6-methoxy-4-(4-nitrophenoxy)quinolin-7-ol | 417723-96-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-methoxy-4-(4-nitrophenoxy)quinolin-7-ol
• CAS: 417723-96-7
• 化学式: C₁₆H₁₂N₂O₅
• 分子量: 312.282
• InChiKey: KGCWNRRNJZUPGK-UHFFFAOYSA-N

物化性质

• 沸点：
  506.9±45.0 °C(Predicted)
• 密度：
  1.408±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  97.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-methoxy-4-(4-nitrophenoxy)quinolin-7-ol 在 吡啶 、 盐酸 、 铁粉 、 caesium carbonate 、 一水合肼 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 24.17h， 生成 (E)-4-((4-(4-(2-(2,3-difluorobenzylidene)hydrazine-1-carboxamido)phenoxy)-6-methoxyquinolin-7-yl)oxy)-N-isopropylpiperidine-1-carboxamide
  参考文献：
  名称：

  Identification of novel quinoline analogues bearing thiazolidinones as potent kinase inhibitors for the treatment of colorectal cancer

  摘要：

  In this investigation, a novel series of quinoline analogues bearing thiazolidinones were designed and synthesized based on our previous study. Among them, the most potent compound 11k, 4-((4-(4-(3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)ureido)phenoxy)-6-methoxyquinolin-7-yl)oxy)-N-iso-propylpiperidine-1-carboxamide, possessed submicromolar c-Met and Ron inhibitory activities. In addition, enzymatic assays against a mini-panel of kinases (c-Kit, B-Raf, c-Src, IGF1R, PDGFR alpha and AXL) were performed, the results showed that compound 11k exhibited moderate inhibitory activity against PDGFR alpha, c-Src and AXL. MTT assay revealed in vitro antitumor activities against HT-29 cells of compound 11k with an IC50 value of 0.31 mu M which was 9.3- and 34.2-fold more potent than that of Regorafenib (IC50 = 2.87 mu M) and Cabozantinib (IC50 = 10.6 mu M). Preliminary antitumor mechanisms were also investigated by cellular assays. Considerable cytotoxicity, antiproliferation and induction of apoptosis of compound 11k in a dose- and time-dependent manner were confirmed by IncuCyte live-cell imaging assays. Treatment with compound 11k caused slight G2-or M-phase arrest in HT-29 cells. Further cell selectivity of compound 11k showed that it was not active against human normal colorectal mucosa epithelial cell FHC at 10.0 mu g/mL. The above results support further structural modification of compound 11k to improve its inhibitory activity, which will lead to more potent anticancer agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112643
• 作为产物：
  描述：

  7-苄氧基-4-羟基-6-甲氧基喹啉 在 氢溴酸 、 溶剂黄146 、 三氯氧磷 作用下， 以 氯苯 为溶剂， 反应 30.0h， 生成 6-methoxy-4-(4-nitrophenoxy)quinolin-7-ol
  参考文献：
  名称：

  一种杂环类化合物、制备方法及应用

  摘要：

  本申请涉及医药技术领域中的一种杂环类化合物，该类化合物为结构通式Ⅰ或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、X、Y、Z、Cy1、Cy2、m、n及t具有在说明书中给出的含义，此外，本发明还公开了该类化合物及其药学上可接受的盐在制备治疗由于酪氨酸激酶异常高表达所引起疾病的药物中的用途，特别是在制备治疗和预防癌症的药物中的用途。

  公开号：

  CN111253385A

文献信息

• Nitrogen-containing aromatic derivatives
  申请人：——

  公开号：US20040053908A1

  公开（公告）日：2004-03-18

  Compounds represented by the following general formula: 1 [wherein A g is an optionally substituted 5- to 14-membered heterocyclic group, etc.; X g is —O—, —S—, etc.; Y g is an optionally substituted C 6 - 14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and T g1 is a group represented by the following general formula: 2 (wherein E g is a single bond or —N(R g2 )—, R g1 and R g2 each independently represent a hydrogen atom, an optionally substituted C 1-6 alkyl group, etc. and Z g represents a C 1-8 alkyl group, a C 3-8 alicyclic hydrocarbon group, a C 6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.

  由以下一般式表示的化合物： 1 [其中 A g 是可选择地取代的5-至14-成员杂环基团，等等；X g 是—O—，—S—，等等；Y g 是可选择地取代的C 6 - 14 芳基团，可选择地取代的5-至14-成员杂环基团，等等；以及 T g1 是由以下一般式表示的基团： 2 [其中 E g 是单键或—N(R g2 )—，R g1 和R g2 各自独立地表示氢原子，可选择地取代的C 1-6 烷基基团，等等，Z g 表示C 1-8 烷基基团，C 3-8 脂环烃基团，C 6-14 芳基团，等等]， 其盐或上述化合物的水合物。
• Discovery of 4-((4-(4-(3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)ureido)-2-fluorophenoxy)-6-methoxyquinolin-7-yl)oxy)-N,N-diethylpiperidine-1-carboxamide as kinase inhibitor for the treatment of colorectal cancer
  作者：Yuting Zhou、Xingwei Xu、Fei Wang、Huan He、Baohui Qi

