(Z)-2-oxo-3-[phenyl-(4-piperidin-1-ylmethyl-phenylamino)-methylene]-2,3-dihydro-1H-indole-6-carboxylic acid isopropylamide | 1168152-10-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (Z)-2-oxo-3-[phenyl-(4-piperidin-1-ylmethyl-phenylamino)-methylene]-2,3-dihydro-1H-indole-6-carboxylic acid isopropylamide
• 英文别名: (3Z)-2-oxo-3-[phenyl-[4-(piperidin-1-ylmethyl)anilino]methylidene]-N-propan-2-yl-1H-indole-6-carboxamide
• CAS: 1168152-10-0
• 化学式: C₃₁H₃₄N₄O₂
• 分子量: 494.637
• InChiKey: JBCISKARNROCAA-ZIADKAODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  73.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (Z)-2-oxo-3-[phenyl-(4-(piperidin-1-ylmethyl)phenylamino)methylene]-2,3-dihydro-1H-indole-6-carboxylic acid 、 异丙胺 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以74%的产率得到(Z)-2-oxo-3-[phenyl-(4-piperidin-1-ylmethyl-phenylamino)-methylene]-2,3-dihydro-1H-indole-6-carboxylic acid isopropylamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120)

  摘要：

  Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a new treatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as Fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.

  DOI：

  10.1021/jm900431g