1-(8-amino-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-(2,6-dichlorophenyl)thiourea | 333458-24-5

• 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-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-(2,6-dichlorophenyl)thiourea
• 英文别名: 1-(8-Amino-4,4-dimethyl-1,3-dioxoisoquinolin-7-yl)-3-(2,6-dichlorophenyl)thiourea
• CAS: 333458-24-5
• 化学式: C₁₈H₁₆Cl₂N₄O₂S
• 分子量: 423.323
• InChiKey: YDNXHVNYTLJRFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 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-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-3-(2,6-dichlorophenyl)thiourea 在 sodium tetrahydroborate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2-(2,6-Dichlorophenylamino)-6,6-dimethyl-7-hydroxy-7,8-dihydro-1H,6H-imidazo[4,5-h]isoquinoline-9-one
  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：

  7-amino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione 在 platinum(IV) oxide 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， -20.0~70.0 ℃ 、344.75 kPa 条件下， 反应 12.25h， 生成 1-(8-amino-4,4-dimethyl-1,3-dioxo-1,2,3,4-tetrahydroisoquinolin-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