3-((7-chloroquinolin-4-yl)amino)benzaldehyde | 1079041-41-0

• 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: 3-((7-chloroquinolin-4-yl)amino)benzaldehyde
• 英文别名: 3-((7-Chloroquinolin-4-yl)amino)benzaldehyde；3-[(7-chloroquinolin-4-yl)amino]benzaldehyde
• CAS: 1079041-41-0
• 化学式: C₁₆H₁₁ClN₂O
• 分子量: 282.729
• InChiKey: NCADCVCPPWLYND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-((7-chloroquinolin-4-yl)amino)benzaldehyde 在 盐酸 、 水 作用下， 以 甲醇 为溶剂， 反应 25.0h， 生成 N-{3-[(pyrrolidin-1-yl)(1H-tetrazol-5-yl)methyl]phenyl}-7-chloroquinolin-4-amine
  参考文献：
  名称：

  Tetrazole-based deoxyamodiaquines: Synthesis, ADME/PK profiling and pharmacological evaluation as potential antimalarial agents

  摘要：

  A series of new deoxyamodiaquine-based compounds was synthesized via the modified TMSN3-Ugi multi-component reaction and evaluated in vitro for antiplasmodial activity. The most potent compounds, 6b, 6c and 6j, showed IC50 values in the range of 6-77 nM against chloroquine-resistant gland W2-strains of Plasmodium falciparum. In vitro ADME characterization of frontrunner compounds 6b and 6c indicates that these two compounds are rapidly metabolized and have a high clearance rate in human and rat liver microsomes. This result correlated well with an in vivo pharmacokinetics study, which showed low bioavailability of 6c in rats. Tentative metabolite identification was determined by LC-MS and suggested metabolic lability of groups attached to the tertiary nitrogen. Preliminary studies on 6b and 6c suggested strong inhibitory activity against the major CYP450 enzymes. In silico docking studies were used to rationalize strong inhibition of CYP3A4 by 6c. Full characterization and biological evaluation of the metabolites is currently underway in our laboratories. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.067
• 作为产物：
  描述：

  3-硝基苯甲醛乙二醇缩醛 在 一水合肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 4.08h， 生成 3-((7-chloroquinolin-4-yl)amino)benzaldehyde
  参考文献：
  名称：

  新型基于喹啉的4,5-二氢-1H-吡唑类化合物的合成，具有潜在的抗癌，抗真菌，抗菌和抗原生动物作用。

  摘要：

  从[（7-氯喹啉-4-基）氨基]查耳酮8a的环缩合反应中获得了一系列新的N-取代的2-吡唑啉9a-f，10a-f，11a-f，12a-f和13a-f。 -f与水合肼及其衍生物。美国国家癌症研究所（NCI）选择了包括起始查耳酮在内的14种合成化合物来测试其对60种不同人类癌细胞系的抗癌活性，其中最重要的GI50值范围为0.28至11.7μM（0.13-6.05μg/查耳酮8a，d和吡唑啉10c，d的LC50值范围为2.6至> 100μM（1.2至> 51.7μg/ mL）。评估了所有化合物对野生型和多重耐药革兰氏阴性和革兰氏阳性细菌的抗菌活性，MIC值为31.25至500μg/ mL。此外，测试了这些新型化合物的抗真菌和抗寄生虫特性。尽管这些化合物显示出对白色念珠菌的温和活性，但查耳酮8a和8e显示出对新隐球菌的高活性，MIC50 = 7.8μg/ mL。对于恶性疟原虫活性，2-吡唑啉11b的活性最高，EC50

  DOI：

  10.1016/j.ejmech.2017.03.016

文献信息

• Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking
  作者：Luka Krstulović、Marijana Leventić、Vesna Rastija、Kristina Starčević、Maja Jirouš、Ivana Janić、Maja Karnaš、Kornelija Lasić、Miroslav Bajić、Ljubica Glavaš-Obrovac

  DOI：10.3390/molecules28020540

  日期：——

  In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d, 8d, and 12d, showed strong cytotoxic activity (the GI50 ranged from 0.4 to 8 µM) and effectively suppressed the cell cycle progression in the leukemia and lymphoma cells. After 24 h of treatment, compounds 5d and 12d induced the disruption of the mitochondrial membrane potential as well as apoptosis in HuT78 cells. The drug-like properties and bioavailability of the compounds were calculated using the Swiss ADME web tool, and a molecular docking study was performed on tyrosine-protein kinase c-Src (PDB: 3G6H). Compound 12d showed good solubility and permeability and bound to c-Src with an energy of −119.99 kcal/mol, forming hydrogen bonds with Glu310 and Asp404 in the active site and other residues with van der Waals interactions. The results suggest that compound 12d could be a leading compound in the further design of effective antitumor drugs.

