8-溴-6-氟-4-羟基-3-喹啉羧酸 | 1019016-15-9

• 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-6-氟-4-羟基-3-喹啉羧酸
• 中文别名: 8-溴-6-氟-4-羟基喹啉-3-羧酸
• 英文名称: 8-Bromo-6-fluoro-4-hydroxyquinoline-3-carboxylic acid
• 英文别名: 8-bromo-6-fluoro-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 1019016-15-9
• 化学式: C₁₀H₅BrFNO₃
• 分子量: 286.057
• InChiKey: LVUZMPYPFCZPIL-UHFFFAOYSA-N

物化性质

• 沸点：
  434.7±45.0 °C(Predicted)
• 密度：
  1.931±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 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：
  5

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  8-溴-6-氟-4-羟基-3-喹啉羧酸 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-6-fluoro-8-(6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-yl)quinoline-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-氟苯胺 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-溴-6-氟-4-羟基-3-喹啉羧酸
  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

文献信息

• 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.