Methyl 2-[4-cyano-2-(2,6-dichloroanilino)-3-methylbenzimidazol-5-yl]-3-oxobutanoate | 500735-24-0

• 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: Methyl 2-[4-cyano-2-(2,6-dichloroanilino)-3-methylbenzimidazol-5-yl]-3-oxobutanoate
• CAS: 500735-24-0
• 化学式: C₂₀H₁₆Cl₂N₄O₃
• 分子量: 431.278
• InChiKey: KTCNVKPSHQYRAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  Methyl 2-[4-cyano-2-(2,6-dichloroanilino)-3-methylbenzimidazol-5-yl]-3-oxobutanoate 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-dihydro-imidazo[4,5-h]isoquinoline-6-carboxylic acid methyl 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
• 作为产物：
  描述：

  6-氯-2-甲基氨基-3-硝基苯甲腈 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 mercury(II) oxide 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 Methyl 2-[4-cyano-2-(2,6-dichloroanilino)-3-methylbenzimidazol-5-yl]-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