N-(3-chlorophenyl)-2-hydroxynaphthalene-1-carboxamide | 1463483-72-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(3-chlorophenyl)-2-hydroxynaphthalene-1-carboxamide
• 英文别名: N-(3-chlorophenyl)-2-hydroxy-naphthalene-1-carboxamide
• CAS: 1463483-72-8
• 化学式: C₁₇H₁₂ClNO₂
• 分子量: 297.741
• InChiKey: VJYDLGVJLHGMMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-羟基-1-萘甲酸 在 三氯化磷 作用下， 以 氯苯 为溶剂， 生成 N-(3-chlorophenyl)-2-hydroxynaphthalene-1-carboxamide
  参考文献：
  名称：

  Searching new structural scaffolds for BRAF inhibitors. An integrative study using theoretical and experimental techniques

  摘要：

  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.

  DOI：

  10.1016/j.bioorg.2019.103125

文献信息

• Antibacterial and Herbicidal Activity of Ring-Substituted 2-Hydroxynaphthalene-1-carboxanilides
  作者：Tomas Gonec、Jiri Kos、Iveta Zadrazilova、Matus Pesko、Rodney Govender、Stanislava Keltosova、Barbara Chambel、Diogo Pereira、Peter Kollar、Ales Imramovsky、Jim O'Mahony、Aidan Coffey、Alois Cizek、Katarina Kralova、Josef Jampilek

  DOI：10.3390/molecules18089397

  日期：——

  of twenty-two ring-substituted 2-hydroxynaphthalene-1‑carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium marinum, M. kasasii, M. smegmatis. and M. avium paratuberculosis. The compounds were also tested for their activity related to inhibition

  在本研究中，制备并表征了一系列 22 个环取代的 2-羟基萘-1-甲酰苯胺。针对金黄色葡萄球菌、三种耐甲氧西林金黄色葡萄球菌菌株、海分枝杆菌、卡萨斯分枝杆菌、耻垢分枝杆菌进行了合成化合物的初步体外筛选。和M. avium paratuberculosis。还测试了这些化合物与抑制菠菜 (Spinacia oleracea L.) 叶绿体中光合电子传递 (PET) 相关的活性。2-Hydroxy-N-phenylnaphthalene-1-carboxanilide 和 2-hydroxy-N-(3-trifluoromethylphenyl)naphthalene-1-carboxamide (IC₅₀ = 29 µmol/L) 是最活跃的 PET 抑制剂。一些测试化合物对测试菌株的抗菌和抗分枝杆菌活性与标准氨苄青霉素或异烟肼相当或更高。因此，例如，2-羟基-N-(3-硝基苯基)萘-1-甲酰胺对耐甲氧西林的金黄色葡萄球菌的
• US5317093A
  申请人：——

  公开号：US5317093A

  公开（公告）日：1994-05-31
• 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.