(Z)-3-((1H-pyrrol-2-yl)methylene)-6-(4-hydroxy-3-methoxyphenyl)indolin-2-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (Z)-3-((1H-pyrrol-2-yl)methylene)-6-(4-hydroxy-3-methoxyphenyl)indolin-2-one
• 英文别名: (3Z)-6-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrol-2-ylmethylene)-1,3-dihydro-2H-indol-2-one；(3Z)-6-(4-hydroxy-3-methoxyphenyl)-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one
• 化学式: C₂₀H₁₆N₂O₃
• 分子量: 332.359
• InChiKey: AYSXURJZVXBSRV-WJDWOHSUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-硝基-4-溴苯乙酸 在 哌啶 、 四(三苯基膦)钯 、 硫酸 、 cesium fluoride 、 锌 作用下， 以 甲醇 为溶剂， 生成 (Z)-3-((1H-pyrrol-2-yl)methylene)-6-(4-hydroxy-3-methoxyphenyl)indolin-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-ethylidene-1,3-dihydro-indol-2-ones as novel checkpoint 1 inhibitors

  摘要：

  Chk1 inhibitors have emerged as a novel class of neoplastic agents for abrogating the G2 DNA damage checkpoint arrest. Analogs of the Chk1 inhibitor, 3-ethylidene-1,3-dihydro-indol-2-one, were synthesized and tested in vitro for their inhibitory activities. The most promising compound identified from this series is analog 28, which possesses potent enzymatic and cellular activities.

  DOI：

  10.1016/j.bmcl.2005.09.064

文献信息

• Indolin-2-one derivatives as selective Aurora B kinase inhibitors targeting breast cancer
  作者：Eman M.E. Dokla、Amal Kamal Abdel-Aziz、Sandra N. Milik、Amr H. Mahmoud、Mona Kamal Saadeldin、Martin J. McPhillie、Saverio Minucci、Khaled A.M. Abouzid

  DOI：10.1016/j.bioorg.2021.105451

  日期：2021.12

  indicated that 6e and 8a induced G2/M cell cycle arrest, apoptosis, and necrosis of MDA-MB-468 cells and western blot analysis of 8a effect on MDA-MB-468 cells revealed 8a‘s ability to reduce Aurora B and its downstream target, Histone H3 phosphorylation. 6e and 8a displayed better safety profiles than multikinase inhibitors such as sunitinib, showing no cytotoxic effects on normal rat cardiomyoblasts

  Aurora B 是一种关键的细胞周期调节剂，其功能错误会导致多倍体、遗传不稳定和肿瘤发生。它在许多癌症中过度表达，因此，用小分子抑制剂靶向 Aurora B 构成了一种有前途的抗癌治疗方法。在基于结构的设计和分子杂交方法的指导下，我们基于先前报道的基于 indolin-2-one 的多激酶抑制剂开发了一系列十五种 indolin-2-one 衍生物 ( 1 )。七种衍生物5g、6a、6c - e、7和8a在 NCI-60 细胞系筛选中显示出优先的抗增殖活性，其中氨基甲酸酯6e和环丙基脲8a衍生物对 Aurora B（IC 50 分别为 16.2 和 10.5 nM）和 MDA-MB-468 细胞（IC 50  = 32.6 ± 9.9 和 29.1 ± 7.3 nM）显示出最佳活性。此外，6e和8a损害了 MDA-MB-468 细胞的克隆形成潜力。机制研究表明，6e和8a诱导 MDA-MB-468
• PROCESSES FOR THE PREPARATION OF 3-(PYRROL-2-YL)METHYLENE)-2-PYRROLONES USING 2-SILYLOXY-PYRROLES
  申请人：Henscheke Julian P.

  公开号：US20130190512A1

  公开（公告）日：2013-07-25

  The present invention provides for synthetic processes for the making of substituted 3-((pyrrol-2-yl)methylene)-2-pyrrolones, including sunitinib. The present invention also provides for a process of crystallizing substantially pure sunitinib L-malate.

  本发明提供了用于合成取代的3-((吡咯-2-基)亚甲基)-2-吡咯酮的方法，包括舒尼替尼。本发明还提供了一种结晶基本纯度舒尼替尼L-苹果酸盐的方法。
• Protein kinase inhibitors
  申请人：——

  公开号：US20030162785A1

  公开（公告）日：2003-08-28

  Compounds having the formula 1 or therapeutically acceptable salts thereof, are protein kinase inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.

  具有公式1或其治疗上可接受的盐的化合物是蛋白激酶抑制剂。 揭示了该化合物的制备、含有该化合物的组合物以及使用该化合物治疗疾病。
• PROTEIN KINASE INHIBITORS
  申请人：Abbott Laboratories

  公开号：EP1453800A2

  公开（公告）日：2004-09-08
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.