卡博替尼杂质50 | 202917-05-3

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 卡博替尼杂质50
• 英文名称: 6,7-Dimethoxy-4-(3-nitro-phenoxy)-quinoline
• 英文别名: 6,7-dimethoxy-4-(3-nitrophenoxy)quinoline
• CAS: 202917-05-3
• 化学式: C₁₇H₁₄N₂O₅
• 分子量: 326.309
• InChiKey: OMYGYNKHKZLDSH-UHFFFAOYSA-N

物化性质

• 沸点：
  482.8±45.0 °C(Predicted)
• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 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：
  86.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  卡博替尼杂质50 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 以59.7 %的产率得到3-((6,7-dimethoxyquinolin-4-yl)oxy)aniline
  参考文献：
  名称：

  发现 4-oxo-N-phenyl-1,4-dihydroquinoline-3-carboxamide 衍生物作为治疗急性肺损伤和败血症的新型抗炎药

  摘要：

  以全身炎症反应综合征为特征的急性肺损伤（ALI）和败血症仍然是重症患者死亡的主要原因。抑制促炎细胞因子的释放被认为是治疗炎症相关疾病的一种有前途的方法。本研究共设计合成了 28 个 4-oxo- N -phenyl-1,4-dihydroquinoline-3-carboxamide 衍生物，并评价了它们在 J774A.1 中的抗炎活性。其中，衍生物13a被发现可显着抑制脂多糖 (LPS) 诱导的 J774A.1、THP-1 和 LX 上促炎细胞因子白细胞介素 6 (IL-6) 和肿瘤坏死因子-α (TNF-α) 的表达-2 细胞，并抑制 NF-κB 通路的激活。此外，管理13a 在体内显着改善 LPS 诱导的 ALI 小鼠的症状，包括减轻肺组织的病理变化、减轻肺水肿和抑制巨噬细胞浸润。此外，体内施用13a 可显着促进 LPS 诱导的脓毒症小鼠的存活。13a显示出良好的药代动力学特性，T 1/2值为

  DOI：

  10.1016/j.ejmech.2023.115144
• 作为产物：
  描述：

  4-羟基-6,7-二甲氧基喹啉 在 三氯氧磷 作用下， 以 二乙二醇二甲醚 为溶剂， 生成 卡博替尼杂质50
  参考文献：
  名称：

  A novel series of 4-phenoxyquinolines: potent and highly selective inhibitors of PDGF receptor autophosphorylation

  摘要：

  A novel series of 4-phenoxyquinolines, some of which showed potent and highly selective inhibitory activities for PDGF receptor autophosphorylation, was discovered. Interestingly, their structures were very similar to those of the selective inhibitors for EGF receptor autophosphorylation. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10117-2

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。
• 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.
• Discovery of the Diphenyl 6-Oxo-1,6-dihydropyridazine-3-carboxylate/carboxamide Analogue J27 for the Treatment of Acute Lung Injury and Sepsis by Targeting JNK2 and Inhibiting the JNK2-NF-κB/MAPK Pathway
  作者：Jing Liao、Jun Yang、Xiaobo Li、Chenghong Hu、Weiwei Zhu、Ying Zhou、Yu Zou、Mi Guo、Zhichao Chen、Xiang Li、Jintian Dai、Yuye Xu、Zhiwei Zheng、Pan Chen、Won-Jea Cho、Guang Liang、Qidong Tang

  DOI：10.1021/acs.jmedchem.3c00832

  日期：2023.9.14
• 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