3-bromo-4,4',5-trimethoxy-3'-hydroxy-Z-stilbene | 861995-16-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3-bromo-4,4',5-trimethoxy-3'-hydroxy-Z-stilbene
• 英文别名: 5-[(Z)-2-(3-bromo-4,5-dimethoxyphenyl)ethenyl]-2-methoxyphenol
• CAS: 861995-16-6
• 化学式: C₁₇H₁₇BrO₄
• 分子量: 365.224
• InChiKey: LDMARZLQOPWXCV-PLNGDYQASA-N

物化性质

• 熔点：
  108-109 °C(Solv: hexane (110-54-3))
• 沸点：
  498.8±45.0 °C(Predicted)
• 密度：
  1.408±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-bromo-4,4',5-trimethoxy-3'-hydroxy-Z-stilbene 、 亚磷酸二苄酯 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氯化碳 、 乙腈 为溶剂， 反应 3.0h， 以94%的产率得到dibenzyl 3-bromo-4,4',5-trimethoxy-(Z)-stilbene 3'-O-phosphate
  参考文献：
  名称：

  Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes^,1

  摘要：

  The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (> 10-100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3'-O-phosphate derivative (16c) by the route 7 -> 8a -> 11a -> 14 -> 16c illustrates the general synthetic pathway. The 3'-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (la) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans.

  DOI：

  10.1021/np058038i
• 作为产物：
  描述：

  3-bromo-4,4',5-trimethoxy-3'-O-tert-butyldiphenylsilyl-(Z)-stilbene 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以92%的产率得到3-bromo-4,4',5-trimethoxy-3'-hydroxy-Z-stilbene
  参考文献：
  名称：

  Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes^,1

  摘要：

  The present SAR study of combretastatin A-3 (3a) focused on replacement of the 3-hydroxyl group by a series of halogens. That approach with Z-stilbenes resulted in greatly enhanced (> 10-100-fold) cancer cell growth inhibition against a panel of human cancer cell lines and the murine P388 lymphocytic leukemia cell line. Synthesis of the 3-fluoro-Z-stilbene designated fluorcombstatin (11a) and its potassium 3'-O-phosphate derivative (16c) by the route 7 -> 8a -> 11a -> 14 -> 16c illustrates the general synthetic pathway. The 3'-O-phosphoric acid ester (15) of 3-bromo-Z-stilbene 13a was also converted to representative cation salts to evaluate the potential for improved aqueous solubility, and the potassium salt (16 mg/mL in water) proved most useful. The fluoro (11a), chloro (12a), and bromo (13a) halocombstatins were nearly equivalent to combretastatin A-4 (1a) as inhibitors of tubulin polymerization and of the binding of colchicine to tubulin. The tubulin binding in cell-free systems was also retained in human umbilical vein endothelial cells. All three halocombstatins retained the powerful human cancer cell line inhibitory activity of combretastatin A-4 (la) and proved superior to combretastatin A-3 (3a). In addition, the halocombstatins targeted Gram-positive bacteria and Cryptococcus neoformans.

  DOI：

  10.1021/np058038i

文献信息

• Halocombstatins and methods of synthesis thereof
  申请人：Pettit R. George

  公开号：US20050176688A1

  公开（公告）日：2005-08-11

  The invention relates to novel compounds denominated halocombstatins. The halocombstatins are derivatives of combretastatin A-3, and include compounds that exhibit cancer growth cell inhibition against a panel of human cancer cell lines and the murine P388 leukemia, as well as activity as inhibitors of tubulin polymerization and inhibitors of the binding of colchicine to tubulin.

  这项发明涉及一种名为卤化康柏斯塔汀（halocombstatins）的新化合物。卤化康柏斯塀是康柏斯塀A-3的衍生物，包括对一系列人类癌细胞系和小鼠P388白血病表现出癌细胞生长抑制作用的化合物，以及作为微管聚合抑制剂和结合秋水仙碱对微管的抑制剂的活性。
• HALOCOMBSTATINS AND METHODS OF SYNTHESIS THEREOF
  申请人：Pettit R. George

  公开号：US20070167412A1

  公开（公告）日：2007-07-19

  The invention relates to novel compounds denominated halocombstatins. The halocombstatins are derivatives of combretastatin A-3, and include compounds that exhibit cancer growth cell inhibition against a panel of human cancer cell lines and the murine P388 leukemia, as well as activity as inhibitors of tubulin polymerization and inhibitors of the binding of colchicine to tubulin.

  本发明涉及一种新型化合物，称为卤代联合斯达汀。卤代联合斯达汀是联合斯达汀A-3的衍生物，包括对一系列人类癌细胞系和小鼠P388白血病的癌细胞生长抑制作用以及作为微管聚合抑制剂和秋水仙碱结合到微管的抑制剂的化合物。
• US7223747B2
  申请人：——

  公开号：US7223747B2

  公开（公告）日：2007-05-29
• US7507851B2
  申请人：——

  公开号：US7507851B2

  公开（公告）日：2009-03-24
• [EN] HALOCOMBSTATINS AND METHODS OF SYNTHESIS THEREOF<br/>[FR] HALOCOMBSTATINES ET LEURS METHODES DE SYNTHESE
  申请人：UNIV ARIZONA

  公开号：WO2006036743A2

  公开（公告）日：2006-04-06

  The invention relates to novel compounds denominated halocombstatins. The halocombstatins are derivatives of combretastatin A-3, and include compounds that exhibit cancer growth cell inhibition against a panel of human cancer cell lines and the murine P388 leukemia, as well as activity as inhibitors of tubulin polymerization and inhibitors of the binding of colchicine to tubulin.