1-(4-甲氧基苯基)-3-(4-硝基苯基)脲 | 40387-34-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-(4-甲氧基苯基)-3-(4-硝基苯基)脲
• 英文名称: 1-(4-methoxyphenyl)-3-(4-nitrophenyl)urea
• 英文别名: 1-[(4-methoxyphenyl)azaniumyl]-N-(4-nitrophenyl)methanimidate
• CAS: 40387-34-6
• 化学式: C₁₄H₁₃N₃O₄
• 分子量: 287.275
• InChiKey: WRKICABANNBAHW-UHFFFAOYSA-N

物化性质

• 熔点：
  208 °C(Solv: ethanol (64-17-5))
• 沸点：
  376.9±27.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  96.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-甲氧基苯基)-3-(4-硝基苯基)脲 在 palladium on activated charcoal 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.0h， 生成 (Z/E)1-(4-((5-fluoro-2-oxoindolin-3-ylidene)amino)phenyl)-3-(4-methoxyphenyl)urea
  参考文献：
  名称：

  Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking

  摘要：

  In our effort to develop potent and effective agents with anti-proliferative activity towards HepG2 hepatocellular carcinoma cells with potential inhibitory activity against VEGFR-2, a novel series of 1-(4-((2oxoindolin-3-ylidene)amino)phenyl)-3-arylureas was designed and synthesized. All the newly prepared ureas 9a-x were evaluated in vitro for their anti-proliferative activity against HepG2 hepatocellular carcinoma cell line. Compounds 9a-c, 9e, 9f, 9j, 9m-o, 9t-v and 9x exhibited good activity against HepG2 cancer cells (IC50 = 1.22 +/- 0.11-8.37 +/- 0.85 mu M) comparable to that of doxorubicin and sorafinib (IC50 = 2.90 +/- 0.36 and 3.40 +/- 0.25 mu M, respectively). These thirteen compounds were further evaluated for their inhibitory activity against VEGFR-2. Compound 9x emerged as the most active counterpart against VEGFR-2 with IC50 value of 031 +/- 0.04 mu M. Furthermore, a molecular docking of the tested compounds was carried out in order to investigate their binding pattern with the prospective target, VEGFR-2 (PDB-code: 4ASD). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.040
• 作为产物：
  描述：

  1-(4-Methoxyphenyl)-3-(4-nitrophenyl)thiourea 在 potassium superoxide 作用下， 以 二甲基亚砜 为溶剂， 反应 10.0h， 以86%的产率得到1-(4-甲氧基苯基)-3-(4-硝基苯基)脲
  参考文献：
  名称：

  通过二甲基亚砜中的过氧化物自由基阴离子 (O2·−) 将 1,3-二取代硫脲轻松转化为相应的脲醛

  摘要：

  在 20 °C 的二甲基亚砜中用超氧自由基阴离子 (O2·-) 处理 1,3-二取代硫脲导致以极好的产率形成 1,3-二取代脲。脱硫似乎是通过形成过氧-硫中间体如过氧-亚磺酸盐、-亚磺酸盐和/或-磺酸盐进行的。

  DOI：

  10.1246/cl.1984.309

文献信息

• Multicomponent, One-Pot Sequential Synthesis of 1,3,5- and 1,3,5,5-Substituted Barbiturates
  作者：Alessandro Volonterio、Matteo Zanda

  DOI：10.1021/jo801288s

  日期：2008.10.3

  represents a general and straightforward one-pot sequential synthesis of 1,3,5-trisubstituted barbiturates in very mild conditions (organic solvent/2 N NaOH aqueous solution, 20 degrees C). Performing the reaction in the presence of an electrophile resulted in the formation of fully substituted (namely, 1,3,5,5-tetrasubstituted) barbiturates through a three-component one-pot sequential process. The latter

  碳二亚胺和丙二酸单乙酯容易反应，得到N-酰脲衍生物，可以通过添加合适的碱原位环化。该方法代表在非常温和的条件下（有机溶剂/ 2 N NaOH水溶液，20摄氏度）进行的简单直接的一锅顺序合成1,3,5-三取代的巴比妥酸盐。在亲电子试剂的存在下进行反应，通过三组分一锅法连续反应形成了完全取代的（即1,3,5,5-四取代的）巴比妥酸酯。然而，后者仅在高反应性亲电试剂例如苄基和在某些情况下是烯丙基卤的情况下发生。为了扩大该方法的范围，我们寻求开发一种用于1,3,5-三取代的巴比妥酸酯的C-烷基化的通用方法。我们发现，在无水K2CO3存在下于120℃下在CH3CN中用烷基卤处理1,3,5-三取代的巴比妥酸酯时发生C-烷基化，从而以良好的收率提供目标1,3,5,5-四取代的巴比妥酸酯。多组分工艺是通过以下三个步骤以一锅顺序方式组合完成的，即碳二亚胺与丙二酸单乙酯的缩合，所得N-酰基脲的环化以及所得1,3的C-烷基化，
• Substituent effects on nitrosation of 1,3-diarylureas with nitrosyl chloride, dinitrogen trioxide, and dinitrogen tetroxide.
  作者：MAKOTO MIYAHARA

