2-(1-(7-fluoroquinolin-6-yl)ethyl)isoindoline-1,3-dione | 1266237-80-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(1-(7-fluoroquinolin-6-yl)ethyl)isoindoline-1,3-dione
• 英文别名: 2-[1-(7-fluoroquinolin-6-yl)ethyl]isoindole-1,3-dione
• CAS: 1266237-80-2
• 化学式: C₁₉H₁₃FN₂O₂
• 分子量: 320.323
• InChiKey: SQVYMEUHRYRAIX-UHFFFAOYSA-N

物化性质

• 沸点：
  486.7±35.0 °C(Predicted)
• 密度：
  1.394±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(1-(7-fluoroquinolin-6-yl)ethyl)isoindoline-1,3-dione 在 吡啶 、 hydrazine hydrate 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 溴 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 四氯化碳 、 乙醇 、 水 为溶剂， 反应 5.0h， 生成 1-(7-fluoro-3-(4-fluorophenyl)quinolin-6-yl)ethan-1-amine
  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
• 作为产物：
  描述：

  6-溴-7-氟喹啉 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 三溴化磷 、 potassium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 2-(1-(7-fluoroquinolin-6-yl)ethyl)isoindoline-1,3-dione
  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

• [EN] HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION<br/>[FR] COMPOSÉS HYDRAZONE HÉTÉROCYCLIQUES ET LEURS UTILISATIONS POUR TRAITER LE CANCER ET L'INFLAMMATION
  申请人：NOVARTIS AG

  公开号：WO2011018454A1

  公开（公告）日：2011-02-17

  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).

  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，并且公式(I)的化合物的制备方法。
• 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。
• 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 HYDRAZONE COMPOUNDS
  申请人：He Feng

  公开号：US20120142681A1

  公开（公告）日：2012-06-07

  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).

  本发明涉及式（I）的化合物及其盐：其中取代基如说明书所定义；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症；使用式（I）的化合物制造用于治疗此类疾病的药物；包含式（I）的化合物的药物组合物，可选地与组合伙伴共存，以及制备式（I）的化合物的过程。
• Heterocyclic hydrazone compounds
  申请人：He Feng

  公开号：US08497368B2

  公开（公告）日：2013-07-30

  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).

  本发明涉及化合物的公式（I）及其盐：其中取代基的定义如规范中所述；化合物的公式（I）用于治疗人体或动物体，特别是与c-Met酪氨酸激酶介导的疾病或状况有关；化合物的公式（I）的用途用于制造用于治疗此类疾病的药物；包含化合物的公式（I）的制药组合物，可选择在合作伙伴的存在下，以及制备化合物的公式（I）的过程。