5-chloro-2-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazoline | 1354958-11-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-chloro-2-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazoline
• 英文别名: 2-Methylsulfanyl-5-chloro-[1,2,4]triazolo[1,5-a]quinazoline；5-chloro-2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazoline
• CAS: 1354958-11-4
• 化学式: C₁₀H₇ClN₄S
• 分子量: 250.711
• InChiKey: UTGCXMLIYBIRDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  68.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-2-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazoline 在 肼 作用下， 以 乙醇 为溶剂， 生成 2-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazolin-5-yl-hydrazine
  参考文献：
  名称：

  Cytotoxicity and Anti-Inflammatory Activity of Methylsulfanyl-triazoloquinazolines

  摘要：

  此前合成了一系列二十五个2-甲硫基-[1,2,4]三唑并[1,5-a]喹唑啉衍生物1至25。我们现已研究了它们对肝细胞Hep-G2和结肠HCT-116癌细咆的毒性作用，以及对巨噬细胞生长的影响，还包括它们对炎症介质[一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、前列腺素E-2（PGE-2）以及在细菌脂多糖（LPS）刺激的巨噬细胞中]的影响。研究结果显示，化合物13和17显示出最高的细胞毒性，而3、6-8和25是具有良好前景的多效抗炎剂。

  DOI：

  10.3390/molecules18021434
• 作为产物：
  描述：

  在 盐酸 、 三氯氧磷 作用下， 以 水 、 苯 为溶剂， 反应 2.0h， 生成 5-chloro-2-methylsulfanyl[1,2,4]triazolo[1,5-a]quinazoline
  参考文献：
  名称：

  Synthesis of Novel 2-Methylsulfanyl-4H-[1,2,4]triazolo[1,5-a]quinazolin-5-one and Derivatives

  摘要：

  A novel 2-methylsulfanyl-4H-[1,2,4]triazolo[1,5-a] quinazolin-5-one was synthesized using dimethyl-n-cyanoimidodithiocarbonate and 2-hydrazinobenzoic acid as building blocks. Chemical transformation of the inherent lactam moiety in the targeted 2-methylsulfanyl-[1,2,4]triazolo[1,5-a] quinazolin-5-one offered access to a variety of derivatives.

  DOI：

  10.1080/00397911.2010.518780

文献信息

• Antimicrobial activity of newly synthesized methylsulfanyl-triazoloquinazoline derivatives
  作者：Rashad Al-Salahi、Mohamed Marzouk、Ghada Awad、Mohamed Al-Omar、Essam Ezzeldin

  DOI：10.1111/jphp.12039

  日期：2013.5.5

  The aim of this research was to study and evaluate the antimicrobial activity of a novel 2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazoline and its derivatives. Antibacterial activity of the target compounds was tested against a variety of species of Gram-positive bacteria such as Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC6633, and Gram-negative bacteria such as Pseudomonas aeruginosa ATCC27953 and Escherichia coli ATCC 25922. In addition some yeast and fungi, Candida albicans NRRL Y-477 and Aspergillus niger, respectively, were screened.

  Antimicrobial tests were carried out by the agar well diffusion method, using 100 μl of suspension containing 1 × 108 CFU/ml of pathological tested bacteria, 1 × 106 CFU/ml of yeast, and 1 × 104 spore/ml of fungi spread on nutrient agar (NA), Sabourand dextrose agar (SDA), and potato dextrose agar (PDA), respectively.

  The minimum inhibitory concentration (MIC) of the tested compounds was determined using the broth double dilution method (serially diluted technique) in proper nutrient. For comparison, ciprofloxacin and ketoconazole were used as antibacterial and antifungal reference drugs, respectively. Compounds 6, 9, 13, 14, and 11 were found to have the highest broad-spectrum antibacterial activity against S. aureus ATCC 29213, B. subtilis ATCC6633 and Gram-negative bacteria such as P. aeruginosa ATCC27953 and E. coli ATCC 25922 with MIC values of 6.25 and 12.50 μg/ml.