  DOI：10.1248/cpb.34.1950

  日期：——

  Twenty-eight para-substituted and eleven ortho-substituted 1, 3-diarylureas were prepared.Their proton nuclear magnetic resonance (1H-NMR) spectra were measured to evaluate the acidity of the ureido protons in the para-substituted ureas, and to estimate the conformations of ortho-substituted molecules. The chemical shifts and acidities of two ureido protons were additively controlled by the two para-substituents in the 1, 3-diarylureas. The sixteen para-substitued diarylureas were nitrosated with gaseous nitrosating reagents (dinitrogen trioxide, dinitrogen tetroxide or nitroxyl chloride) to give unstable isomeric mixtures of 1, 3-diaryl-1-nitrosoureas [R1-C6H4-N(NO)-CO-NH-C6H4-R2] and 1, 3-diaryl-3-nitrosoureas [R1-C6H4-NH-CO-N(NO)-C6H4-R2]. The isomer ratio of each nitrosated urea was correlated with the difference between the chemical shifts (d[NH]) of the two ureido protons in the 1H-NMR spectrum of the starting urea. When d[NH] was below 0.25 ppm (with NOCl) or 0.45 ppm (with N2O3), good linearity was obtained (r(NOCl)=0.943, n=11; r(N2O3)=0.869, n=15). When d[NH] was over 0.25 ppm (NOCl) or 0.45 ppm (N2O3), the 1-nitrosated isomer [R1-C6H4-N(NO)-CO-NH-C6H4-R2] was the sole product. These principles ould not be extended to dinitrogen tetroxide.Thirteen para-substituted diarylureas gave 1- or 3-nitrosated ureido derivatives as sole products and only four gave nitrosated isomeric mixtures.The 1H-NMR spectra of 5 types of ortho-substituted 1, 3-diarylureas were measured for comformational analysis. Their conformations seem to be different from those of para-substituted diarylureas. Eleven ortho-substituted 1, 3-diarylureas were nitrosated with nitrosyl chloride and dinitrogen tetroxide. In many cases, the nitroso group was predominantly introduced at the ureido nitrogen, which is less hindered sterically, and isomeric mixtures of 1- and 3-nitrosated ureas were obtained.

  制备了28个对位取代和11个邻位取代的1,3-二芳基脲。测得的质子核磁共振（1H-NMR）谱图用于评估对位取代脲脲基质子的酸性并估计邻位取代分子的构象。两个脲基质子的化学位移和酸度受1,3-二芳基脲中两个对位取代基的加和性控制。16个对位取代二芳基脲与气体亚硝化试剂（三氧化二氮、四氧化二氮或亚硝酰氯）经亚硝化反应得到不稳定的1,3-二芳基-1-亚硝基脲[R1-C6H4-N(NO)-CO-NH-C6H4-R2]和1,3-二芳基-3-亚硝基脲[R1-C6H4-NH-CO-N(NO)-C6H4-R2]异构体混合物。每种亚硝化脲的异构体比例与原始脲1H-NMR谱图中两个脲基质子化学位移差（d[NH]）相关。当d[NH]低于0.25 ppm（用NOCl）或0.45 ppm（用N2O3）时，获得了较好的线性关系（r(NOCl) = 0.943，n = 11；r(N2O3) = 0.869，n = 15）。当d[NH]高于0.25 ppm（用NOCl）或0.45 ppm（用N2O3）时，1-亚硝化异构体[R1-C6H4-N(NO)-CO-NH-C6H4-R2]是唯一产物。这些原理不能扩展到四氧化二氮。13个对位取代二芳基脲仅得到1-或3-亚硝化脲基衍生物作为唯一产物，只有4个得到亚硝化异构体混合物。测定了5种邻位取代1,3-二芳基脲的1H-NMR谱图用于构象分析。它们的构象似乎与对位取代二芳基脲不同。11个邻位取代1,3-二芳基脲与亚硝酰氯和四氧化二氮进行亚硝化反应。在许多情况下，亚硝基主要引入空间位阻较小的脲基氮，得到了1-和3-亚硝化脲的异构体混合物。
• Design, synthesis and molecular modeling study of certain VEGFR-2 inhibitors based on thienopyrimidne scaffold as cancer targeting agents
  作者：Amna Ghith、Khairia M. Youssef、Nasser S.M. Ismail、Khaled A.M. Abouzid

