7-(((4-methylpyrimidin-2-yl)amino)(4-(trifluoromethyl)phenyl)methyl)quinolin-8-ol | 1351140-16-3

• 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: 7-(((4-methylpyrimidin-2-yl)amino)(4-(trifluoromethyl)phenyl)methyl)quinolin-8-ol
• 英文别名: 7-[[(4-methylpyrimidin-2-yl)amino]-[4-(trifluoromethyl)phenyl]methyl]quinolin-8-ol
• CAS: 1351140-16-3
• 化学式: C₂₂H₁₇F₃N₄O
• 分子量: 410.398
• InChiKey: PFCKQDHXCWWBSM-UHFFFAOYSA-N

物化性质

• 沸点：
  607.9±65.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• 储存条件：
  存储条件：2-8°C，避光，并在氮气环境中保存。

反应信息

• 作为产物：
  描述：

  2-氨基-4-甲基嘧啶 、 对三氟甲基苯甲醛 、 8-羟基喹啉 在 甲酸 作用下， 以 乙腈 为溶剂， 以46%的产率得到7-(((4-methylpyrimidin-2-yl)amino)(4-(trifluoromethyl)phenyl)methyl)quinolin-8-ol
  参考文献：
  名称：

  8-羟基喹啉贝蒂产品的合成和细胞保护作用。

  摘要：

  已经证明8-羟基喹啉药效团支架具有一系列活性，例如金属螯合，酶抑制，细胞毒性和细胞保护。基于我们以前的发现，我们着手优化支架的细胞保护活性，以使其潜在地应用于中枢神经系统相关疾病。通过利用甲酸介导的工业相容性偶联物，与苯胺，恶唑，吡啶和嘧啶等芳香族伯胺，以及（杂）芳族醛和8-氢氧喹啉衍生物，构建48位成员的Betti库。经柱层析和重结晶后，得到相应的类似物，产率为13-90％。通过利用化学诱导的氧化应激的细胞保护测定法对合成的类似物进行了优化，并在正交测定，实时细胞生存力方法，基于荧光激活细胞分选（FACS）的测定线粒体膜电位变化的测定以及基因表达分析中进一步测试了活性最高的化合物。最好的候选者在所有测试系统中均显示出强大的纳摩尔活性，并支持将来需要对中枢神经系统（CNS）疾病的动物模型进行研究。

  DOI：

  10.3390/molecules23081934

文献信息

• [EN] 8-HYDROXY-QUINOLINE DERIVATIVES<br/>[FR] DÉRIVÉS 8-HYDROXY-QUINOLINE
  申请人：AVIDIN KUTATO FEJLESZTO ES KERESKEDELMI KORLATOLT FELELOSSEGU TARSASAG

  公开号：WO2011148208A1

  公开（公告）日：2011-12-01

  The invention relates to compounds of the general formula (I) and their pharmaceutically acceptable salts (in which formula R1 represents a hydrogen atom, lower alkyl group, lower alkenyl group, lower cycloalkyl group, aryl group, aralkyl group or heterocyclic group, wherein the above groups are optionally substituted in ortho, meta and/or para position with 1, 2, 3 or 4 electron withdrawing groups or electron donating groups; R2 represents a hydrogen atom, lower alkyl group, aryl group, aralkyl group or heterocyclic group wherein the above groups are optionally substituted with one or more halogen atoms; R3 represents a lower alkyl group, aryl group, aralkyl group or heterocyclic group wherein the above groups are optionally substituted in ortho, meta or para position with 1, 2, 3 or 4 electron withdrawing groups or electron donating groups; R4 represents a hydrogen atom, lower alkyl group or any acidic functional group; n is 1 or 2). The compounds according to the invention can be used in the medicine mainly for the treatment of diseases associated with neurological and/or oxidative stress.

  该发明涉及通式(I)的化合物及其药用可接受的盐（其中通式中R1代表氢原子、较低的烷基、较低的烯基、较低的环烷基、芳基、芳基烷基或杂环基，上述基团可以选择性地在邻位、间位和/或对位上用1、2、3或4个电子吸引基团或电子供给基团替代；R2代表氢原子、较低的烷基、芳基、芳基烷基或杂环基，上述基团可以选择性地用一个或多个卤素原子替代；R3代表较低的烷基、芳基、芳基烷基或杂环基，上述基团可以选择性地在邻位、间位或对位上用1、2、3或4个电子吸引基团或电子供给基团替代；R4代表氢原子、较低的烷基或任何酸性官能团；n为1或2）。根据该发明的化合物主要可用于治疗与神经和/或氧化应激有关的疾病。
• Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent
  作者：László Hackler、Márió Gyuris、Orsolya Huzián、Róbert Alföldi、Gábor J. Szebeni、Ramóna Madácsi、Levente Knapp、Iván Kanizsai、László G. Puskás

  DOI：10.3390/molecules24234269

  日期：——

  combat these diseases by activators of cytoprotective protein induction. We have selected a candidate molecule from our cytoprotective hydroxyquinoline library and developed a novel enantioselective synthesis for the production of its enantiomers. The use of quinidine or quinine as a catalyst enabled the preparation of enantiomer-pure products. We have utilized in vitro assays to evaluate cytoprotective

