1-(4-aminophenyl)-3-(4-methoxyphenyl)urea | 50906-32-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-aminophenyl)-3-(4-methoxyphenyl)urea
• CAS: 50906-32-6
• 化学式: C₁₄H₁₅N₃O₂
• 分子量: 257.292
• InChiKey: WCTLZJANTKDUCA-UHFFFAOYSA-N

物化性质

• 熔点：
  >250 °C
• 沸点：
  360.0±27.0 °C(Predicted)
• 密度：
  1.311±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 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：
  76.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-aminophenyl)-3-(4-methoxyphenyl)urea 、 靛红 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以71%的产率得到(Z/E)1-(4-methoxyphenyl)-3-(4-((2-oxoindolin-3-ylidene)amino)phenyl)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：

  异氰酸对硝基苯 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.0h， 生成 1-(4-aminophenyl)-3-(4-methoxyphenyl)urea
  参考文献：
  名称：

  以噻吩并嘧啶骨架为靶标的某些VEGFR-2抑制剂的设计，合成和分子模型研究

  摘要：

  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

  DOI：

  10.1016/j.bioorg.2018.10.008

文献信息

• Phenyl and Diaryl Ureas with Thiazolo[5,4‐ <i>d</i> ]pyrimidine Scaffold as Angiogenesis Inhibitors: Design, Synthesis and Biological Evaluation
  作者：Wen‐Jun Xue、Ya‐Hui Deng、Zhong‐Hui Yan、Ji‐Ping Liu、Yu Liu、Li‐Ping Sun

  DOI：10.1002/cbdv.201800493

  日期：2019.4

  receptor‐2 (VEGFR‐2) is an important factor in angiogenesis. In this work, a novel series of thiazolo[5,4‐d]pyrimidine derivatives inhibiting angiogenesis were rationally designed and synthesized. Their inhibitory activities against human umbilical vein endothelial cells (HUVEC) were investigated in vitro. 1‐(4‐Fluorophenyl)‐3‐4‐[(5‐methyl‐2‐phenyl[1,3]thiazolo[5,4‐d]pyrimidin‐7‐yl)amino]phenyl}urea (19b)

  血管生成对肿瘤生长至关重要，抑制血管生成已被视为癌症治疗的一种有前途的方法。血管内皮生长因子受体-2 (VEGFR-2) 是血管生成的重要因素。在这项工作中，合理设计和合成了一系列抑制血管生成的新型噻唑并[5,4-d]嘧啶衍生物。在体外研究了它们对人脐静脉内皮细胞 (HUVEC) 的抑制活性。1-(4-氟苯基)-3-4-[(5-甲基-2-苯基[1,3]噻唑并[5,4-d]嘧啶-7-基)氨基]苯基}脲(19b)和1-(3-氟苯基)-3-4-[(5-methyl-2-phenyl[1,3]thiazolo[5,4-d]pyrimidin-7-yl)amino]phenyl}urea (19g)对 HUVEC 增殖最有效的抑制作用（IC50 分别为 12.8 和 5.3 μm）。化合物19g可抑制人脐静脉内皮细胞的迁移。这些结果支持进一步研究这些化合物作为有效的抗癌剂。
• Increasing the binding affinity of VEGFR-2 inhibitors by extending their hydrophobic interaction with the active site: Design, synthesis and biological evaluation of 1-substituted-4-(4-methoxybenzyl)phthalazine derivatives
  作者：Wagdy M. Eldehna、Sahar M. Abou-Seri、Ahmed M. El Kerdawy、Rezk R. Ayyad、Abdallah M. Hamdy、Hazem A. Ghabbour、Mamdouh M. Ali、Dalal A. Abou El Ella

  DOI：10.1016/j.ejmech.2016.02.029

  日期：2016.5

  promising activity (IC50 = 0.636–5.76 μM). Molecular docking studies guidance was used to improve the binding affinity for series 4a–j towards VEGFR-2 active site. This improvement was achieved by increasing the hydrophobic interaction with the hydrophobic back pocket of the VEGFR-2 active site lined with the hydrophobic side chains of Ile888, Leu889, Ile892, Val898, Val899, Leu1019 and Ile1044. Increasing

