2-methyl-8-hydroxy-5-quinoline carboxylic acid | 103853-87-8

• 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: 2-methyl-8-hydroxy-5-quinoline carboxylic acid
• 英文别名: 8-hydroxy-2-methylquinoline-5-carboxylic acid；8-hydroxy-2-methyl-quinoline-5-carboxylic acid；2-Methyl-8-hydroxy-chinolin-carbonsaeure-(5)
• CAS: 103853-87-8
• 化学式: C₁₁H₉NO₃
• 分子量: 203.197
• InChiKey: OSIQYUORWIAWMM-UHFFFAOYSA-N

物化性质

• 熔点：
  240 °C(Solv: water (7732-18-5))
• 沸点：
  446.0±45.0 °C(Predicted)
• 密度：
  1.410±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-8-hydroxy-5-quinoline carboxylic acid 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex sodium hydroxide 、 碘 、 potassium carbonate 、 臭氧 、 potassium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -78.0~100.0 ℃ 、101.33 kPa 条件下， 反应 61.5h， 生成 8-Hydroxy-2-methylquinoline-5,7-dicarboxylic acid
  参考文献：
  名称：

  苯乙烯基喹啉类的HIV-1复制抑制剂：在喹啉C-5位置引入一个额外的羧基

  摘要：

  已经合成了苯乙烯基喹啉类的HIV-1复制抑制剂的新型变体，其在喹啉的C-5位带有一个额外的酸基或一个丙酸部分。关键步骤包括Heck反应和5-卤代喹哪啶衍生物的钯催化的羰基化反应。这些化合物表现出增强的抗整合酶效力和显着的抗病毒活性。

  DOI：

  10.1016/j.tetlet.2005.02.033
• 作为产物：
  描述：

  巴豆醛 、 3-氨基-4-羟基苯甲酸 在 盐酸 作用下， 以 水 为溶剂， 反应 2.5h， 以47.8%的产率得到2-methyl-8-hydroxy-5-quinoline carboxylic acid
  参考文献：
  名称：

  基于5-羧基-8-HQ的新型组蛋白脱甲基酶JMJD2A抑制剂：在喹啉的C-2位引入一个额外的羧基。

  摘要：

  通过分析5-羧基-8-羟基喹啉（5-羧基-8-HQ）与JMJD2A的结合方式，设计了一系列JMJD2A抑制剂。确定了合成化合物对JMJD2A的抑制活性，然后进行对接模拟以了解结构-活性关系。具有有效JMJD2A抑制活性的化合物对JMJD2A的选择性优于PHD2。选择了几种有效的化合物以评估其对肿瘤细胞系的抗增殖活性。其中，化合物6p表现出最好的抗增殖活性。基于这些体外生物学数据，选择了7种化合物以确定其理化性质。与5-羧基-8-HQ相比，化合物6p显示出良好的水溶性和更好的渗透性。

  DOI：

  10.1016/j.ejmech.2015.09.013

文献信息

• Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases
  作者：C. C. Thinnes、A. Tumber、C. Yapp、G. Scozzafava、T. Yeh、M. C. Chan、T. A. Tran、K. Hsu、H. Tarhonskaya、L. J. Walport、S. E. Wilkins、E. D. Martinez、S. Müller、C. W. Pugh、P. J. Ratcliffe、P. E. Brennan、A. Kawamura、C. J. Schofield

  DOI：10.1039/c5cc06095h

  日期：——

  A Betti reaction was used for efficient generation of 2OG oxygenase inhibitors, including for KDM4 demethylases.

  使用Betti反应高效生成2OG氧化酶抑制剂，包括KDM4去甲基酶。
• Process for making a substituted oxazole
  申请人：Schering Corporation

  公开号：EP2385051A1

  公开（公告）日：2011-11-09

  A process for making a compound of formula IXab: by reacting an anhydride with a compound containing the group -C(SCH3)NCH2CO2Et to produce an oxazole ester, hydrolysing the ester and reacting with an appropriately protected amino salt to give the desired compound.

