1-(quinolin-6-yl)ethan-1-one oxime | 30074-91-0

• 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: 1-(quinolin-6-yl)ethan-1-one oxime
• 英文别名: 1-(quinolin-6-yl)ethanone oxime；Methyl-6-chinolyl-ketoxim；1-Quinolin-6-yl-ethanone oxime；N-(1-quinolin-6-ylethylidene)hydroxylamine
• CAS: 30074-91-0
• 化学式: C₁₁H₁₀N₂O
• 分子量: 186.213
• InChiKey: ZXVXDQGYKWEPRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(quinolin-6-yl)ethan-1-one oxime 在 异戊腈 、 氨 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 18.0h， 生成 6-[1-(6-bromo-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)-ethyl]-quinoline
  参考文献：
  名称：

  Lessons from (S)-6-(1-(6-(1-Methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an Inhibitor of Receptor Tyrosine Kinase c-Met with High Protein Kinase Selectivity but Broad Phosphodiesterase Family Inhibition Leading to Myocardial Degeneration in Rats

  摘要：

  The hepatocyte growth factor (HGF)/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. An exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol -4-yl) - [1,2,4] triazolo [4,3-b pyridazin- 3-yl) ethyl) quinoline (8) was discovered from a highly selective high-throughput screening hit. via structure-based drug design and medicinal chemistry lead optimization. Compound 8 had many attractive properties meriting preclinical evaluation. Broad off-target screens identified 8 as a pan-phosphodiesterase (PDE) family inhibitor, which was implicated in a sustained increase in heart rate, increased cardiac output, and decreased contractility indices, as well as myocardial degeneration in in vivo safety evaluations in rats. Compound 8 was terminated as a preclinical candidate because of a narrow therapeutic window in cardio-related safety. The learning from multiparameter lead optimization and strategies to avoid the toxicity attrition at the late stage of drug discovery are discussed.

  DOI：

  10.1021/jm400926x
• 作为产物：
  描述：

  6-乙酰基喹啉 在 盐酸羟胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以99%的产率得到1-(quinolin-6-yl)ethan-1-one oxime
  参考文献：
  名称：

  发现和优化一系列咪唑并[4,5-b]吡嗪衍生物，作为间充质-上皮转化因子（c-Met）蛋白激酶的强效和精细选择性抑制剂。

  摘要：

  异常的c-Met激活与多种肿瘤致癌过程和耐药性有关。本研究设计并合成了一系列咪唑并[4,5-b]吡嗪衍生物，并对其体外抑菌活性进行了评价。系统地研究了结构活性关系（SAR），并进行了对接分析以阐明结合模式，从而鉴定出最有前途的化合物1D-2，该化合物对酶促（IC50 = 1.45nM）和细胞（ H1993细胞系中的IC50 = 24.7nM，以及在人和大鼠肝微粒体中的精湛选择性和令人满意的代谢稳定性。

  DOI：

  10.1016/j.bmc.2016.07.019

文献信息

• 喹啉类化合物、其制备方法、中间体、药物组合 物和应用
  申请人：上海医药集团股份有限公司

  公开号：CN105968115B

  公开（公告）日：2018-11-09

  本发明公开了喹啉类化合物、其制备方法、中间体、药物组合物和应用。本发明提供了一种如式1所示的喹啉类化合物、其药学上可接受的盐、溶剂化物、代谢产物、代谢前体或其药物前体。本发明的喹啉类化合物对酪氨酸激酶C‑Met有良好的抑制效果，可以用于制备预防、治疗或辅助治疗与C‑Met的表达或活性有关的多种疾病、尤其是肿瘤疾病的药物。
• TRIAZOLOPYRAZINE DERIVATIVES
  申请人：Cheng Hengmiao

  公开号：US20070265272A1

  公开（公告）日：2007-11-15

  The invention relates to compounds of the formula I or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 and R 4 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R1、R2、R3和R4如本文所定义。本发明还涉及含有公式I化合物的药物组合物，以及通过给予公式I化合物治疗哺乳动物的过度增殖性疾病的方法。
• Triazolopyrazine derivatives
  申请人：Pfizer Inc.

  公开号：US07732604B2

  公开（公告）日：2010-06-08

  The invention relates to compounds of the formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3 and R4 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.

  本发明涉及公式I化合物或其药学上可接受的盐，其中R1、R2、R3和R4的定义如本文所述。本发明还涉及含有公式I化合物的药物组合物，并通过给予公式I化合物的方法治疗哺乳动物的高增殖性疾病。
• Discovery and optimization of a series of imidazo[4,5-b]pyrazine derivatives as highly potent and exquisitely selective inhibitors of the mesenchymal–epithelial transition factor (c-Met) protein kinase
  作者：Fei Zhao、Jing Zhang、Leduo Zhang、Yu Hao、Chen Shi、Guangxin Xia、Jianxin Yu、Yanjun Liu

  DOI：10.1016/j.bmc.2016.07.019

  日期：2016.9

  identification of the most promising compound 1D-2 which exhibited significant inhibitory effect on both enzymatic (IC50=1.45nM) and cellular (IC50=24.7nM in H1993 cell line) assays, as well as exquisite selectivity and satisfactory metabolic stability in human and rat liver microsomes.

  异常的c-Met激活与多种肿瘤致癌过程和耐药性有关。本研究设计并合成了一系列咪唑并[4,5-b]吡嗪衍生物，并对其体外抑菌活性进行了评价。系统地研究了结构活性关系（SAR），并进行了对接分析以阐明结合模式，从而鉴定出最有前途的化合物1D-2，该化合物对酶促（IC50 = 1.45nM）和细胞（ H1993细胞系中的IC50 = 24.7nM，以及在人和大鼠肝微粒体中的精湛选择性和令人满意的代谢稳定性。
• Lessons from (<i>S</i>)-6-(1-(6-(1-Methyl-1<i>H</i>-pyrazol-4-yl)-[1,2,4]triazolo[4,3-<i>b</i>]pyridazin-3-yl)ethyl)quinoline (PF-04254644), an Inhibitor of Receptor Tyrosine Kinase c-Met with High Protein Kinase Selectivity but Broad Phosphodiesterase Family Inhibition Leading to Myocardial Degeneration in Rats
  作者：J. Jean Cui、Hong Shen、Michelle Tran-Dubé、Mitchell Nambu、Michele McTigue、Neil Grodsky、Kevin Ryan、Shinji Yamazaki、Shirley Aguirre、Max Parker、Qiuhua Li、Helen Zou、James Christensen

  DOI：10.1021/jm400926x

  日期：2013.9.12

  The hepatocyte growth factor (HGF)/c-Met signaling axis is deregulated in many cancers and plays important roles in tumor invasive growth and metastasis. An exclusively selective c-Met inhibitor (S)-6-(1-(6-(1-methyl-1H-pyrazol -4-yl) - [1,2,4] triazolo [4,3-b pyridazin- 3-yl) ethyl) quinoline (8) was discovered from a highly selective high-throughput screening hit. via structure-based drug design and medicinal chemistry lead optimization. Compound 8 had many attractive properties meriting preclinical evaluation. Broad off-target screens identified 8 as a pan-phosphodiesterase (PDE) family inhibitor, which was implicated in a sustained increase in heart rate, increased cardiac output, and decreased contractility indices, as well as myocardial degeneration in in vivo safety evaluations in rats. Compound 8 was terminated as a preclinical candidate because of a narrow therapeutic window in cardio-related safety. The learning from multiparameter lead optimization and strategies to avoid the toxicity attrition at the late stage of drug discovery are discussed.