3,3-bis(methoxycarbonyl)-6-nitroindolin-2-one | 185433-47-0

• 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: 3,3-bis(methoxycarbonyl)-6-nitroindolin-2-one
• 英文别名: dimethyl 6-nitro-2-oxo-1,2-dihydroindol-3,3-dicarboxylate；3,3-di(methoxycarbonyl)-6-nitro-2-indolone；dimethyl 6-nitro-2-oxo-1H-indole-3,3-dicarboxylate
• CAS: 185433-47-0
• 化学式: C₁₂H₁₀N₂O₇
• 分子量: 294.221
• InChiKey: KCFWYXKAPVHBLQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3,3-bis(methoxycarbonyl)-6-nitroindolin-2-one 在 4-二甲氨基吡啶 、 dimethyl sulfide borane 、 sodium methylate 、 二异丁基氢化铝 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (+/-)-1-(tert-butyloxycarbonyl)-3-[[(methylsulfonyl)oxy]methyl]-6-nitroindoline
  参考文献：
  名称：

  A novel nitro-substituted seco-CI: Application as a reductively activated adept prodrug

  摘要：

  An alternative synthesis of seco-CI alkylating agents bearing a nitrogen substituent at C-6 is reported. The nitro compound 3 prepared by this route exhibits a 400-fold increase in cytotoxicity against UV4 cells in the presence of a nitroreductase enzyme from Escherichia coli B, suggesting it as a potential prodrug for use in antibody-directed enzyme prodrug therapy. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00508-2
• 作为产物：
  描述：

  2-氯-5-硝基苯甲酸 在 氯化亚砜 、 叠氮磷酸二苯酯 、 potassium tert-butylate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二甲基亚砜 、 甲苯 为溶剂， 反应 5.58h， 生成 3,3-bis(methoxycarbonyl)-6-nitroindolin-2-one
  参考文献：
  名称：

  WO2008/152014

  摘要：

  公开号：

文献信息

• Cyclopropylindoles and their seco precursors, and their use as prodrugs
  申请人：Cancer Research Campaign Technology Limited

  公开号：US05985909A1

  公开（公告）日：1999-11-16

  The present invention provides compounds of formula (I) and (II) which may be used as anticancer drugs.

  本发明提供了化合物(I)和(II)的公式，可用作抗癌药物。
• WO2008/152013
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120)
  作者：Gerald J. Roth、Armin Heckel、Florian Colbatzky、Sandra Handschuh、Jörg Kley、Thorsten Lehmann-Lintz、Ralf Lotz、Ulrike Tontsch-Grunt、Rainer Walter、Frank Hilberg

  DOI：10.1021/jm900431g

  日期：2009.7.23

  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.
• A novel nitro-substituted seco-CI: Application as a reductively activated adept prodrug
  作者：M. Tercel、W.A. Denny、W.R. Wilson

  DOI：10.1016/s0960-894x(96)00508-2

  日期：1996.11

  An alternative synthesis of seco-CI alkylating agents bearing a nitrogen substituent at C-6 is reported. The nitro compound 3 prepared by this route exhibits a 400-fold increase in cytotoxicity against UV4 cells in the presence of a nitroreductase enzyme from Escherichia coli B, suggesting it as a potential prodrug for use in antibody-directed enzyme prodrug therapy. Copyright (C) 1996 Elsevier Science Ltd
• NEW COMPOUNDS
  申请人：Engelhardt Harald

  公开号：US20100222331A1

  公开（公告）日：2010-09-02

  The present invention encompasses compounds of general Formula (1) wherein R 2 , R 3 , Q, W, X, Y and Z are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and the use thereof for preparing a medicament having the above-mentioned properties.