7-hydroxy-6-methoxy-2-(4-N-methylpyrazolyl)-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-hydroxy-6-methoxy-2-(4-N-methylpyrazolyl)-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan
• 英文别名: 2-(4-N-methylpyrazolyl)-3-(3,4,5-trimethoxybenzoyl)-6-methoxy-7-hydroxy-benzofuran；[7-Hydroxy-6-methoxy-2-(1-methylpyrazol-4-yl)-1-benzofuran-3-yl]-(3,4,5-trimethoxyphenyl)methanone
• 化学式: C₂₃H₂₂N₂O₇
• 分子量: 438.437
• InChiKey: IARVWTIWWVZVBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-hydroxy-6-methoxy-2-(4-N-methylpyrazolyl)-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan 、 亚磷酸二苄酯 在 四溴化碳 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以20%的产率得到2-(4-N-methylpyrazolyl)-3-(3,4,5-trimethoxybenzoyl)-7-O-dibenzylphosphate-6-methoxybenzo[b]furan
  参考文献：
  名称：

  WO2006/84338

  摘要：

  公开号：
• 作为产物：
  描述：

  1-甲基-4-((三甲基甲硅烷基)乙炔基)-1H-吡唑 在 aluminum (III) chloride 、 bis-triphenylphosphine-palladium(II) chloride 、 四丁基氟化铵 、 甲基氯化镁 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.42h， 生成 7-hydroxy-6-methoxy-2-(4-N-methylpyrazolyl)-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

• NOVEL TUBULIN POLYMERISATION INHIBITORS
  申请人：Chaplin Jason Hugh

  公开号：US20120309768A1

  公开（公告）日：2012-12-06

  The present invention relates to compounds of general formula (I) as tublin polymerisation inhibitors and methods for preparing such compounds.

  本发明涉及一般式（I）的化合物，作为微管聚合抑制剂以及制备这些化合物的方法。
• US8278290B2
  申请人：——

  公开号：US8278290B2

  公开（公告）日：2012-10-02
• US8557982B2
  申请人：——

  公开号：US8557982B2

  公开（公告）日：2013-10-15
• WO2006/84338
  申请人：——

  公开号：——

  公开（公告）日：——
• 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).