马来酰亚胺-酰胺-PEG8-四氟苯酚酯

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 中文名称: 马来酰亚胺-酰胺-PEG8-四氟苯酚酯
• 英文名称: MAL-dPEG8-TFP ester
• 英文别名: Mal-amido-PEG8-TFP ester；(2,3,5,6-tetrafluorophenyl) 3-[2-[2-[2-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate
• 化学式: C₃₂H₄₄F₄N₂O₁₃
• 分子量: 740.701
• InChiKey: YQFZOPSEPCSFQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  51
• 可旋转键数：
  32
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  167
• 氢给体数：
  1
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  马来酰亚胺-酰胺-PEG8-四氟苯酚酯 、 (2S,3S,4S,5R,6S)-6-(4-((((11S,11aS)-8-(3-(((11S,11aS)-10-(((4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl)oxy)carbonyl)-11-hydroxy-7-methoxy-2-methylene-5-oxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-11-hydroxy-7-methoxy-2-methylene-5-oxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid 在 吡啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 92.0h， 以19%的产率得到(2S,3S,4S,5R,6S)-6-(4-((((11S,11aS)-8-(3-(((11S,11aS)-10-(((4-((2S,5S)-37-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,35-trioxo- 10,13,16,19,22,25,28,31-octaoxa-3,6,34-triazaheptatriacontanamido)benzyl)oxy)carbonyl)-11-hydroxy-7-methoxy-2-methylene-5-oxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-11-hydroxy-7-methoxy-2-methylene-5-oxo-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid
  参考文献：
  名称：

  [EN] PYRROLOBENZODIAZEPINE CONJUGATES
  [FR] CONJUGUÉS DE PYRROLOBENZODIAZÉPINE

  摘要：

  一个化学式为（I）的化合物：（I）及其共轭物。

  公开号：

  WO2018069490A1

文献信息

• [EN] THERAPEUTIC B7-H4 BINDING MOLECULES<br/>[FR] MOLÉCULES THÉRAPEUTIQUES SE LIANT À B7-H4
  申请人：MEDIMMUNE LTD

  公开号：WO2022053650A1

  公开（公告）日：2022-03-17

  The present invention relates to binding molecules (e.g. antibodies) for the treatment of cancer, and related antibody-drug conjugates.

  本发明涉及用于治疗癌症的结合分子（例如抗体）以及相关的抗体药物结合物。
• [EN] AMATOXIN DERIVATIVES AND CONJUGATES THEREOF AS INHIBITORS OF RNA POLYMERASE<br/>[FR] DÉRIVÉS D'AMATOXINE ET LEURS CONJUGUÉS COMME INHIBITEURS DE L'ARN POLYMÉRASE
  申请人：NOVARTIS AG

  公开号：WO2016071856A1

  公开（公告）日：2016-05-12

  The invention disclosed herein relates to cytotoxic cyclic peptides of Formula (I), methods of inhibiting RNA polymerase with such cyclic peptides, immunoconjugates comprising such cyclic peptides (i.e Antibody Drug Conjugates), pharmaceutical compositions comprising such cyclic peptides immunoconjugates, compositions comprising such cyclic peptides immunoconjugates with a therapeutic co-agent and methods of treatment using such cyclic peptides immunoconjugates: Formula (I).

  本发明涉及一种公式（I）的细胞毒性环肽，使用这种环肽抑制RNA聚合酶的方法，包含这种环肽的免疫结合物（即抗体药物结合物），包含这种环肽免疫结合物的药物组合物，包含这种环肽免疫结合物和治疗辅助剂的组合物以及使用这种环肽免疫结合物进行治疗的方法：公式（I）。
• Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual β-glucuronide and dipeptide triggers
  作者：Stephen J. Gregson、Allison M. Barrett、Neki V. Patel、Gyoung-Dong Kang、Davide Schiavone、Erin Sult、Conor S. Barry、Balakumar Vijayakrishnan、Lauren R. Adams、Luke A. Masterson、Francois D'Hooge、Mike Snaith、Jay Harper、John A. Hartley、Philip W. Howard

  DOI：10.1016/j.ejmech.2019.06.044

  日期：2019.10

  Antibody-drug conjugates (ADCs) containing pyrrolobenzodiazepine (PBD) dimers are currently being evaluated in human oncology clinical trials with encouraging results. To further improve the therapeutic window, next-generation PBD drug-linker design has focused on the inclusion of additional tumor-selective triggers and use of lower-potency PBDs. beta-Glucuronidase is a well-known target for discovery prodrugs due to increased presence in tumor cells and microenvironment. In this study, a beta-glucuronidase cleavable cap was investigated at the PBD NW-position and compared with corresponding free imine ADCs. SG3600 (glucuronide) ADCs showed in vitro and in vivo efficacy/tolerability comparable to SG3400 (imine) ADCs, and good 50% inhibitory concentration differentials were observed in vitro between control non-antigen-targeted ADCs and targeted ADCs. Dependence on beta-glucuronidase for SG3600 activity was demonstrated through CRISPRCas9 knockdown studies and addition of exogenous beta-glucuronidase. SG3600 showed better serum stability, improved conjugation efficiency and was able to reach high drug-to-antibody ratio without aggregation. (C) 2019 Elsevier Masson SAS. All rights reserved.
• AMATOXIN DERIVATIVES AND CONJUGATES THEREOF AS INHIBITORS OF RNA POLYMERASE
  申请人：Grunewald Jan

  公开号：US20170355731A1

  公开（公告）日：2017-12-14

  The invention disclosed herein relates to cytotoxic cyclic peptides of Formula (I), methods of inhibiting RNA polymerase with such cyclic peptides, immunoconjugates comprising such cyclic peptides (i.e Antibody Drug Conjugates), pharmaceutical compositions comprising such cyclic peptides immunoconjugates, compositions comprising such cyclic peptides immunoconjugates with a therapeutic co-agent and methods of treatment using such cyclic peptides immunoconjugates:
• US9938323B2
  申请人：——

  公开号：US9938323B2

  公开（公告）日：2018-04-10