2-[7-bromo-4-cyano-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester | 333458-60-9

• 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-[7-bromo-4-cyano-2-(2,6-dichlorophenylamino)-3-methyl-3H-benzimidazol-5-yl]-2-methyl-3-oxobutyric acid ethyl ester
• 英文别名: Ethyl 2-[7-bromo-4-cyano-2-(2,6-dichloroanilino)-3-methylbenzimidazol-5-yl]-2-methyl-3-oxobutanoate
• CAS: 333458-60-9
• 化学式: C₂₂H₁₉BrCl₂N₄O₃
• 分子量: 538.228
• InChiKey: NPFKACRIGCQHIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 、 硫酸 作用下， 反应 2.0h， 生成 2-(2,6-Dichlorophenylamino)-4-(2,6-difluoropyridin-3yl)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinoline-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 溴 、 mercury(II) oxide 作用下， 以 1,4-二氧六环 、 氯仿 为溶剂， 生成 2-[7-bromo-4-cyano-2-(2,6-dichlorophenylamino)-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

文献信息

• Optimization of 2-Phenylaminoimidazo[4,5-<i>h</i>]isoquinolin-9-ones:  Orally Active Inhibitors of lck Kinase
  作者：Daniel R. Goldberg、Tanja Butz、Mario G. Cardozo、Robert J. Eckner、Abdelhakim Hammach、Jessica Huang、Scott Jakes、Suresh Kapadia、Mohammed Kashem、Susan Lukas、Tina M. Morwick、Maret Panzenbeck、Usha Patel、Susan Pav、Gregory W. Peet、Jeffrey D. Peterson、Anthony S. Prokopowicz、Roger J. Snow、Rosemarie Sellati、Hidenori Takahashi、Jonathan Tan、Matt A. Tschantz、Xiao-Jun Wang、Yong Wang、John Wolak、Pla Xiong、Neil Moss

  DOI：10.1021/jm020446l

  日期：2003.4.1

  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.