N-methyl-4-(methylthio)-3-nitro-4H-chromen-2-amine | 1173429-43-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-methyl-4-(methylthio)-3-nitro-4H-chromen-2-amine
• 英文别名: N-methyl-4-methylsulfanyl-3-nitro-4H-chromen-2-amine
• CAS: 1173429-43-0
• 化学式: C₁₁H₁₂N₂O₃S
• 分子量: 252.294
• InChiKey: LXLCHXXKIVFGIH-UHFFFAOYSA-N

物化性质

• 沸点：
  371.5±42.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-methyl-4-(methylthio)-3-nitro-4H-chromen-2-amine 在 吡啶 作用下， 以 乙醇 为溶剂， 反应 28.0h， 生成 2-[2-(methylamino)-3-nitro-4H-4-chromenyl]phenyl acetate
  参考文献：
  名称：

  Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

  摘要：

  A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac(2)O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.08.045
• 作为产物：
  描述：

  (E-)-N-methyl-1-(methylthio)-2-nitroethanamine 、 水杨醛 在 胆碱 作用下， 以 水 为溶剂， 反应 5.0h， 生成 N-methyl-4-(methylthio)-3-nitro-4H-chromen-2-amine
  参考文献：
  名称：

  氢氧化胆碱：一种高效且可生物降解的催化剂，用于在水性介质中合成 2-氨基-3-硝基-4H-色烯衍生物

  摘要：

  摘要 通过各种 2-羟基苯甲醛和 (E)-N-methyl-1-(E)-N-methyl-1-(甲硫基）-2-硝基乙胺在碱性离子液体催化剂（氢氧化胆碱（ChOH））的存在下，在室温和水性介质中。该方法的优点是可生物降解和可回收的催化剂，反应时间短，反应温和，环境友好，产品收率高（83-96%）。图形概要

  DOI：

  10.1080/10426507.2018.1469489

文献信息

• Synthesis and antimicrobial evaluation of 2-hydroxynaphthalene-1,4-dione and 4H-chromene conjugates
  作者：H. Surya Prakash Rao、Venkata Swamy Tangeti、Lakshmi Narayana Adigopula

  DOI：10.1007/s11164-016-2536-5

  日期：2016.10

  considered to be medicinally privileged scaffolds. We have designed novel conjugates that incorporated both these scaffolds, as such conjugates exhibit unique biological properties reflecting those due to individual units and collective presence. In this work, we have achieved facile, efficient, and high yielding synthesis of 19 such conjugates from readily available 2-alkylamino-4-methylsulfanyl-3-nitro-4H-chromenes

  通常将4 H -Chromene和1,4-萘醌系统视为具有医学特权的支架。我们设计了结合了这两种支架的新型结合物，因为这种结合物表现出独特的生物学特性，反映出由于单个单元和集体存在而产生的生物学特性。在这项工作中，我们已经从容易获得的2-烷基氨基-4-甲基硫烷基-3-硝基-4 H-色烯和2-羟基萘-1,4-二酮中轻松，高效且高收率地合成了19种此类共轭物。高极性nitroketene- Ø，ñ存在于缀合物中的β-乙缩醛单元被设计为防止穿过血脑屏障。我们已经进行了结构活性关系（SAR）研究，该研究基于对三种革兰氏阳性细菌[枯草芽孢杆菌，金 黄色葡萄球菌（MSSA），金黄色葡萄球菌（MRSA）]，一种革兰氏阴性细菌（大肠杆菌）的十种结合物进行初步抗菌筛选的研究）和两种真菌（黑曲霉，白色念珠菌）。SAR研究表明，在4 H的C（6）和C（8）位置具有卤素的共轭物具有C（2）NMe基团的-色烯环显示
• Copper-Catalyzed C(sp³)-C(sp²) Cross-Coupling: Synthesis of 4-Aryl-2-alkyl­amino-3-nitro-4<i>H</i>-chromenes
  作者：H. Surya Prakash Rao、A. Veera Bhadra Rao

  DOI：10.1002/ejoc.201402003

  日期：2014.6

  Inexpensive copper(II) acetate effectively catalyzes cross-coupling of electron-deficient as well as electron-rich arylboronic acids with 4-methylsulfanyl-2-alkylamino-3-nitro-4H-chromenes under near neutral conditions at room temp. to furnish a range of 4-aryl-4H-chromenes. This new strategy enabled substitution of the C(4)SMe group present on a sp3 hybridized carbon of the 4H-chromenes with aryl/heteroaryl

