1-(2,5-dioxopyrrolidin-1-yloxy)-4-((5-nitropyridin-2-yl)disulfanyl)-1-oxobutane-2-sulfonic acid | 1193111-37-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 1-(2,5-dioxopyrrolidin-1-yloxy)-4-((5-nitropyridin-2-yl)disulfanyl)-1-oxobutane-2-sulfonic acid
• 英文别名: 1-(2,5-dioxopyrrolidin-1-yloxy)-4-(5-nitropyridin-2-yl)disulfanyl-1-oxobutane-2-sulfonic acid；N-succinimidyl 4-(5-nitropyridin-2-yl)disulfanyl-2-sulfobutyrate；1-(2,5-dioxopyrrolidin-1-yl)oxy-4-[(5-nitropyridin-2-yl)disulfanyl]-1-oxobutane-2-sulfonic acid
• CAS: 1193111-37-3
• 化学式: C₁₃H₁₃N₃O₉S₃
• 分子量: 451.459
• InChiKey: LWDVHPVQKVSTGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  236
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4-((5-nitropyridin-2-yl)disulfanyl)-2-sulfobutanoic acid 在 1,2-二氯乙烷 作用下， 以 2,4-滴二甲胺盐 为溶剂， 以82%的产率得到1-(2,5-dioxopyrrolidin-1-yloxy)-4-((5-nitropyridin-2-yl)disulfanyl)-1-oxobutane-2-sulfonic acid
  参考文献：
  名称：

  CROSS-LINKERS AND THEIR USES

  摘要：

  具有带电或前带电交联基团的细胞结合剂和药物的共轭物，以及制备这些物质的方法。

  公开号：

  US20090274713A1

文献信息

• Synthesis and Evaluation of Hydrophilic Linkers for Antibody–Maytansinoid Conjugates
  作者：Robert Y. Zhao、Sharon D. Wilhelm、Charlene Audette、Gregory Jones、Barbara A. Leece、Alexandru C. Lazar、Victor S. Goldmacher、Rajeeva Singh、Yelena Kovtun、Wayne C. Widdison、John M. Lambert、Ravi V. J. Chari

  DOI：10.1021/jm2002958

  日期：2011.5.26

  SPDB and SMCC linkers used earlier without triggering aggregation or loss of affinity of the resulting conjugate. Antibody–maytansinoid conjugates (AMCs) bearing these sulfonate- or PEG-containing hydrophilic linkers were, depending on the nature of the targeted cells, equally to more cytotoxic to antigen-positive cells and equally to less cytotoxic to antigen-negative cells than conjugates made with SPDB

  描述了亲水性异双功能交联剂的合成和生物学评估，用于抗体与高细胞毒性剂的缀合。这些连接基除具有胺反应性N以外，还包含带负电荷的磺酸盐基团或亲水，不带电荷的PEG基团。-羟基琥珀酰亚胺（NHS）酯和巯基反应性末端。这些亲水性接头能够使疏水性有机分子药物（例如美登木素生物碱）以比之前使用的疏水性SPDB和SMCC接头更高的药物/抗体比（DAR）进行缀合，而不会引发聚集或丧失所产生的偶联物的亲和力。取决于靶细胞的性质，带有这些含磺酸盐或PEG的亲水性接头的抗体-类美登素偶联物（AMC）与制备的偶联物相比，对抗原阳性细胞的细胞毒性更高，对抗原阴性细胞的细胞毒性更低与SPDB或SMCC接头结合使用，因此通常显示出更宽的选择性窗口，尤其是针对体外的多药耐药（MDR）癌细胞系和体内的肿瘤异种移植模型。
• Methods for Decreasing Ocular Toxicity of Antibody Drug Conjugates
  申请人：Lutz Robert J.

  公开号：US20120282282A1

  公开（公告）日：2012-11-08

  The invention relates to charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of using the same to reduce ocular toxicity associated with administration of antibody drug conjugates.

  本发明涉及带电或前置带电的交联基团及细胞结合剂和药物的共轭物，其中包括带电或前置带电的交联基团，并使用相同的方法来减少与抗体药物共轭物的给药相关的眼部毒性。
• Methods for preparing antibody-drug conjugates
  申请人：ImmunoGen, Inc.

  公开号：US10233257B2

  公开（公告）日：2019-03-19

  This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues.

  本发明描述了一种将细胞结合剂（如抗体）与效应基团（如细胞毒剂）或报告基团（如放射性核素）共轭的方法，其中报告基团或效应基团首先与双官能团连接剂反应，然后将混合物用于与细胞结合剂的共轭反应而无需纯化。本发明所述方法有利于制备细胞结合剂（如带有效应基团或报告基团的抗体）的稳定连接共轭物。这种共轭方法可提供高纯度和高均匀度的共轭物，这些共轭物没有链间交联和失活的连接残基。
• Cross-linkers and their uses
  申请人：IMMUNOGEN, INC.

  公开号：US11046762B2

  公开（公告）日：2021-06-29

  Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

  带电荷或原电荷的交联分子和细胞结合剂的共轭物，以及包含带电荷或原电荷交联分子的药物和制作方法。
• CONJUGATION METHODS
  申请人：ImmunoGen, Inc.

  公开号：US20140179906A1

  公开（公告）日：2014-06-26

  This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues