(RS)-6,7-difluoro-3-(4-fluorophenyl)-3-(4-hydroxyphenyl)indolin-2-one | 1033127-28-4

• 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: (RS)-6,7-difluoro-3-(4-fluorophenyl)-3-(4-hydroxyphenyl)indolin-2-one
• 英文别名: 6,7-difluoro-3-(4-fluorophenyl)-3-(4-hydroxyphenyl)-1,3-dihydro-2H-indol-2-one；6,7-difluoro-3-(4-fluorophenyl)-3-(4-hydroxyphenyl)-1H-indol-2-one
• CAS: 1033127-28-4
• 化学式: C₂₀H₁₂F₃NO₂
• 分子量: 355.316
• InChiKey: CSDYBXLQWQTGIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  碳酸乙烯酯 、 (RS)-6,7-difluoro-3-(4-fluorophenyl)-3-(4-hydroxyphenyl)indolin-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以31%的产率得到6,7-difluoro-3-(4-fluorophenyl)-1-(2-hydroxyethyl)-3-(4-hydroxyphenyl)-1,3-dihydro-2H-indol-2-one
  参考文献：
  名称：

  WO2008/71387

  摘要：

  公开号：
• 作为产物：
  描述：

  (RS)-6,7-difluoro-3-(4-fluorophenyl)-3-hydroxyindolin-2-one 、 苯酚 在 对甲苯磺酸 作用下， 以 1,2-二氯乙烷 为溶剂， 以89%的产率得到(RS)-6,7-difluoro-3-(4-fluorophenyl)-3-(4-hydroxyphenyl)indolin-2-one
  参考文献：
  名称：

  Synthesis and Antitumor Effect in Vitro and in Vivo of Substituted 1,3-Dihydroindole-2-ones

  摘要：

  Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC(50) of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (R.S)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft.

  DOI：

  10.1021/jm100763j

文献信息

• PRODRUGS OF DIPHENYL OX- INDOL- 2 -ONE COMPOUNDS FOR THE TREATMENT OF CANCERS
  申请人：Topo Target A/S

  公开号：EP2102158A1

  公开（公告）日：2009-09-23
• PRODRUGS OF DIPHENYL OX-INDOL-2-ONE COMPOUNDS
  申请人：Christensen Mette Knak

  公开号：US20100029646A1

  公开（公告）日：2010-02-04

  The present application discloses prodrugs of substituted 3,3-diphenyl-1,3-dihydro-indol-2-one compounds having the general formula (I). The 4-position of the phenyl moieties and the N-position of the indole represent useful handles for the introduction of particular prodrug groups, in particular those comprising an amino acid moiety. The prodrug compounds are believed to be useful for the treatment of cancer in a mammal, possibly in combination with one or more other chemotherapeutic agents. The application also discloses the compounds for use in a method of treating a mammal suffering from or being susceptible to cancer
• [EN] PRODRUGS OF DIPHENYL OX- INDOL- 2 -ONE COMPOUNDS FOR THE TREATMENT OF CANCERS<br/>[FR] PRO-MÉDICAMENTS DE COMPOSÉS DIPHÉNYL OX-INDOL-2-ONE POUR LE TRAITEMENT DE CANCERS
  申请人：TOPOTARGET AS

  公开号：WO2008071387A1

  公开（公告）日：2008-06-19

  [EN] The present application discloses prodrugs of substituted 3,3-diphenyl-l,3-dihydro-indol-2-one compounds having the general formula (I). The 4-position of the phenyl moieties and the N -position of the indole represent useful handles for the introduction of particular prodrug groups, in particular those comprising an amino acid moiety. The prodrug compounds are believed to be useful for the treatment of cancer in a mammal, possibly in combination with one or more other chemotherapeutic agents. The application also discloses the compounds for use in a method of treating a mammal suffering from or being susceptible to cancer.
  [FR] La présente invention concerne des pro-médicaments de composés 3,3-diphényl-1,3-dihydro-indol-2-one substitués. La position 4 des groupements phényle et la position N de l'indole représentent des points d'attache utiles pour l'introduction de groupes pro-médicaments particuliers, en particulier ceux comprenant un groupement acide aminé. Les composés pro-médicaments sont censés être utiles dans le traitement du cancer chez un mammifère, éventuellement en association avec un ou plusieurs autres agents chimiothérapiques. L'invention concerne également des composés destinés à être utilisés dans un procédé de traitement d'un mammifère souffrant du cancer ou susceptible d'avoir le cancer.
• Synthesis and Antitumor Effect in Vitro and in Vivo of Substituted 1,3-Dihydroindole-2-ones
  作者：Mette K. Christensen、Kamille D. Erichsen、Christina Trojel-Hansen、Jette Tjørnelund、Søren J. Nielsen、Karla Frydenvang、Tommy N. Johansen、Birgitte Nielsen、Maxwell Sehested、Peter B. Jensen、Martins Ikaunieks、Andrei Zaichenko、Einars Loza、Ivars Kalvinsh、Fredrik Björkling

  DOI：10.1021/jm100763j

  日期：2010.10.14

  Optimization of the anticancer activity for a class of compounds built on a 1,3-dihydroindole-2-one scaffold was performed. In comparison with recently published derivatives of oxyphenisatin the new analogues exhibited an equally potent antiproliferative activity in vitro and improved tolerability and activity in vivo. The best compounds from this series showed low nanomolar antiproliferative activity toward a series of cancer cell lines (compound (S)-38: IC(50) of 0.48 and 2 nM in MCF-7 (breast) and PC3 (prostate), respectively) and potent antitumor effects in well tolerated doses in xenograft models. The racemic compound (R.S)-38 showed complete tumor regression at a dose of 20 mg/kg administered iv on days 1 and 7 in a PC3 rat xenograft.
• WO2008/71387
  申请人：——

  公开号：——

  公开（公告）日：——