  廉价的醋酸铜 (II) 在室温下近中性条件下有效催化缺电子和富电子芳基硼酸与 4-甲基硫基-2-烷基氨基-3-硝基-4H-色烯的交叉偶联。以提供一系列 4-芳基-4H-色烯。这种新策略使存在于 4H-色烯的 sp3 杂化碳上的 C(4)SMe 基团替换为芳基/杂芳基基团。机理探测表明，CuI-CuIII 循环参与催化。通过 Cu(OAc)2 和 Pd2(dba)3（Suzuki 耦合）催化实现了 C(4)SMe 和 C(6)Br 与芳基的一锅顺序取代。
• One-Pot Synthesis of Densely Substituted Pyrazolo[3,4-<i>b</i>]-4,7-dihydropyridines
  作者：H. Surya Prakash Rao、Lakshmi Narayana Adigopula、Krishna Ramadas

  DOI：10.1021/acscombsci.6b00156

  日期：2017.5.8

  We have achieved a facile synthesis of a combinatorial library of densely substituted pyrazolo[3,4-b]-4,7-dihydropyridines— the mimics of antigenital wart drug podophyllotoxin—from 5-aminopyrazoles and 4-(methylthio) 4H-chromenes. The C(4) pyrazolyl 4H-chromenes, which also possess structural features of podophyllotoxin, were isolable intermediates in the two-step, one-pot condensation. The condensation

  我们已经实现了密集的取代的吡唑并[3,4的组合文库的简便合成b ] -4,7- dihydropyridines- antigenital疣药物鬼臼毒素从5-氨基吡唑和4-（甲硫基）4的模拟物ħ -chromenes 。C（4）吡唑基4 H-色酮，也具有鬼臼毒素的结构特征，是两步一锅缩合反应中的可分离中间体。当将3-氧代-3-苯基丙腈，肼（5-氨基吡唑的前体）和4-（甲硫基）-4 H-色烯在回流的乙醇中加热时，缩合反应以单锅，多组分的方式进行。但是，冷凝在4 H处停止-甲基chrome阶段，其中使用甲基肼或苯肼。我们的发现为鬼臼毒素模拟物的组合文库的合成提供了机会，从而为发现潜在的癌症治疗候选药物铺平了道路。
• Design, synthesis, molecular docking, and biological evaluation of N-methyl-3-nitro-4-(nitromethyl)-4H-chromen-2-amine derivatives as potential anti-cancer agents
  作者：A. Parthiban、J. Muthukumaran、A. Moushumi Priya、S. Jayachandran、R. Krishna、H. Surya Prakash Rao

  DOI：10.1007/s00044-013-0642-0

  日期：2014.2

  A series of N-methyl-3-nitro-4-(nitromethyl)4H-chromen-2-amine derivatives 8 were synthesized from 2-((E)-2-nitrovinyl)phenol 7 and ((E)-N-methyl)-1-(methylthio)-2-nitroethenamine 5. The cytotoxic activity of these molecules was tested against two cancer cell lines namely HeLa (cervical cancer) and HEp-2 (epidermoid laryngeal carcinoma). Among them, two molecules (4H-chromenes 8h and 8i) displayed potent anti-proliferative activity with IC50 values of 115.04 and 18.96 mu M for HeLa and 86.94 and 25.08 mu M for Hep-2 cell lines, respectively. Morphological evaluation of the cell lines revealed that both 8h and 8i induce the apoptotic process. Molecular docking studies of all the 4H-chromenes 8 with antiapoptotic Bcl-2, Bcl-w, and Bcl-xL proteins revealed that the 4H-chromenes 8h and 8i have good docking score and thus corroborated in vitro studies. Furthermore, evaluation of Lipinski and ADMET properties revealed their drug-like pharmacokinetic profiles. Thus, 4H-chromenes 8h and 8i exhibit promising anti-cancer properties and can be used as lead compounds for further development.
• Synthesis, in vitro and in silico anti-proliferative activity of 4-aryl-4H-chromene derivatives
  作者：A. Parthiban、M. Kumaravel、J. Muthukumaran、R. Rukkumani、R. Krishna、H. Surya Prakash Rao

  DOI：10.1007/s00044-016-1569-z

  日期：2016.7

  A new series of C4-N,N-dialkylaniline-substituted 4-aryl-4H-chromenes were synthesized, and their anti-proliferative properties were evaluated against human cancer cell lines, namely, laryngeal carcinoma (Hep2), lung adenocarcinoma (A549), and cervical cancer (HeLa). The best among them, the 4-aryl-4H-chromene with C4-1-phenylpiperidine substitution was selected for further structure activity relationship (SAR) studies. Among the derivatives, N,6-dimethyl-3-nitro-4-(4-(piperidine-1-yl)phenyl)-4H-chromene-2-amine 3k showed most potent cytotoxic activity against all three cancer cell lines. Toxicity studies revealed that the 4-aryl-4H-chromenes specifically target the cancer cell lines. Molecular docking studies of this compound revealed its efficient interaction with the active site of alpha beta-tubulin protein.