7-((6-methylpyridin-2-ylamino)(3-(trifluoromethyl)phenyl)methyl)quinolin-8-ol | 1314510-28-5

• 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-((6-methylpyridin-2-ylamino)(3-(trifluoromethyl)phenyl)methyl)quinolin-8-ol
• 英文别名: 7-[[(6-Methylpyridin-2-yl)amino]-[3-(trifluoromethyl)phenyl]methyl]quinolin-8-ol
• CAS: 1314510-28-5
• 化学式: C₂₃H₁₈F₃N₃O
• 分子量: 409.411
• InChiKey: FYPUIPYMWVYSSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  58
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-6-甲基吡啶 、 8-羟基喹啉 、 3-三氟甲基苯甲醛 在 甲酸 作用下， 以 乙腈 为溶剂， 以62%的产率得到7-((6-methylpyridin-2-ylamino)(3-(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。
• METHODS AND COMPOSITIONS OF TARGETED DRUG DEVELOPMENT
  申请人：Errico Joseph P.

  公开号：US20110301193A1

  公开（公告）日：2011-12-08

  Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

  本文提供具有抗增殖作用的化合物。还提供一些化合物，可以调节由二聚化臂和域间系带组成的多域蛋白的活性，例如EGFR，其中未系带的延伸构象是活性状态，而系带的构象是非活性状态，导致自抑制构型。还提供了用于识别此类化合物的方法和药效团。其他方面提供了治疗增殖性疾病、疾病或病状的方法或治疗。例如与EGFR相关的疾病。
• COMPOSITIONS OF TARGETED DRUG DEVELOPMENT
  申请人：Errico Joseph P.

  公开号：US20140163069A1

  公开（公告）日：2014-06-12

  Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

  本文提供具有抗增殖效应的化合物。还提供了可以调节多域蛋白质活性的化合物，包括具有二聚化臂和域间系索的EGFR，其中无系索的伸展构象是活性状态，而系索的构象是非活性状态，导致自抑制构型。还提供了用于识别此类化合物的方法和药效团。其他方面提供了治疗增殖性疾病、疾病或病情的方法或治疗。例如与EGFR相关的疾病。
• METHODS OF TARGETED DRUG DEVELOPMENT
  申请人：Errico Joseph P.

  公开号：US20140194439A1

  公开（公告）日：2014-07-10

  Provided herein are compounds having anti-proliferative effect. Also provided are compounds that can modulate the activity of multi-domain proteins comprising a dimerization arm and interdomain tether, such as EGFR, where an untethered, extended conformation is the active state and a tethered conformation is the inactive state, resulting in an autoinhibited configuration. Also provided are methods and pharmacophores for identifying such compounds. Other aspects provide methods or therapeutic treatment for proliferative diseases, disorders, or conditions, such as those associated with EGFR.

  本文提供了具有抗增殖作用的化合物。还提供了可以调节包括二聚化臂和域间连接的多域蛋白活性的化合物，例如EGFR，其中未连接的扩展构象是活性状态，连接的构象是非活性状态，导致自抑制构型。还提供了用于识别此类化合物的方法和药效团。其他方面提供了用于增殖性疾病、疾病或病情的方法或治疗，例如与EGFR相关的疾病。
• 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。