  最初合成了一系列 苯并酞菁衍生物4a – j，并测试了其对VEGFR-2的抑制活性，并显示出有希望的活性（IC 50 = 0.636–5.76μM）。分子对接研究指南用于改善4a – j系列的结合亲和力朝向VEGFR-2活性位点。通过增加与衬有Ile888，Leu889，Ile892，Val898，Val899，Leu1019和Ile1044的疏水性侧链的VEGFR-2活性位点的疏水性后口袋的疏水性相互作用，实现了这一改进。疏水相互作用的增强是通过将带有取代苯基部分的苯胺基酞嗪支架通过一个uriedo接头延伸而实现的，这应为该延伸提供足够的灵活性，以使其自身能够深深地容纳在疏水性后袋中。按计划，设计的尿酸-苯胺基酞嗪7a – i的结合亲和力比其苯胺基 酞嗪母体好（IC 50 = 0.083–0.473μM）。特别是化合物7g – i的IC 50分别为0.086、0.083和0.086μM，优于参考药物索拉非尼（IC
• [EN] UREIDOPHENYL SUBSTITUTED TRIAZINE DERIVATIVES AND THEIR THERAPEUTICAL APPLICATIONS<br/>[FR] DÉRIVÉS DE LA TRIAZINE SUBSTITUÉE À L'URÉIDOPHÉNYLE ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：ABRAXIS BIOSCIENCE LLC

  公开号：WO2010144522A1

  公开（公告）日：2010-12-16

  The present invention provides Uredophenyl substituted triazine derivatives and provides methods of using these compounds to modulate protein kinases and methods of using these compounds to treat protein kinase mediated diseases and conditions.

  本发明提供了尿苯基取代的三嗪衍生物，并提供使用这些化合物调节蛋白激酶的方法，以及使用这些化合物治疗蛋白激酶介导的疾病和病状的方法。
• Design, synthesis, antitumor, and VEGFR-2 inhibition activities of novel 4-anilino-2-vinyl-quinazolines: Molecular modeling studies
  作者：Abdelrahman Hamdi、Hamed W. El-Shafey、Dina I.A. Othman、Adel S. El-Azab、Nawaf A. AlSaif、Alaa A.-M. Abdel-Aziz

  DOI：10.1016/j.bioorg.2022.105710

  日期：2022.5

  The antitumor activity of newly synthesized 4-anilino-2-vinylquinazolines 8a-r was measured comparable to sorafenib as a standard drug. The 2-vinylquinazolines 8a-r were evaluated for their in vitro antitumor activity. The most active antitumor agents were subjected to in vitro VEGFR-2 inhibition and apoptotic inducing assay. Compounds 8 h, 8 l, and 8r showed potential antitumor activities with IC50

  新合成的 4-anilino-2-vinylquinazolines 8a-r的抗肿瘤活性与作为标准药物的索拉非尼相当。评估了2-乙烯基喹唑啉8a-r的体外抗肿瘤活性。对最有效的抗肿瘤药物进行体外VEGFR-2 抑制和凋亡诱导试验。化合物8 h、8 l和8r显示出潜在的抗肿瘤活性，相对于参考药物索拉非尼，IC 50 值为 4.92–14.37 μM（IC 50值为5.47–9.18 μM）。化合物8 h具有潜在的 VEGFR-2 抑制活性 (IC 50 = 60.27 nM) 与标准药物索拉非尼 (IC 50  = 55.43 nM) 相比，而化合物8 l显示出中等抑制活性 (IC 50  = 93.50 nM)。最活跃的化合物8 h对 MCF-7 细胞的总凋亡率为 36.24%，超过了索拉非尼引起的凋亡效应 (32.46%) 和 G1/S 期停滞的细胞周期。化合物8 h是一种有效的 VEGFR-2
• UREA SUBSTITUTED SULPHONAMIDE DERIVATIVES
  申请人：Koivunen Jarkko Tapani

  公开号：US20120196884A1

  公开（公告）日：2012-08-02

  The present invention relates to sulphonamide derivatives, whith a urea moiety. The invention also relates to the use of the derivatives as inhibitors of collagen receptor integrins, especially α2β1 integrin inhibitors e.g. in connection with diseases and medical conditions that involve the action of cells and platelets expressing collagen receptors, their use as a medicament, e.g. for the treatment of thrombosis, inflammation, cancer and vascular diseases, pharmaceutical compositions containing them and a process for preparing them. The sulphonamide derivatives have the general formula (I) or (I′).

  本发明涉及含有尿素基团的磺酰胺衍生物。本发明还涉及将这些衍生物用作胶原受体整合素的抑制剂，特别是α2β1整合素抑制剂，例如在涉及表达胶原受体的细胞和血小板的疾病和医疗状况中，将其用作药物，例如用于治疗血栓形成、炎症、癌症和血管疾病，包含它们的制药组合物以及制备它们的过程。磺酰胺衍生物具有通式（I）或（I′）。