2-amino-7-(dimethylamino)-4-(3,4,5-trimethoxyphenyl)-4H-chromene-3-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: 2-amino-7-(dimethylamino)-4-(3,4,5-trimethoxyphenyl)-4H-chromene-3-carbonitrile
• 英文别名: 2-Amino-3-cyano-7-dimethylamino-4-(3,4,5-trimethoxyphenyl)-4H-chromene
• 化学式: C₂₁H₂₃N₃O₄
• 分子量: 381.431
• InChiKey: NCOGEMKUOWRKHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  90
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-bromo-2-isothiocyanatobenzene 、 2-amino-7-(dimethylamino)-4-(3,4,5-trimethoxyphenyl)-4H-chromene-3-carbonitrile 在 吡啶 作用下， 反应 24.0h， 以61%的产率得到3-(2-bromophenyl)-5-(3,4,5-trimethoxyphenyl)-8-(dimethylamino)-4-imino-3,4-dihydro-1H-chromeno[2,3-d]pyrimidine-2(5H)-thione
  参考文献：
  名称：

  Synthesis of Novel 4H-Chromenes Containing a Pyrimidine-2-Thione Function in the Presence of Fe₃O₄ Magnetic Nanoparticles and Study of Their Antioxidant Activity

  摘要：

  The aim of the present work was to search for identification of novel reactive oxygen species (ROS) scavengers by testing new fused chromenopyrimidinethiones, which was synthesized using Fe3O4 nanoparticles. The new compounds were also tested for their cytotoxic activity. The obtained results showed that the incorporated pyrimidinethione moiety significantly increase antioxidant activity. In conclusion, the study of the pharmacological properties of the new chromenopyrimidinethiones allowed establishing new structure-activity relationships for splitting antioxidant and cytotoxic activity of these compounds.

  DOI：

  10.1080/10426507.2014.884094
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 哌啶 作用下， 以 丙醇 为溶剂， 反应 0.08h， 生成 2-amino-7-(dimethylamino)-4-(3,4,5-trimethoxyphenyl)-4H-chromene-3-carbonitrile
  参考文献：
  名称：

  Synthesis and anti-inflammatory activities of 4H-chromene and chromeno[2,3-b]pyridine derivatives

  摘要：

  在微波辐照下，通过一锅反应高效地制备了几种 4H-色烯和色烯并[2,3-b]吡啶的衍生物，并评估了它们的抗炎活性。与槲皮素相比，六种合成产物（1b、1c、1h、2d、2j 和 2l）能更有效地抑制肿瘤坏死因子-α 诱导的一氧化氮（NO）的产生，并在人和猪软骨细胞中表现出相当的细胞活力。特别是，剂量为 10 和 20 毫克/千克的 2d 具有非常强的抗炎作用，能抑制角叉菜胶诱导的大鼠爪水肿和前列腺素 E2 的形成。本文的研究结果表明，这些化合物有可能成为设计和开发新型抗炎药物的结构模板。

  DOI：

  10.1007/s11164-015-2081-7

文献信息

• Tris-hydroxymethylaminomethane (THAM): a novel organocatalyst for a environmentally benign synthesis of medicinally important tetrahydrobenzo[b]pyrans and pyran-annulated heterocycles
  作者：Kapil S. Pandit、Pramod V. Chavan、Uday V. Desai、Makarand A. Kulkarni、Prakash P. Wadgaonkar

  DOI：10.1039/c4nj02346c

  日期：——

  A simple, efficient and environmentally benign protocol has been developed for the one-pot, multicomponent synthesis of medicinally important tetrahydrobenzo[b]pyrans and pyran-annulated heterocycles using a commercially available, inexpensive, non-toxic, and biodegradable tris-hydroxymethylaminomethane (THAM) as a novel organocatalyst. Ambient reaction conditions, wide scope, avoidance of conventional

  已经开发了一种简单，有效且对环境无害的方案，用于使用市售，廉价，无毒且可生物降解的三羟甲基甲基甲烷（THAM）一锅，多组分合成重要的药用四氢苯并[ b ]吡喃和吡喃环杂环）作为新型有机催化剂。环境反应条件，宽范围，避免常规分离以及纯化技术以及催化剂连续五次运行的可重复使用性提高了该多组分反应规程歧管的实用性。
• 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-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
• 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. 1. Structure−Activity Relationships of the 4-Aryl Group
  作者：William Kemnitzer、John Drewe、Songchun Jiang、Hong Zhang、Yan Wang、Jianghong Zhao、Shaojuan Jia、John Herich、Denis Labreque、Richard Storer、Karen Meerovitch、David Bouffard、Rabindra Rej、Real Denis、Charles Blais、Serge Lamothe、Giorgio Attardo、Henriette Gourdeau、Ben Tseng、Shailaja Kasibhatla、Sui Xiong Cai

  DOI：10.1021/jm049640t

  日期：2004.12.1

  By applying a novel cell- and caspase-based HTS assay, 2-amino-3-eyano-7-(dimethylamino)4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been identified as a potent apoptosis inducer. Compound la was found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage and to induce apoptosis as determined by the flow cytometry analysis assay in multiple human cell lines (e.g. Jurkat, T47D). Through structure-activity relationship (SAR) studies of the 4-aryl group, a 4- and 7-fold increase in potency was obtained from the screening hit la to the lead compounds 2-amino-4-(3-bromo-4,5-dimethoxyphenyl)-3-cyano-7-(dimethylamino)-4H-chromene (1c) and 2-amino-3-cyano-7-(dimethylamino)4-(5-methyl-3-pyridyl)-4H-chromene (4e), with an EC50 of 19 and 11 nM in the caspase activation assay in T47D breast cancer cells, respectively. The 2-amino-4-aryl-3-cyano-7-(dimethylamino)4H-chromenes also were found to be highly active in the growth inhibition MTT assay, with GI(50) values in the low nanomolar range for compound 1c. Significantly, compound le was found to have a GI(50) value of 2 nM in the paclitaxel resistant, p-glycoprotein overexpressed, MESSA/DX5 tumor cells. Functionally, compound 1c was found to be a potent inhibitor of tubulin polymerization and to effectively inhibit the binding of colchicine to tubulin. These results confirm that the cell-based caspase activation assay is a powerful tool for the discovery of potent apoptosis inducers and suggest that the 4-aryl-4H-chromenes have the potential to be developed into future anticancer agents.
• US6906203B1
  申请人：——

  公开号：US6906203B1

  公开（公告）日：2005-06-14