2-Acetyl-2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-succinic acid diethyl ester | 500735-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 2-Acetyl-2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-succinic acid diethyl ester
• 英文别名: diethyl 2-acetyl-2-[4-cyano-2-(2,6-dichloroanilino)-3-methylbenzimidazol-5-yl]butanedioate
• CAS: 500735-22-8
• 化学式: C₂₅H₂₄Cl₂N₄O₅
• 分子量: 531.395
• InChiKey: RQNLVFWLGJPXSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.84
• 重原子数：
  36.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  123.31
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-Acetyl-2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-succinic acid diethyl ester 在 硫酸 、 溶剂黄146 作用下， 反应 2.5h， 生成 2-(2,6-dichlorophenylamino)-1,7-dimethyl-9-oxo-1,8-dihydroimidazo[4,5-h]isoquinolin-6-ylacetic acid
  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-acetyl-2-(2-cyano-3-methylamino-4-nitrophenyl)succinic acid dimethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 5.0h， 生成 2-Acetyl-2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-succinic acid diethyl 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

• Isoquinolinone synthesis by SNAr reaction: a versatile route to imidazo[4,5-h]isoquinolin-9-ones
  作者：Roger J. Snow、Tanja Butz、Abdelhakim Hammach、Suresh Kapadia、Tina M. Morwick、Anthony S. Prokopowicz、Hidenori Takahashi、Jonathan D. Tan、Matt A. Tschantz、Xiao-Jun Wang

  DOI：10.1016/s0040-4039(02)01802-6

  日期：2002.10

  Reaction of 2-chlorobenzonitriles with beta-ketoesters in an SNAr reaction, followed by cyclization in acid provides a versatile route to isoquinolones. Starting from 2,6-dichloro-3-nitrobenzonitrile 7, sequential displacement of the chlorines by an amine and a beta-ketoester leads to imidazo[4,5-h]isoquinolin-9-ones 1, a new class of kinase inhibitor. (C) 2002 Elsevier Science Ltd. All rights reserved.