7-氯-4-异硫代氰酰基喹啉 | 884647-32-9

• 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
• 中文名称: 7-氯-4-异硫代氰酰基喹啉
• 中文别名: 7-氯-4-异硫氰喹啉
• 英文名称: 7-chloro-4-isothiocyanatoquinoline
• 英文别名: 7-chloroquinoline isothiocyanate
• CAS: 884647-32-9
• 化学式: C₁₀H₅ClN₂S
• 分子量: 220.682
• InChiKey: XFSFMGTURHIVAN-UHFFFAOYSA-N

物化性质

• 熔点：
  85.0-86.5 °C
• 沸点：
  386.2±22.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-氯-4-异硫代氰酰基喹啉 在 氨 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以59%的产率得到1-(7-chloroquinolin-4-yl)thiourea
  参考文献：
  名称：

  Strong in Vitro Cytotoxic Potential of New Ruthenium–Cymene Complexes

  摘要：

  Two p-cymenerutheniumchlorido complexes with thiourea derivative of 7-chloroquinoline (C1) and pyridine-3-imidazole (C2) were synthesized starting from [(eta(6)-p-cymene)RuCl2](2) and corresponding ligands. The structures of complexes were determined with elemental analysis and IR, ESIMS, H-1 and C-13{H-1} NMR, and 2D H-1-N-15 correlation NMR spectroscopy. Cytotoxic activities examined by the MTT assay were performed in five human neoplastic cell lines (HeLa, K562, A549, MDA-MB-231, EA.hy926) and one nontumor human fetal lung fibroblast cell line (MRC-5). Tested complexes exhibited low micromolar activities with IC50 in the range 11.03-56.45 mu M, while ligands L1 and L2 were significantly less active. Complex C1 showed cytoselective activity toward the K562 cell line (IC50 = 11.03 +/- 1.39 mu M) and was 3 times less active against the nontumor MRC-5 cell line. Flow cytometry analysis indicated that complexes C1 and C2 after 24 h treatment caused a concentration-dependent increase of the apoptotic sub-G1 fraction (up to 18.4%), comparable to cis-diamminedichloridoplatinum(II) (cisplatin, CDDP), although without other substantial alterations of the cell cycle. A drug-accumulation and DNA-binding study performed by ICP-MS in the K562 cell line revealed that complex C1 had a high intracellular uptake (1.38 mu g Ru/10 (6) cells), which significantly exceeded the intracellular uptake levels of CDDP (0.29 mu g Pt/10 (6) cells) and C2 (0.08 mu g Ru/10 (6) cells). However, both ruthenium complexes C1 and C2 bind to cellular DNA less efficiently in comparison to CDDP. The structure-activity relationship clearly suggested that introduction of a 7-chloroquinoline moiety in the ruthenium(II)-p-cymene complex significantly contributed to the intracellular uptake of C1 and higher cytotoxicity and cytoselectivity.

  DOI：

  10.1021/acs.organomet.5b00041
• 作为产物：
  描述：

  4,7-二氯喹啉 、 silver thiocyanate 以 甲苯 为溶剂， 反应 12.0h， 以100%的产率得到7-氯-4-异硫代氰酰基喹啉
  参考文献：
  名称：

  合成4-喹啉基异硫氰酸酯的新途径

  摘要：

  由相应的4-氯喹啉和硫氰酸银在回流的甲苯中以区域特异性方式合成4-喹啉异硫氰酸酯。通过简单的过滤和浓缩，以定量收率和高纯度（> 95％）分离出产物。讨论了反应性和反应机理。该新方法将提供合成功能化的4-喹啉基异硫氰酸酯所缺乏的新方法。

  DOI：

  10.1016/j.tetlet.2006.01.119

文献信息

• Copper(0) Catalyzed C-N Coupling Approach for the Synthesis of Thiourea Linked Quinoline Analogues Using Aqueous Media: Rationale and Biological Study
  作者：Dhruvin Shah、Harshad Lakum、Kishor Chikhalia

  DOI：10.2174/1570178612666150203005106

  日期：2015.3.24

  A convergent and facile synthesis of thiourea-based novel 1-(3-nitrophenyl)-3-(7- (substituted phenylamino/piperazino)quinolin-4-yl)thiourea derivatives is presented by approaching copper catalyzed Ullmann reaction. Pliable route was adopted to achieve amination on bioactive 4,7- dichloroquinoline analogous for the first time in which substituted amine/piperazine condensed with C-7 position of quinoline

  通过接近铜催化的乌尔曼反应，提出了一种易于合成的硫脲基新型1-（3-硝基苯基）-3-（7-（取代的苯基氨基/哌嗪子基）喹啉-4-基）硫脲衍生物。首次采用类似的途径，在类似的生物活性4,7-二氯喹啉上实现胺化反应，其中取代的胺/哌嗪与喹啉核心的C-7位缩合。提出的CN偶联反应先于中等至良好的产率。铜（0）催化合成路线还通过讨论其可能的机理进行了解释。在目前可用的抗菌药物的基础上，我们对标题化合物进行了合理化处理，并研究了其生物学效能。与标准环丙沙星（31 mm，0）相比，化合物3i被证明是对蜡状芽孢杆菌菌株最有效的抗微生物衍生物（36 mm，0.39μg/ mL MIC）。39μg/ mL MIC）。与吡嗪酰胺相比，化合物4e对H37Rv株表现出等效的抗结核作用（99％抑制，6.25μg/ mL MIC）。最终类似物的特征在于IR1 H NMR，13 C NMR，质谱和元素分析。
• Discovering Some Novel 7-Chloroquinolines Carrying a Biologically Active Benzenesulfonamide Moiety as a New Class of Anticancer Agents
  作者：Mohammed Salem Al-Dosari、Mostafa Mohamed Ghorab、Mansour Sulaiman Al-Said、Yassin Mohammed Nissan

