2-amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran | 475576-80-8

• 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-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran
• 英文别名: 2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-4,9-dihydropyrano[3,2-g]indole-3-carbonitrile
• CAS: 475576-80-8
• 化学式: C₂₀H₁₆BrN₃O₃
• 分子量: 426.269
• InChiKey: ZTKXVRYVYTZMPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 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：
  93.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-b]pyran 、 碘甲烷 在 caesium carbonate 作用下， 以 丙酮 为溶剂， 以50 mg (24%)的产率得到3-Cyano-4-(3-bromo-4,5-dimethoxyphenyl)-2-methylamino-9-methyl-4H-pyrrolo[3,2-h]chromene
  参考文献：
  名称：

  Substituted 4H-chromenes and analogs as activators of caspases and inducers of apoptosis and the use thereof

  摘要：

  本发明涉及被一般式I表示的取代的4H-香豆素及其类似物： 1 其中R 1 -R 5 ，A，Y和Z在此处被定义。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各种临床病况中发生细胞死亡，其中异常细胞的不受控制的生长和传播。

  公开号：

  US20030065018A1
• 作为产物：
  描述：

  7-羟基吲哚 、 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13%的产率得到2-amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[7,6-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 High-Throughput Screening Assay. 3. Structure−Activity Relationships of Fused Rings at the 7,8-Positions

  摘要：

  As a continuation of our efforts to discover and develop the apoptosis-inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of fused rings at the 7,8-positions. It was found that a five-member aromatic ring, such as pyrrolo with nitrogen at either the 7- or 9-position, is preferred. A six-member aromatic ring, such as benzo or pyrido, also led to potent compounds. The SAR of the 4-aryl group was found to be similar for chromenes with a fused ring at the 7,8-positions. These compounds were found to inhibit tubulin polymerization, indicating that cyclization of the 7,8-positions into a ring does not change the mechanism of action. Compound 2h was identified to be a highly potent apoptosis inducer with an EC50 of 5 nM and a highly potent inhibitor of cell proliferation with a GI(50) of 8 nM in T47D cells.

  DOI：

  10.1021/jm070216c

文献信息

• SUBSTITUTED 4H-CHROMENES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cai Xiong Sui

  公开号：US20060035925A1

  公开（公告）日：2006-02-16

  The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the general Formula I: wherein R 1 -R 5 , A, 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.

  本发明涉及代替的4H-香豆素及其类似物，由通式I表示：其中R1-R5，A，Y和Z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不受控制的异常细胞的生长和扩散引起的细胞死亡。
• Substituted 4-aryl-chromene as activator of caspases and inducer of apoptosis and as antivascular agent and the use thereof
  申请人：Cai Sui Xiong

  公开号：US20080085328A1

  公开（公告）日：2008-04-10

  The present invention is directed to a substituted 4H-chromene represented by the Formula 1R, substantially free from the corresponding (S)-stereoisomer: The present invention also relates to the discovery that compound 1R, substantially free from the corresponding (S)-stereoisomer, is an activator of caspases and inducer of apoptosis, as well as an antivascular agent. Therefore, compound 1R, substantially free from the corresponding (S)-stereoisomer, can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs. Compound 1R, substantially free from the corresponding (S)-stereoisomer, also can be used for the treatment of diseases due to overgrowth of vasculature, such as solid tumors and ocular neovascularization.

  本发明涉及一种由公式1R表示的取代的4H-香豆素，基本上不含相应的（S）立体异构体。本发明还涉及发现化合物1R，基本上不含相应的（S）立体异构体，是caspases的激活剂和诱导凋亡的剂，同时也是抗血管生成剂。因此，基本上不含相应的（S）立体异构体的化合物1R可以用于在各种临床情况下诱导细胞死亡，其中异常细胞的不受控制的生长和扩散发生。基本上不含相应的（S）立体异构体的化合物1R还可用于治疗由于血管增生过度引起的疾病，如实体肿瘤和眼部新生血管形成。
• EP1392683A4
  申请人：——

  公开号：EP1392683A4

  公开（公告）日：2005-10-26
• SUBSTITUTED 4H-CHROMENES AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THEIR USE AS ANTICANCER AGENTS
  申请人：Cytovia, Inc.

  公开号：EP1392683B1

  公开（公告）日：2009-12-02
• SUBSTITUTED 4 i H /i -CHROMENES AND ANALOGS AS ACTIVATORS OFGASP ASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1392683A1

  公开（公告）日：2004-03-03