8-bromo-6-nitro-4-oxo-1H-quinoline-3-carboxylic acid

• 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-bromo-6-nitro-4-oxo-1H-quinoline-3-carboxylic acid
• 化学式: C₁₀H₅BrN₂O₅
• 分子量: 313.064
• InChiKey: KWJKZZOTCVMIHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 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：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-bromo-6-nitro-4-oxo-1H-quinoline-3-carboxylic acid 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 ammonium hydroxide 、 氯化亚砜 、 氨 、 碳酸氢钠 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 4-amino-8-(5-methyl-1H-indazol-6-yl)-6-nitroquinoline-3-carboxamide
  参考文献：
  名称：

  Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.9b00329
• 作为产物：
  描述：

  2-溴-4-硝基苯胺 在 Dowtherm A 、 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 8-bromo-6-nitro-4-oxo-1H-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.9b00329