tert-butyl [3-[(6-chloro-1-oxo-4-phenyl-3-propionylisoquinolin-2(1H)-yl)methyl]-5-(methylthio)-1H-pyrazol-1-yl]acetate | 844870-85-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl [3-[(6-chloro-1-oxo-4-phenyl-3-propionylisoquinolin-2(1H)-yl)methyl]-5-(methylthio)-1H-pyrazol-1-yl]acetate
• 英文别名: Tert-butyl 2-[3-[(6-chloro-1-oxo-4-phenyl-3-propanoylisoquinolin-2-yl)methyl]-5-methylsulfanylpyrazol-1-yl]acetate
• CAS: 844870-85-5
• 化学式: C₂₉H₃₀ClN₃O₄S
• 分子量: 552.094
• InChiKey: AOBNGSZIRNNZNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl [3-[(6-chloro-1-oxo-4-phenyl-3-propionylisoquinolin-2(1H)-yl)methyl]-5-(methylthio)-1H-pyrazol-1-yl]acetate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 Tert-butyl 2-[3-[(6-chloro-1-oxo-4-phenyl-3-propanoylisoquinolin-2-yl)methyl]-5-methylsulfonylpyrazol-1-yl]acetate
  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 、 溴乙酸叔丁酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以52%的产率得到tert-butyl [3-[(6-chloro-1-oxo-4-phenyl-3-propionylisoquinolin-2(1H)-yl)methyl]-5-(methylthio)-1H-pyrazol-1-yl]acetate
  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