3-((6-chloro-1-oxo-4-phenyl-3-propanoyl-2(1H)-isoquinolinyl)methyl)-N-cyclopropyl-1-methyl-1H-pyrazole-5-carboxamide | 844870-61-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-((6-chloro-1-oxo-4-phenyl-3-propanoyl-2(1H)-isoquinolinyl)methyl)-N-cyclopropyl-1-methyl-1H-pyrazole-5-carboxamide
• 英文别名: 3-((6-chloro-1-oxo-4-phenyl-3-propionyl-2(1H)-isoquinolinyl)methyl)-N-cyclopropyl-1-methyl-1H-pyrazole-5-carboxamide；1H-Pyrazole-5-carboxamide, 3-[[6-chloro-1-oxo-3-(1-oxopropyl)-4-phenyl-2(1H)-isoquinolinyl]methyl]-N-cyclopropyl-1-methyl-；5-[(6-chloro-1-oxo-4-phenyl-3-propanoylisoquinolin-2-yl)methyl]-N-cyclopropyl-2-methylpyrazole-3-carboxamide
• CAS: 844870-61-7
• 化学式: C₂₇H₂₅ClN₄O₃
• 分子量: 488.973
• InChiKey: GKVXJRRPJPKFDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  84.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  C₂₄H₁₉Cl₂N₃O₃ 、 环丙胺 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 3-((6-chloro-1-oxo-4-phenyl-3-propanoyl-2(1H)-isoquinolinyl)methyl)-N-cyclopropyl-1-methyl-1H-pyrazole-5-carboxamide
  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