4-(6,7-dimethoxyquinolin-4-yloxy)phenol | 347405-65-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(6,7-dimethoxyquinolin-4-yloxy)phenol
• 英文别名: 4-(6,7-Dimethoxy-4-quinolyloxy)phenol；4-(6,7-dimethoxyquinolin-4-yl)oxyphenol
• CAS: 347405-65-6
• 化学式: C₁₇H₁₅NO₄
• 分子量: 297.31
• InChiKey: QVVCSEHIAWISPY-UHFFFAOYSA-N

物化性质

• 沸点：
  477.2±45.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(6,7-dimethoxyquinolin-4-yloxy)phenol 在 硝酸 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 19.5h， 生成 2-amino-4-(6,7-dimethoxyquinolin-4-yloxy)phenol
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

  DOI：

  10.1021/jm070034i
• 作为产物：
  描述：

  4-苄氧基苯酚 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~85.0 ℃ 、101.33 kPa 条件下， 反应 26.17h， 生成 4-(6,7-dimethoxyquinolin-4-yloxy)phenol
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Orally Active Benzimidazoles and Benzoxazoles as Vascular Endothelial Growth Factor-2 Receptor Tyrosine Kinase Inhibitors

  摘要：

  Inhibition of the VEGF signaling pathway has become a valuable approach in the treatment of cancers. Guided by X-ray crystallography and molecular modeling, a series of 2-aminobenzimidazoles and 2-aminobenzoxazoles were identified as potent inhibitors of VEGFR-2 (KDR) in both enzymatic and HUVEC cellular proliferation assays. In this report we describe the synthesis and structure-activity relationship of a series of 2-aminobenzimidazoles and benzoxazoles, culminating in the identification of benzoxazole 22 as a potent and selective VEGFR-2 inhibitor displaying a good pharmacokinetic profile. Compound 22 demonstrated efficacy in both the murine matrigel model for vascular permeability (79% inhibition observed at 100 mg/kg) and the rat corneal angiogenesis model (ED(50) = 16.3 mg/kg).

  DOI：

  10.1021/jm070034i

文献信息

• Quinoline and quinazoline derivatives and drugs containing the same
  申请人：——

  公开号：US20040132727A1

  公开（公告）日：2004-07-08

  There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof: 1 wherein R 1 and R 2 represent hydrogen, alkyl or the like; R 3 , R 4 , R 5 and R 6 represent hydrogen, halogen, alkyl, alkoxy or the like; R 11 and R 12 represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R 3 , R 4 , R 5 and R 6 represent hydrogen and A represents group (v) wherein u is 0 (zero) and R 19 represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

  提供了一些化合物，可用于治疗由PDGF受体自磷酸化介导的疾病，特别是可抑制新内膜形成肥大的化合物。这些化合物由式（I）或其药理学上可接受的盐或溶剂表示：1其中R1和R2表示氢，烷基或类似物；R3、R4、R5和R6表示氢，卤素，烷基，烷氧基或类似物；R11和R12表示氢，烷基，烷基羰基或类似物；而A表示公式（i）到（x）中的任意一个，但其中R3、R4、R5和R6表示氢，A表示组（v）其中u为0（零）且R19表示苯基，可选地被卤素，烷基或烷氧基取代的化合物被排除。
• Quinoline or quinazoline derivatives inhibiting auto-phosphorylation of fibroblast growth factor receptors
  申请人：Miwa Atsushi

  公开号：US20050049264A1

  公开（公告）日：2005-03-03

  An objective of the present invention is to provide novel compounds which have inhibitory activity against autophosphorylation of an FGF receptor family and, when orally or intraveneously administered, can suppress the growth of cancer cells. The compounds of the present invention are represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; Z represents O or S; Q represents NR 10 , CR 11 R 2 , carbonyl, O, S(═O)m, wherein m is 0 to 2, or urea; R 1 to R 3 each independently represent H, OH, halogen, nitro, amino, alkyl, alkoxy or the like in which the alkyl and alkoxy groups are optionally substituted; R 4 represents H; R 5 to R 8 each independently represent H, halogen, alkyl, or alkoxy; and R 9 represents an optionally substituted carbocyclic or heterocyclic group.

