E-6-chloro-3-(3-chloro-benzylidene)-5-fluoro-1,3-dihydro-indol-2-one | 1200442-07-4

• 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: E-6-chloro-3-(3-chloro-benzylidene)-5-fluoro-1,3-dihydro-indol-2-one
• 英文别名: (3E)-6-chloro-3-[(3-chlorophenyl)methylidene]-5-fluoro-1H-indol-2-one
• CAS: 1200442-07-4
• 化学式: C₁₅H₈Cl₂FNO
• 分子量: 308.139
• InChiKey: NEZZYIBJULLJPH-VZUCSPMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  E-6-chloro-3-(3-chloro-benzylidene)-5-fluoro-1,3-dihydro-indol-2-one 、 3,3-二甲基丁醛 、 (5R,6S)-5,6-二苯基吗啉-2-酮 以 甲苯 为溶剂， 生成 (3S,3'S,4'R,6'R,8'R,8'aR)-6-chloro-8'-(3-chlorophenyl)-6'-(2,2-dimethylpropyl)-5-fluoro-3',4'-diphenylspiro[1H-indole-3,7'-4,6,8,8a-tetrahydro-3H-pyrrolo[2,1-c][1,4]oxazine]-1',2-dione
  参考文献：
  名称：

  Potent and Orally Active Small-Molecule Inhibitors of the MDM2−p53 Interaction

  摘要：

  We report herein the design of potent and orally active small-molecule inhibitors of the MDM2-p53 interaction, Compound 5 binds to MDM2 with a K-i of 0.6 nM, activates p53 at concentrations its low as 40 nM, and potently and selectively inhibits cell growth in tumor cells with wild-type p53 over tumor cells with mutated/deleted p53. Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model.

  DOI：

  10.1021/jm901400z
• 作为产物：
  描述：

  6-氯-5-氟-1,3-二氢-2H-吲哚-2-酮 、 3-氯苯甲醛 在 哌啶 作用下， 以 甲醇 为溶剂， 生成 E-6-chloro-3-(3-chloro-benzylidene)-5-fluoro-1,3-dihydro-indol-2-one
  参考文献：
  名称：

  Potent and Orally Active Small-Molecule Inhibitors of the MDM2−p53 Interaction

  摘要：

  We report herein the design of potent and orally active small-molecule inhibitors of the MDM2-p53 interaction, Compound 5 binds to MDM2 with a K-i of 0.6 nM, activates p53 at concentrations its low as 40 nM, and potently and selectively inhibits cell growth in tumor cells with wild-type p53 over tumor cells with mutated/deleted p53. Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model.

  DOI：

  10.1021/jm901400z

文献信息

• Spiroindolinone derivatives
  申请人：Chen Li

  公开号：US20070213341A1

  公开（公告）日：2007-09-13

  The present invention relates to spiroindolinone derivatives of the formula and enantiomers and pharmaceutically acceptable salts and esters thereof which have utility as antiproliferative agents, especially, as anticancer agents.

  本发明涉及公式的螺环吲哚酮衍生物及其对映体和药学上可接受的盐和酯，具有作为抗增殖剂的效用，特别是作为抗癌剂。
• SPIRO-OXINDOLE MDM2 ANTAGONISTS
  申请人：Wang Shaomeng

  公开号：US20120122947A1

  公开（公告）日：2012-05-17

  Provided herein are compounds, compositions, and methods in the field of medicinal chemistry. The compounds and compositions provided herein relate to spiro-oxindoles which function as antagonists of the interaction between p53 and MDM2, and their use as therapeutics for the treatment of cancer and other diseases.

  本文提供了关于药物化学领域的化合物、组合物和方法。这里提供的化合物和组合物涉及螺环氧吲哚，其作为p53和MDM2相互作用的拮抗剂，并且它们作为治疗癌症和其他疾病的药物的用途。
• SPIROINDOLINONE DERIVATIVES
  申请人：Ding Qingjie

  公开号：US20080188506A1

  公开（公告）日：2008-08-07

  There are provided spiroindolinones of the formula and enantiomers and pharmaceutically acceptable salts and esters thereof which have utility as antiproliferative agents, especially, as anticancer agents.

  提供了公式为的螺吡喃酮及其对映体和药学上可接受的盐和酯，其具有作为抗增殖剂的功效，特别是作为抗癌剂的功效。
• 3, 3' -SPIROINDOLINONE DERIVATIVES AS ANTICANCER AGENTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2398801A1

  公开（公告）日：2011-12-28
• US8680132B2
  申请人：——

  公开号：US8680132B2

  公开（公告）日：2014-03-25