2-chloro-6-isopropoxy-3-quinolinecarbaldehyde | 1225334-95-1

• 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: 2-chloro-6-isopropoxy-3-quinolinecarbaldehyde
• 英文别名: 2-Chloro-6-(propan-2-yloxy)quinoline-3-carbaldehyde；2-chloro-6-propan-2-yloxyquinoline-3-carbaldehyde
• CAS: 1225334-95-1
• 化学式: C₁₃H₁₂ClNO₂
• 分子量: 249.697
• InChiKey: XPMWMYNALTVUMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-6-isopropoxy-3-quinolinecarbaldehyde 在 copper(l) iodide 、 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 3-{3-[(4-ethyl-1-piperazinyl)carbonyl]phenyl}-8-isopropoxy-1-methoxy-1H-pyrano[4,3-b]quinoline
  参考文献：
  名称：

  Overcoming Compound Fluorescence in the FLiK Screening Assay with Red-Shifted Fluorophores

  摘要：

  In the attempt to discover novel chemical scaffolds that can modulate the activity of disease-associated enzymes, such as kinases, biochemical assays are usually deployed in high-throughput screenings. First-line assays, such as activity-based assays, often rely on fluorescent molecules by measuring a change in the total emission intensity, polarization state, or energy transfer to another fluorescent molecule. However, under certain conditions, intrinsic compound fluorescence can lead to difficult data analysis and to false-positive, as well as false-negative, hits. We have reported previously on a powerful direct binding assay called fluorescent labels in kinases ('FLiK'), which enables a sensitive measurement of conformational changes in kinases upon ligand binding. In this assay system, changes in the emission spectrum of the fluorophore acrylodan, induced by the binding of a ligand, are translated into a robust assay readout. However, under the excitation conditions of acrylodan, intrinsic compound fluorescence derived from highly conjugated compounds complicates data analysis. We therefore optimized this method by identifying novel fluorophores that excite in the far red, thereby avoiding compound fluorescence. With this advancement, even rigid compounds with multiple pi-conjugated ring systems can now be measured reliably. This study was performed on three different kinase constructs with three different labeling sites, each undergoing distinct conformational changes upon ligand binding. It may therefore serve as a guideline for the establishment of novel fluorescence-based detection assays.

  DOI：

  10.1021/ja403074j
• 作为产物：
  描述：

  对异丙氧基苯胺 在 三氯氧磷 作用下， 反应 19.0h， 生成 2-chloro-6-isopropoxy-3-quinolinecarbaldehyde
  参考文献：
  名称：

  有效的含喹啉 Combretastatin A-4 类似物：设计、合成、抗增殖和抗微管蛋白活性

  摘要：

  合成了一系列新型考布他汀 A-4 喹啉衍生物，其中包含刚性腙和环状恶二唑连接体，并表现出有效的微管蛋白聚合抑制特性。许多这些新型衍生物在亚微摩尔范围内表现出显着的抗增殖活性。最有效的化合物 19h 对四种癌细胞系表现出优异的 IC50 值，范围为 0.02 至 0.04 µM，同时在 MCF-10A 非癌细胞中保持较低的细胞毒性，从而表明 19h 对增殖的癌细胞具有选择性。除了微管蛋白聚合抑制之外，19h 还导致 MCF-7 细胞的细胞周期停滞在 G2/M 期并诱导细胞凋亡。总的来说，这些发现表明 19h 具有作为针对微管蛋白的有效化疗剂进行进一步研究的潜力。

  DOI：

  10.3390/ph13110393

文献信息

• Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy
  作者：Tarek S. Ibrahim、Mohamed M. Hawwas、Ehab S. Taher、Nabil A. Alhakamy、Mohamed A. Alfaleh、Mohamed Elagawany、Bahaa Elgendy、Gamal M. Zayed、Mamdouh F.A. Mohamed、Zakaria K. Abdel-Samii、Yaseen A.M.M. Elshaier

  DOI：10.1016/j.bioorg.2020.104352

  日期：2020.12

  moderate EGFR inhibition with IC50 of 5.827 ± 0.46 µM, but significantly inhibited the Wnt/β-catenin pathway with IC501286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated

