Indolin-2-one deriv. 9b

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Indolin-2-one deriv. 9b
• 英文别名: 3-[2-[(Z)-(5-bromo-2-oxo-1H-indol-3-ylidene)methyl]-4,5,6,7-tetrahydro-1H-indol-3-yl]propanoic acid
• 化学式: C₂₀H₁₉BrN₂O₃
• 分子量: 415.286
• InChiKey: OICXIBPVOXVRBW-GDNBJRDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-吗啉基-1-环己烯 在 哌啶 、 盐酸 、 sodium hydroxide 、 sodium acetate 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 5.0h， 生成 Indolin-2-one deriv. 9b
  参考文献：
  名称：

  Identification of Substituted 3-[(4,5,6,7-Tetrahydro-1H-indol-2-yl)methylene]- 1,3-dihydroindol-2-ones as Growth Factor Receptor Inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rβ Tyrosine Kinases

  摘要：

  A series of new 3-substituted indolin-2-ones containing a tetrahydroindole moiety was developed as specific inhibitors of receptor tyrosine kinases associated with VEGF-R, FGF-R, and PDGF-R growth factor receptors. These compounds were evaluated for their inhibitory properties toward VEGF-R2 (Flk-1/KDR), FGF-R1, PDGF-R beta, p60(c-Src), and EGF-R tyrosine kinases and their ability to inhibit growth factor-dependent cell proliferation. Structure-activity relationships of this new pharmacophore have been determined at the level of kinase inhibition. Compounds containing a propionic acid moiety at the C-3' position of the tetrahydroindole ring represented the most potent indolin-2-ones to inactivate the VEGF, FGF, and PDGF receptor kinases. The inhibitory activities of 9d against VEGF-R2 (Flk-1), 9h against FGF-R1, and 9b against PDGF-R beta were 4, 80, and 4 nM, respectively. However, all of these compounds were inactive when tested against the EGF-R tyrosine kinase. Compounds 9a and 9b represented the most potent inhibitors of these classes to inhibit both biochemical kinase and growth factor-dependent cell proliferation for these three targets. In addition, compound 9a was cocrystallized with the catalytic domain of FGF-R1 providing evidence to explain the structure-activity relationship results. This study has provided evidence to support the potential of these new tyrosine kinase inhibitors for the treatment of angiogenesis and other growth factor-related diseases including human cancers.

  DOI：

  10.1021/jm9906116

文献信息

• Methods of modulating protein tyrosine kinase function with substituted indolinone compounds
  申请人：SUGEN, INC.

  公开号：US20040067531A1

  公开（公告）日：2004-04-08

  The invention relates to certain indolinone compounds, their method of synthesis, and a combinatorial library consisting of the indolinone compounds. The invention also relates to methods of modulating the function of protein tyrosine kinases using indolinone compounds and methods of treating diseases by modulating the function of protein tyrosine kinases and related signal transduction pathways.

  这项发明涉及某些吲哚酮化合物、它们的合成方法以及由这些吲哚酮化合物组成的组合式库。该发明还涉及使用吲哚酮化合物调节蛋白酪氨酸激酶功能的方法，以及通过调节蛋白酪氨酸激酶和相关信号转导途径的功能来治疗疾病的方法。
• 3-methylidenyl-2-indolinone modulators of protein kinase
  申请人：Sugen, Inc.

  公开号：US20040024010A1

  公开（公告）日：2004-02-05

  The present invention relates to novel 3-methylidenyl-2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

  本发明涉及新型的3-甲基亚烯基-2-吲哚酮化合物及其生理上可接受的盐和前药，这些化合物可调节蛋白激酶的活性，因此预计在预防和治疗蛋白激酶相关的细胞疾病，如癌症方面具有用途。
• Pyrrole substituted 2-indolinone protein kinase inhibitors
  申请人：Sugen, Inc.

  公开号：EP2020408A1

  公开（公告）日：2009-02-04

  The present invention relates to novel pyrrole-substituted 2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases, compositions containing these compounds as well as their use in the prevention and treatment of protein kinase related cellular disorders such as cancer.

  本发明涉及新型吡咯取代的 2-吲哚啉酮化合物及其生理学上可接受的盐类和原药，它们可调节蛋白激酶的活性、含有这些化合物的组合物以及它们在预防和治疗与蛋白激酶相关的细胞疾病（如癌症）中的用途。
• IONIZABLE INDOLINONE DERIVATIVES AND THEIR USE AS PTK LIGANDS
  申请人：Sugen, Inc.

  公开号：EP1233943A2

  公开（公告）日：2002-08-28
• Method of screening compound preventing cells from infection with Hepatitis C virus (HCV)
  申请人：Komoda Yasumasa

  公开号：US20080125362A1

  公开（公告）日：2008-05-29

  The present invention relates to a screening method and identification method for a compound that inhibits the cell infection of hepatitis C virus (HCV), which comprises measuring affinity of a test compound for fibroblast growth factor receptor (FGFR) or the capability of blocking the binding thereof to HCV, and selecting or judging a test compound.