3-((4,5,6,7-Tetrahydro-1H-indol-2-yl)methylene)indolin-2-one

• 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-((4,5,6,7-Tetrahydro-1H-indol-2-yl)methylene)indolin-2-one
• 英文别名: (3Z)-3-(4,5,6,7-tetrahydro-1H-indol-2-ylmethylidene)-1H-indol-2-one
• 化学式: C₁₇H₁₆N₂O
• 分子量: 264.327
• InChiKey: PEQAQVCHUDMZPB-UVTDQMKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  4,5,6,7-四氢吲哚 在 哌啶 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 3-((4,5,6,7-Tetrahydro-1H-indol-2-yl)methylene)indolin-2-one
  参考文献：
  名称：

  Identification of Substituted 3-[(4,5,6,7-Tetrahydro-1H-indol-2-yl)methylene]- 1,3-dihydroindol-2-ones as Growth Factor Receptor Inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rβ Tyrosine Kinases

  摘要：

  A series of new 3-substituted indolin-2-ones containing a tetrahydroindole moiety was developed as specific inhibitors of receptor tyrosine kinases associated with VEGF-R, FGF-R, and PDGF-R growth factor receptors. These compounds were evaluated for their inhibitory properties toward VEGF-R2 (Flk-1/KDR), FGF-R1, PDGF-R beta, p60(c-Src), and EGF-R tyrosine kinases and their ability to inhibit growth factor-dependent cell proliferation. Structure-activity relationships of this new pharmacophore have been determined at the level of kinase inhibition. Compounds containing a propionic acid moiety at the C-3' position of the tetrahydroindole ring represented the most potent indolin-2-ones to inactivate the VEGF, FGF, and PDGF receptor kinases. The inhibitory activities of 9d against VEGF-R2 (Flk-1), 9h against FGF-R1, and 9b against PDGF-R beta were 4, 80, and 4 nM, respectively. However, all of these compounds were inactive when tested against the EGF-R tyrosine kinase. Compounds 9a and 9b represented the most potent inhibitors of these classes to inhibit both biochemical kinase and growth factor-dependent cell proliferation for these three targets. In addition, compound 9a was cocrystallized with the catalytic domain of FGF-R1 providing evidence to explain the structure-activity relationship results. This study has provided evidence to support the potential of these new tyrosine kinase inhibitors for the treatment of angiogenesis and other growth factor-related diseases including human cancers.

  DOI：

  10.1021/jm9906116

文献信息

• 3-(4,5,6,7-Tetrahydroindol-2-ylmethylidiene-2-indolinone derivatives as kinase inhibitors
  申请人：Sugen, Inc.

  公开号：US20030119819A1

  公开（公告）日：2003-06-26

  The present invention relates to certain 3-(4,5,6,7-tetrahydroindol-2-yl-methylidene)-2-indolinone derivatives that inhibit kinases, in particular Src kinase. Pharmaceutical compositions comprising these compounds, methods of treating diseases mediated by kinases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing them are also disclosed.

  本发明涉及抑制激酶的某些3-(4,5,6,7-四氢吲哚-2-基甲基)-2-吲哚酮衍生物，特别是Src激酶。还公开了包括这些化合物的药物组合物、利用包括这些化合物的药物组合物治疗激酶介导的疾病的方法，以及它们的制备方法。
• [EN] POLYMERIC MICELLAR COMPLEXES AND DRUG DELIVERY VEHICLES THEREOF<br/>[FR] COMPLEXES MICELLAIRES POLYMERES ET VEHICULES D'ADMINISTRATION DE MEDICAMENTS
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005058376A1

  公开（公告）日：2005-06-30

  Disclosed are complexes of an amphiphilic copolymer, wherein the amphiphilic copolymer has benzoyl sulfonic acid groups on the hydrophobic segment of the copolymer.

  揭示了一种两性共聚物的复合物，其中两性共聚物在其疏水段上具有苯甲酰磺酸基团。
• Receptor antagonist-lipid conjugates and delivery vehicles containing same
  申请人：——

  公开号：US20040013720A1

  公开（公告）日：2004-01-22

  Disclosed are vesicular drug delivery vehicles, such as liposomes, comprising a targeting ligand which comprises a non-biological, biomitric antagonist to a receptor that is upregulated at a disease site.

  本发明涉及一种含有靶向配体的囊泡药物传递载体，例如脂质体，该靶向配体包括一种非生物、生物模拟拮抗剂，用于靶向一个在疾病部位上调节上调的受体。
• Compositions and methods for inhibiting mucin-type O-linked glycosylation
  申请人：Bertozzi R. Carolyn

  公开号：US20060063736A1

  公开（公告）日：2006-03-23

  The present invention provides inhibitors of mucin-type O-linked glycosylation, and in particular inhibitors of polypeptide N-acetyl-α-galactosaminyltransferases; as well as compositions comprising the inhibitors. The present invention further provides methods of identifying inhibitors of polypeptide N-acetyl-α-galactosaminyltransferases. The inhibitors are useful in various applications, including research applications, and treatment methods.

  本发明提供了黏液型O-连接糖基化抑制剂，特别是多肽N-乙酰-α-半乳糖氨基转移酶的抑制剂；以及包含该抑制剂的组合物。本发明还提供了识别多肽N-乙酰-α-半乳糖氨基转移酶抑制剂的方法。这些抑制剂在各种应用中都很有用，包括研究应用和治疗方法。
• Products and drug delivery vehicles
  申请人：——

  公开号：US20040208844A1

  公开（公告）日：2004-10-21

  Disclosed are products useful as, or in, drug delivry vehicles.

  本发明涉及一种有用于药物传递载体的产品。