6-氯-2-(4-甲氧基苯氧基)吡啶-3-甲腈 | 1402088-16-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 6-氯-2-(4-甲氧基苯氧基)吡啶-3-甲腈
• 英文名称: 6-Chloro-2-(4-methoxyphenoxy)nicotinonitrile
• 英文别名: 6-chloro-2-(4-methoxyphenoxy)pyridine-3-carbonitrile
• CAS: 1402088-16-7
• 化学式: C₁₃H₉ClN₂O₂
• 分子量: 260.68
• InChiKey: QQTRNJAURWQPOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 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：
  55.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为产物：
  描述：

  6-Chloro-2-(4-methoxyphenoxy)-3-nitropyridine 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 nickel(II) chloride hexahydrate 、 氢溴酸 、 碘 、 sodium nitrite 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.41h， 生成 6-氯-2-(4-甲氧基苯氧基)吡啶-3-甲腈
  参考文献：
  名称：

  Design and synthesis of diarylamines and diarylethers as cytotoxic antitumor agents

  摘要：

  Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45 mu M. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC50 values of 2.2-3.0 mu M. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.014

文献信息

• Design and synthesis of diarylamines and diarylethers as cytotoxic antitumor agents
  作者：Xiao-Feng Wang、Xing-Tao Tian、Emika Ohkoshi、Bingjie Qin、Yi-Nan Liu、Pei-Chi Wu、Mann-Jen Hour、Hsin-Yi Hung、Keduo Qian、Rong Huang、Kenneth F. Bastow、William P. Janzen、Jian Jin、Susan L. Morris-Natschke、Kuo-Hsiung Lee、Lan Xie

  DOI：10.1016/j.bmcl.2012.08.014

  日期：2012.10

  Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45 mu M. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC50 values of 2.2-3.0 mu M. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase. (C) 2012 Elsevier Ltd. All rights reserved.