2,3-dimethoxy-8,9-methylenedioxy-11-[2-(methylamino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one | 1070882-30-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2,3-dimethoxy-8,9-methylenedioxy-11-[2-(methylamino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one
• 英文别名: 16,17-Dimethoxy-21-[2-(methylamino)ethyl]-5,7-dioxa-11,12,21-triazapentacyclo[11.8.0.02,10.04,8.014,19]henicosa-1(13),2,4(8),9,11,14,16,18-octaen-20-one
• CAS: 1070882-30-2
• 化学式: C₂₁H₂₀N₄O₅
• 分子量: 408.414
• InChiKey: NJXFWRPLWLTVMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  95
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,3-dimethoxy-8,9-methylenedioxy-11-[2-(benzyl(methyl)amino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one 在 甲酸 、 钯 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以73%的产率得到2,3-dimethoxy-8,9-methylenedioxy-11-[2-(methylamino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one
  参考文献：
  名称：

  与11- [2-（N，N-二甲基氨基）乙基] -2,3-二甲氧基-8,9-亚甲基二氧基-11H-异喹啉[4,3-c]肉桂烯有关的拓扑异构酶I靶向剂的合成及生物学评价-12一（ARC-31）。

  摘要：

  几个在乙基取代基上具有不同功能的11-乙基-2,3-二甲氧基-8,9-亚甲基二氧基-11H-异喹啉[4,3-c] cinnolin-12-具有强力的拓扑异构酶I（TOP1）靶向活性和抗肿瘤活性。评估了11-乙基取代基的2位上的各种极性取代基（包括N-甲基胺，N-异丙基胺，羟基和羟氨基）对TOP1靶向活性和细胞毒性的影响。在具有MDA-MB-435人肿瘤异种移植物的无胸腺裸鼠中，还评估了N-甲基胺和N-异丙基胺衍生物作为抗肿瘤剂。肠胃外或口服给药时，两种化合物均具有抗肿瘤活性。

  DOI：

  10.1016/j.bmc.2008.06.046

文献信息

• SITE-SPECIFIC ANTIBODY-DRUG CONJUGATION THROUGH GLYCOENGINEERING
  申请人：Genzyme Corporation

  公开号：US20140294867A1

  公开（公告）日：2014-10-02

  The current disclosure provides binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof (e.g., antibody-drug conjugates or ADCs), comprising a site-specifically engineered drug-glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

  本公开提供了结合多肽（例如抗体）及其效应物基团共轭物（例如抗体药物共轭物或ADCs），其中包括结合多肽的天然或工程糖醛中的位点特异性设计的药物-糖醛连接。本公开还提供了编码抗原结合多肽的核酸、重组表达载体和宿主细胞，用于制备这种抗原结合多肽。还提供了使用本文所披露的抗原结合多肽治疗疾病的方法。
• Fc containing polypeptides with altered glycosylation and reduced effector function
  申请人：Genzyme Corporation

  公开号：US10836813B2

  公开（公告）日：2020-11-17

  Provided are binding polypeptides (e.g., antibodies), and drug conjugates thereof, comprising an Fc domain with an altered glycosylation profile and reduced effector function. In particular embodiment, the Fc domain comprises: an asparagine residue at amino acid position 298, according to EU numbering; and a serine or threonine residue at amino acid position 300, according to EU numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

  本文提供了结合多肽（如抗体）及其药物共轭物，它们包含一个具有改变的糖基化特征和降低的效应功能的Fc结构域。在特定的实施方案中，Fc 结构域包括：根据欧盟编号，位于氨基酸位置 298 的天冬酰胺残基；以及根据欧盟编号，位于氨基酸位置 300 的丝氨酸或苏氨酸残基。此外，还提供了编码抗原结合多肽的核酸、重组表达载体和用于制造这种抗原结合多肽的宿主细胞。还提供了使用本文公开的抗原结合多肽治疗疾病的方法。
• Site-specific glycoengineering of targeting moieties
  申请人：Genzyme Corporation

  公开号：US10995148B2

  公开（公告）日：2021-05-04

  The current disclosure provides binding polypeptides (e.g., antibodies), and targeting moiety conjugates thereof, comprising a site-specifically engineered glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

  目前公开的内容提供了结合多肽（如抗体）及其靶向分子共轭物，包括结合多肽的本地或工程聚糖内的位点特异性工程聚糖连接。目前公开的内容还提供了编码抗原结合多肽的核酸、重组表达载体以及用于制造这种抗原结合多肽的宿主细胞。还提供了使用本文公开的抗原结合多肽治疗疾病的方法。
• Site-specific antibody-drug conjugation through glycoengineering
  申请人：Genzyme Corporation

  公开号：US11130816B2

  公开（公告）日：2021-09-28

  The current disclosure provides binding polypeptides (e.g., antibodies), and effector moiety conjugates thereof (e.g., antibody-drug conjugates or ADCs), comprising a site-specifically engineered drug-glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

  目前公开的内容提供了结合多肽（如抗体）及其效应分子共轭物（如抗体-药物共轭物或ADCs），包括结合多肽的原生或工程化聚糖内的位点特异性工程化药物-聚糖连接。本公开内容还提供了编码抗原结合多肽的核酸、重组表达载体以及用于制造这种抗原结合多肽的宿主细胞。还提供了使用本文公开的抗原结合多肽治疗疾病的方法。
• Glycoengineered antibody drug conjugates
  申请人：Genzyme Corporation

  公开号：US11160874B2

  公开（公告）日：2021-11-02

  The current disclosure provides binding polypeptides (e.g., antibodies), and targeting moiety conjugates thereof, comprising a site-specifically engineered glycan linkage within native or engineered glycans of the binding polypeptide. The current disclosure also provides nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.

  目前公开的内容提供了结合多肽（如抗体）及其靶向分子共轭物，包括结合多肽的本地或工程聚糖内的位点特异性工程聚糖连接。目前公开的内容还提供了编码抗原结合多肽的核酸、重组表达载体以及用于制造这种抗原结合多肽的宿主细胞。还提供了使用本文公开的抗原结合多肽治疗疾病的方法。