(Z)-3-((4-chlorophenyl)(1H-imidazol-2-yl)methylene)-5-(1-ethylpiperidin-4-ylamino)indolin-2-one | 705946-42-5

• 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: (Z)-3-((4-chlorophenyl)(1H-imidazol-2-yl)methylene)-5-(1-ethylpiperidin-4-ylamino)indolin-2-one
• 英文别名: (3Z)-3-[(4-chlorophenyl)-(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1H-indol-2-one
• CAS: 705946-42-5
• 化学式: C₂₅H₂₆ClN₅O
• 分子量: 447.967
• InChiKey: XHCPCYVQXFHJAU-FCQUAONHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  73
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-硝基-1,3-二氢-2H-吲哚-2-酮 在 palladium on activated charcoal 、 sodium triacetoxyborohydride 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 生成 (Z)-3-((4-chlorophenyl)(1H-imidazol-2-yl)methylene)-5-(1-ethylpiperidin-4-ylamino)indolin-2-one
  参考文献：
  名称：

  The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors

  摘要：

  Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.029

文献信息

• Kinase modulators
  申请人：Xu Wei

  公开号：US20060122171A1

  公开（公告）日：2006-06-08

  The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides oxindole derivatives which inhibit, regulate and/or modulate kinase receptor, particularly VEGF receptor 2 (Flk-1/KDR), FGFR1, and PDGFR (alpha and beta), signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions.

  本发明提供了用于调节蛋白激酶酶活性以调节细胞活动（如增殖、分化、程序性细胞死亡、迁移和化学侵袭）的化合物。更具体地说，本发明提供了氧化吲哚衍生物，其抑制、调节和/或调节激酶受体，特别是VEGF受体2（Flk-1/KDR）、FGFR1和PDGFR（α和β）信号转导通路，与上述细胞活动变化相关的组合物，以及使用它们治疗激酶依赖性疾病和病状的方法。
• Methods of using MEK inhibitors
  申请人：Lamb Peter

  公开号：US20080166359A1

  公开（公告）日：2008-07-10

  The present invention provides methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, in combination with other cancer treatments.

  本发明提供了一种通过给予I式化合物或其药学上可接受的盐或溶剂与其他癌症治疗相结合的方法来治疗癌症的方法。
• METHODS OF TREATING CANCER USING PYRIDOPYRIMIDINONE INHIBITORS OF P13K ALPHA
  申请人：Lamb Peter

  公开号：US20100209420A1

  公开（公告）日：2010-08-19

  The present invention provides methods of treating cancer by administering a compound of Formula I, optionally as a pharmaceutically acceptable salt, solvate and/or hydrate thereof, in combination with other cancer treatments. (Formula I)

  本发明提供了一种通过与其他癌症治疗方法联合使用的方式，给予公式I化合物（可选择其作为药用盐，溶剂或水合物）来治疗癌症的方法。（公式I）
• COMBINATION THERAPIES COMPRISING QUINOXALINE INHIBITORS OF P13K-ALPHA FOR USE IN THE TREATMENT OF CANCER
  申请人：Lamb Peter

  公开号：US20110123434A1

  公开（公告）日：2011-05-26

  The present invention provides methods of treating cancer by administering a compound of Formula I, optionally as a pharmaceutically acceptable salt, solvate and/or hydrate thereof, in combination with other cancer treatments.

  本发明提供了一种通过与其他癌症治疗方法联合使用的方法，给予I式化合物（可选地作为其药学上可接受的盐，溶剂和/或水合物）治疗癌症的方法。
• METHODS OF USING MEK INHIBITORS
  申请人：Exelixis, Inc.

  公开号：EP2101759B1

  公开（公告）日：2018-10-10