33-羟基-4,7,10,13,16,19,22,25,28,31-十氧杂三十三烷酸叔丁基酯 | 778596-26-2

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 33-羟基-4,7,10,13,16,19,22,25,28,31-十氧杂三十三烷酸叔丁基酯
• 中文别名: 十聚乙二醇-丙酸叔丁酯；羟基十聚乙二醇缬氨酸叔丁酯；丙酸叔丁酯-十聚乙二醇
• 英文名称: tert-butyl 3-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
• 英文别名: tert-butyl 1-hydroxy-3,6,9,12,15,18,21,24,27,30-decaoxatritriacontan-33-oate；Hydroxy-PEG10-t-butyl ester
• CAS: 778596-26-2
• 化学式: C₂₇H₅₄O₁₃
• 分子量: 586.718
• InChiKey: AEEGJXDZOJNBIY-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于水、DMSO、DMF、DCM

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  40
• 可旋转键数：
  34
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  13

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储条件：2-8℃，干燥且密封。

制备方法与用途

生物活性

Hydroxy-PEG10-Boc 来源于专利文献 CN108707228 (例 0024)。这是一种用于合成抗体偶联药物 (ADC) 的不可降解 (non-cleavable) 的 ADC 链接剂，能够与紫杉醇（HY-B0015）或多西他赛（HY-B0011）结合。

体外研究

抗体偶联药物 (ADCs) 包含一个通过 ADC 链接剂连接至抗体制毒物。

反应信息

• 作为反应物：
  描述：

  33-羟基-4,7,10,13,16,19,22,25,28,31-十氧杂三十三烷酸叔丁基酯 在 hydroxylamine buffer 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 53.0h， 生成 33-巯基-4,7,10,13,16,19,22,25,28,31-十氧杂三十三烷酸叔丁酯
  参考文献：
  名称：

  Synthesis of Taxoids with Improved Cytotoxicity and Solubility for Use in Tumor-Specific Delivery

  摘要：

  To develop effective taxane-antibody immunoconjugates, we have prepared a series of modified taxanes that have both improved toxicity and solubility in aqueous systems as compared to paclitaxel (1a). These taxanes have been modified at either the C-10 or C-7 position and were found to be very cytotoxic against both normal and multi-drug-resistant (MDR) cells, as well as up to 30 times more soluble than paclitaxel in various buffer systems.

  DOI：

  10.1021/jm049705s
• 作为产物：
  描述：

  六甘醇 在 palladium on activated charcoal 吡啶 、 potassium tert-butylate 、 氢气 作用下， 以 甲醇 、 甲苯 为溶剂， 20.0 ℃ 、193.05 kPa 条件下， 反应 1.0h， 生成 33-羟基-4,7,10,13,16,19,22,25,28,31-十氧杂三十三烷酸叔丁基酯
  参考文献：
  名称：

  Synthesis of Taxoids with Improved Cytotoxicity and Solubility for Use in Tumor-Specific Delivery

  摘要：

  To develop effective taxane-antibody immunoconjugates, we have prepared a series of modified taxanes that have both improved toxicity and solubility in aqueous systems as compared to paclitaxel (1a). These taxanes have been modified at either the C-10 or C-7 position and were found to be very cytotoxic against both normal and multi-drug-resistant (MDR) cells, as well as up to 30 times more soluble than paclitaxel in various buffer systems.

  DOI：

  10.1021/jm049705s

文献信息

• [EN] IMMUNOCONJUGATES TARGETING HER2<br/>[FR] IMMUNOCONJUGUÉS CIBLANT LE HER2
  申请人：BOLT BIOTHERAPEUTICS INC

  公开号：WO2020190731A1

  公开（公告）日：2020-09-24

  The invention provides an immunoconjugate of formula (I) or (II). Antibody-adjuvant immunoconjugates of the invention, comprising an antibody construct that has an antigen binding domain that binds human epidermal growth factor receptor 2 ("HER2") linked to one or more adjuvants, demonstrate superior pharmacological properties over conventional antibody conjugates. The invention further provides compositions comprising and methods of treating cancer with the immunoconjugate.

