5-(N,N-dimethylaminosulfonyl)-7-bromo-8-hydroxyquinaldine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-(N,N-dimethylaminosulfonyl)-7-bromo-8-hydroxyquinaldine
• 英文别名: 7-bromo-8-hydroxy-N,N,2-trimethylquinoline-5-sulfonamide
• 化学式: C₁₂H₁₃BrN₂O₃S
• 分子量: 345.217
• InChiKey: STOYBHUGNFBHFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(N,N-dimethylaminosulfonyl)-7-bromo-8-hydroxyquinaldine 、 碘乙烷 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以98%的产率得到5-(N,N-dimethylaminosulfonyl)-7-bromo-8-ethoxyquinaldine
  参考文献：
  名称：

  Design and synthesis of 8-hydroxyquinoline-based radioprotective agents

  摘要：

  In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. We report herein on the radioprotective activity of 8-hydroxyquinoline (8HQ) derivatives that were initially designed so as to interact with the Zn2+ in p53. Indeed, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against gamma-ray radiation (10 Gy), accompanied by a low cytotoxicity. However, mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and -independent apoptotic pathways. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.017
• 作为产物：
  描述：

  8-hydroxy-2-methyl-quinoline-5-sulfonyl chloride 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 6.0h， 生成 5-(N,N-dimethylaminosulfonyl)-7-bromo-8-hydroxyquinaldine
  参考文献：
  名称：

  Design and synthesis of 8-hydroxyquinoline-based radioprotective agents

  摘要：

  In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. We report herein on the radioprotective activity of 8-hydroxyquinoline (8HQ) derivatives that were initially designed so as to interact with the Zn2+ in p53. Indeed, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against gamma-ray radiation (10 Gy), accompanied by a low cytotoxicity. However, mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and -independent apoptotic pathways. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.06.017

文献信息

• Design and synthesis of 8-hydroxyquinoline-based radioprotective agents
  作者：Shinya Ariyasu、Akiko Sawa、Akinori Morita、Kengo Hanaya、Misato Hoshi、Ippei Takahashi、Bing Wang、Shin Aoki

  DOI：10.1016/j.bmc.2014.06.017

  日期：2014.8

  In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. We report herein on the radioprotective activity of 8-hydroxyquinoline (8HQ) derivatives that were initially designed so as to interact with the Zn2+ in p53. Indeed, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against gamma-ray radiation (10 Gy), accompanied by a low cytotoxicity. However, mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and -independent apoptotic pathways. (C) 2014 Elsevier Ltd. All rights reserved.