3-(1H-indol-3-ylmethylene)-1,3-dihydro-indol-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-(1H-indol-3-ylmethylene)-1,3-dihydro-indol-2-one
• 英文别名: (E)-3-((1H-indol-3-yl)methylene)indolin-2-one；(E)-3-(1H-indol-3-ylmethylene)-1,3-dihydro-indol-2-one；3-[(indole-3-yl)methylene]-2-indolinone；(3E)-3-(1H-indol-3-ylmethylene)-1,3-dihydro-2H-indol-2-one；(3E)-3-(1H-indol-3-ylmethylidene)-1H-indol-2-one
• 化学式: C₁₇H₁₂N₂O
• 分子量: 260.295
• InChiKey: XCGXAWJRNVHWAI-NTEUORMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  3-吲哚甲醛 、 2-吲哚酮 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以24%的产率得到3-(1H-indol-3-ylmethylene)-1,3-dihydro-indol-2-one
  参考文献：
  名称：

  Functionalized 3-benzylidene-indolin-2-ones: Inducers of NAD(P)H-quinone oxidoreductase 1 (NQO1) with antiproliferative activity

  摘要：

  Functionalized benzylidene-indolin-2-ones are widely associated with antiproliferative activity. The scaffold is not normally associated with chemoprevention in spite of the presence of a nitrogen-linked Michael acceptor moiety that may predispose members to induction of NQO1, a widely used biomarker of chemopreventive potential. To investigate this possibility, we have synthesized and evaluated a series of functionalized 3-benzylidene-indolin-2-ones for induction of NQO1 in murine Hepa1c1c7 cells as well as antiproliferative activity against two human cancer cell lines (MCF-7, HCT116). The benzylideneindolinones were found to be good inducers of NQO1 activity, with 85% of test compounds able to increase basal NQO1 activity by more than twofold at concentrations of <= 10 mu M. By contrast, fewer compounds (11%) tested at the same concentration were able to reduce cell viability by more than 50%. Structure activity relationships showed that the nitrogen linked Michael acceptor moiety was an essential requirement for both activities. This common feature notwithstanding, substitution of the 3-benzylidene-indolin-2-one core structure affected NQO1 induction and antiproliferative activities in dissimilar ways, underscoring different structural requirements for these two activities. Nonetheless, promising compounds ( 10, 42, 45-48) were identified that combine selective induction of NQO1 with potent antiproliferative activity. A potential advantage of such agents would be the ability to provide added protection to normal cells by the up-regulation of NQO1 and other phase II enzymes while simultaneously targeting neoplastic cells. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.052

文献信息

• [EN] NOVEL THERAPEUTIC USE OF INDOLINONE DERIVATIVES<br/>[FR] NOUVELLE UTILISATION THERAPEUTIQUE DE DERIVES D'INDOLINONE
  申请人：LEO PHARMA AS

  公开号：WO2005058309A1

  公开（公告）日：2005-06-30

  Certain oxindole compounds have been found to be effective in experimentally induced autoimmune encephalitis and are therefore suggested for the preparation of a medicament for the prevention, treatment or amelioration of multiple sclerosis, or to delay the onset of or reduce the relapse rate in multiple sclerosis.

  某些氧吲哚化合物已被发现在实验诱导的自身免疫性脑炎中具有有效性，因此建议用于制备用于预防、治疗或改善多发性硬化症的药物，或延缓多发性硬化症的发作或减少复发率。
• [EN] INDOLINONE COMBINATORIAL LIBRARIES AND RELATED PRODUCTS AND METHODS FOR THE TREATMENT OF DISEASE<br/>[FR] BANQUES COMBINATOIRES D'INDOLINONE, PRODUITS ET PROCEDES ASSOCIES POUR TRAITER DES MALADIES
  申请人：SUGEN, INC.

  公开号：WO1998007695A1

  公开（公告）日：1998-02-26

  (EN) The present invention relates to organic molecules capable of modulating, regulating and/or inhibiting protein kinase signal transduction. Such compounds are useful for the treatment of diseases related to unregulated protein kinase signal transduction, including cell proliferative diseases such as cancer, atherosclerosis, arthritis and restenosis and metabolic diseases such as diabetes. The present invention features indolinone compounds that potently inhibit protein kinases and related products and methods. Inhibitors specific to the $i(FLK) protein kinase can be obtained by adding chemical substituents to the 3-[(indole-3-yl)methylene]-2-indolinone, in particular at the 1' position of the indole ring. Indolinone compounds that specifically inhibit the $i(FLK) and platelet derived growth factor protein kinases can harbor a tetrahydroindole or cyclopentano-b-pyrrol moiety. Indolinone compounds that are modified with substituents, particularly at the 5 position of the oxindole ring, can effectively activate protein kinases. This invention also features novel hydrosoluble indolinone compounds that are tyrosine kinase inhibitors and related products and methods.(FR) Cette invention concerne des molécules organiques qui sont capables de moduler, de réguler et/ou d'inhiber la transduction du signal de la protéine kinase. Ces composés sont utiles pour traiter des maladies liées à la transduction du signal de la protéine kinase non régulée, y compris les maladies à prolifération cellulaire telles que le cancer, l'athérosclérose, l'arthrite et la resténose, ainsi que les maladies du métabolisme telles que le diabète. Cette invention présente des composés d'indolinone qui inhibent fortement les protéines kinases, ainsi que des produits et des procédés associés. On peut obtenir des inhibiteurs spécifiques contre la protéine kinase $i(FLK) en ajoutant des substituants chimiques au 3-[(indole-3-yl)méthylène]-2-indolinone, en particulier à la position 1' du cycle indole. Les composés d'indolinone qui inhibent spécifiquement les protéines kinase $i(FLK) et du facteur de croissance dérivé des plaquettes peuvent accepter une fracteur tétrahydroindole ou cyclopentano-b-pyrrol. Les composés d'indolinone qui sont modifiés avec des substituants plus particulièrement à la position 5 du cycle oxindole peuvent activer efficacement les protéines kinases. Cette invention concerne également de nouveaux composés d'indolinone hydrosolubles qui sont des inhibiteurs de la tyrosine kinase, ainsi que des produits et des procédés associés.

