6-chloro-2-{[5-(methylsulfonyl)-1H-pyrazol-3-yl]methyl}-4-phenyl-3-propionylisoquinolin-1(2H)-one | 844870-71-9

• 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: 6-chloro-2-{[5-(methylsulfonyl)-1H-pyrazol-3-yl]methyl}-4-phenyl-3-propionylisoquinolin-1(2H)-one
• 英文别名: 6-chloro-2-[(3-methylsulfonyl-1H-pyrazol-5-yl)methyl]-4-phenyl-3-propanoylisoquinolin-1-one
• CAS: 844870-71-9
• 化学式: C₂₃H₂₀ClN₃O₄S
• 分子量: 469.948
• InChiKey: FIXRTNPJXKGYBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-chloro-2-{[5-(methylsulfonyl)-1H-pyrazol-3-yl]methyl}-4-phenyl-3-propionylisoquinolin-1(2H)-one 、 2,2-二氟乙醇 在 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以61%的产率得到6-chloro-2-((1-(2,2-difluoroethyl)-5-(methanesulfonyl)-1H-pyrazol-3-yl)methyl)-4-phenyl-3-propanoylisoquinoline-1(2H)-one
  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：

  6-chloro-2-{[5-(methylthio)-1H-pyrazol-3-yl]methyl}-4-phenyl-3-propionylisoquinolin-1(2H)-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以69%的产率得到6-chloro-2-{[5-(methylsulfonyl)-1H-pyrazol-3-yl]methyl}-4-phenyl-3-propionylisoquinolin-1(2H)-one
  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