  DOI：10.1248/cpb.c12-00812

  日期：——

  Based on the reported anticancer activity of quinolines, a new series of 7-chloroquinoline derivatives bearing the biologically active benzenesulfonamide moiety 2-17 and 19-25 were synthesized starting with 4,7-dichloroquinolne 1. Compound 17 was the most active compound with IC(50) value 64.41, 75.05 and 30.71 µM compared with Doxorubicin as reference drug with IC(50) values 82.53, 88.32 and 73.72

  根据已报道的喹啉抗癌活性，从4,7-二氯喹诺酮1开始合成了一系列具有生物活性的苯磺酰胺部分2-17和19-25的7-氯喹啉衍生物。化合物17是具有IC活性最强的化合物（50）值为64.41、75.05和30.71 µM，而阿霉素作为参考药物，而IC（50）的值为82.53、88.32和73.72 µM，分别针对乳腺癌细胞，皮肤癌细胞和成神经细胞瘤。评价所有合成的化合物对乳腺癌细胞，皮肤癌细胞和神经母细胞瘤细胞的体外抗癌活性。大多数合成的化合物显示中等活性。为了阐明其细胞毒性活性的作用机理，
• Antimalarial activity and docking studies of novel bi-functional hybrids derived from 4-aminoquinoline and 1,3,5-triazine against wild and mutant malaria parasites as pf-DHFR inhibitor
  作者：Hans Raj Bhat、Udaya Pratap Singh、Prashant Gahtori、Surajit Kumar Ghosh、Kabita Gogoi、Anil Prakash、Ramendra K. Singh

  DOI：10.1039/c2ra21915h

  日期：——

  Bi-functional conjugates comprised of 4-aminoquinoline and 1,3,5-triazine were synthesized through facile synthetic routes. These compounds were rigorously screened for determination of their antimalarial activity against wild and mutant cultured Plasmodium falciparum. The results disclosed that the conjugates have considerable antimalarial activity against both wild and mutant parasites with marked variation on changing the pattern of substitutions. The observed activity profiles were additionally substantiated by docking studies on both wild and quadruple mutant P. falciparum dihydrofolate reductase thymidylate synthase (pf-DHFR-TS).

  通过简便的合成路线合成了由 4-氨基喹啉和 1,3,5-三嗪组成的双功能共轭物。对这些化合物进行了严格筛选，以确定它们对野生和变异培养的恶性疟原虫的抗疟活性。结果表明，这些共轭物对野生寄生虫和变异寄生虫都具有相当强的抗疟活性，而且随着取代模式的改变而发生明显变化。此外，对野生和四重突变的恶性疟原虫二氢叶酸还原酶胸苷酸合成酶（pf-DHFR-TS）进行的对接研究也证实了观察到的活性特征。
• Synthesis of new 7-chloroquinolinyl thioureas and their biological investigation as potential antimalarial and anticancer agents
  作者：Aman Mahajan、Susan Yeh、Margo Nell、Constance E.J. van Rensburg、Kelly Chibale

  DOI：10.1016/j.bmcl.2007.07.049

  日期：2007.10

  New 7-chloroquinolinyl thiourea derivatives derived from the corresponding 4,7-dichloroquinoline isothiocyanate were synthesized and evaluated for in vitro antimalarial and anticancer activity. The most active compound from the series displayed an inhibitory IC(50) value of 1.2 microM against the D10 strain of Plasmodium falciparum. Lack of cytotoxicity towards HeLa cells indicates selectivity towards

  合成了衍生自相应的4,7-二氯喹啉异硫氰酸酯的新的7-氯喹啉基硫脲衍生物，并对其体外抗疟和抗癌活性进行了评估。该系列中活性最高的化合物对恶性疟原虫D10菌株的抑制IC（50）值为1.2 microM。对HeLa细胞缺乏细胞毒性表明对寄生虫具有选择性。
• Discovery of highly selective 7-chloroquinoline-thiohydantoins with potent antimalarial activity
  作者：Raghu Raj、Vishu Mehra、Jiri Gut、Philip J. Rosenthal、Kathryn J. Wicht、Timothy J. Egan、Melissa Hopper、Lisa A. Wrischnik、Kirkwood M. Land、Vipan Kumar

  DOI：10.1016/j.ejmech.2014.07.048

  日期：2014.9

  A series of C-3 thiourea functionalized β-lactams, β-lactam-7-chloroquinoline conjugates and 7-chloroquinoline-thiohydantoin derivatives were prepared with the aim of probing antimalarial structure-activity relationships. 7-Chlorquinoline-thiohydantoin derivatives were found to be potent inhibitors of cultured Plasmodium falciparum, with the most potent and non-cytotoxic compound exhibiting an IC50 of 39.8 nM. Studies of β-hematin formation suggested that inhibition of haemozoin formation could be primary mechanism of action, with IC50 values comparable to those of chloroquine. Evaluation of cytotoxicity against HeLa cells demonstrated high selective indices.