1-(5-Chloro-2-methoxy-4-nitrophenyl)-3-(5-cyanopyrazin-2-yl)urea | 886981-62-0

• 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: 1-(5-Chloro-2-methoxy-4-nitrophenyl)-3-(5-cyanopyrazin-2-yl)urea
• CAS: 886981-62-0
• 化学式: C₁₃H₉ClN₆O₄
• 分子量: 348.705
• InChiKey: ZSDRRWCBCAMCMS-UHFFFAOYSA-N

物化性质

• 沸点：
  488.1±45.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 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：
  146
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(5-Chloro-2-methoxy-4-nitrophenyl)-3-(5-cyanopyrazin-2-yl)urea 在 甲醇 、 tin(ll) chloride 作用下， 反应 12.0h， 生成 1-(4-Amino-5-chloro-2-methoxyphenyl)-3-(5-cyanopyrazin-2-yl)urea
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors

  摘要：

  Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl) Urea ill the checkpoint kinase 1 (Chk1) enzyme, we modified R-4, and to a lesser extent, R-2, and R-5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 mu M) and enhanced doxorubicin cytotoxicity (IC50=0.44 mu M) while displaying no single agent activity. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.028
• 作为产物：
  描述：

  2-氨基-4-氯-5-硝基苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 74.0h， 生成 1-(5-Chloro-2-methoxy-4-nitrophenyl)-3-(5-cyanopyrazin-2-yl)urea
  参考文献：
  名称：

  Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors

  摘要：

  Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl) Urea ill the checkpoint kinase 1 (Chk1) enzyme, we modified R-4, and to a lesser extent, R-2, and R-5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 mu M) and enhanced doxorubicin cytotoxicity (IC50=0.44 mu M) while displaying no single agent activity. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.028

文献信息

• Synthesis and biological evaluation of 1-(2,4,5-trisubstituted phenyl)-3-(5-cyanopyrazin-2-yl)ureas as potent Chk1 kinase inhibitors
  作者：Gaoquan Li、Lisa A. Hasvold、Zhi-Fu Tao、Gary T. Wang、Stephen L. Gwaltney、Jyoti Patel、Peter Kovar、Robert B. Credo、Zehan Chen、Haiying Zhang、Chang Park、Hing L. Sham、Thomas Sowin、Saul H. Rosenberg、Nan-Horng Lin

  DOI：10.1016/j.bmcl.2006.01.028

  日期：2006.4

  Based on the X-ray crystallography of our lead compound 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-cyanopyrazin-2-yl) Urea ill the checkpoint kinase 1 (Chk1) enzyme, we modified R-4, and to a lesser extent, R-2, and R-5 of the phenyl ring, and made a variety of N-aryl-N'-pyrazinylurea Chk1 inhibitors. Enzymatic activity less than 20 nM was observed in 15 of 41 compounds. Compound 8i provided the best overall results in the cellular assays as it abrogated doxorubicin-induced cell cycle arrest (IC50=1.7 mu M) and enhanced doxorubicin cytotoxicity (IC50=0.44 mu M) while displaying no single agent activity. (C) 2006 Elsevier Ltd. All rights reserved.