(E)-6-chloro-3-(3-hydroxy-4-methoxybenzylidene)indolin-2-one | 1148119-14-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (E)-6-chloro-3-(3-hydroxy-4-methoxybenzylidene)indolin-2-one
• 英文别名: (3E)-6-chloro-3-[(3-hydroxy-4-methoxyphenyl)methylidene]-1H-indol-2-one
• CAS: 1148119-14-5
• 化学式: C₁₆H₁₂ClNO₃
• 分子量: 301.729
• InChiKey: YCSZRYCZCWVAQF-WUXMJOGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  异香兰素 、 6-氯氧化吲哚 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以53%的产率得到(E)-6-chloro-3-(3-hydroxy-4-methoxybenzylidene)indolin-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 BENZYLIDENE-INDOLINONE AND THEIR MEDICAL AND DIAGNOSTIC USES<br/>[FR] NOUVEAUX BENZYLIDÈNE-INDOLINONES ET LEURS UTILISATIONS MÉDICALE ET EN DIAGNOSTIC
  申请人：UNIV SINGAPORE

  公开号：WO2010044753A1

  公开（公告）日：2010-04-22

  The present invention relates generally to organic chemistry, biochemistry, pharmacology and medicine. More particularly, it relates to 3-benzylidene-indolin-2-one derivatives and their physiologically acceptable salts and prodrugs which modulate the activity of protein kinases ("PKs"), especially protein tyrosine kinase, and, therefore, are expected to exhibit a salutary effect against disorders related to abnormal PK activity. The present invention is further directed to methods of using of these compounds, alone or in combination with other therapeutic agents, for the alleviation, prevention and/or treatment of protein kinase-mediated diseases and disorders, such as cancer.

  本发明通常涉及有机化学、生物化学、药理学和医学。更具体地，涉及到3-苄基亚甲基吲哚啉-2-酮衍生物及其生理上可接受的盐和前药，其调节蛋白激酶（“PKs”）的活性，特别是蛋白酪氨酸激酶，因此预计对与异常PK活性相关的疾病表现出有益效果。本发明进一步涉及使用这些化合物的方法，单独或与其他治疗剂联合使用，用于缓解、预防和/或治疗蛋白激酶介导的疾病和疾病，如癌症。
• NOVEL BENZYLIDENE-INDOLINONE AND THEIR MEDICAL AND DIAGNOSTIC USES
  申请人：National University of Singapore

  公开号：EP2350001A1

  公开（公告）日：2011-08-03
• Functionalized 3-benzylidene-indolin-2-ones: Inducers of NAD(P)H-quinone oxidoreductase 1 (NQO1) with antiproliferative activity
  作者：Wei Zhang、Mei-Lin Go

  DOI：10.1016/j.bmc.2008.12.052

  日期：2009.3

  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.