2-(4-异氰酰基苯氧基)-6-甲基吡嗪 | 921938-98-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(4-异氰酰基苯氧基)-6-甲基吡嗪
• 中文别名: 2-(4-异氰酸苯氧基)-6-甲基吡嗪
• 英文名称: 2-(4-Isocyanatophenoxy)-6-methylpyrazine
• CAS: 921938-98-9
• 化学式: C₁₂H₉N₃O₂
• 分子量: 227.222
• InChiKey: ABVOFXCRJAZHGH-UHFFFAOYSA-N

物化性质

• 熔点：
  >50°C
• 沸点：
  342.4±42.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基-2-氯喹啉 、 2-(4-异氰酰基苯氧基)-6-甲基吡嗪 在 sodium t-butanolate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以15%的产率得到1-(3-Chloro-4-methoxyphenyl)-3-(2-(trifluoromethyl)quinolin-4-yl)urea
  参考文献：
  名称：

  Synthesis of aryl-heteroaryl ureas (AHUs) based on 4-aminoquinoline and their evaluation against the insulin-like growth factor receptor (IGF-1R)

  摘要：

  The insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase (RTK) involved in all stages of the development and propagation of breast and other cancers. The inhibition of IGF-1R by small molecules remains a promising strategy to treat cancer. Herein, we explore SAR around previously characterized lead compound (1), which is an aryl-heteroaryl urea (AHU) consisting of 4-aminoquinaldine and a substituted aromatic ring system. A library of novel AHU compounds was prepared based on derivatives of the 4-aminoquinoline heterocycle (including various 2-substituted derivatives, and naphthyridines). The compounds were screened for in vitro inhibitory activity against IGF-1R, and several compounds with improved activity (3-5 mu M) were identified. Furthermore, a computational docking study was performed, which identifies a fairly consistent lowest energy mode of binding for the more-active set of inhibitors in this series, while the less-active inhibitors do not adopt a consistent mode of binding. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.071

文献信息

• Synthesis of aryl-heteroaryl ureas (AHUs) based on 4-aminoquinoline and their evaluation against the insulin-like growth factor receptor (IGF-1R)
  作者：William Engen、Terrence E. O’Brien、Brendan Kelly、Jacinda Do、Liezel Rillera、Lance K. Stapleton、Jack F. Youngren、Marc O. Anderson

  DOI：10.1016/j.bmc.2010.06.071

  日期：2010.8

  The insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase (RTK) involved in all stages of the development and propagation of breast and other cancers. The inhibition of IGF-1R by small molecules remains a promising strategy to treat cancer. Herein, we explore SAR around previously characterized lead compound (1), which is an aryl-heteroaryl urea (AHU) consisting of 4-aminoquinaldine and a substituted aromatic ring system. A library of novel AHU compounds was prepared based on derivatives of the 4-aminoquinoline heterocycle (including various 2-substituted derivatives, and naphthyridines). The compounds were screened for in vitro inhibitory activity against IGF-1R, and several compounds with improved activity (3-5 mu M) were identified. Furthermore, a computational docking study was performed, which identifies a fairly consistent lowest energy mode of binding for the more-active set of inhibitors in this series, while the less-active inhibitors do not adopt a consistent mode of binding. (C) 2010 Elsevier Ltd. All rights reserved.