5-Bromo-1-(4-chlorobenzoyl)indole-2,3-dione | 1445993-08-7

• 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: 5-Bromo-1-(4-chlorobenzoyl)indole-2,3-dione
• 英文别名: 5-bromo-1-(4-chlorobenzoyl)indole-2,3-dione
• CAS: 1445993-08-7
• 化学式: C₁₅H₇BrClNO₃
• 分子量: 364.582
• InChiKey: LRSMBEQEFDVYCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 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：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-半胱氨酸乙酯 、 5-Bromo-1-(4-chlorobenzoyl)indole-2,3-dione 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以36%的产率得到(2′S,4′R)-ethyl 5-bromo-1-(4-chlorobenzoyl)-2-oxospiro-[indoline-3,2′-thiazolidine]-4′-carboxylate
  参考文献：
  名称：

  Synthesis, in Vitro, and in Cell Studies of a New Series of [Indoline-3,2′-thiazolidine]-Based p53 Modulators

  摘要：

  Analogues of the previously described spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione p53 modulators were prepared to explore new structural requirements at the thiazolidine domain for the antiproliferative activity and p53 modulation. In cell, antiproliferative activity was evaluated against two human tumor cell lines Derivative 5-bromo-3'-(cyclohexane carbonyl)-1-methyl-2-oxospiro[indoline-3,2'-thiazolidine] (4n) emerged as the most potent compound of this series inhibiting in vitro 30% of p53-MDM2 interaction at 5 mu M and the cell growth of different human tumor cells at nanomolar concentrations. Docking studies confirmed the interactions of 4n with the well-known Trp23 and Phe19 clefts, explaining the reasons for its binding affinity, for MDM2. 4n at 50 nM is capable of inducing the accumulation of p53 protein, inducing significant apoptotic,cell death without affecting the cell cycle progression. Comparative studies using nutlin in the same cellular system confirm the potential of 4n as a tool for increasing understanding of the process involved in the nontranscriptional proapoptotic activities of p53.

  DOI：

  10.1021/jm400311n
• 作为产物：
  描述：

  5-溴靛红 、 4-氯苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 5-Bromo-1-(4-chlorobenzoyl)indole-2,3-dione
  参考文献：
  名称：

  Synthesis, in Vitro, and in Cell Studies of a New Series of [Indoline-3,2′-thiazolidine]-Based p53 Modulators

  摘要：

  Analogues of the previously described spiro[imidazo[1,5-c]thiazole-3,3'-indoline]-2',5,7(6H,7aH)-trione p53 modulators were prepared to explore new structural requirements at the thiazolidine domain for the antiproliferative activity and p53 modulation. In cell, antiproliferative activity was evaluated against two human tumor cell lines Derivative 5-bromo-3'-(cyclohexane carbonyl)-1-methyl-2-oxospiro[indoline-3,2'-thiazolidine] (4n) emerged as the most potent compound of this series inhibiting in vitro 30% of p53-MDM2 interaction at 5 mu M and the cell growth of different human tumor cells at nanomolar concentrations. Docking studies confirmed the interactions of 4n with the well-known Trp23 and Phe19 clefts, explaining the reasons for its binding affinity, for MDM2. 4n at 50 nM is capable of inducing the accumulation of p53 protein, inducing significant apoptotic,cell death without affecting the cell cycle progression. Comparative studies using nutlin in the same cellular system confirm the potential of 4n as a tool for increasing understanding of the process involved in the nontranscriptional proapoptotic activities of p53.

  DOI：

  10.1021/jm400311n