  本发明的目标是提供新型化合物，其具有对FGF受体家族自磷酸化的抑制活性，并在口服或静脉注射时能够抑制癌细胞的生长。本发明的化合物由公式（I）或其药学上可接受的盐或溶剂表示：其中X代表CH或N; Z代表O或S; Q代表NR10，CR11R2，羰基，O，S（═O）m，其中m为0到2，或脲基; R1至R3各自独立地表示H、OH、卤素、硝基、氨基、烷基、烷氧基或其类似物，其中烷基和烷氧基基团可选择性地被取代; R4表示H; R5至R8各自独立地表示H、卤素、烷基或烷氧基; R9表示一个可选择性取代的碳环或杂环基团。
• QUINOLINE AND QUINAZOLINE DERIVATIVES AND DRUGS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1243582A1

  公开（公告）日：2002-09-25

  There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof: wherein R1 and R2 represent hydrogen, alkyl or the like; R3, R4, R5, and R6 represent hydrogen, halogen, alkyl, alkoxy or the like; R11 and R12 represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R3, R4, R5 and R6 represent hydrogen and A represents group (v) wherein u is 0 (zero) and R19 represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

  提供了可用于治疗由 PDGF 受体自身磷酸化介导的疾病的化合物，特别是可抑制新内膜形成肥厚的化合物。这些化合物是式 (I) 所代表的化合物或其药理学上可接受的盐或溶液： 其中 R1 和 R2 代表氢、烷基或类似物；R3、R4、R5 和 R6 代表氢、卤素、烷基、烷氧基或类似物；R11 和 R12 代表氢、烷基、烷基羰基或类似物；A 代表式(i)至(x)中的任意一种，但不包括 R3、R4、R5 和 R6 代表氢且 A 代表基团(v)（其中 u 为 0（零）且 R19 代表任选被卤素、烷基或烷氧基取代的苯基）的化合物。
• QUINOLINE OR QUINAZOLINE DERIVATIVES INHIBITING AUTO-PHOSPHORYLATION OF FIBROBLAST GROWTH FACTOR RECEPTORS
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1447405A1

  公开（公告）日：2004-08-18

  An objective of the present invention is to provide novel compounds which have inhibitory activity against autophosphorylation of an FGF receptor family and, when orally or intraveneously administered, can suppress the growth of cancer cells. The compounds of the present invention are represented by formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein X represents CH or N; Z represents 0 or S; Q represents NR10, CR11R12, carbonyl, O, S(=O)m, wherein m is 0 to 2, or urea; R1 to R3 each independently represent H, OH, halogen, nitro, amino, alkyl, alkoxy or the like in which the alkyl and alkoxy groups are optionally substituted; R4 represents H; R5 to R8 each independently represent H, halogen, alkyl, or alkoxy; and R9 represents an optionally substituted carbocyclic or heterocyclic group.

  本发明的目的是提供对 FGF 受体家族的自身磷酸化具有抑制活性的新型化合物，口服或静脉注射后可抑制癌细胞的生长。本发明的化合物由式（I）或其药学上可接受的盐或溶液表示： 其中 X 代表 CH 或 N；Z 代表 0 或 S；Q 代表 NR10、CR11R12、羰基、O、S(＝O)m（其中 m 为 0 至 2）或脲；R1 至 R3 各自独立地代表 H、OH、卤素、硝基、氨基、烷基、烷氧基或类似基团，其中烷基和烷氧基是任选取代的；R4 代表 H；R5 至 R8 各自独立地代表 H、卤素、烷基或烷氧基；R9 代表任选取代的碳环或杂环基团。
• Synthesis and structure–activity relationship for new series of 4-Phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase
  作者：Kazuo Kubo、Shin-ichi Ohyama、Toshiyuki Shimizu、Atsuya Takami、Hideko Murooka、Tsuyoshi Nishitoba、Shinichiro Kato、Mikio Yagi、Yoshiko Kobayashi、Noriko Iinuma、Toshiyuki Isoe、Kazuhide Nakamura、Hiroshi Iijima、Tatsushi Osawa、Toshio Izawa

  DOI：10.1016/j.bmc.2003.08.020

  日期：2003.11

  We discovered a new series of 4-phenoxyquinoline derivatives as potent and selective inhibitors of the platelet-derived growth factor receptor (PDGFr) tyrosine kinase. We researched the highly potent and selective inhibitors on the basis of both PDGFr and epidermal growth factor receptor (EGFr) inhibitory activity. First, we found a compound, Ki6783 (1), which inhibited PDGFr autophosphorylation at 0.13 muM, but it did not inhibit EGFr autophosphorylation at 100 muM. After extensive explorations, we found the two desired compounds, Ki6896 (2) and Ki6945 (3), which are substituted by benzoyl and benzamide at the 4-position of the phenoxy group on 4-phenoxyquinoline, respectively. These inhibitory activities were 0.31 and 0.050 muM, respectively, but neither of them inhibited EGFr autophosphorylation at 100 M. We further investigated the profile of both compounds toward various tyrosine and serine/threonine kinases. The three compounds specifically inhibited PDGFr rather than the other kinases. (C) 2003 Elsevier Ltd. All rights reserved.