1-[2-(2-羟基乙氧基)乙基]吡咯-2,5-二酮 | 34321-81-8

• 物质功能分类: 有机原料 - 氨基化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 1-[2-(2-羟基乙氧基)乙基]吡咯-2,5-二酮
• 中文别名: 马来酰亚胺-二聚乙二醇
• 英文名称: 1-(2-(2-hydroxyethoxy)ethyl)-1H-pyrrole-2,5-dione
• 英文别名: 1-[2-(2-hydroxyethoxy)ethyl]pyrrole-2,5-dione
• CAS: 34321-81-8
• 化学式: C₈H₁₁NO₄
• mdl: MFCD16780862
• 分子量: 185.18
• InChiKey: IIYLRYHFPWHINS-UHFFFAOYSA-N

物化性质

• 沸点：
  361.7±22.0 °C(Predicted)
• 密度：
  1.317±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[2-(2-羟基乙氧基)乙基]吡咯-2,5-二酮 在 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 1-[2-(2-{(2S,3S,4S,6R)-3-Hydroxy-2-methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyran-4-ylamino}-ethoxy)-ethyl]-pyrrole-2,5-dione
  参考文献：
  名称：

  The design, synthesis, and evaluation of two universal doxorubicin-linkers: Preparation of conjugates that retain topoisomerase II activity

  摘要：

  The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3'-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3'-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven DOX-amino acid conjugates were prepared, each displaying similar inhibitory activity as the parent drug. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.046
• 作为产物：
  描述：

  N-[2-(2-hydroxyethoxy)ethyl]-exo-3,6-epoxy-1,2,3,6-tetrahydrophthalimide 以 甲苯 为溶剂， 反应 7.0h， 以41%的产率得到1-[2-(2-羟基乙氧基)乙基]吡咯-2,5-二酮
  参考文献：
  名称：

  [EN] RELEASABLE CONJUGATES
  [FR] CONJUGUÉS LIBÉRABLES

  摘要：

  本申请提供了化合物的公式（B），或其药用盐，其中D是生物活性药物的残留物，在生理条件下经过水解释放出生物活性药物，并且对可能受益于该药物治疗的疾病具有用处。

  公开号：

  WO2018163131A1

文献信息

• [EN] ANTIBODY CONJUGATES COMPRISING TOLL-LIKE RECEPTOR AGONIST AND COMBINATION THERAPIES<br/>[FR] CONJUGUÉS D'ANTICORPS COMPRENANT UN AGONISTE DU RÉCEPTEUR DE TYPE TOLL ET POLYTHÉRAPIES
  申请人：NOVARTIS AG

  公开号：WO2018198091A1

  公开（公告）日：2018-11-01

  Provided herein are antibody conjugates comprising toll-like receptor agonists and the use of such conjugates for the treatment of cancer. In some embodiments, the conjugates comprise anti-HER2 antibodies. In some embodiments, the conjugates are used in combination with a second therapeutic agent.

  本文提供了包含Toll样受体激动剂的抗体偶联物，以及利用这些偶联物治疗癌症的用途。在某些实施例中，这些偶联物包括抗HER2抗体。在某些实施例中，这些偶联物与第二治疗剂联合使用。
• [EN] DC-SIGN ANTIBODY DRUG CONJUGATES<br/>[FR] CONJUGUÉ MÉDICAMENT-ANTICORPS ANTI-DC-SIGN
  申请人：NOVARTIS AG

  公开号：WO2020089811A1

  公开（公告）日：2020-05-07

  Provided herein are antibodies to DC-SIGN, conjugates of DC-SiGN antibodies, and DC-SiGN antibody fusion proteins and the use of such antibodies, conjugates, and fusion proteins for the treatment of diseases such as cancer.

  本文提供了针对DC-SIGN的抗体，DC-SIGN抗体的结合物，以及DC-SIGN抗体融合蛋白，以及利用这些抗体、结合物和融合蛋白治疗癌症等疾病的用途。
• [EN] CELL PROLIFERATION INHIBITORS AND CONJUGATES THEREOF<br/>[FR] INHIBITEURS DE LA PROLIFÉRATION CELLULAIRE ET LEURS CONJUGUÉS
  申请人：NOVARTIS AG

  公开号：WO2014151030A1

  公开（公告）日：2014-09-25

  Disclosed herein are immunoconjugates comprising an inhibitor of Eg5 linked to an antigen binding moiety such as an antibody, useful for treating cell proliferative disorders. Also disclosed are novel inhibitors of Eg5 that can be used either alone or as part of an immunoconjugate to treat cell proliferation disorders. The Eg5 inhibitors include compounds of this formula as described herein: [insert last structure from page 68 here] The invention further provides pharmaceutical compositions comprising these compounds and immunoconjugates, optionally including a therapeutic co-agent, and methods to use these compounds, conjugates and compositions for treating cell proliferation disorders.

