1-[8-Amino-4-methyl-4-(2-methylpropyl)-1,3-dioxoisoquinolin-7-yl]-3-(2,6-dichlorophenyl)thiourea | 1027595-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-[8-Amino-4-methyl-4-(2-methylpropyl)-1,3-dioxoisoquinolin-7-yl]-3-(2,6-dichlorophenyl)thiourea
• CAS: 1027595-95-4
• 化学式: C₂₁H₂₂Cl₂N₄O₂S
• 分子量: 465.403
• InChiKey: MAIIDASMQIQUOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[8-Amino-4-methyl-4-(2-methylpropyl)-1,3-dioxoisoquinolin-7-yl]-3-(2,6-dichlorophenyl)thiourea 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-(2,6-Dichloro-phenylamino)-6-isobutyl-6-methyl-1,6-dihydro-imidazo[4,5-h]isoquinoline-7,9-dione
  参考文献：
  名称：

  Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase

  摘要：

  An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, lick. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.

  DOI：

  10.1021/jm020113o
• 作为产物：
  描述：

  alpha-氰基-邻-苯乙腈 在 platinum(IV) oxide sodium hydroxide 、 硫酸 、 氢气 、 硝酸 、 苄基三丁基溴化铵 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， -20.0~60.0 ℃ 、344.75 kPa 条件下， 反应 113.0h， 生成 1-[8-Amino-4-methyl-4-(2-methylpropyl)-1,3-dioxoisoquinolin-7-yl]-3-(2,6-dichlorophenyl)thiourea
  参考文献：
  名称：

  Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase

  摘要：

  An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, lick. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.

  DOI：

  10.1021/jm020113o