2-chloro-N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)acetamide | 18199-94-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)acetamide
• 英文别名: 2-chloro-N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]acetamide
• CAS: 18199-94-5
• 化学式: C₁₀H₇Cl₂N₃OS
• 分子量: 288.157
• InChiKey: CJKGJCCSHVTXIW-UHFFFAOYSA-N

物化性质

• 熔点：
  243-244 °C(Solv: 1,4-dioxane (123-91-1))
• 密度：
  1.540±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)acetamide 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 5-benzylidene-2-[{5-(4-chlorophenyl)-[1,3,4]-thiadiazol-2-yl}imino]-1,3-thiazolidin-4-one
  参考文献：
  名称：

  噻二唑衍生物作为潜在的抗惊厥药

  摘要：

  一系列噻二唑衍生物通过不同取代的苯甲酸环合得到不同取代的噻唑烷-4-酮。元素分析、红外、$^1H$ NMR、$^{13}C$ NMR 和质谱数据证实了合成化合物的结构。这些基团的衍生物通过MES模型评估了它们的抗惊厥活性，并通过旋转棒方法评估了神经毒性。所合成的化合物显示出良好的抗惊厥活性潜力，此外，这些化合物还表现出神经毒性效应。观察发现，相比于具有未取代苯环的化合物[4(a-l)]，在苯环3, 4位带有$OCH_3$的化合物[5(a-l)]对抗惊厥的保护作用较弱。

  DOI：

  10.5012/bkcs.2011.32.3.1011
• 作为产物：
  描述：

  1-(4-chlorobenzoyl)thiosemicarbazide 在 硫酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 2-chloro-N-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)acetamide
  参考文献：
  名称：

  2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase

  摘要：

  Hepatitis C virus (HCV) NS5B polymerase is an important and attractive target for the development of anti-HCV drugs. Here we report on the design, synthesis and evaluation of twenty-four novel allosteric inhibitors bearing the 4-thiazolidinone scaffold as inhibitors of HCV NS5B polymerase. Eleven compounds tested were found to inhibit HCV NS5B with IC50 values ranging between 19.8 and 64.9 RM. Compound 24 was the most active of this series with an IC50 of 5.6 mu M. A number of these derivatives further exhibited strong inhibition against HCV lb and 2a genotypes in cell based antiviral assays. Molecular docking analysis predicted that the thiazolidinone derivatives bind to the NS5B thumb pocketII (TP-II). Our results suggest that further optimization of the thiazolidinone scaffold may be possible to yield new derivatives with improved enzyme- and cell-based activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.043

文献信息

• Synthesis and evaluation of novel 1,3,4-thiadiazole{ uoroquinolone hybrids as antibacterial, antituberculosis, and anticancer agents
  作者：Demirci, Aslı、Karayel, Kaan Gökçe、Tatar, Esra、Okullu, Sinem ÖKTEM、Unübol, Nihan、Taşli, Pakize Neslihan、Kocagöz, Zühtü Tanıl、Sahin, Fikrettin、Küçükgüzel, Ilkay

  DOI：10.3906/kim-1710-35

  日期：——

  A series of 5-substituted-1,3,4-thiadiazole-based fluoroquinolone derivatives were designed as potential antibacterial and anticancer agents using a molecular hybridization approach. The target compounds 16-25 were synthesized by reacting the corresponding $N$-(5-substituted-1,3,4-thiadiazol-2-yl)-2-chloroacetamides with ciprofloxacin or norfloxacin. The purity and identity of the synthesized compounds were determined by the use of chromatographic and spectral techniques (NMR, IR, MS, etc.) besides elemental analysis. Antibacterial, antituberculosis, and anticancer activity of the target compounds were evaluated against selected strains and cancer cell lines. Compound 20 was appreciated as the most active agent representing antibacterial activity against Escherichia coli and Staphylococcus aureus with MIC values of 4 $\mu $g/mL and 2 $\mu $g/mL, respectively. Amongst the synthesized fluoroquinolone derivatives, compounds 19 and 20were found to have modest antitubercular activity with 8 $\mu $g/mL MIC values for each. Most potent derivative, compound 20 was docked against Staphylococcus aureus and Mycobacterium tuberculosis DNA gyrase enzymes to visualize the possible conformation of the compound. Additionally, anticancer activities of target compounds were evaluated on seven different cancer cell lines.

