N-(3,5-dibromo-4-methoxyphenyl)acetamide | 108761-48-4

• 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: N-(3,5-dibromo-4-methoxyphenyl)acetamide
• 英文别名: acetic acid-(3,5-dibromo-4-methoxy-anilide)；2.6-Dibrom-4-acetamino-phenol-methylaether；Essigsaeure-(3,5-dibrom-4-methoxy-anilid)；2.6-Dibrom-4-acetamino-anisol
• CAS: 108761-48-4
• 化学式: C₉H₉Br₂NO₂
• 分子量: 322.984
• InChiKey: KIFGEWDQZHBHGX-UHFFFAOYSA-N

物化性质

• 熔点：
  145-149 °C
• 沸点：
  408.8±45.0 °C(Predicted)
• 密度：
  1.805±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3,5-dibromo-4-methoxyphenyl)acetamide 在 盐酸 、 水 作用下， 反应 1.0h， 以89%的产率得到3,5-二溴-4-甲氧基苯胺
  参考文献：
  名称：

  A-Ring Dihalogenation Increases the Cellular Activity of Combretastatin-Templated Tetrazoles

  摘要：

  The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (32-34), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G(2)/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity.

  DOI：

  10.1021/ml200149g
• 作为产物：
  描述：

  4-氨基-2,6-二溴苯酚 在 potassium carbonate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 1.0h， 生成 N-(3,5-dibromo-4-methoxyphenyl)acetamide
  参考文献：
  名称：

  Increased endothelial cell selectivity of triazole-bridged dihalogenated A-ring analogues of combretastatin A–1

  摘要：

  The antiproliferative activity on ovarian cancer (SK-OV-3) cells of a series of triazole-bridged combretastatin analogues (37, 38, 40-43) containing dihalogenation of the A-ring is reported, and compared with their trimethoxy analogues (5, 15, 39). It was found that dihalogenation with either bromine or iodine was a tolerated modification when compared to the parent compound combretastatin (CA-4, 1) and had less effect than B-ring modification on potency. These compounds exhibited G(2)/M arrest, and maintained antitubulin activity. Further assays on human umbilical vein endothelial cells (HUVECs) demonstrated the potential antivascular effects of these triazoles. Of particular note was a 3,5-diiodo-4-methoxyaryl triazole (43) which had promising 7-fold selectivity for HUVECs over ovarian cancer cells. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.010

文献信息

• A-Ring Dihalogenation Increases the Cellular Activity of Combretastatin-Templated Tetrazoles
  作者：Thomas M. Beale、Daniel M. Allwood、Andreas Bender、Peter J. Bond、James D. Brenton、D. Stephen Charnock-Jones、Steven V. Ley、Rebecca M. Myers、James W. Shearman、Jill Temple、Jessica Unger、Ciorsdaidh A. Watts、Jian Xian

  DOI：10.1021/ml200149g

  日期：2012.3.8

  The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (32-34), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G(2)/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity.
• Robertson, Journal of the Chemical Society, 1902, vol. 81, p. 1480
  作者：Robertson

  DOI：——

  日期：——
• Increased endothelial cell selectivity of triazole-bridged dihalogenated A-ring analogues of combretastatin A–1
  作者：Thomas M. Beale、Peter J. Bond、James D. Brenton、D. Stephen Charnock-Jones、Steven V. Ley、Rebecca M. Myers

  DOI：10.1016/j.bmc.2012.01.010

  日期：2012.3

  The antiproliferative activity on ovarian cancer (SK-OV-3) cells of a series of triazole-bridged combretastatin analogues (37, 38, 40-43) containing dihalogenation of the A-ring is reported, and compared with their trimethoxy analogues (5, 15, 39). It was found that dihalogenation with either bromine or iodine was a tolerated modification when compared to the parent compound combretastatin (CA-4, 1) and had less effect than B-ring modification on potency. These compounds exhibited G(2)/M arrest, and maintained antitubulin activity. Further assays on human umbilical vein endothelial cells (HUVECs) demonstrated the potential antivascular effects of these triazoles. Of particular note was a 3,5-diiodo-4-methoxyaryl triazole (43) which had promising 7-fold selectivity for HUVECs over ovarian cancer cells. (C) 2012 Elsevier Ltd. All rights reserved.