1-(5,7-difluoroquinolin-6-yl)ethan-1-ol | 1268261-22-8

• 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-(5,7-difluoroquinolin-6-yl)ethan-1-ol
• 英文别名: 1-(5,7-difluoro-6-quinolinyl)ethanol；1-(5,7-difluoroquinolin-6-yl)ethanol
• CAS: 1268261-22-8
• 化学式: C₁₁H₉F₂NO
• 分子量: 209.195
• InChiKey: KCPUQHMEOXUFJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5,7-difluoroquinolin-6-yl)ethan-1-ol 在 四(三苯基膦)钯 盐酸 、 一水合肼 、 溶剂黄146 、 diisopropyl (E)-azodicarboxylate 、 N,N-二异丙基乙胺 、 三苯基膦 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.75h， 生成 (E)-1-(1-(1-(5,7-difluoroquinolin-6-yl)ethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)ethanone O-2-hydroxyethyl oxime
  参考文献：
  名称：

  [EN] HETEROCYCLIC OXIME COMPOUNDS
  [FR] COMPOSÉS D'OXIMES HÉTÉROCYCLIQUES

  摘要：

  该发明涉及公式(I)的化合物及其盐，其中取代基如规范中所定义；公式(I)的化合物用于治疗人体或动物体，特别是针对c-Met酪氨酸激酶介导的疾病或症状；公式(I)的化合物用于制造治疗此类疾病的药物；包含公式(I)的化合物的药物组合物，可选地与组合伙伴一起，并且用于制备公式(I)的化合物的方法。

  公开号：

  WO2011020861A1
• 作为产物：
  描述：

  4-溴-3,5-二氟苯胺 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 硫酸 、 sodium 3-nitrobenzenesulfonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 5.0h， 生成 1-(5,7-difluoroquinolin-6-yl)ethan-1-ol
  参考文献：
  名称：

  Identification of 3-substituted-6-(1-(1 H -[1,2,3]triazolo[4,5- b ]pyrazin-1-yl)ethyl)quinoline derivatives as highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitors via metabolite profiling-based structural optimization

  摘要：

  c-Met/HGF signaling pathway plays an important role in cancer progression, and it was considered to be related to poor prognosis and drug resistance. Based on metabolite profiling of (S)-7-fluoro-6-(1-(6-(1methyl-1H-pyrazol-4-y1)-1H-imidazo[4,5-b]pyrazin-1-yl)ethypquinoline (1), a series of 2-substituted or 3-substituted-6-(1-(1H-[1,2,31triazolo[4,5-b]pyrazin-1-yl)ethyl)quinoline derivatives was rationally designed and evaluated. Most of the 3-substituted derivatives not only exhibited potent activities in both enzymatic and cellular assays, but also were stable in liver microsomes among different species (human, rat and monkey). SAR investigation revealed that introducing of N-methyl-IH-pyrazol-4-yl group at the 3-position of quinoline moiety is beneficial to improve the inhibitory potency, especially in the cellular assays. The influence of fluorine atom at 7-position or 5, 7-position of quinoline moiety and substituents at the 6-position of triazolo[4,5-b]pyrazine core on overall activity is not very significant. Racemate 14, an extremely potent and exquisitely selective c-Met inhibitor, demonstrated favorable pharmacokinetic properties in rats, no significant AO metabolism and effective tumor growth inhibition in c-Met over expressed NSCLC (H1993 cell line) and gastric cancer (SNU-5 cell line) xenograft models. Docking analysis indicated that besides the typical interactions of most selective c-Met inhibitors, the intramolecular halogen bond and additional hydrogen bond interactions with kinase are beneficial to the binding. These results may provide deep insight into potential structural modifications for developing potent c-Met inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.03.085

文献信息

• 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。
• HETEROCYCLIC OXIME COMPOUNDS
  申请人：DAI Miao

  公开号：US20110065708A1

  公开（公告）日：2011-03-17

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及公式（I）的化合物及其盐： 其中取代基如规范中所定义；公式（I）的化合物用于人或动物体内的治疗，特别是针对c-Met酪氨酸激酶介导的疾病或情况；使用公式（I）的化合物制造治疗此类疾病的药物；包括公式（I）的化合物的制药组合物，可选地与联合伙伴一起使用，以及制备公式（I）的化合物的过程。
• Heterocyclic oxime compounds
  申请人：Dai Miao

  公开号：US08410264B2

  公开（公告）日：2013-04-02

  The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).

  本发明涉及公式(I)的化合物及其盐：其中，取代基如规范中所定义；公式(I)的化合物用于治疗人体或动物体，特别是涉及c-Met酪氨酸激酶介导的疾病或病况；使用公式(I)的化合物制造治疗此类疾病的药物；包括公式(I)化合物的制药组合物，可选地与联合伙伴一起，以及制备公式(I)化合物的过程。
• US8410264B2
  申请人：——

  公开号：US8410264B2

  公开（公告）日：2013-04-02
• US8507676B2
  申请人：——

  公开号：US8507676B2

  公开（公告）日：2013-08-13