(3E)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2-(1H)-yl)-N-(3-((1-methyl-1H-imidazol-2yl)methylene)-2-oxoindolin-5-yl)acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3E)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2-(1H)-yl)-N-(3-((1-methyl-1H-imidazol-2yl)methylene)-2-oxoindolin-5-yl)acetamide
• 英文别名: N-[(3E)-2-oxo-3-((1-methyl-1H-imidazol-2-yl)methylidene)-2,3-dihydro-1H-indol-5-yl]-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetamide；2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-N-[(3E)-3-[(1-methylimidazol-2-yl)methylidene]-2-oxo-1H-indol-5-yl]acetamide
• 化学式: C₂₆H₂₇N₅O₄
• 分子量: 473.531
• InChiKey: UXBRVJKDXOQYFD-DEDYPNTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  97.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-硝基-1,3-二氢-2H-吲哚-2-酮 在 四氢吡咯 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 生成 (3E)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2-(1H)-yl)-N-(3-((1-methyl-1H-imidazol-2yl)methylene)-2-oxoindolin-5-yl)acetamide
  参考文献：
  名称：

  [EN] PHARMACEUTICAL COMBINATION FOR THE TREATMENT OF TUMORS
  [FR] COMBINAISON PHARMACEUTIQUE POUR LE TRAITEMENT DE TUMEURS

  摘要：

  该发明涉及一种组合物，其中至少包括一个式（I）的2-氧代吲哚衍生物，其中R1从噻吩基团、咪唑基团和吡啶基团中选择，可选地被（C1-C3）烷基取代，A是-CH2CO-或-SO2-基团；R从6,7-二甲氧基-1,2,3,4-四氢异喹啉基团、3,4-二甲氧基苄胺基团、（C1-C3）烷基、苄基或其药学上可接受的盐中选择，并且至少包括一种抗肿瘤药物。该组合物用于治疗肿瘤，特别是胶质母细胞瘤（GBM）、乳腺肿瘤和胰腺肿瘤。该组合物对治疗耐药肿瘤形式有效。

  公开号：

  WO2016055454A1

文献信息

• [EN] PHARMACEUTICAL COMBINATION FOR THE TREATMENT OF TUMORS<br/>[FR] COMBINAISON PHARMACEUTIQUE POUR LE TRAITEMENT DE TUMEURS
  申请人：INTERNAT SOC FOR DRUG DEV S R L

  公开号：WO2016055454A1

  公开（公告）日：2016-04-14

  The invention concerns a combination comprising at least one 2-oxo-indole derivative of formula (I) in which R1 is selected from the group consisting of thienyl, imidazolyl and pyridyl, optionally substituted by (C1-C3) alkyl, A is a -CH2CO- o -SO2- group; R is selected from the group consisting of 6,7-dimethoxy-1,2,3,4- tetrahydroisoquinolinyl, 3,4-dimethoxy-benzylamino, (C1-C3)alkyl, benzyl or a pharmaceutically acceptable salt thereof and at least one antitumor drug. The combination is for use in the treatment of tumors, in particular glioblastoma multiforme (GBM), breast tumor and pancreatic tumor. The combination is effective in the treatment of resistant tumor forms.

  该发明涉及一种组合物，其中至少包括一个式（I）的2-氧代吲哚衍生物，其中R1从噻吩基团、咪唑基团和吡啶基团中选择，可选地被（C1-C3）烷基取代，A是-CH2CO-或-SO2-基团；R从6,7-二甲氧基-1,2,3,4-四氢异喹啉基团、3,4-二甲氧基苄胺基团、（C1-C3）烷基、苄基或其药学上可接受的盐中选择，并且至少包括一种抗肿瘤药物。该组合物用于治疗肿瘤，特别是胶质母细胞瘤（GBM）、乳腺肿瘤和胰腺肿瘤。该组合物对治疗耐药肿瘤形式有效。
• Synthesis of Novel 3,5-Disubstituted-2-oxindole Derivatives As Antitumor Agents against Human Nonsmall Cell Lung Cancer
  作者：Giulia Nesi、Simona Sestito、Valentina Mey、Simona Ricciardi、Marco Falasca、Romano Danesi、Annalina Lapucci、Maria C. Breschi、Stefano Fogli、Simona Rapposelli

  DOI：10.1021/ml400162g

  日期：2013.12.12

  This study was aimed at investigating the antitumor activity of novel 2-oxindole derivatives against a well-characterized human nonsmall cell lung cancer (NSCLC) cell line. Test compounds produced an antiproliferative activity in the low micromolar/submicromolar range of concentrations and significantly induced typical apoptotic morphology with cell shrinkage, nuclear condensation and fragmentation, and rupture of cells into debris in a relatively low percentage of A549 cells. Cell cycle arrest occurred at the G1/S phase (1a and 2), and Akt phosphorylation was significantly inhibited at Thr308 and Ser473. The most active compound (1a) has an IC50 6-fold lower than the Akt inhibitor, perifosine. These data suggest that the new compounds may be cytostatic and may have maximum clinical effects in NSCLC patients who do not respond to EGFR inhibitors. These findings prompt us to further explore the oxindole structure as leading scaffold to design new molecules with potent antitumor activity against NSCLC.