2-chloro-N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]acetamide

• 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-fluorophenyl)-1,3,4-thiadiazol-2-yl]acetamide
• 化学式: C₁₀H₇ClFN₃OS
• 分子量: 271.702
• InChiKey: GHBBAZLICRNQTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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：
  5

反应信息

• 作为反应物：
  描述：

  2-chloro-N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]acetamide 在 sodium methylate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 10.0h， 生成 2-[[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]imino]-5-(2-fluorobenzylidene)-1,3-thiazolidin-4-one
  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
• 作为产物：
  描述：

  4-fluorobenzoylthiosemicarbazide 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-fluorophenyl)-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
• Synthesis of 1,2,3‐triazole‐1,3,4‐thiadiazole hybrids as novel α‐glucosidase inhibitors by in situ azidation/click assembly
  作者：Hariom Kumar、Manoj Dhameja、Sirisha Kurella、Adepally Uma、Preeti Gupta

  DOI：10.1002/ardp.202300145

  日期：2023.8

  α‐Glucosidase inhibition is widely used in the oral management of diabetes mellitus (DM), a disease characterized by high blood sugar levels (hyperglycemia) and abnormal carbohydrate metabolism. In this respect, a series of 1,2,3‐triazole‐1,3,4‐thiadiazole hybrids 7a–j were synthesized, inspired by a copper‐catalyzed one‐pot azidation/click assembly approach. All the synthesized hybrids were screened for inhibition of the α‐glucosidase enzyme, displaying IC₅₀ values ranging from 63.35 ± 0.72 to 613.57 ± 1.98 μM, as compared to acarbose (reference) with IC₅₀ of 844.81 ± 0.53 μM. The hybrids 7h and 7e with 3‐nitro and 4‐methoxy substituents at the phenyl ring of the thiadiazole moiety were the best active hybrids of this series with IC₅₀ values of 63.35 ± 0.72 μM, and 67.61 ± 0.64 μM, respectively. Enzyme kinetics analysis of these compounds revealed a mixed mode of inhibition. Moreover, molecular docking studies were also performed to gain insights into the structure–activity‐relationships of the potent compounds and their corresponding analogs.

  摘要α-葡萄糖苷酶抑制剂被广泛应用于糖尿病（DM）的口服治疗，DM是一种以高血糖（高血糖症）和碳水化合物代谢异常为特征的疾病。在这方面，受铜催化的一锅叠氮化/点击组装方法的启发，合成了一系列 1,2,3-三唑-1,3,4-噻二唑杂化物 7a-j。对所有合成的杂交化合物进行了抑制α-葡萄糖苷酶的筛选，结果显示，与 IC50 为 844.81 ± 0.53 μM 的阿卡波糖（参照物）相比，这些杂交化合物的 IC50 值在 63.35 ± 0.72 到 613.57 ± 1.98 μM 之间。在噻二唑分子的苯基环上具有 3-硝基和 4-甲氧基取代基的杂交化合物 7h 和 7e 是该系列中活性最好的杂交化合物，其 IC50 值分别为 63.35 ± 0.72 μM 和 67.61 ± 0.64 μM。对这些化合物的酶动力学分析表明它们具有混合抑制模式。此外，还进行了分子对接研究，以深入了解这些强效化合物及其相应类似物的结构-活性关系。
• Derivatives of 2-(1,2,4-triazol-3-ylsulfanyl)-N-1,3,4-thiadiazol-2-yl acetamide which are useful for the treatment of inter alia diabetes
  申请人：APOGLYX AB

  公开号：US10011597B2

  公开（公告）日：2018-07-03

  Disclosed are compounds, pharmaceutical compositions and methods for modulating aquaporin 9.

  所公开的是调节水蒸气素 9 的化合物、药物组合物和方法。
• Synthesis, in-vitro α-glucosidase inhibition and molecular docking studies of 1,3,4-thiadiazole-5,6-diphenyl-1,2,4-triazine hybrids: Potential leads in the search of new antidiabetic drugs
  作者：Hariom Kumar、Manoj Dhameja、Sirisha Kurella、Adepally Uma、Preeti Gupta

  DOI：10.1016/j.molstruc.2022.134339

  日期：2023.2