4-(3-(4-aminophenyl)ureido)benzenesulfonamide

• 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: 4-(3-(4-aminophenyl)ureido)benzenesulfonamide
• 英文别名: 1-(4-Aminophenyl)-3-(4-sulfamoylphenyl)urea
• 化学式: C₁₃H₁₄N₄O₃S
• 分子量: 306.345
• InChiKey: AEQGYCNJSFFQEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-(4-aminophenyl)ureido)benzenesulfonamide 、 5-氯靛红 在 溶剂黄146 作用下， 反应 2.0h， 生成 (Z/E)4-(3-(4-((5-chloro-2-oxoindolin-3-ylidene)amino)phenyl)ureido)benzenesulfonamide
  参考文献：
  名称：

  Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII

  摘要：

  By using a molecular hybridization approach, two series of amido/ureidosubstituted benzenesulfonamides incorporating substituted-isatin moieties were synthesized. The prepared derivatives were in vitro evaluated for their inhibitory activity against human carbonic anhydrase (hCA, EC 4.2.1.1) I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms. All these isoforms were inhibited in variable degrees by the sulfonamides reported here. hCA I was inhibited with K(I)s in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a K-I > 10 mu M); hCA IX in the range of 5.0-240 nM, whereas hCA XII in the range of 0.47-2.83 nM. As all these isoforms are involved in various pathologies, in which their inhibition can be exploited therapeutically, the derivatives reported here may represent interesting extensions to the field of CA inhibitors of the sulfonamide type. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.01.030
• 作为产物：
  描述：

  [4-(3-(4-nitrophenyl)ureido)]benzene sulfonamide 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以83%的产率得到4-(3-(4-aminophenyl)ureido)benzenesulfonamide
  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

文献信息

• がんの診断及び治療用放射性薬品
  申请人：国立大学法人京都大学

  公开号：JP2019043902A

  公开（公告）日：2019-03-22

  【課題】ＣＡ−ＩＸを標的とした低分子薬剤であって、特異性が高く、クリアランスが速く、がんの診断及び治療に使用でき、更にはがんのセラノスティクスにも応用できる薬剤を提供する。【解決手段】 下記一般式（２）で示される化合物。【化１】（式中、Ｍ３+は３価の金属元素である。）【選択図】なし

  这是一段关于针对CA-IX的低分子药物的描述，具有高特异性、快速清除率，可用于癌症的诊断和治疗，并且可以应用于癌症的治疗学。提供一种化合物，其由下述通用式（2）表示。【化合物1】（其中，M3+代表三价金属元素。）【选择图】无
• Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents
  作者：Wagdy M. Eldehna、Mahmoud F. Abo-Ashour、Alessio Nocentini、Radwan S. El-Haggar、Silvia Bua、Alessandro Bonardi、Sara T. Al-Rashood、Ghada S. Hassan、Paola Gratteri、Hatem A. Abdel-Aziz、Claudiu T. Supuran

  DOI：10.1016/j.ejmech.2018.10.068

  日期：2019.1

  report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111

  本文中，我们报道了新型N-取代的isatins-SLC-0111杂种（6a-f和9a-1）的设计和合成。通过结构化部分的N-烷基化和N-苄基化采用结构延伸方法，以增强碳酸酐酶（CA）IX活性位点内的尾部疏水相互作用。此后，通过将Isatin和SLC-0111的药效学元素合并到一个化学框架中，使用了混合药效学方法。按计划，与N-未取代的铅IVa-c相比，目标杂种（K I s：4.7-86.1 nM）对hCA IX的抑制谱有显着改善（K I s：192–239 nM），达到了。按照计划，设计的杂种分子在CA IX活性位点的分子对接揭示了N-烷基化和N-苄基化的靛红部分适应由T73，P75，P76，L91，L123和A128形成的宽疏水口袋的能力，从而确立了强烈的范德华相互作用。杂种6c在低氧条件下对乳腺癌MDA-MB-231和MCF-7细胞系表现出良好的抗增殖活性（IC 50分别 为7.43±0
• Indoline ureas as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro biological evaluation and molecular docking
  作者：Wagdy M. Eldehna、Mohamed Fares、Hany S. Ibrahim、Mohamed H. Aly、Suher Zada、Mamdouh M. Ali、Sahar M. Abou-Seri、Hatem A. Abdel-Aziz、Dalal A. Abou El Ella

  DOI：10.1016/j.ejmech.2015.05.040

  日期：2015.7

  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.
• Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII
  作者：Wagdy M. Eldehna、Mohamed Fares、Mariangela Ceruso、Hazem A. Ghabbour、Sahar M. Abou-Seri、Hatem A. Abdel-Aziz、Dalal A. Abou El Ella、Claudiu T. Supuran

  DOI：10.1016/j.ejmech.2016.01.030

  日期：2016.3

  By using a molecular hybridization approach, two series of amido/ureidosubstituted benzenesulfonamides incorporating substituted-isatin moieties were synthesized. The prepared derivatives were in vitro evaluated for their inhibitory activity against human carbonic anhydrase (hCA, EC 4.2.1.1) I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms. All these isoforms were inhibited in variable degrees by the sulfonamides reported here. hCA I was inhibited with K(I)s in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a K-I > 10 mu M); hCA IX in the range of 5.0-240 nM, whereas hCA XII in the range of 0.47-2.83 nM. As all these isoforms are involved in various pathologies, in which their inhibition can be exploited therapeutically, the derivatives reported here may represent interesting extensions to the field of CA inhibitors of the sulfonamide type. (C) 2016 Elsevier Masson SAS. All rights reserved.