  缺氧是神经退行性疾病的一个共同特征，包括可能导致疾病发病机制和进展的阿尔茨海默病。因此，负责缺氧适应的缺氧诱导因子 (HIF)1 系统是通过细胞保护蛋白诱导激活剂对抗这些疾病的潜在治疗靶点。我们从我们的细胞保护性羟基喹啉库中选择了一种候选分子，并开发了一种新型的对映选择性合成来生产其对映异构体。使用奎尼丁或奎宁作为催化剂可以制备纯对映体产品。我们利用体外测定来评估细胞保护活性、基于荧光激活细胞分选 (FACS) 的测定线粒体膜电位变化以及基因和蛋白质表达分析。我们的数据表明，Q134 的对映异构体在所有测试分析中都显示出有效且相似的活性。我们已经得出结论，对映异构体通过 HIF1A 蛋白稳定作用通过 HIF1 系统发挥其细胞保护活性。
• 8-HYDROXY-QUINOLINE DERIVATIVES
  申请人：Puskas Laszlo

  公开号：US20130131096A1

  公开（公告）日：2013-05-23

  The invention relates to compounds of the general formula (I) and their pharmaceutically acceptable salts (in which formula R 1 represents a hydrogen atom, lower alkyl group, lower alkenyl group, lower cycloalkyl group, aryl group, aralkyl group or heterocyclic group, wherein, the above groups are optionally substituted in ortho, meta and/or para position with 1, 2, 3 or 4 electron withdrawing groups or electron donating groups; R 2 represents a hydrogen atom, lower alkyl group, aryl group, aralkyl group or heterocyclic group wherein the above groups are optionally substituted with one or more halogen atoms; R 3 represents a lower alkyl group, aryl group, aralkyl group or heterocyclic group wherein the above groups are optionally substituted in ortho, meta or para position with 1, 2, 3 or 4 electron withdrawing groups or electron donating groups; R 4 represents a hydrogen atom, lower alkyl group or any acidic functional group; n is 1 or 2). The compounds according to the invention can be used in the medicine mainly for the treatment of diseases associated with neurological and/or oxidative stress.

  本发明涉及一般式（I）的化合物及其药学上可接受的盐（其中R1表示氢原子，低碳基，低烯基，低环烷基，芳基，芳基烷基或杂环基，其中上述基团在邻位，间位和/或对位上可以选择性地被1、2、3或4个电子提取基团或电子捐赠基团取代；R2表示氢原子，低碳基，芳基，芳基烷基或杂环基，其中上述基团可以选择性地被一个或多个卤素原子取代；R3表示低碳基，芳基，芳基烷基或杂环基，其中上述基团在邻位，间位或对位上可以选择性地被1、2、3或4个电子提取基团或电子捐赠基团取代；R4表示氢原子，低碳基或任何酸性官能团；n为1或2）。根据本发明的化合物主要可用于治疗与神经学和/或氧化应激相关的疾病。
• Enantiomers of 8-hydroxyquinoline derivatives and the synthesis thereof
  申请人：AVIDIN Co. Ltd.

  公开号：US10287265B2

  公开（公告）日：2019-05-14

  Our invention relates to novel enantiomer derivatives of 8-hydroxyquinoline derivatives with general formula (I) and (II) and the synthesis thereof and pharmaceutically acceptable salts and metal complexes thereof, and the medicinal and/or pharmaceutical compositions comprising these compounds. The essence of the subject matter of the invention relates to the fact that prior art discloses the biological effect and characteristics only of the racemic products, the novel enantiomer derivatives according to the invention appear in our application for the first. The subject matter of the invention furthermore relates to a novel, stereoselective synthesis for the preparation of the novel enantiomer derivatives according to the invention. The novel medicinal and/or pharmaceutical compositions comprising these enantiomers are suitable for the treatment of the named diseases, and the enanatiomers are used for manufacture of these compositions. These applications for manufacture of the compositions are also the subject matters of the invention. The compounds according to the invention can be used preferably as cytoprotective, neuroprotective, cardioprotective, anxiolytic and antidepressant agent for treatment of neuropsychiatric and neurologic diseases and diseases in connections with transplantations and with ischemia and reperfusion injuries thereof, and inhibition of organ, advantageously skin graft rejection. According to our studies the R-enantiomer has either sole or high biological effect in some cases.

  我们的发明涉及通式（I）和（II）的 8-羟基喹啉衍生物的新型对映体衍生物及其合成、其药用盐和金属络合物，以及包含这些化合物的药用和/或药物组合物。 本发明主题的实质在于，现有技术仅公开了外消旋产物的生物效应和特征，而根据本发明的新型对映体衍生物在我们的申请中首次出现。 本发明的主题还涉及一种用于制备本发明新型对映体衍生物的新型立体选择性合成方法。由这些对映体组成的新型药物和/或医药组合物适用于治疗上述疾病，而对映体则用于制造这些组合物。这些组合物的制造应用也是本发明的主题。根据本发明的化合物可优先用作细胞保护剂、神经保护剂、心脏保护剂、抗焦虑剂和抗抑郁剂，用于治疗神经精神疾病和神经系统疾病以及与移植有关的疾病及其缺血和再灌注损伤，并抑制器官、尤其是皮肤移植的排斥反应。根据我们的研究，R-对映体在某些情况下具有唯一或较高的生物效应。
• ENANTIOMERS OF 8-HYDROXYQUINOLINE DERIVATIVES AND THE SYNTHESIS THEREOF
  申请人：AVIDIN Co. Ltd.

  公开号：US20190330188A1

  公开（公告）日：2019-10-31

  Enantiomer derivatives of 8-hydroxyquinoline derivatives with general formula (I) and (II) and the synthesis thereof and pharmaceutically acceptable salts and metal complexes thereof, and the medicinal and/or pharmaceutical compositions comprise these compounds: The compounds according to the invention can be used preferably as cytoprotective, neuroprotective, cardioprotective, anxiolytic and antidepressant agent for treatment of neuropsychiatric and neurologic diseases and diseases in connections with transplantations and with ischemia and reperfusion injuries thereof, and inhibition of organ, advantageously skin graft rejection.