  DOI：10.1016/j.bioorg.2018.10.008

  日期：2019.3

  compound 10a. Flow cytometric analysis on both MCV-7 and PC-3 cancer cells revealed that it induced cell-cycle arrest in the G0-G1phase and reinforced apoptosis via activation of caspase-3. Furthermore, molecular modeling studies have been carried out to gain further understanding of the binding mode in the active site of VEGFR-2 enzyme and predict pharmacokinetic properties of all the synthesized inhibitors

  设计，合成和评价了不同系列的新型噻吩并[2，3- d ]嘧啶衍生物（9a-d，10a-f，l，m和15a-m）在体外抑制VEGFR-2酶的能力。而且，通过NCI对60种不同的人类癌细胞系进行了测试，以测试最终化合物的细胞毒性。VEGFR-2酶的抑制结果表明，化合物10d，15d和15 g是活性最高的抑制剂，IC 50值分别为2.5、5.48和2.27 µM，而化合物10a显着显示出最高的细胞生长抑制率，平均生长抑制率（GI）为31.57％。它对几种NCI细胞系表现出广谱的抗增殖活性，特别是对人乳腺癌（T7-47D）和肾癌（A498）细胞系分别具有85.5％和77.65％的抑制作用。为了研究该活性的机制，对化合物10a进行了进一步的生物学研究，例如流式细胞术细胞周期与caspase-3比色测定。对MCV-7和PC-3癌细胞的流式细胞仪分析表明，它诱导了G0-G1期的细胞周期停滞，并通过激活c
• Spontaneous and Direct Transformation of <i>N</i>,<i>O</i>-Diaryl Carbamates into <i>N</i>,<i>N</i>′-Diarylureas
  作者：Ryu Yamasaki、Yutaka Honjo、Ai Ito、Kazuo Fukuda、Iwao Okamoto

  DOI：10.1248/cpb.c18-00394

  日期：2018.9.1

  discovered a spontaneous reaction of N,O-diaryl carbamates to afford symmetrical N,N'-diarylureas. Optimization of the conditions indicated that N,N-dimethylformamide (DMF) was the best solvent and triethylamine (Et3N) was the best additive for this transformation. The reaction requires the presence of aryl groups on the nitrogen and oxygen atoms of carbamates. Substrates bearing an electron-donating

  我们已经发现N，O-二芳基氨基甲酸酯的自发反应以提供对称的N，N′-二芳基脲。条件的优化表明，N，N-二甲基甲酰胺（DMF）是最佳溶剂，三乙胺（Et3N）是该转化的最佳添加剂。该反应需要在氨基甲酸酯的氮和氧原子上存在芳基。在这些条件下，两个芳基上均带有供电子甲氧基的底物反应缓慢。
• Pd/C-Catalyzed Domino Synthesis of Urea Derivatives Using Chloroform as the Carbon Monoxide Source in Water
  作者：Liang Wang、Hao Wang、Guiqing Li、Shuliang Min、Fangyuan Xiang、Shiqi Liu、Waigang Zheng

  DOI：10.1002/adsc.201800954

  日期：2018.12.3

  A Pd/C‐catalyzed domino synthesis of symmetrical and unsymmetrical ureas from aryl iodides, sodium azide, amines and CHCl3 in water has been developed. This reaction proceeds with sequential carbonylation, Curtius rearrangement and nucleophilic addition. CHCl3 serves as a convenient and safe alternation of CO gas in the presence of KOH. A series of urea derivatives were obtained in moderate to good

  已经开发了一种Pd / C催化由水中的芳基碘化物，叠氮化钠，胺和CHCl 3合成对称和不对称脲的多米诺骨牌。该反应以顺序的羰基化，Curtius重排和亲核加成进行。在KOH存在下，CHCl 3可作为一种方便，安全的CO气体替代气体。以中等至良好的产率获得了具有良好的官能团耐受性的一系列脲衍生物。此外，连续六次运行后，Pd / C催化剂很容易被回收，催化活性略有下降。