium carbonate 、 silver(l) oxide 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 32.0h， 生成 (2S,3R,4S,5S,6S)-2-(2-((tert-butoxycarbonyl)(methyl)amino)-4-nitrophenoxy)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  [EN] GLUCURONIDE PRODRUGS OF TOFACITINIB
  [FR] PROMÉDICAMENTS À BASE DE GLUCURONIDE DE TOFACITINIB

  摘要：

  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。

  公开号：

  WO2018165250A1

文献信息

• GLUCURONIDE PRODRUGS OF JANUS KINASE INHIBITORS
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20180339990A1

  公开（公告）日：2018-11-29

  The invention relates to glucuronide prodrug compounds of Janus kinase (JAK) inhibitors having formula I: where W 1 , R 1 and A 1 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。
• 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。
• 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。
• Glucuronide prodrugs of Janus kinase inhibitors
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US10745405B2

  公开（公告）日：2020-08-18

  The invention relates to glucuronide prodrug compounds of Janus kinase (JAK) inhibitors having formula I: where W1, R1 and A1 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）抑制剂的葡糖醛酸原药化合物： 其中 W1、R1 和 A1 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疾病的方法；以及制备此类化合物的工艺和中间体。
• GLUCURONIDE PRODRUGS OF TOFACITINIB
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20180258094A1

  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: where A 1 and R 1 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.