2-[4-cyano-2-(2,6-dichlorophenylamino)-7-formyl-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester | 333458-64-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-[4-cyano-2-(2,6-dichlorophenylamino)-7-formyl-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester
• 英文别名: Ethyl 2-[4-cyano-2-(2,6-dichloroanilino)-7-formyl-3-methylbenzimidazol-5-yl]-2-methyl-3-oxobutanoate
• CAS: 333458-64-3
• 化学式: C₂₃H₂₀Cl₂N₄O₄
• 分子量: 487.342
• InChiKey: FYYNXLVDWLKSAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[4-cyano-2-(2,6-dichlorophenylamino)-7-formyl-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester 在 硫酸 、 溶剂黄146 作用下， 反应 1.5h， 以60%的产率得到2-(2,6-dichlorophenylamino)-1,6,7-trimethyl-9-oxo-1,8-dihydroimidazo[4,5-h]isoquinoline-4-carbaldehyde
  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-[7-bromo-4-cyano-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester 在 N-甲基吡咯烷酮 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium periodate 、 四氧化锇 作用下， 以 四氢呋喃 为溶剂， 反应 72.5h， 生成 2-[4-cyano-2-(2,6-dichlorophenylamino)-7-formyl-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester
  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