2-(3,4-diamino-2-cyanophenyl)-2-methyl-3-oxobutyric acid ethyl ester | 524695-75-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(3,4-diamino-2-cyanophenyl)-2-methyl-3-oxobutyric acid ethyl ester
• 英文别名: Ethyl 2-(3,4-diamino-2-cyanophenyl)-2-methyl-3-oxobutanoate
• CAS: 524695-75-8
• 化学式: C₁₄H₁₇N₃O₃
• 分子量: 275.307
• InChiKey: AZPSBXSMYVHAQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(3,4-diamino-2-cyanophenyl)-2-methyl-3-oxobutyric acid ethyl ester 在 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 ethyl 2-[4-cyano-2-(2,6-dichloroanilino)-1H-benzimidazol-5-yl]-2-methyl-3-oxobutanoate
  参考文献：
  名称：

  Isoquinolinone synthesis by SNAr reaction: a versatile route to imidazo[4,5-h]isoquinolin-9-ones

  摘要：

  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.

  DOI：

  10.1016/s0040-4039(02)01802-6
• 作为产物：
  描述：

  2-甲基乙酰乙酸乙酯 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(3,4-diamino-2-cyanophenyl)-2-methyl-3-oxobutyric acid ethyl ester
  参考文献：
  名称：

  Isoquinolinone synthesis by SNAr reaction: a versatile route to imidazo[4,5-h]isoquinolin-9-ones

  摘要：

  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.

  DOI：

  10.1016/s0040-4039(02)01802-6

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.
• 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.