2-amino-3-cyano-4-(2-methoxyphenyl)-7-(dimethylamino)-4H-benzopyran

• 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-(2-methoxyphenyl)-7-(dimethylamino)-4H-benzopyran
• 英文别名: 2-amino-3-cyano-7-(dimethylamino)-4-(2-methoxyphenyl)-4H-chromene；2-amino-7-(dimethylamino)-4-(2-methoxyphenyl)-4H-chromene-3-carbonitrile
• 化学式: C₁₉H₁₉N₃O₂
• 分子量: 321.379
• InChiKey: FUBZFCWMCGQOOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  邻甲氧基苯甲醛 、 丙二腈 、 3-羟基-N,N-二甲基苯胺 在 mesoporous Al-MCM-41 functionalized by layered double hydroxide nanosheets and (3-aminopropyl)triethoxysilane 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以84%的产率得到2-amino-3-cyano-4-(2-methoxyphenyl)-7-(dimethylamino)-4H-benzopyran
  参考文献：
  名称：

  有机催化级联 Knoevenagel-Michael 加成反应：多取代 2-氨基-4H-色烯衍生物的直接合成

  摘要：

  在本报告中，我们记录了在异质 Al-MCM-41-LDH@APTES (ALAM) 催化下合成生物活性多取代 2-氨基-4H-色胺衍生物的新策略。开发了一种合成程序来制备 Al-MCM-41-LDH@APTES (ALAM) 多相碱性催化剂。介孔 Al-MCM-41 通过已知的接枝化学通过层状双氢氧化物 (LDH) 纳米片和 (3-氨基丙基) 三乙氧基硅烷 (APTES) 部分作为碱性有机催化剂进行功能化。所得催化剂的外表面和层内都含有氨基官能团，并且可以通过加载 APTES 来调节碱度。通过 29Si 和 13C CP/MAS NMR、红外吸收光谱、TEM、XPS、EDX、TGA、XRD、CO2-TPD、N2 吸附等温线测量对样品进行了全面表征，并且他们成功地检测了级联型 Knoevenagel-Michael 加成反应。优化了与这些底物相关的产物产量，并确定了影响产量的关键反应参数。本

  DOI：

  10.1007/s10562-019-03089-8

文献信息

• 一种2-氨基-3-氰基-4H-吡喃类化合物的机械球磨辅助合成方法
  申请人：浙江工业大学

  公开号：CN113620919A

  公开（公告）日：2021-11-09

  本发明涉及化学合成技术领域，为解决现有现有技术下用化学法合成2‑氨基‑3‑氰基‑4H‑吡喃类化合物污染大，所用催化剂制备繁琐的问题，公开了一种2‑氨基‑3‑氰基‑4H‑吡喃类化合物的机械球磨辅助合成方法，包括以下步骤：（a）将底物1、底物2及丙二腈作为原料，加入蛋白质催化剂及助磨剂后进行机械球磨；（b）球磨结束后将反应物刮出，加入溶剂，过滤后经浓缩、柱层析制得2‑氨基‑3‑氰基‑4H‑吡喃类化合物。机械球磨技术有利于反应物分子相互接触，实现无溶剂反应，蛋白类催化剂易得对环境友好。本发明有效地实现了对2‑氨基‑3‑氰基‑4H‑吡喃类化合物的绿色合成，制备条件温和，操作简便，反应速率快。
• 4-Aryl-4H-Chromene-3-Carbonitrile Derivatives: Evaluation of Src Kinase Inhibitory and Anticancer Activities
  作者：Asal Fallah-Tafti、Rakesh Tiwari、Amir Nasrolahi Shirazi、Tahmineh Akbarzadeh、Deendayal Mandal、Abbas Shafiee、Keykavous Parang、Alireza Foroumadi

  DOI：10.2174/157340611796799258

  日期：2011.9.1

  Src kinase mutations and/or overexpression have been implicated in the development of a number of human cancers including colon, breast, and lung cancers. Thus, designing potent and selective Src kinase inhibitors as anticancer agents is a subject of major interest. A series of 4-aryl substituted derivatives of 2-amino-7-dimethylamino-4H-chromene- 3-carbonitrile were synthesized using one-pot reaction of appropriate substituted aromatic aldehydes, malononitrile, and 3-(dimethylamino)phenol in the presence of piperidine. All 23 compounds were evaluated for inhibition of Src kinase and cell proliferation in human colon adenocarcinoma (HT-29) and leukemia (CCRF-CEM) cell lines. Among the tested compounds, 2-chlorophenyl- (4c), 3-nitrophenyl- (4h), 4-trifluoromethyphenyl- (4i), and 2,3-dichlorophenyl- (4k) substituted chromenes showed Src kinase inhibitory effect with IC50 values of 11.1-18.3 μM. Compound 4c was relatively selective against Src (IC50 = 11.1 μM), when compared with selected kinases, epidermal growth factor receptor (EGFR, IC50 300 μM), C-terminal Src kinase (Csk, IC50 = 101.7 μM), and lymphocyte-specific protein tyrosine kinase (Lck, IC50 = 46.8 μM). 3-Chlorophenyl substituted thiazole (4v) and 2-chlorophenylsubstituted thiazole (4u) chromene derivatives inhibited the cell proliferation of HT-29 and CCRF-CEM by 80% and 50%, respectively, at a concentration of 50 μM. The data indicate that 4H-chromene-3-carbonitrile scaffold has the potential to be optimized further for designing more potent Src kinase inhibitors and/or anticancer lead compounds.

