2-吲哚酮-6-甲酸乙酯 | 954239-49-7

• 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
• 中文名称: 2-吲哚酮-6-甲酸乙酯
• 中文别名: 2-氧代-2,3-二氢-1H-吲哚-6-羧酸乙酯
• 英文名称: ethyl 2-oxoindoline-6-carboxylate
• 英文别名: 2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid ethyl ester；ethyl 2-indolinone-6-carboxylate；ethyl 2-oxo-1,3-dihydroindole-6-carboxylate
• CAS: 954239-49-7
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: SDMAVFXBWFYTCI-UHFFFAOYSA-N

物化性质

• 沸点：
  394.5±42.0 °C(Predicted)
• 密度：
  1.240

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-吲哚酮-6-甲酸乙酯 在 potassium hydroxide 、 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 6.17h， 生成 6-羧基吲哚酮
  参考文献：
  名称：

  EP2130829

  摘要：

  公开号：
• 作为产物：
  描述：

  4-羧甲基-3-硝基苯甲酸乙酯 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 20.0 ℃ 、344.75 kPa 条件下， 反应 1.0h， 以83%的产率得到2-吲哚酮-6-甲酸乙酯
  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

文献信息

• Substituted indolines which inhibit receptor tyrosine kinases
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US06762180B1

  公开（公告）日：2004-07-13

  Indolinones of the formula having an inhibitory effect on receptor tyrosine kinases and cyclin/CDK complexes, as well as on the proliferation of endothelial cells and various tumor cells. Exemplary are: (a) 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-ethoxycarbonyl-2-indolinone, (b) 3-Z-[(1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-carbamoyl-2-indolinone, and (c) 3-Z-[1-(4-(piperidin-1-yl-methyl)-anilino)-1-phenyl-methylene]-6-metboxycarbonyl-2-indolinone.

  公式为的吲哚酮对受体酪氨酸激酶和细胞周期蛋白/CDK复合物，以及内皮细胞和各种肿瘤细胞的增殖具有抑制作用。示例包括： (a) 3-Z-[1-(4-(哌啶-1-基甲基)-苯胺基)-1-苯基亚甲基]-6-乙氧羰基-2-吲哚酮， (b) 3-Z-(1-(4-(哌啶-1-基甲基)-苯胺基)-1-苯基亚甲基)-6-氨基甲酰基-2-吲哚酮，以及 (c) 3-Z-[1-(4-(哌啶-1-基甲基)-苯胺基)-1-苯基亚甲基]-6-甲氧羰基-2-吲哚酮。
• Substituted indolinones
  申请人：——

  公开号：US20030092756A1

  公开（公告）日：2003-05-15

  The present invention relates to indolinones substituted in the 6-position of general formula 1 wherein R 1 to R 5 and X are defined as in claim 1, the isomers and the salts thereof, particularly the physiologically acceptable salts thereof which have valuable pharmacological properties, in particular an inhibiting effect on various receptor tyrosine kinases and cyclin/CDK complexes and on the proliferation of endothelial cells and various, pharmaceutical compositions containing these compounds, their use and processes for preparing them.

  本发明涉及一种通式1中6位取代的吲哚酮，其中R1至R5和X的定义如权利要求1中定义的，其异构体和盐，特别是具有有价值的药理特性的生理上可接受的盐，特别是对各种受体酪氨酸激酶和细胞周期蛋白/CDK复合物以及内皮细胞增殖具有抑制作用的物质，含有这些化合物的药物组合物，其用途和制备这些化合物的方法。
• NOVEL OXINDOLE DERIVATIVE
  申请人：Shinobu Noriaki

  公开号：US20100076049A1

  公开（公告）日：2010-03-25

  A compound or a pharmaceutically acceptable salt thereof of the present invention is represented by the following general formula (I): [wherein, R 1 to R 8 may have a hydrogen atom, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C2-C8 alkenyl group, a C1-C6 alkylcarbonyl group or —COOR 9 (wherein R 9 represents a hydrogen atom, a C1-C6 alkyl group or a C2-C8 alkenyl group) as a substituent; and X represents a sulfur atom, an oxygen atom or NR 10 (wherein R 10 represents a hydrogen atom, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C2-C8 alkenyl group or a C1-C6 alkoxy group)].

  本发明的化合物或其药学上可接受的盐的通式（I）如下：[其中，R1至R8可能是氢原子、卤素原子、羟基、C1-C6烷基、C2-C8烯基、C1-C6烷基羰基或—COOR9（其中，R9表示氢原子、C1-C6烷基或C2-C8烯基）作为取代基；X表示硫原子、氧原子或NR10（其中，R10表示氢原子、卤素原子、羟基、C1-C6烷基、C2-C8烯基或C1-C6烷氧基）]。
• Oxindole derivative
  申请人：Theravalues Corporation

  公开号：US08053461B2

  公开（公告）日：2011-11-08

  A compound or a pharmaceutically acceptable salt thereof of the present invention is represented by the following general formula (I): [wherein, R1 to R8 may have a hydrogen atom, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C2-C8 alkenyl group, a C1-C6 alkylcarbonyl group or —COOR9 (wherein R9 represents a hydrogen atom, a C1-C6 alkyl group or a C2-C8 alkenyl group) as a substituent; and X represents a sulfur atom, an oxygen atom or NR10 (wherein R10 represents a hydrogen atom, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C2-C8 alkenyl group or a C1-C6 alkoxy group)].

  本发明的化合物或其药学上可接受的盐由以下通式（I）表示：[其中，R1至R8可以是氢原子、卤素原子、羟基、C1-C6烷基、C2-C8烯基、C1-C6烷基羰基或—COOR9（其中，R9表示氢原子、C1-C6烷基或C2-C8烯基）作为取代基；而X表示硫原子、氧原子或NR10（其中，R10表示氢原子、卤素原子、羟基、C1-C6烷基、C2-C8烯基或C1-C6烷氧基）]。
• NOVEL HYDROXYINDOLE DERIVATIVE
  申请人：Theravalues Corporation

  公开号：EP2130829A1

  公开（公告）日：2009-12-09

  A compound or a pharmaceutically acceptable salt thereof of the present invention is represented by the following general formula (I): [wherein, R1 to R8 may have a hydrogen atom, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C2-C8 alkenyl group, a C1-C6 alkylcarbonyl group or -COOR9 (wherein R9 represents a hydrogen atom, a C1-C6 alkyl group or a C2-C8 alkenyl group) as a substituent; and X represents a sulfur atom, an oxygen atom or NR10 (wherein R10 represents a hydrogen atom, a halogen atom, a hydroxy group, a C1-C6 alkyl group, a C2-C8 alkenyl group or a C1-C6 alkoxy group)].

  本发明的化合物或其药学上可接受的盐由以下通式 (I) 表示： [其中，R1 至 R8 可具有氢原子、卤素原子、羟基、C1-C6 烷基、C2-C8 烯基、C1-C6 烷基羰基或 -COOR9（其中 R9 代表氢原子、C1-C6 烷基或 C2-C8 烯基）作为取代基；X 代表硫原子、氧原子或 NR10（其中 R10 代表氢原子、卤素原子、羟基、C1-C6 烷基、C2-C8 烯基或 C1-C6 烷氧基）]。