6-Chloro-2-[[1-(3-hydroxy-3-methylbutyl)-5-methylsulfonylpyrazol-3-yl]methyl]-4-phenyl-3-propanoylisoquinolin-1-one | 844871-55-2

• 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-[[1-(3-hydroxy-3-methylbutyl)-5-methylsulfonylpyrazol-3-yl]methyl]-4-phenyl-3-propanoylisoquinolin-1-one
• CAS: 844871-55-2
• 化学式: C₂₈H₃₀ClN₃O₅S
• 分子量: 556.082
• InChiKey: NSOWFIRCXBENCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  异戊二醇 、 6-chloro-2-{[5-(methylsulfonyl)-1H-pyrazol-3-yl]methyl}-4-phenyl-3-propionylisoquinolin-1(2H)-one 在 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以56%的产率得到6-Chloro-2-[[1-(3-hydroxy-3-methylbutyl)-5-methylsulfonylpyrazol-3-yl]methyl]-4-phenyl-3-propanoylisoquinolin-1-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

文献信息

• Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (1)
  作者：Yasutomi Asano、Shuji Kitamura、Taiichi Ohra、Kazuyoshi Aso、Hideki Igata、Tomoko Tamura、Tomohiro Kawamoto、Toshimasa Tanaka、Satoshi Sogabe、Shin-ichi Matsumoto、Masashi Yamaguchi、Hiroyuki Kimura、Fumio Itoh

  DOI：10.1016/j.bmc.2008.02.027

  日期：2008.4

  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.