3-((2-benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-5-bromo-3-hydroxyindolin-2-one | 258264-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 3-((2-benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-5-bromo-3-hydroxyindolin-2-one
• 英文别名: 3-[2-(1,3-benzodioxol-5-yl)-2-oxoethyl]-5-bromo-3-hydroxy-1,3-dihydro-2H-indol-2-one；3-[2-(1,3-benzodioxol-5-yl)-2-oxoethyl]-5-bromo-3-hydroxy-1H-indol-2-one
• CAS: 258264-62-9
• 化学式: C₁₇H₁₂BrNO₅
• 分子量: 390.19
• InChiKey: WFYHAKOLBICHEZ-UHFFFAOYSA-N

物化性质

• 沸点：
  646.1±55.0 °C(Predicted)
• 密度：
  1.690±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO: 50mg/mL, nearly colorless

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4-亚甲二氧苯乙酮 、 5-溴靛红 在 二乙胺 作用下， 以 甲醇 为溶剂， 反应 11.0h， 以21%的产率得到3-((2-benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-5-bromo-3-hydroxyindolin-2-one
  参考文献：
  名称：

  Synthesis and characterization of radioiodinated 3-phenethyl-2-indolinone derivatives for SPECT imaging of survivin in tumors

  摘要：

  Survivin, overexpressed in most cancers, is associated with poor prognosis and resistance to radiation therapy and chemotherapy. Herein, we report the synthesis of three 3-phenethyl-2-indolinone derivatives and their application as in vivo imaging agents for survivin. Of these, 3-(2-(benzo[d][1,3] dioxol-5-yl)- 2-oxoethyl)-3-hydroxy-5- iodoindolin-2-one (IPI-1) showed the highest binding affinity (K-d = 68.3 nM) to recombinant human survivin, as determined by quartz crystal microbalance (QCM). In vitro studies demonstrated that the [I-125]IPI-1 binding in survivin-positive MDA-MB-231 cells was significantly higher than that in survivin-negative MCF-10A cells. In addition, uptake of [I-125]IPI-1 by MDA-MB-231 cells decreased in a dose-dependent manner in the presence of the high-affinity survivin ligand S12; this is indicative of specific binding of [I-125]IPI-1 to cellular survivin protein in vitro. Biodistribution studies in MDA-MB-231 tumor-bearing mice demonstrated the moderate uptake of [I-125]IPI-1 in the tumor tissue (1.37% ID/g) at 30 min that decreased to 0.32% ID/g at 180 min. Co-injection of S12 (2.5 mg/kg) slightly reduced tumor uptake and the tumor/muscle ratio of [I-125]IPI-1. Although further structural modifications are necessary to improve pharmacokinetic properties, our results indicate that PI derivatives may be useful as tumor-imaging probes targeting survivin. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.034

文献信息

• METHOD OF TREATING CANCER USING A SURVIVIN INHIBITOR
  申请人：Berezov Alan

  公开号：US20120122910A1

  公开（公告）日：2012-05-17

  Disclosed herein are methods of treating cancer by administering to a patient a small molecule inhibitor of Survivin. Also disclosed herein are methods of inhibiting Survivin dimerization in a patient by administering a compound of formula (I), (II), (III), or (IV). Methods of inducing cell cycle arrest in cancer cells, comprising G2/M stage arrest, in a patient by administering a compound of formula (I), (II), (III), or (IV) are also disclosed. Further disclosed herein are methods of inducing apoptosis in cancer cells in a patient by administering a compound of formula (I), (II), (III), or (IV).
• [EN] METHOD OF TREATING CANCER USING A SURVIVIN INHIBITOR<br/>[FR] PROCÉDÉ DE TRAITEMENT D'UN CANCER À L'AIDE D'UN INHIBITEUR DE SURVIVINE
  申请人：UNIV PENNSYLVANIA

  公开号：WO2010083505A1

  公开（公告）日：2010-07-22

  Disclosed herein are methods of treating cancer by administering to a patient a small molecule inhibitor of Survivin. Also disclosed herein are methods of inhibiting Survivin dimerization in a patient by administering a compound of formula (I), (II), (III), or (IV). Methods of inducing cell cycle arrest in cancer cells, comprising G2/M stage arrest, in a patient by administering a compound of formula (I), (II), (III), or (IV) are also disclosed. Further disclosed herein are methods of inducing apoptosis in cancer cells in a patient by administering a compound of formula (I), (II), (III), or (IV).
• Synthesis and characterization of radioiodinated 3-phenethyl-2-indolinone derivatives for SPECT imaging of survivin in tumors
  作者：Natsumi Ishikawa、Takeshi Fuchigami、Tatsuya Mizoguchi、Sakura Yoshida、Mamoru Haratake、Morio Nakayama

  DOI：10.1016/j.bmc.2018.04.034

  日期：2018.7

  Survivin, overexpressed in most cancers, is associated with poor prognosis and resistance to radiation therapy and chemotherapy. Herein, we report the synthesis of three 3-phenethyl-2-indolinone derivatives and their application as in vivo imaging agents for survivin. Of these, 3-(2-(benzo[d][1,3] dioxol-5-yl)- 2-oxoethyl)-3-hydroxy-5- iodoindolin-2-one (IPI-1) showed the highest binding affinity (K-d = 68.3 nM) to recombinant human survivin, as determined by quartz crystal microbalance (QCM). In vitro studies demonstrated that the [I-125]IPI-1 binding in survivin-positive MDA-MB-231 cells was significantly higher than that in survivin-negative MCF-10A cells. In addition, uptake of [I-125]IPI-1 by MDA-MB-231 cells decreased in a dose-dependent manner in the presence of the high-affinity survivin ligand S12; this is indicative of specific binding of [I-125]IPI-1 to cellular survivin protein in vitro. Biodistribution studies in MDA-MB-231 tumor-bearing mice demonstrated the moderate uptake of [I-125]IPI-1 in the tumor tissue (1.37% ID/g) at 30 min that decreased to 0.32% ID/g at 180 min. Co-injection of S12 (2.5 mg/kg) slightly reduced tumor uptake and the tumor/muscle ratio of [I-125]IPI-1. Although further structural modifications are necessary to improve pharmacokinetic properties, our results indicate that PI derivatives may be useful as tumor-imaging probes targeting survivin. (C) 2018 Elsevier Ltd. All rights reserved.