  It was clear that many of the synthesized compounds exhibited good antimicrobial activity. This study has revealed that compounds 6, 9, 13, 14, and 11 have been disclosed as moderate antimicrobial agents. These compounds could be useful as templates for further development through modification or derivatization to design more potent antimicrobial agents.

  本研究的目的是研究和评估一种新型2-甲基硫基-[1,2,4]三唑并[1,5-a]喹唑啉及其衍生物的抗菌活性。目标化合物的抗菌活性针对多种革兰氏阳性细菌，如金黄色葡萄球菌ATCC 29213，枯草芽孢杆菌ATCC6633，以及革兰氏阴性细菌，如铜绿假单胞菌ATCC27953和大肠杆菌ATCC 25922进行了测试。此外，还对一些酵母菌和真菌，分别为白念珠菌NRRL Y-477和黑曲霉进行了筛选。

  采用琼脂孔扩散法进行抗菌测试，使用含有1 × 10^8 CFU/ml病原菌、1 × 10^6 CFU/ml酵母菌和1 × 10^4 孢子/ml真菌的悬浮液100 μl分别涂布在营养琼脂（NA）、沙氏葡萄糖琼脂（SDA）和马铃薯葡萄糖琼脂（PDA）上。

  通过在适当营养基中使用双倍稀释法（串联稀释技术）确定了被测试化合物的最小抑制浓度（MIC）。为了比较，分别使用环丙沙星和酮康唑作为抗菌和抗真菌参考药物。发现化合物6、9、13、14和11对金黄色葡萄球菌ATCC 29213、枯草芽孢杆菌ATCC6633以及革兰氏阴性细菌如铜绿假单胞菌ATCC27953和大肠杆菌ATCC 25922具有最高的广谱抗菌活性，MIC值为6.25和12.50 μg/ml。

  许多合成化合物表现出良好的抗菌活性。本研究揭示了化合物6、9、13、14和11作为中等抗菌剂。这些化合物可以作为进一步开发的模板，通过修饰或衍生设计更有效的抗菌剂。

• Synthesis and Antitumor Activity of 1,2,4-Triazolo[1,5-a]quinazolines
  作者：R. Al-Salahi、M. Marzouk、A.E. Ashour、I. Alswaidan

  DOI：10.14233/ajchem.2014.16849

  日期：——

  Cytotoxicity of 22 triazoloquinazoline compounds was evaluated in vitro against medulloblastoma (Daoy), hepatocellular carcinoma (HepG2) and melanoma (SK-MEL28) cell lines. This study showed that compounds 17, 18 and 21 exhibited remarkable in vitro cytotoxicity against all tested cell lines. Moreover, it was found that compounds 10, 17, 6, 18, 21, 7 and 19 are active against Daoy cell line with IC50 values of 1.29, 2.93, 5.53, 6.14, 6.59, 9.71 and 19 μg/mL, respectively, as compared to that of the reference drug dasatinib (7.26 μg/mL). The HepG2 cell line was affected by compounds 17, 6, 21, 19 and 18 with IC50 values of 4.52, 11.33, 14.69, 16.96 and 24.49 μg/mL, respectively, relative to that of dasatinib (8.21 μg/mL). In addition, compounds 17, 18 and 21 have shown significant antiproliferative activity against SK-MEL28 with IC50 values of 3.88, 13.85 and 14.96, respectively, relative to an IC50 value of 23.83 μg/mL of the reference drug. It is worth mentioning that compounds 6, 10, 17, 18 and 21 are more potent than the reference drug against Daoy cell. In the same manner, 17, 18 and 21 revealed higher cytotoxicity than dasatinib against SK-MEL28 cells. Notably, compound 17 was also more potent than the reference drug against HepG2 cells. In the term of selectivity, compound 10 was found to possess the highest selectivity, as it was active only against Daoy cells. These compounds could be useful as templates for further development through their structural modification to design more potent antitumor agents.

