oxiran-2-ylmethyl 4-[(butoxycarbonyl)amino]benzoate | 545357-96-8

• 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: oxiran-2-ylmethyl 4-[(butoxycarbonyl)amino]benzoate
• 英文别名: Oxiran-2-ylmethyl 4-(butoxycarbonylamino)benzoate
• CAS: 545357-96-8
• 化学式: C₁₅H₁₉NO₅
• 分子量: 293.32
• InChiKey: ZXGQQYQASOKCQM-UHFFFAOYSA-N

物化性质

• 沸点：
  391.2±17.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  oxiran-2-ylmethyl 4-[(butoxycarbonyl)amino]benzoate 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 5.0h， 生成 (3-{4-[(butoxycarbonyl)amino]benzoyloxy}-2-hydroxypropyl)dimethylammonium chloride
  参考文献：
  名称：

  3-（二烷基氨基）-2-羟丙基4-[（（烷氧基-羰基）氨基]苯甲酸酯和它们的季铵盐的合成，分析，抑制胆碱酯酶的活性和分子模型研究。

  摘要：

  合成了叔胺3-（二烷基氨基）-2-羟丙基4-[（烷氧羰基）氨基]苯甲酸酯及其季铵盐。季铵盐的合成的最后一步是通过微波辅助合成进行的。软件计算的数据提供了根据其理化性质比较十五种新化合物的背景。测定了叔胺的酸解离常数（pKa）和亲脂性指数（log P）。季铵盐通过软件计算的亲脂性指数和表面张力表征。生物学评估旨在测试合成化合物的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。这些化合物可能的作用机理是通过结合对接技术的分子模型研究确定的。分子动力学模拟和量子力学计算。

  DOI：

  10.3390/molecules22122048
• 作为产物：
  描述：

  氯甲酸丁酯 在 吡啶 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 、 甲苯 为溶剂， 反应 7.5h， 生成 oxiran-2-ylmethyl 4-[(butoxycarbonyl)amino]benzoate
  参考文献：
  名称：

  3-（二烷基氨基）-2-羟丙基4-[（（烷氧基-羰基）氨基]苯甲酸酯和它们的季铵盐的合成，分析，抑制胆碱酯酶的活性和分子模型研究。

  摘要：

  合成了叔胺3-（二烷基氨基）-2-羟丙基4-[（烷氧羰基）氨基]苯甲酸酯及其季铵盐。季铵盐的合成的最后一步是通过微波辅助合成进行的。软件计算的数据提供了根据其理化性质比较十五种新化合物的背景。测定了叔胺的酸解离常数（pKa）和亲脂性指数（log P）。季铵盐通过软件计算的亲脂性指数和表面张力表征。生物学评估旨在测试合成化合物的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。这些化合物可能的作用机理是通过结合对接技术的分子模型研究确定的。分子动力学模拟和量子力学计算。

  DOI：

  10.3390/molecules22122048

文献信息

• Mokry; Zemanova; Csoellei, Pharmazie, 2003, vol. 58, # 1, p. 18 - 21
  作者：Mokry、Zemanova、Csoellei、Racanska、Tumova

  DOI：——

  日期：——
• Searching new structural scaffolds for BRAF inhibitors. An integrative study using theoretical and experimental techniques
  作者：Ludmila E. Campos、Francisco M. Garibotto、Emilio Angelina、Jiri Kos、Tihomir Tomašič、Nace Zidar、Danijel Kikelj、Tomas Gonec、Pavlina Marvanova、Petr Mokry、Josef Jampilek、Sergio E. Alvarez、Ricardo D. Enriz

  DOI：10.1016/j.bioorg.2019.103125

  日期：2019.10

  The identification of the V600E activating mutation in the protein kinase BRAF in around 50% of melanoma patients has driven the development of highly potent small inhibitors (BRAFi) of the mutated protein. To date, Dabrafenib and Vemurafenib, two specific BRAFi, have been clinically approved for the treatment of metastatic melanoma. Unfortunately, after the initial response, tumors become resistant and patients develop a progressive and lethal disease, making imperative the development of new therapeutic options. The main objective of this work was to find new BRAF inhibitors with different structural scaffolds than those of the known inhibitors. Our study was carried out in different stages; in the first step we performed a virtual screening that allowed us to identify potential new inhibitors. In the second step, we synthesized and tested the inhibitory activity of the novel compounds founded. Finally, we conducted a molecular modelling study that allowed us to understand interactions at the molecular level that stabilize the formation of the different molecular complexes.Our theoretical and experimental study allowed the identification of four new structural scaffolds, which could be used as starting structures for the design and development of new inhibitors of BRAF. Our experimental data indicate that the most active compounds reduced significantly ERK1/2 phosphorylation, a measure of BRAF inhibition, and cell viability. Thus, from our theoretical and experimental results, we propose new substituted hydroxynaphthalenecarboxamides, N-(hetero)aryl-piperazinylhydroxyalkylphenylcarbamates, substituted piperazinylethanols and substituted piperazinylpropandiols as initial structures for the development of new inhibitors for BRAF. Moreover, by performing QTAIM analysis, we are able to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analysis indicates which portion of the different molecules must be changed in order to obtain an increase in the binding affinity of these new ligands.
• An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors
  作者：Marcela Vettorazzi、Emilio Angelina、Santiago Lima、Tomas Gonec、Jan Otevrel、Pavlina Marvanova、Tereza Padrtova、Petr Mokry、Pavel Bobal、Lina M. Acosta、Alirio Palma、Justo Cobo、Janette Bobalova、Jozef Csollei、Ivan Malik、Sergio Alvarez、Sarah Spiegel、Josef Jampilek、Ricardo D. Enriz

  DOI：10.1016/j.ejmech.2017.08.017

  日期：2017.10

  Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b] pyrimido[5,4-f]azepine and two alkyl3-/4-[-1-hydroxy-2-(4-arylpiperazin-1-yl)ethyliphenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Synthesis, Analysis, Cholinesterase-Inhibiting Activity and Molecular Modelling Studies of 3-(Dialkylamino)-2-hydroxypropyl 4-[(Alkoxy-carbonyl)amino]benzoates and Their Quaternary Ammonium Salts
  作者：Tereza Padrtova、Pavlina Marvanova、Klara Odehnalova、Renata Kubinova、Oscar Parravicini、Adriana Garro、Ricardo Enriz、Otakar Humpa、Michal Oravec、Petr Mokry

  DOI：10.3390/molecules22122048

  日期：——

  amines 3-(dialkylamino)-2-hydroxypropyl 4-[(alkoxycarbonyl)amino]benzoates and their quaternary ammonium salts were synthesized. The final step of synthesis of quaternary ammonium salts was carried out by microwave-assisted synthesis. Software-calculated data provided the background needed to compare fifteen new resulting compounds by their physicochemical properties. The acid dissociation constant (pKa)

  合成了叔胺3-（二烷基氨基）-2-羟丙基4-[（烷氧羰基）氨基]苯甲酸酯及其季铵盐。季铵盐的合成的最后一步是通过微波辅助合成进行的。软件计算的数据提供了根据其理化性质比较十五种新化合物的背景。测定了叔胺的酸解离常数（pKa）和亲脂性指数（log P）。季铵盐通过软件计算的亲脂性指数和表面张力表征。生物学评估旨在测试合成化合物的乙酰胆碱酯酶和丁酰胆碱酯酶抑制活性。这些化合物可能的作用机理是通过结合对接技术的分子模型研究确定的。分子动力学模拟和量子力学计算。