  本发明涉及能够调节、调控和/或抑制蛋白激酶信号转导的有机分子。这样的化合物对于治疗与未调节的蛋白激酶信号转导相关的疾病非常有用，包括细胞增殖性疾病，如癌症、动脉粥样硬化、关节炎和再狭窄，以及代谢性疾病，如糖尿病。本发明涉及强力抑制蛋白激酶及其相关产品和方法的吲哚酮化合物。通过向3-[(吲哚-3-基)甲基]-2-吲哚酮的吲哚环的1'位置添加化学取代基，可以获得特异性抑制$i(FLK)$蛋白激酶的抑制剂。具有四氢吲哚或环戊烯基-β-吡咯烷基的吲哚酮化合物可以特异性地抑制$i(FLK)$和血小板源性生长因子蛋白激酶。在氧吲哚环的5位添加取代基的吲哚酮化合物可以有效激活蛋白激酶。本发明还涉及新型水溶性吲哚酮化合物，其是酪氨酸激酶抑制剂及其相关产品和方法。
• Indolinone combinatorial libraries and related products and methods for the treatment of disease
  申请人：——

  公开号：US20020022626A1

  公开（公告）日：2002-02-21

  The present invention relates to organic molecules capable of modulating, regulating and/or inhibiting protein kinase signal transduction. Such compounds are useful for the treatment of diseases related to unregulated protein kinase signal transduction, including cell proliferative diseases such as cancer, atherosclerosis, arthritis and restenosis and metabolic diseases such as diabetes. The present invention features indolinone compounds that potently inhibit protein kinases and related products and methods. Inhibitors specific to the FLK protein kinase can be obtained by adding chemical substituents to the 3-[(indole-3-yl)methylene]-2-indolinone, in particular at the 1′ position of the indole ring. Indolinone compounds that specifically inhibit the FLK and platelet derived growth factor protein kinases can harbor a tetrahydroindole or cyclopentano-b-pyrrol moiety. Indolinone compounds that are modified with substituents, particularly at the 5 position of the oxindole ring, can effectively activate protein kinases. This invention also features novel hydrosoluble indolinone compounds that are tyrosine kinase inhibitors and related products and methods.

  本发明涉及有机分子，能够调节、调控和/或抑制蛋白激酶信号传导。这些化合物对于治疗与未调节的蛋白激酶信号传导相关的疾病，包括细胞增殖性疾病如癌症、动脉硬化、关节炎和再狭窄以及代谢性疾病如糖尿病非常有用。本发明以吲哚酮化合物为特色，其能够有效地抑制蛋白激酶及相关产物和方法。通过在吲哚环的1'位置添加化学取代基，可以获得特异性抑制FLK蛋白激酶的抑制剂。特异性抑制FLK和血小板源性生长因子蛋白激酶的吲哚酮化合物可以含有四氢吲哚或环戊基-β-吡咯基团。在氧吲哚环的5位置上修饰取代基的吲哚酮化合物可以有效地激活蛋白激酶。本发明还具有新型水溶性吲哚酮化合物，是酪氨酸激酶抑制剂及相关产品和方法。
• Novel therapeutic use
  申请人：Bouerat Duvold Maud Elysa Laetitia

  公开号：US20070167488A1

  公开（公告）日：2007-07-19

  Certain oxindole compounds have been found to be effective in experimentally induced autoimmune encephalitis and are therefore suggested for the preparation of a medicament for the prevention, treatment or amelioration of multiple sclerosis, or to delay the onset of or reduce the relapse rate in multiple sclerosis.

  某些恶唑酮化合物已被发现在实验性自身免疫脑炎中具有疗效，因此建议用于制备用于预防、治疗或改善多发性硬化症的药物，或者延迟多发性硬化症的发作或减少复发率。
• Indolinone compounds suitable for modulation of protein kinases
  申请人：Sugen, Inc.

  公开号：EP1247803A2

  公开（公告）日：2002-10-09

  The invention relates to indolinone compounds capable of modulating, regulating and/or inhibiting protein kinases. Such compounds are useful for the treatment of diseases related to unregulated protein kinase signal transduction.

  本发明涉及能够调节、调节和/或抑制蛋白激酶的吲哚啉酮化合物。此类化合物可用于治疗与未调节的蛋白激酶信号转导有关的疾病。