  在体外评估了 22 种三唑并喹唑啉化合物对髓母细胞瘤（Daoy）、肝细胞癌（HepG2）和黑色素瘤（SK-MEL28）细胞系的细胞毒性。研究结果表明，化合物 17、18 和 21 对所有测试细胞株都具有显著的体外细胞毒性。此外，研究还发现化合物 10、17、6、18、21、7 和 19 对 Daoy 细胞系具有活性，其 IC50 值分别为 1.29、2.93、5.53、6.14、6.59、9.71 和 19 μg/mL，而参考药物达沙替尼的 IC50 值为 7.26 μg/mL。相对于达沙替尼的 IC50 值（8.21 μg/mL），化合物 17、6、21、19 和 18 对 HepG2 细胞株的影响分别为 4.52、11.33、14.69、16.96 和 24.49 μg/mL。此外，化合物 17、18 和 21 对 SK-MEL28 显示出显著的抗增殖活性，IC50 值分别为 3.88、13.85 和 14.96，而参考药物的 IC50 值为 23.83 μg/mL。值得一提的是，6、10、17、18 和 21 号化合物对 Daoy 细胞的作用比对照药物更强。同样，17、18 和 21 对 SK-MEL28 细胞的细胞毒性也高于达沙替尼。值得注意的是，化合物 17 对 HepG2 细胞的药效也高于参比药物。在选择性方面，化合物 10 具有最高的选择性，因为它只对 Daoy 细胞有活性。这些化合物可以作为进一步开发的模板，通过对其结构进行修饰，设计出更有效的抗肿瘤药物。
• Cytotoxicity and Anti-Inflammatory Activity of Methylsulfanyl-triazoloquinazolines
  作者：Rashad Al-Salahi、Amira Gamal-Eldeen、Amer Alanazi、Mohamed Al-Omar、Mohamed Marzouk、Moustafa Fouda

  DOI：10.3390/molecules18021434

  日期：——

  A series of twenty five 2-methylsulfanyl-[1,2,4]triazolo[1,5-a]quinazoline derivatives 1–25 was previously synthesized. We have now investigated their cytotoxic effects against hepatocellular Hep-G2 and colon HCT-116 carcinoma cells and effect on the macrophage growth, in addition to their influence of the inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), prostaglandin E-2 (PGE-2) and in bacterial lipopolysachharide (LPS)-stimulated macrophages]. The findings revealed that compounds 13 and 17 showed the highest cytotoxicity and that 3, 6–8 and 25 are promising multi-potent anti-inflammatory agents.

  此前合成了一系列二十五个2-甲硫基-[1,2,4]三唑并[1,5-a]喹唑啉衍生物1至25。我们现已研究了它们对肝细胞Hep-G2和结肠HCT-116癌细咆的毒性作用，以及对巨噬细胞生长的影响，还包括它们对炎症介质[一氧化氮（NO）、肿瘤坏死因子-α（TNF-α）、前列腺素E-2（PGE-2）以及在细菌脂多糖（LPS）刺激的巨噬细胞中]的影响。研究结果显示，化合物13和17显示出最高的细胞毒性，而3、6-8和25是具有良好前景的多效抗炎剂。
• Synthesis of Novel 2-Methylsulfanyl-4<i>H</i>-[1,2,4]triazolo[1,5-<i>a</i>]quinazolin-5-one and Derivatives
  作者：Rashad Al-Salahi、Detlef Geffken

  DOI：10.1080/00397911.2010.518780

  日期：2011.12.1

  A novel 2-methylsulfanyl-4H-[1,2,4]triazolo[1,5-a] quinazolin-5-one was synthesized using dimethyl-n-cyanoimidodithiocarbonate and 2-hydrazinobenzoic acid as building blocks. Chemical transformation of the inherent lactam moiety in the targeted 2-methylsulfanyl-[1,2,4]triazolo[1,5-a] quinazolin-5-one offered access to a variety of derivatives.