2-(3-amino-4-methoxyphenyl)-6-methoxy-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan | 1319803-93-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 2-芳基苯并呋喃类黄酮
• 英文名称: 2-(3-amino-4-methoxyphenyl)-6-methoxy-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan
• 英文别名: [2-(3-Amino-4-methoxyphenyl)-6-methoxy-1-benzofuran-3-yl]-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1319803-93-4
• 化学式: C₂₆H₂₅NO₇
• 分子量: 463.487
• InChiKey: CMEFMOKLOSBTSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-碘-2-甲氧基苯胺 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 potassium fluoride 、 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 甲基氯化镁 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 2-(3-amino-4-methoxyphenyl)-6-methoxy-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan
  参考文献：
  名称：

  Discovery of 7-Hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan (BNC105), a Tubulin Polymerization Inhibitor with Potent Antiproliferative and Tumor Vascular Disrupting Properties

  摘要：

  A structure activity relationship (SAR) guided design of novel tubulin polymerization inhibitors has resulted in a series of benzo[b]furans with exceptional potency toward cancer cells and activated endothelial cells. The potency of early lead compounds has been substantially improved through the synergistic effect of introducing a conformational bias and additional hydrogen bond donor to the pharmacophore. Screening of a focused library of potent tubulin polymerization inhibitors for selectivity against cancer cells and activated endothelial cells over quiescent endothelial cells has afforded 7-hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo-[b]furan (BNC105, 8) as a potent and selective antiproliferative. Because of poor solubility, 8 is administered as its disodium phosphate ester prodrug 9 (BNC105P), which is rapidly cleaved in vivo to return the active 8. 9 exhibits both superior vascular disrupting and tumor growth inhibitory properties compared with the benchmark agent combretastatin A-4 disodium phosphate 5 (CA4P).

  DOI：

  10.1021/jm200454y

文献信息

• Discovery of 7-Hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[<i>b</i>]furan (BNC105), a Tubulin Polymerization Inhibitor with Potent Antiproliferative and Tumor Vascular Disrupting Properties
  作者：Bernard L. Flynn、Gurmit S. Gill、Damian W. Grobelny、Jason H. Chaplin、Dharam Paul、Annabell F. Leske、Tina C. Lavranos、David K. Chalmers、Susan A. Charman、Edmund Kostewicz、David M. Shackleford、Julia Morizzi、Ernest Hamel、M. Katherine Jung、Gabriel Kremmidiotis

  DOI：10.1021/jm200454y

  日期：2011.9.8

  A structure activity relationship (SAR) guided design of novel tubulin polymerization inhibitors has resulted in a series of benzo[b]furans with exceptional potency toward cancer cells and activated endothelial cells. The potency of early lead compounds has been substantially improved through the synergistic effect of introducing a conformational bias and additional hydrogen bond donor to the pharmacophore. Screening of a focused library of potent tubulin polymerization inhibitors for selectivity against cancer cells and activated endothelial cells over quiescent endothelial cells has afforded 7-hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo-[b]furan (BNC105, 8) as a potent and selective antiproliferative. Because of poor solubility, 8 is administered as its disodium phosphate ester prodrug 9 (BNC105P), which is rapidly cleaved in vivo to return the active 8. 9 exhibits both superior vascular disrupting and tumor growth inhibitory properties compared with the benchmark agent combretastatin A-4 disodium phosphate 5 (CA4P).