  本研究合成了新的 7-氯-4-氨基喹啉-苯并咪唑化合物，并通过核磁共振、质谱和元素分析对其进行了表征。这些新型杂交化合物在连接剂类型和苯并咪唑分子上的取代基方面存在差异。通过 MTT 试验和流式细胞仪分析，评估了它们对一种非肿瘤细胞系（MDCK1）和七种选定肿瘤细胞系（CaCo-2、MCF-7、CCRF-CEM、Hut78、THP-1 和 Raji）的抗增殖活性。具有不同类型连接体和未取代苯并咪唑环的化合物 5d、8d 和 12d 显示出很强的细胞毒活性（GI50 在 0.4 至 8 µM 之间），并能有效抑制白血病和淋巴瘤细胞的细胞周期进展。经过 24 小时的处理后，化合物 5d 和 12d 引发了 HuT78 细胞线粒体膜电位的破坏和细胞凋亡。利用瑞士 ADME 网络工具计算了化合物的类药物特性和生物利用度，并对酪氨酸蛋白激酶 c-Src （PDB：3G6H）进行了分子对接研究。化合物 12d 显示出良好的溶解性和渗透性，与 c-Src 结合的能量为 -119.99 kcal/mol，与活性位点中的 Glu310 和 Asp404 形成氢键，并与其他残基形成范德华相互作用。结果表明，化合物 12d 可能成为进一步设计有效抗肿瘤药物的主要化合物。
• Synthesis of novel quinoline–based 4,5–dihydro–1 H –pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents
  作者：Jonathan Ramírez–Prada、Sara M. Robledo、Iván D. Vélez、María del Pilar Crespo、Jairo Quiroga、Rodrigo Abonia、Alba Montoya、Laura Svetaz、Susana Zacchino、Braulio Insuasty

  DOI：10.1016/j.ejmech.2017.03.016

  日期：2017.5

  to > 51.7 μg/mL), for chalcones 8a,d and pyrazolines 10c,d. All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against Candida

  从[（7-氯喹啉-4-基）氨基]查耳酮8a的环缩合反应中获得了一系列新的N-取代的2-吡唑啉9a-f，10a-f，11a-f，12a-f和13a-f。 -f与水合肼及其衍生物。美国国家癌症研究所（NCI）选择了包括起始查耳酮在内的14种合成化合物来测试其对60种不同人类癌细胞系的抗癌活性，其中最重要的GI50值范围为0.28至11.7μM（0.13-6.05μg/查耳酮8a，d和吡唑啉10c，d的LC50值范围为2.6至> 100μM（1.2至> 51.7μg/ mL）。评估了所有化合物对野生型和多重耐药革兰氏阴性和革兰氏阳性细菌的抗菌活性，MIC值为31.25至500μg/ mL。此外，测试了这些新型化合物的抗真菌和抗寄生虫特性。尽管这些化合物显示出对白色念珠菌的温和活性，但查耳酮8a和8e显示出对新隐球菌的高活性，MIC50 = 7.8μg/ mL。对于恶性疟原虫活性，2-吡唑啉11b的活性最高，EC50
• Tetrazole-based deoxyamodiaquines: Synthesis, ADME/PK profiling and pharmacological evaluation as potential antimalarial agents
  作者：Matshawandile Tukulula、Mathew Njoroge、Grace C. Mugumbate、Jiri Gut、Philip J. Rosenthal、Samuel Barteau、Judith Streckfuss、Olivier Heudi、Jacques Kameni-Tcheudji、Kelly Chibale

  DOI：10.1016/j.bmc.2013.06.067

  日期：2013.9

  A series of new deoxyamodiaquine-based compounds was synthesized via the modified TMSN3-Ugi multi-component reaction and evaluated in vitro for antiplasmodial activity. The most potent compounds, 6b, 6c and 6j, showed IC50 values in the range of 6-77 nM against chloroquine-resistant gland W2-strains of Plasmodium falciparum. In vitro ADME characterization of frontrunner compounds 6b and 6c indicates that these two compounds are rapidly metabolized and have a high clearance rate in human and rat liver microsomes. This result correlated well with an in vivo pharmacokinetics study, which showed low bioavailability of 6c in rats. Tentative metabolite identification was determined by LC-MS and suggested metabolic lability of groups attached to the tertiary nitrogen. Preliminary studies on 6b and 6c suggested strong inhibitory activity against the major CYP450 enzymes. In silico docking studies were used to rationalize strong inhibition of CYP3A4 by 6c. Full characterization and biological evaluation of the metabolites is currently underway in our laboratories. (C) 2013 Elsevier Ltd. All rights reserved.