ethyl 4-(3-(4-methoxyphenyl)ureido)benzoate

• 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: ethyl 4-(3-(4-methoxyphenyl)ureido)benzoate
• 英文别名: Ethyl 4-{[(4-methoxyphenyl)carbamoyl]amino}benzoate；ethyl 4-[(4-methoxyphenyl)carbamoylamino]benzoate
• 化学式: C₁₇H₁₈N₂O₄
• 分子量: 314.341
• InChiKey: YLMMEGPKOWGIQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(3-(4-methoxyphenyl)ureido)benzoate 在 hydrazine hydrate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 1-(4-(2-(5-bromo-2-oxoindolin-3-ylidene)hydrazine-1-carbonyl)phenyl)-3-(4-methoxyphenyl)urea
  参考文献：
  名称：

  IIA型-IIB型蛋白酪氨酸激酶抑制剂杂交是有效开发多激酶抑制剂的有效方法：新型基于吲哚啉酮的脲类和酰胺的设计，合成，抗增殖活性，多激酶抑制活性和分子模型

  摘要：

  基于我们对开发新型多激酶抑制剂的努力，在此我们报告了新型基于2-吲哚满酮的酰脲6a-u和酰胺10a - j的设计和合成。在这项工作中，我们采用IIA型PTK抑制剂（索拉非尼）和IIB型PTK抑制剂（舒尼替尼和nintedanib）之间的杂交策略。这是通过以下方式实现的舒尼替尼和nintedanib中的吲哚酮核心之间的连接非常合适，而索拉非尼中的茚满酮核心适合于激酶结构域前裂的铰链区和联芳基脲延伸区，而索拉非尼则位于门区域和疏水性后袋中。按照计划，设计的杂合化合物在VEGFR-2和FGFR-1活性位点上的分子对接揭示了它们建立由原始IIA型和IIB型抑制剂实现的结合相互作用的能力。评价所设计的化合物对VEGFR-2，PDGFR-b和FGFR-1的多激酶抑制活性以及对HepG2，MCF-7，A549和A498癌细胞系的抗增殖活性。脲基类似物6u成为具有VEGFR-2，FGFR-1和PDGFR-b

  DOI：

  10.1016/j.ejmech.2018.11.061
• 作为产物：
  描述：

  对甲氧基苯异氰酸酯 、 苯佐卡因 以 乙腈 为溶剂， 反应 3.0h， 生成 ethyl 4-(3-(4-methoxyphenyl)ureido)benzoate
  参考文献：
  名称：

  IIA型-IIB型蛋白酪氨酸激酶抑制剂杂交是有效开发多激酶抑制剂的有效方法：新型基于吲哚啉酮的脲类和酰胺的设计，合成，抗增殖活性，多激酶抑制活性和分子模型

  摘要：

  基于我们对开发新型多激酶抑制剂的努力，在此我们报告了新型基于2-吲哚满酮的酰脲6a-u和酰胺10a - j的设计和合成。在这项工作中，我们采用IIA型PTK抑制剂（索拉非尼）和IIB型PTK抑制剂（舒尼替尼和nintedanib）之间的杂交策略。这是通过以下方式实现的舒尼替尼和nintedanib中的吲哚酮核心之间的连接非常合适，而索拉非尼中的茚满酮核心适合于激酶结构域前裂的铰链区和联芳基脲延伸区，而索拉非尼则位于门区域和疏水性后袋中。按照计划，设计的杂合化合物在VEGFR-2和FGFR-1活性位点上的分子对接揭示了它们建立由原始IIA型和IIB型抑制剂实现的结合相互作用的能力。评价所设计的化合物对VEGFR-2，PDGFR-b和FGFR-1的多激酶抑制活性以及对HepG2，MCF-7，A549和A498癌细胞系的抗增殖活性。脲基类似物6u成为具有VEGFR-2，FGFR-1和PDGFR-b

  DOI：

  10.1016/j.ejmech.2018.11.061

文献信息

• Diaryl Ureas as CB1 Antagonists
  申请人：Hutchison Alan J.

  公开号：US20090239841A1

  公开（公告）日：2009-09-24

  Compounds of Formula I are provided. In which the variables are as described herein. Such compounds may be used to modulate CB1 activity in vivo or in vitro, and are particularly useful in the treatment of conditions responsive to CB1 modulation in humans, domesticated companion animals and livestock animals, including appetite disorders, obesity and addictive disorders. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such ligands for receptor localization studies and various in vitro assays.