  一种制造式 IXab 化合物的工艺： 将酸酐与含有基团-C(SCH3)NCH2CO2Et 的化合物反应生成噁唑酯，水解该酯并与适当保护的氨基盐反应得到所需的化合物。
• Synthesis of Red-Shifted 8-Hydroxyquinoline Derivatives Using Click Chemistry and Their Incorporation into Phosphorylation Chemosensors
  作者：Juan A. González-Vera、Elvedin Luković、Barbara Imperiali

  DOI：10.1021/jo901369k

  日期：2009.10.2

  Protein phosphorylation is a ubiquitous post-translational modification, and protein kinases, the enzymes that catalyze the phosphoryl transfer, are involved in nearly every aspect of normal, as well as aberrant, cell function. Here we describe the synthesis of novel. red-shifted 8-hydroxyquinoline-based fluorophores and their incorporation into peptidyl kinase activity reporters. Replacement of the sulfonamide group of the sulfonamido-oxine (1, Sox) chromophore, which has been previously used In kinase sensing, by a 1,4-substituted triazole moiety prepared via click chemistry resulted in a significant bathochromic shift in the fluorescence excitation (15 nm) and emission (40 rim) maxima for the Mg2+ chelate. Furthermore, when a click derivative was incorporated into a chemosensor for MK2, the kinase accepted the new substrate as efficiently as the previously reported Sox-based sensor. Taken together, these results extend the utility range of kinase sensors that are based on chelation-enhanced fluorescence (CHEF).
• Identification and structure–activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase
  作者：Faten Sliman、Mélina Blairvacq、Emilie Durieu、Laurent Meijer、Jordi Rodrigo、Didier Desmaële

  DOI：10.1016/j.bmcl.2010.03.061

  日期：2010.5

  Pim-1 kinase is a cytoplasmic serine/threonine kinase that controls programmed cell death by phosphorylating substrates that regulate both apotosis and cellular metabolism. A series of 2-styrylquinolines and quinoline-2-carboxamides has been identified as potent inhibitors of the Pim-1 kinase. The 8-hydroxyquinoline 7-carboxylic acid moiety appeared to be a crucial pharmacophore for activity. Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency. (C) 2010 Elsevier Ltd. All rights reserved.
• Novel 5-carboxy-8-HQ based histone demethylase JMJD2A inhibitors: Introduction of an additional carboxyl group at the C-2 position of quinoline
  作者：Taotao Feng、Dongdong Li、Hai Wang、Jian Zhuang、Fang Liu、Qichao Bao、Yonghua Lei、Weilin Chen、Xiaojin Zhang、Xiaoli Xu、Haopeng Sun、Qidong You、Xiaoke Guo

  DOI：10.1016/j.ejmech.2015.09.013

  日期：2015.11

  A series of JMJD2A inhibitors had been designed by analyzing the binding mode of 5-carboxy-8-hydroxyquinoline (5-carboxy-8-HQ) with JMJD2A. The inhibitory activity of the synthesized compounds against JMJD2A was determined, followed by docking simulations to understand the structure-activity relationships. Compounds with potent JMJD2A inhibitory activity demonstrated outstanding selectivity for JMJD2A

  通过分析5-羧基-8-羟基喹啉（5-羧基-8-HQ）与JMJD2A的结合方式，设计了一系列JMJD2A抑制剂。确定了合成化合物对JMJD2A的抑制活性，然后进行对接模拟以了解结构-活性关系。具有有效JMJD2A抑制活性的化合物对JMJD2A的选择性优于PHD2。选择了几种有效的化合物以评估其对肿瘤细胞系的抗增殖活性。其中，化合物6p表现出最好的抗增殖活性。基于这些体外生物学数据，选择了7种化合物以确定其理化性质。与5-羧基-8-HQ相比，化合物6p显示出良好的水溶性和更好的渗透性。