6-bromo-N-phenylquinolin-4-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-bromo-N-phenylquinolin-4-amine
• 英文别名: 6-Bromo-N-phenyl-4-quinolinamine
• 化学式: C₁₅H₁₁BrN₂
• 分子量: 299.17
• InChiKey: UIQHLUXEVJQXCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  18
• 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：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-bromo-N-phenylquinolin-4-amine 在 四(三苯基膦)钯 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 26.0h， 生成 N-(6-(4-hydroxyphenyl)quinolin-4-yl)-N-phenyl-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamide
  参考文献：
  名称：

  4-(N-Phenyl-N′-substituted benzenesulfonyl)-6-(4-hydroxyphenyl)quinolines as inhibitors of mammalian target of rapamycin

  摘要：

  A series of 4-(N-phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl) quinolines was designed, synthesized and evaluated for their biological potential as anticancer agents by screening the molecules against panel of five human cancer cell lines viz. HL-60, MiaPaCa-2, HCT116, PC-3 and HEP-G2. The series has shown good mTOR inhibitory activity at 0.5 mu M concentration. The representative compound 7h was found to be most active with the IC50 of 613 nM against mTOR. In supportive evidence, the western blotting experiment revealed that compound 7h is more potent in inhibiting p-mTOR (S2448) activity in 2-4 h at 5 and 10 mu M concentrations and was selective and specific towards mTORC1 versus mTORC2. Towards understanding the mechanistic aspects we studied cell cycle analysis, mitochondrial membrane potential loss in MiaPaca-2 cells for compound 7h. The docking study for this series was performed to understand the binding mode of the compounds and its consequent effect in biological activity, the initial interaction studies were found to be useful in design of molecules, where compound 7h has shown additional H-bond interaction with Lys2171 apart from Val2240 and also a small hydrophobic cleft was observed with Leu2185, Met2345 and Ile2356. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.046
• 作为产物：
  描述：

  6-溴-4-氯喹啉 、 苯胺 以 叔丁醇 为溶剂， 以84.3 %的产率得到6-bromo-N-phenylquinolin-4-amine
  参考文献：
  名称：

  4-氨基喹啉衍生物作为受体相互作用蛋白激酶 2 (RIPK2) 抑制剂的设计、合成和生物学评价

  摘要：

  摘要 受体相互作用蛋白激酶 2 (RIPK2) 是一种必需的蛋白激酶，通过 NOD1 和 NOD2 介导信号转导，在调节免疫信号传导中起重要作用。在这项研究中，我们设计并合成了一系列新的基于 4-氨基喹啉的衍生物作为 RIPK2 抑制剂。在体外，化合物14表现出高亲和力 (IC 50 = 5.1 ± 1.6 nM) 和对 RIPK2 的出色选择性，显示在人类激酶组系统发育树的树状图中。具有良好的亲脂性和合格的亲脂配体效率 (LipE)，化合物14被选择用于研究细胞抗炎作用，并被鉴定为一种有效的抑制剂，可以以剂量依赖的方式减少 MDP 诱导的 TNF-α 的分泌。此外，化合物14在人肝微粒体中表现出适度的稳定性。鉴于这些有希望的结果，化合物14可以作为 RIPK2 的有利抑制剂，用于进一步的生理和生化研究，以用于治疗。

  DOI：

  10.1080/14756366.2022.2148317

文献信息

• Anticancer-Active <i>N</i>-Heteroaryl Amines Syntheses: Nucleophilic Amination of <i>N</i>-Heteroaryl Alkyl Ethers with Amines
  作者：Xia Wang、Qiu-Xia Yang、Cheng-Yu Long、Yan Tan、Yi-Xin Qu、Min-Hui Su、Si-Jie Huang、Weihong Tan、Xue-Qiang Wang

  DOI：10.1021/acs.orglett.9b01711

  日期：2019.7.5

  A mild amination protocol of N-heteroaryl alkyl ethers with various amines is described. This transformation is achieved by utilizing simple and readily available base as promoter via C–O bond cleavage, offering a new amination strategy to access several anticancer-active compounds. This work is highlighted by the excellent functional group compatibility, scalability, wide substrate scope, and easy

  描述了N-杂芳基烷基醚与各种胺的温和胺化方案。通过使用简单易用的碱基作为启动子通过C–O键裂解来实现这种转化，从而提供了一种新的胺化策略来使用多种抗癌活性化合物。出色的官能团兼容性，可扩展性，广泛的底物范围以及多种药物的容易衍生化，突出了这项工作。
• [EN] METHODS AND COMPOUNDS FOR RESTORING MUTANT P53 FUNCTION<br/>[FR] MÉTHODES ET COMPOSÉS POUR LA RESTAURATION D'UNE FONCTION DE MUTANTS DE P53
  申请人：PMV PHARMACEUTICALS INC

  公开号：WO2021262596A1

  公开（公告）日：2021-12-30

  Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

  癌基因和肿瘤抑制基因的突变促进了癌症的发展和进展。本公开描述了一种恢复p53突变体DNA结合亲和力的化合物和方法。本公开的化合物可以结合突变的p53，并恢复p53突变体结合DNA和激活与肿瘤抑制有关的下游效应子的能力。公开的化合物可用于减少含有p53突变的癌症的进展。
• 4-(N-Phenyl-N′-substituted benzenesulfonyl)-6-(4-hydroxyphenyl)quinolines as inhibitors of mammalian target of rapamycin
  作者：Vunnam Venkateswarlu、Anup Singh Pathania、K.A. Aravinda Kumar、Priya Mahajan、Amit Nargotra、Ram A. Vishwakarma、Fayaz A. Malik、Sanghapal D. Sawant

  DOI：10.1016/j.bmc.2015.06.046

  日期：2015.8

  A series of 4-(N-phenyl-N'-substituted benzenesulfonyl)-6-(4-hydroxyphenyl) quinolines was designed, synthesized and evaluated for their biological potential as anticancer agents by screening the molecules against panel of five human cancer cell lines viz. HL-60, MiaPaCa-2, HCT116, PC-3 and HEP-G2. The series has shown good mTOR inhibitory activity at 0.5 mu M concentration. The representative compound 7h was found to be most active with the IC50 of 613 nM against mTOR. In supportive evidence, the western blotting experiment revealed that compound 7h is more potent in inhibiting p-mTOR (S2448) activity in 2-4 h at 5 and 10 mu M concentrations and was selective and specific towards mTORC1 versus mTORC2. Towards understanding the mechanistic aspects we studied cell cycle analysis, mitochondrial membrane potential loss in MiaPaca-2 cells for compound 7h. The docking study for this series was performed to understand the binding mode of the compounds and its consequent effect in biological activity, the initial interaction studies were found to be useful in design of molecules, where compound 7h has shown additional H-bond interaction with Lys2171 apart from Val2240 and also a small hydrophobic cleft was observed with Leu2185, Met2345 and Ile2356. (C) 2015 Elsevier Ltd. All rights reserved.