seco-DUBA | 1227961-59-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: seco-DUBA
• 英文别名: N-[2-[(1S)-1-(chloromethyl)-5-hydroxy-9-methyl-1,2-dihydrobenzo[e]indole-3-carbonyl]imidazo[1,2-a]pyridin-6-yl]-4-hydroxybenzamide
• CAS: 1227961-59-2
• 化学式: C₂₉H₂₃ClN₄O₄
• 分子量: 526.979
• InChiKey: VQAFBYLFRCCWNB-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  seco-DUBA 在 硫酰氟 、 potassium carbonate 、 2-叔丁基亚氨基-2-二乙基氨基-1,3-二甲基全氢-1,3,2-二氮杂磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  硫酸芳基酯是结合和释放酚类分子的有用基元：硫氟交换点击化学能够发现邻羟基保护的芳基硫酸盐连接基。

  摘要：

  设计了一种新的自消灭性连接基序，邻羟基保护的芳基硫酸盐（OHPAS），并在体内和体外测试了含OHPAS的抗体药物偶联物（ADC）。它是使用硫氟交换（SuFEx）化学方法方便地合成的，结构上是基于硫酸二芳基酯，其中一个芳基充当有效负载，另一个芳基充当在邻位具有潜在苯酚功能的自消灭硫酸盐单元。化学稳定的OHPAS接头在来自5个不同物种的血浆样品中稳定，但是在化学或生物触发时，它可以平稳地释放有效负载分子。有效负载的释放通过分子内环化进行，产生环状硫酸盐副产物，最终水解为邻苯二酚单硫酸盐。制备了一组基于曲妥珠单抗的含OHPAS的ADC，药物与抗体的比率为〜2，并且在5种不同的癌细胞系中具有体外细胞毒性，并在NCI-N87小鼠异种移植物中剂量依赖性地抑制了肿瘤的生长。模型。我们得出的结论是，OHPAS共轭物将在将含酚的有效载荷输送到靶向医学干预的组织中具有重要用途。

  DOI：

  10.1021/acs.bioconjchem.9b00340

文献信息

• [EN] COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF<br/>[FR] COMPOSÉS COMPRENANT UN LIEUR CLIVABLE ET LEURS UTILISATIONS
  申请人：INTOCELL INC

  公开号：WO2019008441A1

  公开（公告）日：2019-01-10

  Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

  提供了一种包括可切割连接物的化合物，其用途，以及用于制备该化合物的中间体化合物，更具体地，本发明的包括可切割连接物的化合物可能包括具有特定功能或活性的活性剂（例如，药物，毒素，配体，用于检测的探针等），能够选择性释放活性剂的SO2官能团，以及通过外部刺激触发化学反应，物理化学反应和/或生物反应的官能团，并且还可以包括具有与所需靶受体结合特异性的配体（例如，寡肽，多肽，抗体等）。
• CC-1065 ANALOGS AND THEIR CONJUGATES
  申请人：Syntarga B.V.

  公开号：EP2344478B1

  公开（公告）日：2017-09-27
• CONJUGATES OF CC-1065 ANALOGS AND BIFUNCTIONAL LINKERS
  申请人：Syntarga B.V.

  公开号：EP2560645B1

  公开（公告）日：2016-07-13
• Novel cc-1065 Analogs and Their Conjugates
  申请人：Beusker Patrick Henry

  公开号：US20110207767A1

  公开（公告）日：2011-08-25

  This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.
• NOVEL CONJUGATES OF CC-1065 ANALOGS AND BIFUNCTIONAL LINKERS
  申请人：Beusker Patrick Henry

  公开号：US20130224227A1

  公开（公告）日：2013-08-29

  This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.