Methyl 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carboxylate | 475577-27-6

• 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: Methyl 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carboxylate
• CAS: 475577-27-6
• 化学式: C₂₁H₁₉BrN₂O₅
• 分子量: 459.296
• InChiKey: MUUUAXXGRZQQIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  95.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-羟基吲哚 、 3-溴-4,5-二甲氧基苯甲醛 、 氰乙酸甲酯 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 Methyl 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carboxylate
  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

• 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.