8-amino-6-(3-bromo-4,5-dimethoxyphenyl)-3-methyl-6H-pyrano[2,3-e]benzimidazole-7-carbonitrile | 475577-30-1

• 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: 8-amino-6-(3-bromo-4,5-dimethoxyphenyl)-3-methyl-6H-pyrano[2,3-e]benzimidazole-7-carbonitrile
• CAS: 475577-30-1
• 化学式: C₂₀H₁₇BrN₄O₃
• 分子量: 441.284
• InChiKey: VDQIPHZGVJIVPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  95.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-溴-4,5-二甲氧基苯甲醛 、 丙二腈 、 1-甲基-1H-苯并咪唑-4-醇 在 哌啶 作用下， 以 乙醇 为溶剂， 以48%的产率得到8-amino-6-(3-bromo-4,5-dimethoxyphenyl)-3-methyl-6H-pyrano[2,3-e]benzimidazole-7-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 High Throughput Screening Assay. 4. Structure–Activity Relationships of N-Alkyl Substituted Pyrrole Fused at the 7,8-Positions

  摘要：

  In our continuing effort to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the structure-activity relationship (SAR) of alkyl substituted pyrrole fused at the 7,8-positions. A methyl group substituted at the nitrogen in the 7-position of the pyrrole ring led to a series of potent apoptosis inducers with potency in the low nanomolar range. These compounds were also found to be low nanomolar or subnanomolar inhibitors of cell growth, and they inhibited tubulin polymerization, indicating that methylation of the 7-position nitrogen does not change the mechanism of action of these chromenes. Compound 2d was identified as a highly potent apoptosis inducer with an EC50 value of 2 nM and a highly potent inhibitor of cell growth with a GI(50) value of 0.3 nM in T47D cells.

  DOI：

  10.1021/jm7010657

文献信息

• US7528164B2
  申请人：——

  公开号：US7528164B2

  公开（公告）日：2009-05-05
• Discovery of 4-Aryl-4<i>H</i>-chromenes as a New Series of Apoptosis Inducers Using a Cell- and Caspase-Based High Throughput Screening Assay. 4. Structure–Activity Relationships of <i>N</i>-Alkyl Substituted Pyrrole Fused at the 7,8-Positions
  作者：William Kemnitzer、John Drewe、Songchun Jiang、Hong Zhang、Candace Crogan-Grundy、Denis Labreque、Monica Bubenick、Giorgio Attardo、Real Denis、Serge Lamothe、Henriette Gourdeau、Ben Tseng、Shailaja Kasibhatla、Sui Xiong Cai

  DOI：10.1021/jm7010657

  日期：2008.2.1

  In our continuing effort to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the structure-activity relationship (SAR) of alkyl substituted pyrrole fused at the 7,8-positions. A methyl group substituted at the nitrogen in the 7-position of the pyrrole ring led to a series of potent apoptosis inducers with potency in the low nanomolar range. These compounds were also found to be low nanomolar or subnanomolar inhibitors of cell growth, and they inhibited tubulin polymerization, indicating that methylation of the 7-position nitrogen does not change the mechanism of action of these chromenes. Compound 2d was identified as a highly potent apoptosis inducer with an EC50 value of 2 nM and a highly potent inhibitor of cell growth with a GI(50) value of 0.3 nM in T47D cells.