  DOI：10.1016/j.bioorg.2020.104511

  日期：2021.1

  this study, a novel series of 4,6,7-trisubstituted quinoline analogues bearing thiazolidinones were designed and synthesized based on our previous study. Among them, the most potent compound 15i, 4-((4-(4-(3-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)ureido)-2-fluorophenoxy)-6-methoxyquinolin-7-yl)oxy)-N,N-diethylpiperidine-1-carboxamide was identified as a multi-kinase inhibitor. The results of

  在这项研究中，基于我们之前的研究，设计并合成了一系列带有噻唑烷酮的新型 4,6,7-三取代喹啉类似物。其中，效力最强的化合物15i，4-((4-(4-(3-(2-(2,6-二氟苯基)-4-oxothiazolidin-3-yl)ureido)-2-fluorophenoxy)-6-甲氧基喹啉-7-基)氧基) -N,N-二乙基哌啶-1-甲酰胺被鉴定为多激酶抑制剂。MTT 测定结果显示化合物15i对 HT-29 细胞的体外抗肿瘤活性，IC 50值 0.19 μM，比 Regorafenib 强 14.5 倍。在细胞环境中，通过 IncuCyte 活细胞成像分析证实了 HT-29 细胞以剂量和时间依赖性方式显着的抗增殖、细胞毒性和凋亡诱导。此外，化合物15i通过将细胞周期阻滞到 G2/M 期来强烈诱导细胞凋亡。在10.0 μg/mL或更低浓度下未观察到对人正常结直肠粘膜上皮细胞FHC的抗增殖和细
• Nitrogen-Containing Aromatic Derivatives
  申请人：Funahashi Yasuhiro

  公开号：US20100197911A1

  公开（公告）日：2010-08-05

  Compounds represented by the following general formula: [wherein A g is an optionally substituted 5- to 14-membered heterocyclic group, etc.; X g is —O—, —S—, etc.; Y g is an optionally substituted C 6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and T g1 is a group represented by the following general formula: (wherein E g is a single bond or —N(R g2 )—, R g1 and R g2 each independently represent a hydrogen atom, an optionally substituted C 1-6 alkyl group, etc. and Z g represents a C 1-8 alkyl group, a C 3-8 alicyclic hydrocarbon group, a C 6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.

  以下是由下列通式表示的化合物：[其中Ag是可选取代的5-至14-成员杂环基团等；Xg是-O-，-S-等；Yg是可选取代的C6-14芳基团，可选取代的5-至14-成员杂环基团等；Tg1是由下列通式表示的基团：（其中Eg是单键或-N（Rg2）-，Rg1和Rg2各自独立地表示氢原子，可选取代的C1-6烷基团等；Zg表示C1-8烷基团，C3-8萜环碳氢基团，C6-14芳基团等）]，其盐或上述化合物的水合物。
• NITROGEN-CONTAINING AROMATIC DERIVATIVES
  申请人：FUNAHASHI Yasuhiro

  公开号：US20110118470A1

  公开（公告）日：2011-05-19

  Compounds represented by the following general formula: wherein A g is an optionally substituted 5- to 14-membered heterocyclic group, etc.; X g is —O—, —S—, etc.; Y g is an optionally substituted C 6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and T g1 is a group represented by the following general formula: (wherein E g is a single bond or —N(R g2 )—), R g1 and R g2 each independently represent a hydrogen atom, an optionally substituted C 1-6 alkyl group, etc. and Z g represents a C 1-8 alkyl group, a C 3-8 alicyclic hydrocarbon group, a C 6-14 aryl group, etc.), salts thereof or hydrates of the foregoing.

  以下通式所表示的化合物：其中Ag是可选取代的5-至14-成员杂环基团等；Xg是-O-，-S-等；Yg是可选取代的C6-14芳基团，可选取代的5-至14-成员杂环基团等；Tg1是以下通式所表示的基团：其中Eg为单键或-N（Rg2）-，Rg1和Rg2各自独立地表示氢原子，可选取代的C1-6烷基基团等，而Zg则表示C1-8烷基基团，C3-8萜烃环基团，C6-14芳基团等，其盐或以上化合物的水合物。
• Nitrogen-containing aromatic heterocycles
  申请人：Eisai Co. Ltd.

  公开号：EP1506962A2

  公开（公告）日：2005-02-16

  Compounds represented by the following general formula: [wherein Ag is an optionally substituted 5- to 14-membered heterocyclic group, etc.; Xg is -O-, -S-, etc.; Yg is an optionally substituted C6-14 aryl group, an optionally substituted 5- to 14-membered heterocyclic group, etc.; and Tg1 is a group represented by the following general formula: (wherein Eg is a single bond or -N(Rg2)-, Rg1 and Rg2 each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, etc. and Zg represents a C1-8 alkyl group, a C3-8 alicyclic hydrocarbon group, a C6-14 aryl group, etc.)], salts thereof or hydrates of the foregoing.

  由以下通式代表的化合物： [其中 Ag 是任选取代的 5 至 14 元杂环基团等；Xg 是-O-、-S-等；Yg 是任选取代的 C6-14 芳基、任选取代的 5 至 14 元杂环基团等；以及 Tg1 是由下通式表示的基团： (其中 Eg 是单键或-N(Rg2)-，Rg1 和 Rg2 各自独立地代表氢原子、任选取代的 C1-6 烷基等，Zg 代表 C1-8 烷基、C3-8 脂环烃基、C6-14 芳基等）]、其盐或上述物质的水合物。