2-cyano-7-hydroxy-6-methoxy-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan | 945771-78-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-cyano-7-hydroxy-6-methoxy-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan
• 英文别名: 2-Cyano-7-hydroxy-3-(3,4,5-trimethoxybenzoyl)-6-methoxybenzo[b]furan；7-hydroxy-6-methoxy-3-(3,4,5-trimethoxybenzoyl)-1-benzofuran-2-carbonitrile
• CAS: 945771-78-8
• 化学式: C₂₀H₁₇NO₇
• 分子量: 383.357
• InChiKey: BFELXBREUXKJES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-cyano-7-hydroxy-6-methoxy-3-(3,4,5-trimethoxybenzoyl)benzo[b]furan 在 sodium azide 、 氯化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以21%的产率得到7-hydoxy-6-methoxy-2-(2H-tetrazol-5-yl)-3-(3,4,5-trimethoxybenzoyl)-benzo[b]furan
  参考文献：
  名称：

  WO2006/84338

  摘要：

  公开号：
• 作为产物：
  描述：

  2-t-butyldimethylsilyl-7-acetoxy-3-(3,4,5-trimethoxybenzoyl)-6-methoxybenzofuran 在 溴 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 2-cyano-7-hydroxy-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

• An Efficient Synthesis and Substitution of 3-Aroyl-2-bromobenzo[<i>b</i>]furans
  作者：Gurmit S. Gill、Damian W. Grobelny、Jason H. Chaplin、Bernard L. Flynn

  DOI：10.1021/jo701656z

  日期：2008.2.1

  A convenient method for the synthesis of 2-bromo-3-aroyl-benzo[b]furans from readily accessible precursors has been developed. The 2-bromo group has been employed as a versatile synthetic handle in both palladium-mediated couplings and direct nucleophilic substitutions to give access to a wide range of 2-substituted-3-aroyl-benzo[b]furans.

  已经开发了从容易获得的前体合成2-溴-3-芳酰基-苯并[ b ]呋喃的简便方法。2-溴基团已在钯介导的偶联和直接亲核取代中用作通用合成手柄，从而可使用各种2-取代-3-芳酰基-苯并[ b ]呋喃。
• SUBSTITUTED BENZOFURANS, BENZOTHIOPHENES, BENZOSELENOPHENES AND INDOLES AND THEIR USE AS TUBULIN POLYMERISATION INHIBITORS
  申请人：Chaplin Jason Hugh

  公开号：US20100004208A1

  公开（公告）日：2010-01-07

  The present invention relates generally to substituted benzofurans, benzothiophenes, and indoles and their use as tubulin polymerisation inhibitors.

  本发明涉及取代苯并呋喃、苯并噻吩和吲哚，以及它们作为微管聚合抑制剂的用途。
• COMBINATION THERAPY FOR TREATING PROLIFERATIVE DISEASES
  申请人：Kremmidiotis Gabriel

  公开号：US20120149665A1

  公开（公告）日：2012-06-14

  A pharmaceutical composition of a tubulin polymerisation inhibitor and an mTOR inhibitor and a method of treating proliferative disease with a combination of a tubulin polymerisation inhibitor and an mTOR inhibitor.

  一种包含微管聚合抑制剂和mTOR抑制剂的药物组合物，以及使用微管聚合抑制剂和mTOR抑制剂的组合物治疗增殖性疾病的方法。
• Tubulin polymerisation inhibitors
  申请人：Biononics Limited

  公开号：US08278290B2

  公开（公告）日：2012-10-02

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

  本发明涉及一般式（I）化合物作为微管聚合抑制剂和制备这些化合物的方法。
• 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。