2-(2,6-Dichloro-phenylamino)-7-(1-hydroxy-2-trimethylsilanyl-ethyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one | 620590-67-2

• 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: 2-(2,6-Dichloro-phenylamino)-7-(1-hydroxy-2-trimethylsilanyl-ethyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one
• CAS: 620590-67-2
• 化学式: C₂₃H₂₆Cl₂N₄O₂Si
• 分子量: 489.477
• InChiKey: PHJACOHEBPOCOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.15
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  82.94
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(2,6-Dichloro-phenylamino)-7-(1-hydroxy-2-trimethylsilanyl-ethyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one 在 platinum(IV) oxide 三氟化硼乙醚 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 生成 2-(2,6-Dichloro-phenylamino)-7-ethyl-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one
  参考文献：
  名称：

  Optimization of 2-Phenylaminoimidazo[4,5-h]isoquinolin-9-ones:  Orally Active Inhibitors of lck Kinase

  摘要：

  The tyrosine kinase p56lck (lck) is essential for T cell activation; thus, inhibitors of lck have potential utility as autoimmune agents. Our initial disclosure of a new class of lck inhibitors based on the phenylaminoimidazoisoquinolin-9-one showed reasonable cellular activity but did not work in vivo upon oral administration. Our current work highlights the further use of rational drug design and molecular modeling to produce a series of lck inhibitors that demonstrate cellular activity below 100 nM and are as efficacious as cyclosporin A in an in vivo mouse model of anti-CD3-induced IL-2 production.

  DOI：

  10.1021/jm020446l
• 作为产物：
  描述：

  2-(4-amino-2-cyano-3-methylaminophenyl)-2-methyl-3-oxobutyric acid ethyl ester 在 selenium(IV) oxide 、 硫酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 13.5h， 生成 2-(2,6-Dichloro-phenylamino)-7-(1-hydroxy-2-trimethylsilanyl-ethyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one
  参考文献：
  名称：

  Optimization of 2-Phenylaminoimidazo[4,5-h]isoquinolin-9-ones:  Orally Active Inhibitors of lck Kinase

  摘要：

  The tyrosine kinase p56lck (lck) is essential for T cell activation; thus, inhibitors of lck have potential utility as autoimmune agents. Our initial disclosure of a new class of lck inhibitors based on the phenylaminoimidazoisoquinolin-9-one showed reasonable cellular activity but did not work in vivo upon oral administration. Our current work highlights the further use of rational drug design and molecular modeling to produce a series of lck inhibitors that demonstrate cellular activity below 100 nM and are as efficacious as cyclosporin A in an in vivo mouse model of anti-CD3-induced IL-2 production.

  DOI：

  10.1021/jm020446l