MX-76747 | 339062-49-6

• 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: MX-76747
• 英文别名: 2-amino-3-cyano-4-(3-bromo-4,5-dimethoxyphenyl)-4H-indolo[4,5-b]pyran；2-Amino-4-(3-bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-carbonitrile
• CAS: 339062-49-6
• 化学式: C₂₀H₁₆BrN₃O₃
• 分子量: 426.269
• InChiKey: ZQNNHAWSCLTIPN-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：

  MX-76747 在 2-甲基-2-硝基丙烷 、 sodium tetrahydroborate 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以40%的产率得到4-(3-Bromo-4,5-dimethoxyphenyl)-4,7-dihydropyrano[2,3-e]indole-3-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 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
• 作为产物：
  描述：

  4-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， 反应 12.0h， 以10%的产率得到MX-76747
  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。
• Substituted 4h-chromens, 2h-chromenes, chromans and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cai Xiong Sui

  公开号：US20050176750A1

  公开（公告）日：2005-08-11

  The present invention is directed to substituted 4H-chromenes, 2H-chromenes, chromans and analogs thereof, represented by the general Formula (I) wherein R 5 , A, B, X, Y, Z and dotted lines 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-色烯、2H-色烯、色烷及其类似物，由通式（I）所表示，其中R5、A、B、X、Y、Z和虚线在此定义。本发明还涉及发现具有通式（I）的化合物是caspase的激活剂和凋亡的诱导剂。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出现的异常细胞的无控制生长和扩散的细胞死亡。
• 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。
• 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
• SUBSTITUTED 4H-CHROMENES, 2H-CHROMENES, CHROMANS AND ANALOGS AS ACTIVATORS OF CASPASES AND INDUCERS OF APOPTOSIS AND THE USE THEREOF
  申请人：Cytovia, Inc.

  公开号：EP1513515A2

  公开（公告）日：2005-03-16