8-溴-4-羟基喹啉-3-羧酸 | 35973-17-2

• 物质功能分类: 医药中间体 - 喹啉类化合物
• 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
• 中文名称: 8-溴-4-羟基喹啉-3-羧酸
• 中文别名: 8-溴-4-羟基-3-喹啉羧酸；4-羟基-8-溴喹啉-3-羧酸
• 英文名称: 8-bromo-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 8-bromo-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 35973-17-2
• 化学式: C₁₀H₆BrNO₃
• mdl: MFCD02179785
• 分子量: 268.067
• InChiKey: NKUGXZLINWIUOR-UHFFFAOYSA-N

物化性质

• 沸点：
  436.9±45.0 °C(Predicted)
• 密度：
  1.862±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 安全说明：
  S26
• 危险类别码：
  R36
• WGK Germany：
  3
• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  8-溴-4-羟基喹啉-3-羧酸 在 potassium carbonate 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 N-(adamantan-1-yl)-8-bromo-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 4. Identification of New Potent and Selective Ligands for the Cannabinoid Type 2 Receptor with Diverse Substitution Patterns and Antihyperalgesic Effects in Mice

  摘要：

  Experimental evidence suggests that selective CB2 receptor modulators may provide access to antihyperalgesic agents devoid of psychotropic effects. Talcing advantage of previous findings on structure-activity/selectivity relationships for a class of 4-quinolone-3-carboxamides, further structural modifications of the heterocyclic scaffold were explored, leading to the discovery of the 8-methoxy derivative 4a endowed with the highest affinity and selectivity ever reported for a CB2 ligand. The compound, evaluated in vivo in the formalin test, behaved as an inverse agonist by reducing at a dose of 6 mg/kg the second phase of the formalin-induced nocifensive response in mice.

  DOI：

  10.1021/jm200476p
• 作为产物：
  描述：

  2-[(2-bromo-phenylamino)methylene]malonic acid diethyl ester 在 sodium hydroxide 作用下， 以 二苯醚 、 水 为溶剂， 反应 5.0h， 生成 8-溴-4-羟基喹啉-3-羧酸
  参考文献：
  名称：

  Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 4. Identification of New Potent and Selective Ligands for the Cannabinoid Type 2 Receptor with Diverse Substitution Patterns and Antihyperalgesic Effects in Mice

  摘要：

  Experimental evidence suggests that selective CB2 receptor modulators may provide access to antihyperalgesic agents devoid of psychotropic effects. Talcing advantage of previous findings on structure-activity/selectivity relationships for a class of 4-quinolone-3-carboxamides, further structural modifications of the heterocyclic scaffold were explored, leading to the discovery of the 8-methoxy derivative 4a endowed with the highest affinity and selectivity ever reported for a CB2 ligand. The compound, evaluated in vivo in the formalin test, behaved as an inverse agonist by reducing at a dose of 6 mg/kg the second phase of the formalin-induced nocifensive response in mice.

  DOI：

  10.1021/jm200476p

文献信息

• 治疗类风湿性关节炎的小分子可逆性BTK抑 制剂
  申请人：清华大学

  公开号：CN110003171B

  公开（公告）日：2020-11-06

  本发明涉及治疗类风湿性关节炎的小分子可逆性BTK抑制剂，具体地，本发明提出了化合物，其为式I所示化合物或其立体异构体、几何异构体、互变异构体、氮氧化物、水合物、溶剂化物、代谢产物、药学上可接受的盐或前药。发明人发现，式I所示多取代喹啉类化合物或其衍生物可作为BTK抑制剂，用于治疗类风湿性关节炎时，具有较好的活性。
• Evaluation of 3-Carboxy-4(1<i>H</i>)-quinolones as Inhibitors of Human Protein Kinase CK2
  作者：Andriy G. Golub、Olexander Ya. Yakovenko、Volodymyr G. Bdzhola、Vladislav M. Sapelkin、Piotr Zien、Sergiy M. Yarmoluk

  DOI：10.1021/jm050048t

  日期：2006.11.1

  Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitorss3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC50 = 0.3 mu M) and 4-oxo-1,4-dihydrobenzo[h] quinoline-3-carboxylic acid (9) (IC50 = 1 AM), are ATP competitive (K-i values are 0.06 and 0.28 mu M, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.
• Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis
  作者：Xia Yao、Xiuyun Sun、Shuyu Jin、Ling Yang、Hongjiang Xu、Yu Rao

  DOI：10.1021/acs.jmedchem.9b00329

  日期：2019.7.25

  A structure-hopping strategy was applied to discover a series of novel 4-aminoquinoline-3-carboxamide derivatives as potent, reversible BTK inhibitors. Compared to the previously described cinnoline scaffold compounds, the 4-aminoquinoline analogues showed significantly improved drug-like properties, especially in their aqueous solubility. The most potent compound, 25, displayed a stronger inhibitory effect on both BTKWT (IC50 = 5.3 nM) and BTKC481S (IC50 = 39 nM). In a rodent collagen-induced arthritis model, compound 25 efficiently reduced paw swelling without a loss in body weight. On the basis of potency, drug-like properties, stability, and noncovalent mode of inhibition, our representative inhibitors could have a promising profile to be treatments for a wide range of autoimmune diseases.