3-((6-chloro-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl)-1H-pyrazole-5-carboxylic acid | 844870-53-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-((6-chloro-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl)-1H-pyrazole-5-carboxylic acid
• 英文别名: 5-[(6-chloro-1-oxo-4-phenyl-3-propanoylisoquinolin-2-yl)methyl]-1H-pyrazole-3-carboxylic acid
• CAS: 844870-53-7
• 化学式: C₂₃H₁₈ClN₃O₄
• 分子量: 435.867
• InChiKey: FNHFVOLIIWTQQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-((6-chloro-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl)-1H-pyrazole-5-carboxylic acid 在 草酰氯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 C₂₃H₁₇Cl₂N₃O₃
  参考文献：
  名称：

  Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)

  摘要：

  A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modi. cation at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.027
• 作为产物：
  描述：

  methyl 3-((6-chloro-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl)-1H-pyrazole-5-carboxylate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 以49%的产率得到3-((6-chloro-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl)-1H-pyrazole-5-carboxylic acid
  参考文献：
  名称：

  Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)

  摘要：

  A novel series of 4-phenylisoquinolones were synthesized and evaluated as c-Jun N-terminal kinase (JNK) inhibitors. Initial modi. cation at the 2- and 3-positions of the isoquinolone ring of hit compound 4, identified from high-throughput screening, led to the lead compound 6b. The optimization was carried out using a JNK1-binding model of 6b and several compounds exhibited potent JNK inhibition. Among them, 11g significantly inhibited cardiac hypertrophy in rat pressure-overload models without affecting blood pressure and the concept of JNK inhibitors as novel therapeutic agents for heart failure was confirmed. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.027