  提供式I的化合物，其中变量如本文所述。这些化合物可用于体内或体外调节CB1活性，并且在治疗对CB1调节敏感的人类、家养伴侣动物和家畜动物的食欲障碍、肥胖和成瘾障碍方面特别有用。提供了用于治疗这些障碍的制药组合物和方法，以及用于受体定位研究和各种体外测定的配体的使用方法。
• Rh(III)-Catalyzed Oxidative Domino C–H/N–H Annulation: Diarylureas as Arylamine Donors for the Assembly of Indolo[2,1-<i>a</i>]isoquinolines
  作者：Xiyang Cao、Zhiguo Zhang、Jingya Li、Bingbing Shi、Mengjuan Li、Guisheng Zhang、Xingjie Zhang

  DOI：10.1021/acs.joc.2c01334

  日期：2022.11.4

  convenient Rh(III)-catalyzed double aryl C(sp2)–H bond and N–H activation and annulation reaction is reported for the synthesis of indolo[2,1-a]isoquinolines in the presence of the Cu(OAc)2 oxidant under heating conditions. Distinct from previous works with other arylamine donors, one molecule of 1,3-diarylurea can serve as a precursor of two molecules of arylamine in the reaction with diaryl-substituted

  报道了一种高效便捷的 Rh(III) 催化的双芳基 C(sp2)-H 键和 N-H 活化和环化反应，用于在 Cu(OAc) 存在下合成吲哚[2,1- a ]异喹啉) 2加热条件下的氧化剂。与以前与其他芳胺供体的工作不同，一个分子的 1,3-二芳基脲可以作为两分子芳胺与二芳基取代的炔烃反应的前体。
• Modulation of endoplasmic reticulum stress response in gut-origin encephalopathy: Impact of vascular endothelial growth factor receptor-2 manipulation
  作者：Doaa A. Zaky、Walaa Wadie、Wagdy M. Eldehna、Ahmed M. El Kerdawy、Dalaal M. Abdallah、Hanan S. El Abhar

  DOI：10.1016/j.lfs.2020.117654

  日期：2020.7

  Background: Septic encephalopathy, the most frequent complication of sepsis, is orchestrated by a complex interplay of signals that leads to high mortality rates among intensive care unit patients. However, the role of the vascular endothelial growth factor receptor-2 (VEGFR2) in endoplasmic reticulum stress response (ERSR), during septic encephalopathy, is still elusive.Aim: This study was aimed to examine the effect of an in-house designed/synthesized VEGFR2 antagonist, named WAG-4S, on septic encephalopathy using cecal ligation and perforation (CLP).Main methods: Rats were intraperitoneally injected with WAG-4S (1 mg/kg/d) for 7 days post-CLP.Key findings: In septic animals, VEGFR2 antagonism declined the expression of cortical p-VEGFR2 and p-mammalian target of rapamycin complex-1 (p-mTORC1). It also worsened the behavioral and histopathological alterations beyond CLP. However, and contrary to CLP, WAG-4S decreased the p-protein kinase R-like ER kinase (p-PERK) and eukaryotic initiation factor-2 alpha (p-eIF2 alpha) expression. Moreover, VEGFR2 blockade upregulated the mRNA expression of activating transcription factor-4 (ATF4), binding immunoglobulin protein/glucose-regulated protein-78 (Bip/GRP78), growth arrest and DNA damage-34 (GADD34) and spliced X-box binding protein1 (XBP1s) above CLP. Similarly, it boosted inositol requiring enzyme-1 alpha (IRE1 alpha) activation and redox imbalance. In the same context, WAG-4S augmented the protein levels of CLP-induced ERSR apoptotic markers, namely C/EBP homologous protein (CHOP/GADD153), c-jun N-terminal kinase (JNK) and caspase-3.Significance: In conclusion, the PERK/eIF2 alpha axis inhibition, during septic encephalopathy, is VEGFR2-independent, whereas the activated IRE1 alpha/XBP1s/CHOP/JNK/caspase-3 cue promotes the ERSR execution module through VEGFR2 inhibition. This has turned VEGFR2 into a potential therapeutic target for ameliorating such an ailment.