(E)-6-fluoro-3-(3-trifluoromethyl-benzylidene)-1,3-dihydro-indol-2-one | 1148119-16-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-6-fluoro-3-(3-trifluoromethyl-benzylidene)-1,3-dihydro-indol-2-one
• 英文别名: (E)-6-fluoro-3-(3-(trifluoromethyl)benzylidene)indolin-2-one；(3E)-6-fluoro-3-[[3-(trifluoromethyl)phenyl]methylidene]-1H-indol-2-one
• CAS: 1148119-16-7
• 化学式: C₁₆H₉F₄NO
• 分子量: 307.247
• InChiKey: JDXZLNNXAKQAQR-NTUHNPAUSA-N

物化性质

• 熔点：
  132-135 °C
• 沸点：
  422.0±45.0 °C(predicted)
• 密度：
  1.418±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氟吲哚酮 、 3-三氟甲基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以24%的产率得到(E)-6-fluoro-3-(3-trifluoromethyl-benzylidene)-1,3-dihydro-indol-2-one
  参考文献：
  名称：

  具有理想理化特性和强抑制肝细胞癌生长活性的6-氟苄叉亚吲哚满酮的N'-烷基氨基磺酰基类似物

  摘要：

  据报道，亚苄基吲哚酮6-氯-3-（3'-三氟甲基亚苄基）-1,3-二氢吲哚-2-一（4）对肝细胞癌（HCC）表现出有效的选择性生长抑制作用。证实性证据支持多受体酪氨酸激酶（RTK）抑制是一种可能的作用方式。然而，较差的物理化学性质4限制了它的赞助作为先导化合物。在这项研究中，对4的修饰进行了研究，以提高其效力和理化特性。发现带有3'- N-丙基氨基磺酰基取代基的6-氟亚苄基茚满酮3-12是有前途的替代品。化合物3-12 [6-氟-3-（3'-[N-丙基氨基磺酰基亚苄基] -1,3-二氢吲哚-2-1]的溶解度是4的十倍，并且对HCC细胞具有亚微摩尔的生长抑制活性。它具有凋亡作用，可抑制HuH7中多个RTK的磷酸化，其中对FGFR4和HER3的抑制作用尤为明显。在生理相关的原位HCC异种移植小鼠模型中，化合物3-12降低了肿瘤负荷。构效关系支持氟和N'-丙基氨基磺酰基部分在增强基于细胞的活性和

  DOI：

  10.1002/cmdc.201500235

文献信息

• BENZYLIDENE-INDOLINONE COMPOUNDS AND THEIR MEDICAL USE
  申请人：GO Mei Lin

  公开号：US20130035364A1

  公开（公告）日：2013-02-07

  Compounds of general formula I: wherein R 1a , R 1b , R 2 , R 3a , R 3b and X are as defined herein are tyrosine kinase inhibitors and are useful for the treatment of various diseases and conditions, for example cancer.

  通式I的化合物： 其中 R 1a ，R 1b ，R 2 ，R 3a ，R 3b 和X如本文所定义的那样是酪氨酸激酶抑制剂，对于治疗各种疾病和病况，例如癌症，是有用的。
• [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。
• 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.
• 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
• US8877946B2
  申请人：——

  公开号：US8877946B2

  公开（公告）日：2014-11-04