5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-morpholin-4-yl-ethyl)-amide

• 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: 5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-morpholin-4-yl-ethyl)-amide
• 英文别名: 5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-N-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide；5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide
• 化学式: C₂₂H₂₅FN₄O₃
• 分子量: 412.464
• InChiKey: HGAQQKPBNGSIMU-ATVHPVEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  86.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二甲基-1-氢-吡咯-2-羧酸叔丁酯-4-羧酸乙酯 在 哌啶 、 氢氧化钾 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-morpholin-4-yl-ethyl)-amide
  参考文献：
  名称：

  Discovery of 5-[5-Fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic Acid (2-Diethylaminoethyl)amide, a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial and Platelet-Derived Growth Factor Receptor Tyrosine Kinase

  摘要：

  To improve the antitumor properties and optimize the pharmaceutical properties including solubility and protein binding of indolin-2-ones, a number of different basic and weakly basic analogues were designed and synthesized. 5-[5-Fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl- 1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide (12b or SU11248) has been found to show the best overall profile in terms of potency for the VEGF-R2 and PDGF-Rbeta tyrosine kinase at biochemical and cellular levels, solubility, protein binding, and bioavailability. 12b is currently in phase I clinical trials for the treatment of cancers.

  DOI：

  10.1021/jm0204183

文献信息

• Process for preparing indolinone derivatives
  申请人：Jin Qingwu

  公开号：US20050171357A1

  公开（公告）日：2005-08-04

  The present invention refers to a process for preparing indolinone derivatives of the general formula (VI) as defined in the specification and intermediates of that process.

  本发明涉及一种制备通式（VI）所定义的吲哚酮衍生物及其中间体的过程。
• PROCESS FOR PREPARING INDOLINONE DERIVATIVES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP1476443A2

  公开（公告）日：2004-11-17
• US7119209B2
  申请人：——

  公开号：US7119209B2

  公开（公告）日：2006-10-10
• [EN] PROCESS FOR PREPARING INDOLINONE DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES DE L'INDOLINONE
  申请人：UPJOHN CO

  公开号：WO2003070725A2

  公开（公告）日：2003-08-28

  The present invention refers to a process for preparing indolinone derivatives of the general formula (VI) as defined in the specification and intermediates of that process.
• Discovery of 5-[5-Fluoro-2-oxo-1,2- dihydroindol-(3<i>Z</i>)-ylidenemethyl]-2,4- dimethyl-1<i>H</i>-pyrrole-3-carboxylic Acid (2-Diethylaminoethyl)amide, a Novel Tyrosine Kinase Inhibitor Targeting Vascular Endothelial and Platelet-Derived Growth Factor Receptor Tyrosine Kinase
  作者：Li Sun、Chris Liang、Sheri Shirazian、Yong Zhou、Todd Miller、Jean Cui、Juri Y. Fukuda、Ji-Yu Chu、Asaad Nematalla、Xueyan Wang、Hui Chen、Anand Sistla、Tony C. Luu、Flora Tang、James Wei、Cho Tang

  DOI：10.1021/jm0204183

  日期：2003.3.1

  To improve the antitumor properties and optimize the pharmaceutical properties including solubility and protein binding of indolin-2-ones, a number of different basic and weakly basic analogues were designed and synthesized. 5-[5-Fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl- 1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide (12b or SU11248) has been found to show the best overall profile in terms of potency for the VEGF-R2 and PDGF-Rbeta tyrosine kinase at biochemical and cellular levels, solubility, protein binding, and bioavailability. 12b is currently in phase I clinical trials for the treatment of cancers.