N-{4-[(6,7-Dimethoxy-4-quinolinyl)oxy]phenyl}-(4-butylphenyl)carboxamide | 651054-47-6

• 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: N-{4-[(6,7-Dimethoxy-4-quinolinyl)oxy]phenyl}-(4-butylphenyl)carboxamide
• 英文别名: 4-Butyl-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)benzamide；4-butyl-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]benzamide
• CAS: 651054-47-6
• 化学式: C₂₈H₂₈N₂O₄
• 分子量: 456.541
• InChiKey: MTXZLMZGDVRVQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-羟基-6,7-二甲氧基喹啉 在 palladium dihydroxide 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 二乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 N-{4-[(6,7-Dimethoxy-4-quinolinyl)oxy]phenyl}-(4-butylphenyl)carboxamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship for new series of 4-Phenoxyquinoline derivatives as specific inhibitors of platelet-derived growth factor receptor tyrosine kinase

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2003.08.020

文献信息

• Quinoline and quinazoline derivatives inhibiting platelet-derived growth
  申请人：Kirin Beer Kabushiki Kaisha

  公开号：US06143764A1

  公开（公告）日：2000-11-07

  The present invention relates to novel quinoline derivatives and quinazoline derivatives represented by the following formula (I): ##STR1## [wherein R.sub.1 and R.sub.2 are each independently H or C.sub.1 -C.sub.4 -alkyl, or R.sub.1 and R.sub.2 together form C.sub.1 -C.sub.3 -alkylene, X is O, S or CH.sub.2, W is CH or N, and Q is a substituted aryl group or substituted heteroaryl group] and their pharmaceutically acceptable salts, having platelet-derived growth factor receptor autophosphorylation inhibitory activity, to pharmaceutical compositions containing these compounds, and to methods for the treatment of diseases associated with abnormal cell growth such as tumors.

  本发明涉及一种新型喹啉衍生物和喹嗪衍生物，其由以下式子（I）所表示：##STR1## [其中R.sub.1和R.sub.2各自独立地为H或C.sub.1-C.sub.4-烷基，或者R.sub.1和R.sub.2共同形成C.sub.1-C.sub.3-亚烷基，X为O、S或CH.sub.2，W为CH或N，Q为取代芳基或取代杂环芳基]及其药学上可接受的盐，具有血小板源性生长因子受体自磷酸化抑制活性，以及含有这些化合物的制药组合物，以及用于治疗与异常细胞生长相关的疾病，如肿瘤的方法。
• QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES INHIBITING AUTOPHOSPHORYLATION OF GROWTH FACTOR RECEPTOR ORIGINATING IN PLATELET AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP0860433B1

  公开（公告）日：2002-07-03
• US6143764A
  申请人：——

  公开号：US6143764A

  公开（公告）日：2000-11-07
• 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.