  该发明提供了公式(I)或(II)的免疫结合物。该发明的抗体-佐剂免疫结合物包括一个抗体构建物，具有结合人类表皮生长因子受体2（"HER2"）的抗原结合结构域，与一个或多个佐剂相连，展示出比传统抗体结合物更优越的药理特性。该发明还提供了包含该免疫结合物的组合物和用于治疗癌症的方法。
• [EN] MACROMOLECULE-SUPPORTED TLR AGONISTS<br/>[FR] AGONISTES DE TLR SUPPORTÉS PAR DES MACROMOLÉCULES
  申请人：BOLT BIOTHERAPEUTICS INC

  公开号：WO2020190762A1

  公开（公告）日：2020-09-24

  The invention provides a macromolecule-supported compound of formula (I) or (II). Macromolecule-supported compounds of the invention, comprising macromolecular support linked to one or more TLR agonists, are recognized by TLRs (e.g., TLR7 and/or TLR8) with high affinity providing utility in therapeutics, diagnostics, and chemical assays. The invention further provides compositions comprising and methods of treating cancer with the macromolecule- supported compounds.

  该发明提供了公式（I）或（II）的大分子支持化合物。该发明的大分子支持化合物包括与一个或多个TLR激动剂连接的大分子支持，在治疗学、诊断学和化学分析方面被TLR（例如TLR7和/或TLR8）高亲和力地识别。该发明还提供了包含该大分子支持化合物的组合物和治疗癌症的方法。
• [EN] MACROMOLECULE-SUPPORTED THIENOAZEPINE COMPOUNDS, AND USES THEREOF<br/>[FR] COMPOSÉS DE THIÉNOAZÉPINE SUPPORTÉS PAR DES MACROMOLÉCULES ET LEURS UTILISATIONS
  申请人：BOLT BIOTHERAPEUTICS INC

  公开号：WO2021081402A1

  公开（公告）日：2021-04-29

  The invention provides macromolecule-supported compounds of Formula I comprising a macromolecular support linked by conjugation to one or more thienoazepine derivatives. The invention also provides thienoazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the macromolecule-supported compounds through a linker or linking moiety. The invention further provides methods of treating cancer with the macromolecule-supported compounds.

  该发明提供了一种由大分子支持物质和一种或多种噻吩氮杂环庚烷衍生物通过共轭连接而形成的化合物，其化学式为I。该发明还提供了一种包含具有反应性功能基团的噻吩氮杂环庚烷衍生物中间体组合物。这种中间体组合物适用于通过连接物或连接基团形成大分子支持化合物的底物。该发明还提供了使用这种大分子支持化合物治疗癌症的方法。
• [EN] THIENOAZEPINE IMMUNOCONJUGATES, AND USES THEREOF<br/>[FR] IMMUNOCONJUGUÉS DE THIÉNOAZÉPINE ET LEURS UTILISATIONS
  申请人：BOLT BIOTHERAPEUTICS INC

  公开号：WO2021081407A1

  公开（公告）日：2021-04-29

  The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more thienoazepine derivatives. The invention also provides thienoazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

  本发明提供了公式I的免疫结合物，包括通过共轭连接与一种或多种噻唑烷衍生物相连的抗体。该发明还提供了噻唑烷衍生物中间体组合物，包括反应性功能基团。这种中间体组合物适合用作通过连接物或连接基团形成免疫结合物的底物。本发明还提供了使用这些免疫结合物治疗癌症的方法。
• [EN] PYRAZOLOAZEPINE IMMUNOCONJUGATES, AND USES THEREOF<br/>[FR] IMMUNOCONJUGUÉS DE PYRAZOLOAZÉPINE ET LEURS UTILISATIONS
  申请人：BOLT BIOTHERAPEUTICS INC

  公开号：WO2022036101A1

  公开（公告）日：2022-02-17

  The invention provides immunoconjugates of Formula I comprising an antibody linked by conjugation to one or more pyrazoloazepine derivatives. The invention also provides pyrazoloazepine derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

  本发明提供了公式I的免疫结合物，其包括通过共轭连接与一种或多种嘧唑并丙氨酸衍生物相连的抗体。本发明还提供了嘧唑并丙氨酸衍生物中间体组成，其中包括反应性官能团。这种中间体组成物是通过连接物或连接基物质的形成免疫结合物的合适底物。本发明还提供了使用免疫结合物治疗癌症的方法。