2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-hydroxymethyl-4H-pyrrolo[2,3-h]chromene

• 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: 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-hydroxymethyl-4H-pyrrolo[2,3-h]chromene
• 英文别名: 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-7-(hydroxymethyl)-4H-pyrano[2,3-e]indole-3-carbonitrile
• 化学式: C₂₁H₁₈BrN₃O₄
• 分子量: 456.296
• InChiKey: BNVXPQZDGJVZBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-hydroxymethyl-4H-pyrrolo[2,3-h]chromene 、 (4E,7E,10E,13E,16E,19E)-Docosa-4,7,10,13,16,19-hexaenoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以43%的产率得到4,7,10,13,16,19-docosahexaenoic acid {2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-4H-pyrrolo[2,3-h]chromene}-7-ylmethyl ester
  参考文献：
  名称：

  Substituted 4-aryl-4h-pyrrolo[2,3-h]chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof

  摘要：

  本发明涉及被代替的4H-香豆素及其类似物，由式（I）表示：其中R1，R3-R5，A，D，Y和Z在此处定义。本发明还涉及发现具有式（I）的化合物是caspase的激活剂和凋亡诱导剂。因此，本发明的caspase激活剂和凋亡诱导剂可用于诱导在发生细胞不受控制生长和异常细胞扩散的各种临床状况中的细胞死亡。

  公开号：

  US20060104998A1
• 作为产物：
  描述：

  4-hydroxy-1-hydroxymethyl-1H-indole 、 3-溴-4,5-二甲氧基苯甲醛 、 丙二腈 在 哌啶 作用下， 以 乙醇 为溶剂， 以42%的产率得到2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-hydroxymethyl-4H-pyrrolo[2,3-h]chromene
  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
• Substituted 4-aryl-4h-pyrrolo[2,3-h]chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cai Xiong Sui

  公开号：US20060104998A1

  公开（公告）日：2006-05-18

  The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the Formula (I): wherein R 1 , R 3 -R 5 , A, D, Y and Z 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-香豆素及其类似物，由式（I）表示：其中R1，R3-R5，A，D，Y和Z在此处定义。本发明还涉及发现具有式（I）的化合物是caspase的激活剂和凋亡诱导剂。因此，本发明的caspase激活剂和凋亡诱导剂可用于诱导在发生细胞不受控制生长和异常细胞扩散的各种临床状况中的细胞死亡。
• 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.