6-chloro-7-(piperidin-1-yl)-5,8-quinolinedione | 67380-51-2

• 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: 6-chloro-7-(piperidin-1-yl)-5,8-quinolinedione
• 英文别名: 6-chloro-7-piperidinylquinoline-5,8-dione；6-chloro-7-piperidin-1-yl-quinoline-5,8-dione；6-Chlor-7-piperidinochinolin-5,8-dion；6-chloro-7-piperidin-1-ylquinoline-5,8-dione
• CAS: 67380-51-2
• 化学式: C₁₄H₁₃ClN₂O₂
• 分子量: 276.722
• InChiKey: RAIPNFWGYIHRPN-UHFFFAOYSA-N

物化性质

• 熔点：
  203-204 °C (decomp)
• 沸点：
  403.9±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  50.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  8-羟基喹啉 在 盐酸 、 sodium chlorate 作用下， 以 水 为溶剂， 反应 7.0h， 生成 6-chloro-7-(piperidin-1-yl)-5,8-quinolinedione
  参考文献：
  名称：

  The synthesis and evaluation of quinolinequinones as anti-mycobacterial agents

  摘要：

  A library of thirty-two quinolinequinones (QQs) with various amine substituents at the 6- and 7-positions were synthesised efficiently and in good yields for evaluation as potential anti-tuberculosis agents. Mycobacterium tuberculosis growth inhibition assays demonstrated that QQs bearing moderate length alkyl chains (i.e. heptyl-phenylamino-and octylamino-QQs), and aryl groups (i.e. phenylethylamino-and benzylamino-QQs) exhibited encouraging inhibitory activity, while QQ analogue 7-chloro-6-propargylamino-quinoline-5,8-dione (16b) had excellent inhibitory activity (MIC=8 mu M). The cLogP values and redox activities of the QQs were determined, and neither readout correlated with the anti-mycobacterial activities of the compounds. Notwithstanding, mode of action studies of 16b revealed that treatment of M. tuberculosis with this compound led to activation of NADH-dependent oxygen consumption suggesting a redox cycling mechanism. To this end, the promising anti-mycobacterial activity of several QQs and their ability to perturb oxygen management leading to an uncontrolled respiratory burst, as identified in this work and by others, demonstrates the merit of further optimising the anti-mycobacterial activity of this readily synthesised class of compound.

  DOI：

  10.1016/j.bmc.2019.06.002

文献信息

• Compound capable of cytoskeleton and induction of cell elongation and process for synthesizing the same
  申请人：Chao Jui-I

  公开号：US20080015221A1

  公开（公告）日：2008-01-17

  A compound capable of cytoskeleton and induction of cell elongation, 7-chloro-6-piperidin-1-yl-quinoline-5,8-dione with a chemical formula of C 14 H 13 CIN 2 O 2 , is designated as PT-262. The PT-262 can induce cell elongation by stabilization of the F-actin and induction of the abnormal actin polymerization in cancer cells, further, the PT-262 possesses antitumor activity and can block survival pathway of the cancer cells, resulting in cancer cells apoptosis, and the PT-262 can induce growth arrest and inhibition of cell cycle. PT-262 stabilizes cancer cells cytoskeleton that results in an irreversible cell elongation, decreases the levels of cyclin B1 and phospho-cdc2 proteins, and inhibits the survival signal pathway of Ras-ERK proteins. The PT-262 also inhibits the mitochondrial membrane potential and induces the caspase-3 activation and apoptosis in the cancer cells.

  一种具有细胞骨架和诱导细胞延长能力的化合物，化学式为C14H13CIN2O2的7-氯-6-哌啶-1-基喹啉-5,8-二酮被指定为PT-262。PT-262可以通过稳定F-肌动蛋白和诱导癌细胞中异常肌动蛋白聚合来诱导细胞延长，此外，PT-262具有抗肿瘤活性，可以阻断癌细胞的生存途径，导致癌细胞凋亡，PT-262还可以诱导生长停滞和抑制细胞周期。PT-262稳定了癌细胞的细胞骨架，导致不可逆的细胞延长，降低了细胞周期素B1和磷酸化cdc2蛋白的水平，并抑制了Ras-ERK蛋白的生存信号途径。PT-262还抑制了线粒体膜电位，诱导了癌细胞中caspase-3的激活和凋亡。
• The regioselectivity in the reaction of 6,7-dihaloquinoline-5,8-diones with amine nucleophiles in various solvents
  作者：Eun Young Yoon、Han Young Choi、Kye Jung Shin、Kyung Ho Yoo、Dae Yoon Chi*、Dong Jin Kim

  DOI：10.1016/s0040-4039(00)01278-8

  日期：2000.9

  The regioselectivity in the reaction of 6,7-dihaloquinoline-5,8-diones with amine nucleophiles was described. In this reaction the solvent played an important role.

