dibenzyl 3-bromo-4,4',5-trimethoxy-(Z)-stilbene 3'-O-phosphate | 861995-19-9

• 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: dibenzyl 3-bromo-4,4',5-trimethoxy-(Z)-stilbene 3'-O-phosphate
• 英文别名: dibenzyl [5-[(Z)-2-(3-bromo-4,5-dimethoxyphenyl)ethenyl]-2-methoxyphenyl] phosphate
• CAS: 861995-19-9
• 化学式: C₃₁H₃₀BrO₇P
• 分子量: 625.453
• InChiKey: WENPWOCUTCNYOO-PFONDFGASA-N

物化性质

• 沸点：
  271 °C(Press: 0.01 Torr)
• 密度：
  1.360±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dibenzyl 3-bromo-4,4',5-trimethoxy-(Z)-stilbene 3'-O-phosphate 在 三甲基溴硅烷 、 sodium methylate 作用下， 以 二氯甲烷 、 乙醇 为溶剂， 反应 1.0h， 生成 sodium 3-bromo-4,4',5-trimethoxy-Z-stilbene 3'-O-phosphate
  参考文献：
  名称：

  Halocombstatins and methods of synthesis thereof

  摘要：

  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。

  公开号：

  US20050176688A1
• 作为产物：
  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

文献信息

• Antineoplastic Agents. 509. Synthesis of Fluorcombstatin Phosphate and Related 3-Halostilbenes^,1
  作者：George R. Pettit、Mathew D. Minardi、Heidi J. Rosenberg、Ernest Hamel、Michael C. Bibby、Sandie W. Martin、M. Katherine Jung、Robin K. Pettit、Timothy J. Cuthbertson、Jean-Charles Chapuis

  DOI：10.1021/np058038i

  日期：2005.10.1

  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.
• 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。