4-(3-Bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile | 627532-13-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: 4-(3-Bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile
• CAS: 627532-13-2
• 化学式: C₂₀H₁₅BrN₂O₃
• 分子量: 411.255
• InChiKey: AANXHYPCMZAPKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  67.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  溴乙烷 、 4-(3-Bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile 在 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 60.0h， 以97%的产率得到4-(3-Bromo-4,5-dimethoxyphenyl)-3-cyano-7-ethyl-4H-indolo[4,5-b]pyran
  参考文献：
  名称：

  Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based HTS assay. Part 5: Modifications of the 2- and 3-positions

  摘要：

  As a continuation of our efforts to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored modifications at the 2- and 3-positions. It was found that replacement of the 3-cyano group by an ester, including metbyl and ethyl ester, resulted in > 200-fold reduction of activity. Conversion of the 2-amino group into an amide or urea resulted in 4- to 10-fold drop of activity. Similarly, converting the 2-amino group into a hydrogen resulted in 4- to 10-fold reduction of activity. Compound 3d was highly active with an EC50 value of 29 nM and a GI(50) value of 6 nM in T47D cells. Importantly, the 2H analog 3d was found to be much more stable under acidic conditions compared to the 2-NH2 analog 3b, suggesting that 2-H analogs might have better bioavailability than the 2-NH2 analogs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.078
• 作为产物：
  描述：

  MX-76747 在 2-甲基-2-硝基丙烷 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以40%的产率得到4-(3-Bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile
  参考文献：
  名称：

  Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based HTS assay. Part 5: Modifications of the 2- and 3-positions

  摘要：

  As a continuation of our efforts to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored modifications at the 2- and 3-positions. It was found that replacement of the 3-cyano group by an ester, including metbyl and ethyl ester, resulted in > 200-fold reduction of activity. Conversion of the 2-amino group into an amide or urea resulted in 4- to 10-fold drop of activity. Similarly, converting the 2-amino group into a hydrogen resulted in 4- to 10-fold reduction of activity. Compound 3d was highly active with an EC50 value of 29 nM and a GI(50) value of 6 nM in T47D cells. Importantly, the 2H analog 3d was found to be much more stable under acidic conditions compared to the 2-NH2 analog 3b, suggesting that 2-H analogs might have better bioavailability than the 2-NH2 analogs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.078

文献信息

• Substituted 4h-chromens, 2h-chromenes, chromans and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cai Xiong Sui

  公开号：US20050176750A1

  公开（公告）日：2005-08-11

  The present invention is directed to substituted 4H-chromenes, 2H-chromenes, chromans and analogs thereof, represented by the general Formula (I) wherein R 5 , A, B, X, Y, Z and dotted lines are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及被代替的4H-色烯、2H-色烯、色烷及其类似物，由通式（I）所表示，其中R5、A、B、X、Y、Z和虚线在此定义。本发明还涉及发现具有通式（I）的化合物是caspase的激活剂和凋亡的诱导剂。因此，本发明的caspase激活剂和凋亡诱导剂可用于诱导在各种临床情况下出现的异常细胞的无控制生长和扩散的细胞死亡。
• SUBSTITUTED 4H-CHROMENES, 2H-CHROMENES, CHROMANS AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1513515A2

  公开（公告）日：2005-03-16
• US7476741B2
  申请人：——

  公开号：US7476741B2

  公开（公告）日：2009-01-13
• [EN] SUBSTITUTED 4H-CHROMENES, 2H-CHROMENES, CHROMANS AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF<br/>[FR] 4H-CHROMENES, 2H-CHROMENES SUBSTITUES, CHROMANS ET ANALOGUES UTILISES COMME ACTIVATEURS DE CASPASES ET INDUCTEURS DE L'APOPTOSE, ET UTILISATION DE CES COMPOSES
  申请人：CYTOVIA INC

  公开号：WO2003096982A2

  公开（公告）日：2003-11-27

  The present invention is directed to substituted 4H-chromenes, 2H-chromenes, chromans and analogs thereof, represented by the general Formula (I) wherein R5, A, B, X, Y, Z and dotted lines are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
• Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based HTS assay. Part 5: Modifications of the 2- and 3-positions
  作者：William Kemnitzer、Songchun Jiang、Yan Wang、Shailaja Kasibhatla、Candace Crogan-Grundy、Monica Bubenik、Denis Labrecque、Real Denis、Serge Lamothe、Giorgio Attardo、Henriette Gourdeau、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2007.11.078

  日期：2008.1

  As a continuation of our efforts to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored modifications at the 2- and 3-positions. It was found that replacement of the 3-cyano group by an ester, including metbyl and ethyl ester, resulted in > 200-fold reduction of activity. Conversion of the 2-amino group into an amide or urea resulted in 4- to 10-fold drop of activity. Similarly, converting the 2-amino group into a hydrogen resulted in 4- to 10-fold reduction of activity. Compound 3d was highly active with an EC50 value of 29 nM and a GI(50) value of 6 nM in T47D cells. Importantly, the 2H analog 3d was found to be much more stable under acidic conditions compared to the 2-NH2 analog 3b, suggesting that 2-H analogs might have better bioavailability than the 2-NH2 analogs. (c) 2007 Elsevier Ltd. All rights reserved.