2-acetyl-2-(2-cyano-3-methylamino-4-nitrophenyl)succinic acid dimethyl ester | 500735-14-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-acetyl-2-(2-cyano-3-methylamino-4-nitrophenyl)succinic acid dimethyl ester
• 英文别名: Diethyl 2-acetyl-2-[2-cyano-3-(methylamino)-4-nitrophenyl]butanedioate
• CAS: 500735-14-8
• 化学式: C₁₈H₂₁N₃O₇
• 分子量: 391.381
• InChiKey: XFWWWHIYOBJPJV-UHFFFAOYSA-N

物化性质

• 沸点：
  567.9±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  151
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-acetyl-2-(2-cyano-3-methylamino-4-nitrophenyl)succinic acid dimethyl ester 在 palladium on activated charcoal 硫酸 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~100.0 ℃ 、344.74 kPa 条件下， 反应 25.5h， 生成 2-(2,6-Dichloro-phenylamino)-1,7-dimethyl-6-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethyl]-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：

  2,6-二氯-3-硝基苯肼 在 caesium carbonate 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 2-acetyl-2-(2-cyano-3-methylamino-4-nitrophenyl)succinic acid dimethyl 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.