  PDE5靶向由于其在多种类型的人类癌症中的过表达而代表了凋亡诱导和抑制肿瘤细胞生长的新的有前途的策略。因此，我们报告了吡唑并[3,4- d ]嘧啶-4-酮系列载有喹啉部分（11a-r）的合成，具有潜在的双重PDE5抑制和凋亡诱导作用，可用于癌症治疗。这些杂化物在结构上得到阐明，并通过变谱技术表征为1 H NMR，13 C NMR和元素分析。已经宣布对其抗癌活性进行评估。所有合理化的化合物11a-r已通过NCI选择它们的细胞毒性活性来针对60个细胞系进行筛选。化合物11a，11b，11j和11k是最活跃的杂种。在所有化合物中，进一步选择了化合物11j进行五次剂量测试，它在GI 50水平下显示出出色的活性，对测试的九种肿瘤亚板具有很强的抗肿瘤活性，选择性比范围为0.019至8.3 。此外，对活性最高的靶标11a，b，j和k的PDE5抑制活性化合物11j进行了筛选（IC 50为1.57 nM）表
• Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity
  作者：Tarek S. Ibrahim、Mohamed M. Hawwas、Azizah M. Malebari、Ehab S. Taher、Abdelsattar M. Omar、Niamh M. O'Boyle、Eavan McLoughlin、Zakaria K. Abdel-Samii、Yaseen A. M. M. Elshaier

  DOI：10.3390/ph13110393

  日期：——

  A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging

  合成了一系列新型考布他汀 A-4 喹啉衍生物，其中包含刚性腙和环状恶二唑连接体，并表现出有效的微管蛋白聚合抑制特性。许多这些新型衍生物在亚微摩尔范围内表现出显着的抗增殖活性。最有效的化合物 19h 对四种癌细胞系表现出优异的 IC50 值，范围为 0.02 至 0.04 µM，同时在 MCF-10A 非癌细胞中保持较低的细胞毒性，从而表明 19h 对增殖的癌细胞具有选择性。除了微管蛋白聚合抑制之外，19h 还导致 MCF-7 细胞的细胞周期停滞在 G2/M 期并诱导细胞凋亡。总的来说，这些发现表明 19h 具有作为针对微管蛋白的有效化疗剂进行进一步研究的潜力。
• Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition
  作者：Amany M. Ghanim、Samar Rezq、Tarek S. Ibrahim、Damian G. Romero、Hend Kothayer

  DOI：10.1016/j.ejmech.2021.113457

  日期：2021.7
• Overcoming Compound Fluorescence in the FLiK Screening Assay with Red-Shifted Fluorophores
  作者：Ralf Schneider、Anne Gohla、Jeffrey R. Simard、Dharmendra B. Yadav、Zhizhou Fang、Willem A. L. van Otterlo、Daniel Rauh

  DOI：10.1021/ja403074j

  日期：2013.6.5

  In the attempt to discover novel chemical scaffolds that can modulate the activity of disease-associated enzymes, such as kinases, biochemical assays are usually deployed in high-throughput screenings. First-line assays, such as activity-based assays, often rely on fluorescent molecules by measuring a change in the total emission intensity, polarization state, or energy transfer to another fluorescent molecule. However, under certain conditions, intrinsic compound fluorescence can lead to difficult data analysis and to false-positive, as well as false-negative, hits. We have reported previously on a powerful direct binding assay called fluorescent labels in kinases ('FLiK'), which enables a sensitive measurement of conformational changes in kinases upon ligand binding. In this assay system, changes in the emission spectrum of the fluorophore acrylodan, induced by the binding of a ligand, are translated into a robust assay readout. However, under the excitation conditions of acrylodan, intrinsic compound fluorescence derived from highly conjugated compounds complicates data analysis. We therefore optimized this method by identifying novel fluorophores that excite in the far red, thereby avoiding compound fluorescence. With this advancement, even rigid compounds with multiple pi-conjugated ring systems can now be measured reliably. This study was performed on three different kinase constructs with three different labeling sites, each undergoing distinct conformational changes upon ligand binding. It may therefore serve as a guideline for the establishment of novel fluorescence-based detection assays.