  本发明公开了包含Eg5抑制剂的免疫偶联物，该抑制剂与抗原结合部分如抗体相连，用于治疗细胞增殖紊乱。还公开了新颖的Eg5抑制剂，可以单独使用或作为免疫偶联物的一部分来治疗细胞增殖紊乱。Eg5抑制剂包括如本文所述的这种化合物的化合物：[在此插入第68页的最后一个结构]本发明进一步提供了包含这些化合物和免疫偶联物的药物组合物，可选地包括治疗共剂，以及使用这些化合物、偶联物和组合物来治疗细胞增殖紊乱的方法。
• Novel Silyl Ether-Based Acid-Cleavable Antibody-MMAE Conjugates with Appropriate Stability and Efficacy
  作者：Yanming Wang、Shiyong Fan、Dian Xiao、Fei Xie、Wei Li、Wu Zhong、Xinbo Zhou

  DOI：10.3390/cancers11070957

  日期：——

  Antibody-drug conjugate (ADC) is a novel efficient drug delivery system that has been successfully used in clinical practice, and it has become a research hotspot in the anti-tumor drug field. Acid-cleavable linkers were first used in clinical ADCs, but their structural variety (e.g., hydrazone and carbonate) is still limited, and their stability is usually insufficient. Designing novel acid-cleavable linkers for the conjugation of the popular cytotoxin monomethyl auristatin E (MMAE) has always been a significant topic. In this paper, we generate a novel, silyl ether-based acid-cleavable antibody-MMAE conjugate, which skillfully achieves efficient combination of amino-conjugated MMAE with the acid-triggered silyl ether group by introducing p-hydroxybenzyl alcohol (PHB). The stability, acid-dependence cleavage, effective mechanism, efficacy and safety of the resulting ADC were systematically studied; the results show that it exhibits a significant improvement in stability, while maintaining appropriate efficacy and controlled therapeutic toxicity. This strategy is expected to expand a new type of acid-cleavable linkers for the development of ADCs with highly potent payloads.

  抗体药物偶联物（ADC）是一种新颖的高效药物传递系统，已在临床实践中成功使用，并成为抗肿瘤药物领域的研究热点。酸性切割连接剂最初被用于临床ADCs，但它们的结构多样性（例如，腙和碳酸酯）仍然有限，而且它们的稳定性通常不足。设计新型酸性切割连接剂用于将流行的细胞毒素单甲基奥里司亭E（MMAE）进行偶联一直是一个重要的课题。在本文中，我们生成了一种新型的、基于硅醚的酸性切割抗体-MMAE偶联物，它巧妙地通过引入对羟基苄醇（PHB）实现了氨基偶联MMAE与酸性触发硅醚基团的 有效结合。研究了所得ADC的稳定性、酸性依赖切割、有效机制、疗效和安全性；结果表明，它在大稳定性方面有显著改善，同时保持了适当的疗效和可控的治疗毒性。这种策略有望为开发具有高活性载荷的ADCs扩展新型酸性切割连接剂。
• [EN] HUMANIZED ANTI-TN-MUC1 ANTIBODIES AND THEIR CONJUGATES<br/>[FR] ANTICORPS ANTI-TN-MUC1 HUMANISÉS ET LEURS CONJUGUÉS
  申请人：CANCER REC TECH LTD

  公开号：WO2015159076A1

  公开（公告）日：2015-10-22

  Humanized anti-Tn-MUC1 antibodies and conjugates thereof. Conjugates comprising pyrrolobenzodiazepines (PBDs) having a labile protecting group in the form of a linker to the antibody are described.

  人性化抗Tn-MUC1抗体及其结合物。描述了包含吡咯苯并二氮杂环己烷（PBDs）的结合物，其具有作为连接物的不稳定保护基团。