1-(3-methoxyphenyl)-3-(2-propynyl)urea | 1090394-90-3

• 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-(3-methoxyphenyl)-3-(2-propynyl)urea
• 英文别名: 1-(3-methoxyphenyl)-3-prop-2-ynylurea
• CAS: 1090394-90-3
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: WQLCINCNABQRGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-azido-1H-indazole 、 1-(3-methoxyphenyl)-3-(2-propynyl)urea 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 乙醇 、 水 、 叔丁醇 为溶剂， 反应 12.0h， 以62%的产率得到1-((1-(1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl)methyl)-3-(3-methoxyphenyl)urea
  参考文献：
  名称：

  Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

  摘要：

  We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1,2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 mu M. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 mu M, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.042
• 作为产物：
  描述：

  1-(3-甲氧基苯基)-3-(2-丙炔基)脲 以 甲苯 为溶剂， 反应 1.5h， 生成 1-(3-methoxyphenyl)-3-(2-propynyl)urea
  参考文献：
  名称：

  Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach

  摘要：

  We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1,2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 mu M. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 mu M, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.042

文献信息

• A facile synthesis of unsymmetrical ureas
  作者：Andrey V. Bogolubsky、Sergey V. Ryabukhin、Sergey E. Pipko、Oleg Lukin、Alexander Shivanyuk、Dmytro Mykytenko、Andrey Tolmachev

  DOI：10.1016/j.tet.2011.03.101

  日期：2011.5

  versatile method for the synthesis of unsymmetrical ureas from readily available reagents is reported. In the first step trifluoroethylchloroformate is reacted with a stoichiometric amount of a primary amine to give an intermediate trifluoroethyl carbamate. The addition of a second amine (primary or secondary) to the trifluoroethyl carbamate furnishes corresponding unsymmetrical ureas in 75–85% yield. A

  报道了一种由容易获得的试剂合成不对称脲的简便而通用的方法。在第一步中，使三氟乙基氯甲酸酯与化学计算量的伯胺反应，得到中间体三氟乙基氨基甲酸酯。在氨基甲酸三氟乙酯中添加第二种胺（伯胺或仲胺）可提供相应的不对称脲，产率为75-85％。简单的后处理程序，获得的高收率和分离产物的纯度适用于具有高结构和功能多样性的不对称脲组合库的平行合成。
• Discovery of the first-in-class potent and isoform-selective human carbonic anhydrase III inhibitors
  作者：Simone Giovannuzzi、Alessandro Bonardi、Paola Gratteri、Alessio Nocentini、Claudiu T. Supuran

  DOI：10.1080/14756366.2023.2202360

  日期：2023.12.31

  unrecognised physio-pathological role of human carbonic anhydrase III (hCA III), a structure-based drug design was set up to identify the first-in-class potent and selective inhibitors of this neglected isoform. hCA III targeting was planned considering a unique feature of its active site among the other hCA isoforms, i.e. the Leu198/Phe198 substitution which interferes with the binding of aromatic/heterocyclic

  摘要 考虑到人碳酸酐酶 III (hCA III) 尚未被认识的生理病理作用，我们建立了基于结构的药物设计，以确定这种被忽视的亚型的一流的有效和选择性抑制剂。hCA III 靶向的计划考虑到其活性位点在其他 hCA 同工型中的独特特征，即干扰芳香族/杂环磺酰胺和其他抑制剂结合的 Leu198/Phe198 取代。因此，具有长而灵活的(CH 2 ) n SO 2 NH 2部分的新型脂肪族伯磺酰胺被设计来配位锌(II)离子，绕过庞大的Phe198残基。它们结合了 1,2,3-三唑连接体，将尾部部分连接到磺酰胺头部，从而增强了活性位点入口处的接触。其中一些化合物比其他亚型更能作为 hCA III 的纳摩尔选择性抑制剂。对接/分子动力学模拟用于研究这些磺胺类药物的配体/靶标相互作用，这可能会提高我们对 hCA III 生理病理作用的理解。
• Novel VEGFR-2 kinase inhibitors identified by the back-to-front approach
  作者：Kingkan Sanphanya、Suvara K. Wattanapitayakul、Suwadee Phowichit、Valery V. Fokin、Opa Vajragupta

  DOI：10.1016/j.bmcl.2013.03.042

  日期：2013.5

  We report a novel VEGFR-2 inhibitor, developed by the back-to-front approach. Docking experiments indicated that the 3-chloromethylphenylurea motif of the lead compound occupied the back pocket of VEGFR-2 kinase. An attempt was made to enhance the binding affinity of 1 by expanding the structure to access the front pocket using a triazole linker. A library of 1,4-(disubstituted)-1H-1,2,3-triazoles were screened in silico, and one compound (VH02) was identified with an IC50 against VEGFR-2 of 0.56 mu M. VH02 showed antiangiogenic effects, inhibiting tube formation in HUVEC cells (EA.hy926) at 0.3 mu M, 13 times lower than its cytotoxic dose. These enzymatic and cellular activities suggest that VH02 has potential as a lead for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.