3-amino-1-(3-bromo-4,5-dimethoxy-phenyl)-1H-4-oxa-5-aza-phenanthrene-2-carbonitrile

• 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: 3-amino-1-(3-bromo-4,5-dimethoxy-phenyl)-1H-4-oxa-5-aza-phenanthrene-2-carbonitrile
• 英文别名: 3-amino-1-(3-bromo-4,5-dimethoxyphenyl)-1H-4-oxa-5-azaphenanthrene-2-carbonitrile；2-Amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-quino[8,7-b]pyran；2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-4H-pyrano[3,2-h]quinoline-3-carbonitrile
• 化学式: C₂₁H₁₆BrN₃O₃
• 分子量: 438.28
• InChiKey: OYSNFWFWWNCTSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  8-羟基喹啉 、 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41%的产率得到3-amino-1-(3-bromo-4,5-dimethoxy-phenyl)-1H-4-oxa-5-aza-phenanthrene-2-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. 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-chromene and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Drewe A. John

  公开号：US20050154015A1

  公开（公告）日：2005-07-14

  The present invention is directed to substituted 4H-chromene and analogs thereof, represented by the general Formula I: wherein A, B, X, Y, Z and R 5 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.

  本发明涉及取代的4H-香豆素及其类似物，通式如下：其中A、B、X、Y、Z和R5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以用于诱导各种临床情况下不受控制的异常细胞的生长和扩散导致的细胞死亡。
• CHROMENE DERIVATIVES AND THEIR ANALOGA AS WNT PATHWAY ANTAGONISTS
  申请人：Boutros Michael

  公开号：US20130296344A1

  公开（公告）日：2013-11-07

  Compounds according to the general formula (I) wherein X 1 , X 2 , X 3 and X 4 independently from each other are N or CR 8 wherein R 8 may be same or different, and wherein up to 3 of the group X 1 , X 2 , X 3 and X 4 may be N; A is a 5- or 6-membered aromatic or heteroaromtic cycle containing 1 to 3 heteroatoms selected from the group consisting of N, O and S wherein A may be substituted by 1 to 5 substituents R which may be same or different; their solvates, hydrates, and pharmaceutically acceptable salts for the treatment of a disorder or disease associated with an aberrant activation of Wnt signalling in a mammal selected from a cell proliferative disorder, rheumatoid arthritis, increased bone density, aging or age-related disorders and/or diseases or Dupuytren disease (superficial fibromatosis).

  根据通式（I），其中X1、X2、X3和X4独立地为N或CR8，其中R8可以相同或不同，且X1、X2、X3和X4中最多3个可以为N；A是一个含有1至3个异原子（选自N、O和S）的5-或6元芳香或杂芳基环，其中A可以被1至5个基团R取代，这些基团可以相同或不同；它们的溶剂化物、水合物和药学上可接受的盐用于治疗与哺乳动物中Wnt信号通路异常激活相关的疾病或症状，包括细胞增殖性疾病、类风湿性关节炎、骨密度增加、衰老或与年龄相关的疾病或疾病或杜普伊特伦病（表浅性纤维瘤病）。
• Chromene derivatives and their analoga as Wnt pathway antagonists
  申请人：Boutros Michael

  公开号：US09371333B2

  公开（公告）日：2016-06-21

  Compounds of formula (IIc); wherein X3 and X4 independently from each other are N or CR8 wherein R8 may be same or different; Y1, Y2, Y3 and Y4 independently from each other are N or CR9 wherein R9 may be same or different and wherein up to 3 of the group Y1, Y2, Y3 and Y4 may be N; their solvates, hydrates, and pharmaceutically acceptable salts, their use for modulating the Wnt signalling pathway activity and their use as a medicament, preferably for the treatment of cancer.

  式子(IIc)的化合物; 其中X3和X4独立地是N或CR8，其中R8可以相同或不同; Y1、Y2、Y3和Y4独立地是N或CR9，其中R9可以相同或不同，其中Y1、Y2、Y3和Y4中最多有3个可以是N; 它们的溶剂化物、水合物和药学上可接受的盐，它们用于调节Wnt信号通路活性和作为药物使用，优选用于治疗癌症。
• Chromene derivatives and their analogs as Wnt pathway antagonists
  申请人：Deutsches Krebsforschungszentrum

  公开号：US10065939B2

  公开（公告）日：2018-09-04

  Compounds of formula (IIc); wherein X3 and X4 independently from each other are N or CR8 wherein R8 may be same or different; Y1, Y2, Y3 and Y4 independently from each other are N or CR9 wherein R9 may be same or different and wherein up to 3 of the group Y1, Y2, Y3 and Y4 may be N; their solvates, hydrates, and pharmaceutically acceptable salts, their use for modulating the Wnt signalling pathway activity and their use as a medicament, preferably for the treatment of cancer.

  式（IIc）化合物；其中 X3 和 X4 相互独立地为 N 或 CR8（其中 R8 可以相同或不同）；Y1、Y2、Y3 和 Y4 相互独立地为 N 或 CR9（其中 R9 可以相同或不同），且 Y1、Y2、Y3 和 Y4 组中最多有 3 个可以是 N；它们的溶解物、水合物和药学上可接受的盐；它们在调节 Wnt 信号通路活性方面的用途以及它们作为药物（最好用于治疗癌症）的用途。
• SUBSTITUTED 4H-CHROMENE AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1230232B1

  公开（公告）日：2004-02-25