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

文献信息

• Discovery of 2-Phenylamino-imidazo[4,5-<i>h</i>]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase
  作者：Roger J. Snow、Mario G. Cardozo、Tina M. Morwick、Carl A. Busacca、Yong Dong、Robert J. Eckner、Stephen Jacober、Scott Jakes、Suresh Kapadia、Susan Lukas、Maret Panzenbeck、Gregory W. Peet、Jeffrey D. Peterson、Anthony S. Prokopowicz、Rosemarie Sellati、Robert M. Tolbert、Matt A. Tschantz、Neil Moss

  DOI：10.1021/jm020113o

  日期：2002.8.1

  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.