  Src 激酶突变和/或过度表达与结肠癌、乳腺癌和肺癌等多种人类癌症的发病有关。因此，设计强效且具有选择性的 Src 激酶抑制剂作为抗癌药物是一个备受关注的课题。在哌啶的存在下，利用适当取代的芳香醛、丙二腈和 3-（二甲基氨基）苯酚的一锅反应，合成了一系列 2-amino-7-dimethylamino-4H-chromene- 3-carbonitrile 的 4-芳基取代衍生物。对所有 23 种化合物在人结肠腺癌（HT-29）和白血病（CCRF-CEM）细胞系中对 Src 激酶和细胞增殖的抑制作用进行了评估。在测试的化合物中，2-氯苯基（4c）、3-硝基苯基（4h）、4-三氟甲基苯基（4i）和 2,3-二氯苯基（4k）取代的色烯类化合物具有抑制 Src 激酶的作用，IC50 值为 11.1-18.3 μM。与选定的激酶、表皮生长因子受体（EGFR，IC50 300 μM）、C-末端 Src 激酶（Csk，IC50 = 101.7 μM）和淋巴细胞特异性蛋白酪氨酸激酶（Lck，IC50 = 46.8 μM）相比，化合物 4c 对 Src 具有相对的选择性（IC50 = 11.1 μM）。3-氯苯基取代的噻唑（4v）和 2-氯苯基取代的噻唑（4u）色烯衍生物在 50 μM 浓度下分别抑制 HT-29 和 CCRF-CEM 细胞增殖 80% 和 50%。这些数据表明，4H-色烯-3-甲腈支架具有进一步优化的潜力，可用于设计更有效的 Src 激酶抑制剂和/或抗癌先导化合物。
• Mechano-Biocatalytic Rapid Synthesis of 2-Amino-3-cyano-4H-pyran Derivatives
  作者：Xiaohe Chu、Ling Jiang、Qingqing Lu、Jingwen Dong

  DOI：10.3987/com-21-14608

  日期：——

  A series of 2-amino-3-cyano-4H-pyrans 4a-4s and 5a-5r were synthesized in good to excellent yields via a simple one-pot reaction. The facile method depended on one-pot three-component reaction of aromatic aldehyde, malononitrile and dimedone or 3-(dimethylamino)phenol in the presence of bovine serum albumin (BSA) as the catalyst under ball-milling conditions. The reactions were completed in 40 min

  通过简单的一锅法反应合成了一系列 2-氨基-3-氰基-4 H-吡喃4a - 4s和5a - 5r ，收率良好。简便的方法依赖于在球磨条件下，在牛血清白蛋白（BSA）作为催化剂存在下，芳香醛、丙二腈和二甲酮或3-（二甲氨基）苯酚的一锅三组分反应。反应在 40 分钟内完成，产率为 80-98%。合成的化合物通过1 H NMR、13 C NMR和ESI-MS进行了表征。
• 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.
• Polyethyleneimine-modified superparamagnetic Fe3O4 nanoparticles: An efficient, reusable and water tolerance nanocatalyst
  作者：Mehdi Khoobi、Tayebeh Modiri Delshad、Mohsen Vosooghi、Masoumeh Alipour、Hosein Hamadi、Eskandar Alipour、Majid Pirali Hamedani、Seyed Esmaeil Sadat ebrahimi、Zahra Safaei、Alireza Foroumadi、Abbas Shafiee

  DOI：10.1016/j.jmmm.2014.09.044

  日期：2015.2

  A novel magnetically separable catalyst was prepared based on surface modification of Fe304 magnetic nanoparticle (IVINPs) with polyethyleneimine (PEI) via covalent bonding. 13-(2,3-Epoxypropoxy)propyl] trimethoxysilane (EPO) was used as cross linker to bond PEI on the surface of MNPs with permanent stability in contrast to PEl coating via electrostatic interactions. The synthesized catalyst was characterized by Fourier transform infrared (FT-IR), thermogravimetric analysis (TGA). X-ray powder diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The catalyst show high efficiency for one-pot synthesis of 2-amino-3-cyano 4/1 pyran derivatives via multi-component reaction (MCR). This procedure offers the advantages of green reaction media, high yield, short reaction time, easy purification of the products and simple recovery and reuse of the catalyst by simple magnetic decantation without significant loss of catalytic activity. (C) 2014 Elsevier B.V. All rights reserved,