  一系列5-取代-1,3,4-噻二唑基氟喹诺酮衍生物被设计为潜在的抗菌和抗癌药物，采用分子杂交方法。目标化合物16-25是通过将相应的 $N$-（5-取代-1,3,4-噻二唑-2-基）-2-氯乙酰胺与环丙沙星或诺氟沙星反应合成的。合成化合物的纯度和身份通过色谱和光谱技术（NMR、IR、MS等）以及元素分析确定。目标化合物的抗菌、抗结核和抗癌活性针对选定的菌株和癌细胞系进行了评估。化合物20被认为是最活跃的抗菌剂，对大肠杆菌和金黄色葡萄球菌的MIC值分别为4 $\mu $g/mL和2 $\mu $g/mL。在合成的氟喹诺酮衍生物中，化合物19和20被发现具有适度的抗结核活性，每个化合物的MIC值为8 $\mu $g/mL。最强大的衍生物，化合物20与金黄色葡萄球菌和结核分枝杆菌DNA拓扑异构酶酶对接，以可视化化合物的可能构象。此外，目标化合物的抗癌活性在七种不同的癌细胞系上进行了评估。
• Synthesis, docking, and biological evaluation of thiazolidinone derivatives against hepatitis C virus genotype 4a
  作者：Ahmed S. Al-Behery、Kamel M. Elberembally、Mohammed A. Eldawy

  DOI：10.1007/s00044-021-02721-w

  日期：2021.5

  docked into thumb II site of HCV NS5B GT4a using rigid docking approach. Eighteen compounds (7a–r) that show good docking scores were synthesized and tested in vitro against NS5B GT4a. Compounds 7b and 7n showed the best inhibitory activity (IC50 = 0.338 and 0.342 µM, respectively). Compounds 7a, 7b, 7c, 7d, 7k, 7n, 7q, and 7r that have IC50 values less than 2 µM were assessed for cellular anti-HCV GT4a

  丙型肝炎病毒（HCV）基因型4a（GT4a）在埃及盛行。尽管具有很高的抵抗力，但它并没有获得必要的科学关注。由于HCV GT4a的晶体结构NS5B（RNA依赖性RNA聚合酶）到目前为止尚未解析，因此进行了同源建模以建立和验证该酶的3D模型。检测到配体结合位点，包括变构拇指II型口袋，并将其用于前导优化。虚拟设计了六十种新的4-噻唑烷酮衍生物，并使用刚性对接方法将其对接到HCV NS5B GT4a的Thumb II位点。合成了18个具有良好对接分数的化合物（7a–r），并在体外针对NS5B GT4a进行了测试。化合物7b和7n表现出最佳的抑制活性（IC50  = 0.338和0.342 µM。使用人肝癌细胞系（Huh 7.5）对IC 50值小于2 µM的化合物7a，7b，7c，7d，7k，7n，7q和7r进行了细胞抗HCV GT4a活性评估。病毒生长抑制的百分比在79.67和94.77％之间
• [EN] COMPOUNDS FOR MODULATING AQUAPORINS<br/>[FR] COMPOSÉS POUR MODULER LES AQUAPORINES
  申请人：APOGLYX AB

  公开号：WO2017186893A1

  公开（公告）日：2017-11-02

  The invention relates to compounds of formula (I) pharmaceutical compositions thereof and methods for modulating aquaporin 9.

  该发明涉及公式（I）化合物、其药物组合物以及调节水通道蛋白9的方法。
• Design of Benzothiazole-1,3,4-thiadiazole Conjugates: Synthesis and Anticonvulsant Evaluation
  作者：Nadeem Siddiqui、Priya Ahuja、Sachin Malik、Satish K. Arya

  DOI：10.1002/ardp.201300083

  日期：2013.11

  3‐benzothiazol‐2‐yl)amino]‐N‐[5‐substituted‐phenyl‐1,3,4‐thiadiazol‐2‐yl]acetamides were synthesized with a prospective exploration of “lead hopping”, using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test

  各种2-[(6-取代-1,3-苯并噻唑-2-基)氨基]-N-[5-取代-苯基-1,3,4-噻二唑-2-基]乙酰胺的合成与前瞻性探索“铅跳跃”，使用药效元素进行体内抗惊厥活性。这在使用最大电击癫痫 (MES) 和皮下戊四唑 (scPTZ) 测试的初步筛选中产生了三个有效的候选者（5i、5t 和 5u），显示出最小的神经毒性。他们的定量研究表明，在保护指数方面，MES 测试增加了近 2-10 倍，scPTZ 测试增加了 7-67 倍，这是抗惊厥活性药物发现的关键。
• Synthesis, characterization and biological evaluation of some novel fluoroquinolones
  作者：Neelanjana Pandit、Kamal Shah、Neetu Agrawal、Neeraj Upmanyu、Sushant K. Shrivastava、Pradeep Mishra

  DOI：10.1007/s00044-016-1526-x

  日期：2016.5

  Different derivatives of fluoroquinolones were synthesized by combining it with different thiadiazoles. The synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance and mass spectral data. The compounds were screened for their antibacterial and antifungal activity. Ciprofloxacin derivatives with thiadiazoles 7c showed good antibacterial as well as antifungal

  通过将氟喹诺酮与不同的噻二唑结合，可以合成出不同的氟喹诺酮衍生物。通过红外光谱，质子核磁共振和质谱数据对合成的化合物进行表征。筛选化合物的抗菌和抗真菌活性。环丙沙星衍生物与噻二唑7c表现出良好的抗菌和抗真菌活性，而13c和13e分别表现出抗菌和抗真菌活性。司帕沙星衍生物8c表现出抗菌和抗真菌活性。司帕沙星衍生物14b和14e分别显示出抗菌和抗真菌活性。