8-hydroxy-N-methylquinoline-5-sulfonamide | 145327-14-6

• 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: 8-hydroxy-N-methylquinoline-5-sulfonamide
• CAS: 145327-14-6
• 化学式: C₁₀H₁₀N₂O₃S
• 分子量: 238.267
• InChiKey: LUEVQSISFJYPEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  8-羟基喹啉-5-磺酸水合物 在 氯磺酸 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 8-hydroxy-N-methylquinoline-5-sulfonamide
  参考文献：
  名称：

  Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)

  摘要：

  The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil, and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG analogues and related compounds using differential scanning fluorometry- and liquid chromatography-based assays. The results revealed sets of both cyclic and acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include small molecules that have been used in clinical studies for the inhibition of other 2OG oxygenases. Crystallo-graphic analyses reveal inhibition by 2OG cosubstrate or primary substrate competitors as well as compounds that bind across both cosubstrate and primary substrate binding sites. The results will aid the development of more potent and selective FTO inhibitors.

  DOI：

  10.1021/jm400193d

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.
• SOX-BASED KINASE SENSOR
  申请人：Massachusetts Institute of Technology

  公开号：EP2059510B1

  公开（公告）日：2016-11-09
• Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)
  作者：WeiShen Aik、Marina Demetriades、Muhammad K. K. Hamdan、Eleanor. A. L. Bagg、Kar Kheng Yeoh、Clarisse Lejeune、Zhihong Zhang、Michael A. McDonough、Christopher J. Schofield

  DOI：10.1021/jm400193d

  日期：2013.5.9

  The fat mass and obesity associated protein (FTO) is a potential target for anti-obesity medicines. FTO is a 2-oxoglutarate (2OG)-dependent N-methyl nucleic acid demethylase that acts on substrates including 3-methylthymidine, 3-methyluracil, and 6-methyladenine. To identify FTO inhibitors, we screened a set of 2OG analogues and related compounds using differential scanning fluorometry- and liquid chromatography-based assays. The results revealed sets of both cyclic and acyclic 2OG analogues that are FTO inhibitors. Identified inhibitors include small molecules that have been used in clinical studies for the inhibition of other 2OG oxygenases. Crystallo-graphic analyses reveal inhibition by 2OG cosubstrate or primary substrate competitors as well as compounds that bind across both cosubstrate and primary substrate binding sites. The results will aid the development of more potent and selective FTO inhibitors.