3-[2-(2,6-Dichlorophenylamino)-1,7-dimethyl-9-oxo-1,8-dihydro-imidazo[4,5-h]isoquinolin-6-yl]propionic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-[2-(2,6-Dichlorophenylamino)-1,7-dimethyl-9-oxo-1,8-dihydro-imidazo[4,5-h]isoquinolin-6-yl]propionic acid ethyl ester
• 英文别名: ethyl 3-[2-(2,6-dichloroanilino)-1,7-dimethyl-9-oxo-8H-imidazo[4,5-h]isoquinolin-6-yl]propanoate
• 化学式: C₂₃H₂₂Cl₂N₄O₃
• 分子量: 473.359
• InChiKey: WWBWJMOQGDBNAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  乙酰戊二酸二乙酯 在 palladium on activated charcoal 硫酸 、 氢气 、 caesium carbonate 、 mercury(II) oxide 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[2-(2,6-Dichlorophenylamino)-1,7-dimethyl-9-oxo-1,8-dihydro-imidazo[4,5-h]isoquinolin-6-yl]propionic 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

• Heterocyclic compounds useful as inhibitors of tyrosine kinases
  申请人：——

  公开号：US20020016460A1

  公开（公告）日：2002-02-07

  Disclosed are novel compounds of formula (I): 1 wherein Ar 1 , R a , R 4 , R 5 , X and Y are defined below, which are useful as inhibitors of certain protein tyrosine kinases and are thus useful for treating diseases associated with such kinases, for example, diseases resulting from inappropriate cell proliferation, which include autoimmune diseases, chronic inflammatory diseases, allergic diseases, transplant rejection and cancer, as well as conditions resulting from cerebral ischemia, such as stroke. Also disclosed are processes for preparing these compounds, novel intermediates useful in these processes and compositions comprising compounds of the formula (I).

  揭示了式（I）的新化合物：其中Ar1、Ra、R4、R5、X和Y的定义如下，这些化合物可用作某些蛋白酪氨酸激酶的抑制剂，因此可用于治疗与这些激酶相关的疾病，例如由于细胞不当增殖而导致的疾病，包括自身免疫疾病、慢性炎症性疾病、过敏疾病、移植排斥和癌症，以及由脑缺血引起的疾病，如中风。还披露了制备这些化合物的方法，这些方法中有用的新中间体以及包含式（I）化合物的组合物。
• HETEROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF TYROSINE KINASES
  申请人：BOEHRINGER INGELHEIM PHARMACEUTICALS INC.

  公开号：EP1222187B1

  公开（公告）日：2004-09-22
• US6506769B2
  申请人：——

  公开号：US6506769B2

  公开（公告）日：2003-01-14
• US6770639B2
  申请人：——

  公开号：US6770639B2

  公开（公告）日：2004-08-03
• 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.