  描述了6,7-二卤喹啉-5,8-二酮与胺亲核试剂反应中的区域选择性。在该反应中，溶剂起重要作用。
• Metal-assisted regioselectivity in nucleophilic substitutions: a study by Raman spectroscopy and density functional theory calculations
  作者：Andrea Defant、Barbara Rossi、Gabriele Viliani、Graziano Guella、Ines Mancini

  DOI：10.1002/jrs.2631

  日期：2010.12

  A series of complexes (FeII, CuII and NiII) of the N,O bidentate ligand 6,7-dichloroquinoline-5,8-dione in water was investigated by using Raman spectroscopy, and the experimental peaks were assigned with the help of computed spectra by density functional theory (DFT) calculations. A strong shift to lower wavenumbers was observed for the vibration of the CO group involved in chelation, depending on the type of metal ion. When each complex was used in the substitution reaction by the nucleophilic reagent piperidine, two products having the same molecular composition but showing the substituent in different regions of the molecule were obtained, and moreover their regioselective formation was in agreement with the size of the Raman shifts previously observed for the complexes. This example confirms the potential of the approach involving Raman spectroscopy combined with DFT calculations in the characterization of metal complexes as key intermediates in organic reactions, with the possibility of predicting the metal system capable to achieve the highest selectivity. Copyright © 2010 John Wiley & Sons, Ltd.

  利用拉曼光谱研究了水中 N，O 双齿配体 6，7-二氯喹啉-5，8-二酮的一系列配合物（FeII、CuII 和 NiII），并借助密度泛函理论（DFT）计算的光谱对实验峰进行了分配。根据金属离子的类型，参与螯合的 CO 基团的振动出现了向低波段的强烈偏移。当使用亲核试剂哌啶对每种络合物进行取代反应时，会得到两种具有相同分子组成但在分子不同区域显示取代基的产物，而且它们的区域选择性与之前观察到的络合物拉曼偏移的大小一致。这个例子证实了拉曼光谱与 DFT 计算相结合的方法在表征作为有机反应关键中间体的金属配合物方面的潜力，并有可能预测出能够实现最高选择性的金属体系。Copyright © 2010 John Wiley & Sons, Ltd. All Rights Reserved.
• Use of a Compound in Obtaining Cytoskeleton Blockage and Cell Elongation
  申请人：CHAO Jui-I

  公开号：US20100093794A1

  公开（公告）日：2010-04-15

  A use of a compound in obtaining cytoskeleton and cell elongation is disclosed, the compound is 7-chloro-6-piperidin-1-yl-quinoline-5,8-dione with a chemical formula of C 14 H 13 CIN 2 O 2 , is designated as PT-262. The PT-262 can induce cell elongation by stabilization of the F-actin and induction of the abnormal actin polymerization in cancer cells, further, the PT-262 possesses antitumor activity and can block survival pathway of the cancer cells, resulting in cancer cells apoptosis, and the PT-262 can induce growth arrest and inhibition of cell cycle. PT-262 stabilizes cancer cells cytoskeleton that results in an irreversible cell elongation, decreases the levels of cyclin B1 and phospho-cdc2 proteins, and inhibits the survival signal pathway of Ras-ERK proteins. The PT-262 also inhibits the mitochondrial membrane potential and induces the caspase-3 activation and apoptosis in the cancer cells.

  本文揭示了一种利用化合物获得细胞骨架和细胞延伸的方法，该化合物是7-氯-6-哌啶-1-基喹啉-5,8-二酮，化学式为C14H13CIN2O2，被指定为PT-262。PT-262能够通过稳定F-actin和诱导癌细胞中异常的肌动蛋白聚合来诱导细胞延伸，此外，PT-262具有抗肿瘤活性，可以阻断癌细胞的生存途径，导致癌细胞凋亡，并且PT-262可以诱导细胞生长停滞和细胞周期抑制。PT-262稳定癌细胞的细胞骨架，导致不可逆的细胞延伸，降低cyclin B1和磷酸化cdc2蛋白的水平，并抑制Ras-ERK蛋白的生存信号通路。PT-262还抑制线粒体膜电位，在癌细胞中诱导caspase-3激活和凋亡。
• The synthesis and evaluation of quinolinequinones as anti-mycobacterial agents
  作者：Kristiana T. Santoso、Ayana Menorca、Chen-Yi Cheung、Gregory M. Cook、Bridget L. Stocker、Mattie S.M. Timmer

  DOI：10.1016/j.bmc.2019.06.002

  日期：2019.8

  A library of thirty-two quinolinequinones (QQs) with various amine substituents at the 6- and 7-positions were synthesised efficiently and in good yields for evaluation as potential anti-tuberculosis agents. Mycobacterium tuberculosis growth inhibition assays demonstrated that QQs bearing moderate length alkyl chains (i.e. heptyl-phenylamino-and octylamino-QQs), and aryl groups (i.e. phenylethylamino-and benzylamino-QQs) exhibited encouraging inhibitory activity, while QQ analogue 7-chloro-6-propargylamino-quinoline-5,8-dione (16b) had excellent inhibitory activity (MIC=8 mu M). The cLogP values and redox activities of the QQs were determined, and neither readout correlated with the anti-mycobacterial activities of the compounds. Notwithstanding, mode of action studies of 16b revealed that treatment of M. tuberculosis with this compound led to activation of NADH-dependent oxygen consumption suggesting a redox cycling mechanism. To this end, the promising anti-mycobacterial activity of several QQs and their ability to perturb oxygen management leading to an uncontrolled respiratory burst, as identified in this work and by others, demonstrates the merit of further optimising the anti-mycobacterial activity of this readily synthesised class of compound.