1-(5-Chloro-2-methoxyphenyl)-3-(2-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)urea | 1245211-38-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-(5-Chloro-2-methoxyphenyl)-3-(2-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-4-yl)urea
• CAS: 1245211-38-4
• 化学式: C₂₁H₁₈N₆O₂
• 分子量: 386.413
• InChiKey: YLVXPQYHRDXGNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  75.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-甲基-1,8-萘啶-4-胺 、 2-(4-异氰酰基苯氧基)-6-甲基吡嗪 以 二甲基亚砜 为溶剂， 反应 0.5h， 以22%的产率得到1-(5-Chloro-2-methoxyphenyl)-3-(2-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-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.